title: The Coronavirus Pandemic and Lessons Learned in Preschools in Norway, Sweden and the United States: OMEP Policy Forum

text: The novel coronavirus, also known as COVID-19, has moved rapidly across the world in 2020. This article reports on the recent consequences of the pandemic for early childhood education in Sweden, Norway, and the United States. The authors illustrate the effects of the pandemic on preschools in their countries, against a backdrop of frequent changes in infection and mortality rates, epidemiological understandings, government strategies, and mitigation strategies regarding preschool closures. Teachers report their experiences and actions in specific early childhood education settings, across the three national contexts. These experiential snapshots identify program priorities, parents’ and children’s reactions, and the commitment and concerns of teachers. The conversations reveal culturally situated similarities of early childhood educational practices but also differences across contexts. Teachers report on the challenges of their experiences but also benefits for their practice and how they engage with children and their families. Ideas about future preparedness for such pandemics are also discussed.


title: Population movement, city closure and spatial transmission of the 2019-nCoV infection in China

text: The outbreak of pneumonia caused by a novel coronavirus (2019-nCoV) in Wuhan City of China obtained global concern, the population outflow from Wuhan has contributed to spatial expansion in other parts of China. We examined the effects of population outflow from Wuhan on the 2019-nCoV transmission in other provinces and cities of China, as well as the impacts of the city closure in Wuhan. We observed a significantly positive association between population movement and the number of cases. Further analysis revealed that if the city closure policy was implemented two days earlier, 1420 (95% CI: 1059, 1833) cases could be prevented, and if two days later, 1462 (95% CI: 1090, 1886) more cases would be possible. Our findings suggest that population movement might be one important trigger of the 2019-nCoV infection transmission in China, and the policy of city closure is effective to prevent the epidemic.


title: CoVID‐19 insights from transfusion medicine

text: The emergence of CoVID‐19 infection in the first months of 2020 resulted in a massive surge in admissions to hospitals and intensive care units due to the nature of the respiratory pathophysiology. In some countries, health care systems were rapidly overwhelmed, while in others their hospitals coped with the first wave and all patients received the level of care needed, depending upon both the containment measured and the level of development of the heath care systems.


title: Xijiao Dihuang Decoction combined with Yinqiao Powder reverses influenza virus-induced F-actin reorganization in PMVECs by inhibiting ERM phosphorylation

text: Abstract Objective It has been documented that ezrin/radixin/moesin (ERM) phosphorylation by the p38 mitogen-activated protein kinase (MAPK), Rho/ROCK, and protein kinase C (PKC) pathways leads to filamentous actin (F-actin) reorganization and microvascular endothelial cell hyperpermeability. In this study, we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder (XDY) on influenza virus (IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1 (ROCK), p38 MAPK, and PKC signaling pathways in pulmonary microvascular endothelial cells (PMVECs). Methods Serum containing XDY (XDY-CS; 13.8 g/kg) was acquired using standard protocols for serum pharmacology. Primary PMVECs were obtained from male Wistar rats and cultured. After adsorption of IV A (multiplicity of infection, 0.01) for 1 h, medium with 20% XDY-CS was added to the PMVECs. The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy, and F-actin expression was measured by flow cytometry. The expression levels of ROCK1, phosphorylated myosin phosphatase target-subunit (p-MYPT), phosphorylated MAPK kinase, phosphorylated p38 (p-p38), phosphorylated PKC (p-PKC), and phosphorylated ERM (p-ERM) were determined by western blotting. Results F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment, which was accompanied by reduced p-ERM production. The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV, which was also inhibited by XDY-CS treatment. In addition, XDY-CS treatment drastically reduced the levels of p-p38, ROCK1, p-MYPT, and p-PKC induced by IV infection in PMVECs. Conclusion These results show that XDY-CS inhibited influenza-induced F-actin reorganization in PMVECs by down-regulating p-ERM expression via inhibition of the Rho/ROCK, p38 MAPK, and PKC pathways. In conclusion, XDY could reduce the damage to endothelial cytoskeleton induced by IV infection, thus protecting the barriers of PMVECs.


COVID-19: (mis)managing an announced Black Swan


title: Simian hemorrhagic fever virus: Recent advances

text: Simian hemorrhagic fever virus (SHFV) is an understudied arterivirus that typically causes asymptomatic, persistent infections in multiple species of African nonhuman primates (NHPs) which are natural hosts but fatal hemorrhagic fever disease in macaques. SHFV genomes found in different species of African primates have recently been sequenced but no biological data for these viruses has yet been reported. The sequence of one SHFV isolate from a long term persistently infected baboon showed a high degree of identity to the genome of SHFV-LVR, the prototype strain isolated in the 1960s. Similar to what was observed in early studies with the prototype SHFV isolate LVR, infection of Japanese macaques with 100 PFU of the baboon isolate efficiently induced fatal hemorrhagic fever disease in macaques. Consistent with the differential infection outcomes observed in macaques and baboons, SHFV infection of macaque macrophages and dendritic cells is more efficiently than that of baboons and infection induces pro39 inflammatory cytokine production in macaque but not baboon cells. A stable full-length SHFV LVR infectious clone was constructed and basic knowledge about the unique functions of SHFV has been expanded by several recent studies. The SHFV genome encodes extra genes compared to those of other arteriviruses; three instead of two papain-like protease one (PLP1) domains are encoded at the 5’ end and two adjacent sets of four minor structural proteins at the 3’ end. SHFV PLP1α, PLP1β and PLP1γ were each shown to be active proteases in vitro and the three expected nsp1proteins were detected in infected cells. The catalytic Cys of PLP1α is adjacent to an Ala instead of canonical Typ and PLP1γ is unique among arterivirus PLPs in being able to cleave at both downstream and upstream sites. Although the duplicated sets of SHFV minor structural proteins were predicted to be functionally redundant, data obtained with a set of mutant infectious clones, each with the start codon of one of the minor structural proteins mutated, showed that all eight of the minor structural proteins are required for production of infectious extracellular virus.


title: Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution?

text: PURPOSE: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. METHODS: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI. RESULTS: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain–Barré syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma. CONCLUSION: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.


title: Detection and phylogenetic characterization of astroviruses in insectivorous bats from Central‐Southern Italy

text: In recent years, bats have been found to harbour many viruses, raising several questions about their role as reservoirs and potential disseminators of zoonotic viruses. We investigated the presence of six virus families in bats in three regions of Central‐Southern Italy. Astroviruses were identified in seven of 13 bat species. Sequence analysis revealed marked genetic heterogeneity among the astroviruses identified, with nucleotide identity ranging between 60.26% and 87.62%. Astrovirus diversity was not associated with the bat species, the geographic areas or the bat colony, suggesting the circulation of several astrovirus strains in Italian ecosystems. Genetic diversification and interspecies transmission appear common in bat astroviruses and could provide, potentially, the bases for transmission to humans and other mammals. Yet overemphasizing this risk might have detrimental consequences for bat conservation and preservation of the important ecosystem services bats provide.


Standardized risk assessment and management of exposure amongst healthcare workers to coronavirus disease 2019


title: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes

text: OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO(2)/FiO(2)≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.


title: High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus

text: Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses, causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix protein VP40 is involved in the virus assembly and budding process. The RNA binding pocket of VP40 is considered as the drug target site for structure based drug design. High Throughput Virtual Screening and molecular docking studies were employed to find the suitable inhibitors against VP40. Ten compounds showing good glide score and glide energy as well as interaction with specific amino acid residues were short listed as drug leads. These small molecule inhibitors could be potent inhibitors for VP40 matrix protein by blocking virus assembly and budding process.


title: Manejo de las infecciones respiratorias bacterianas en pediatría

text: Resumen Las infecciones respiratorias constituyen la principal causa de consulta y de hospitalización en pediatría. Dado que las infecciones respiratorias virales no requieren tratamiento antiviral específico (salvo excepciones puntuales) sino tratamiento sintomático y/o de soporte, en este artículo nos referiremos al manejo de las infecciones respiratorias bacterianas: faringoamigdalitis estreptocócica, sinusitis aguda bacteriana, otitis media aguda bacteriana y neumonía bacteriana adquirida en la comunidad. En el manejo de la faringitis estreptocócica destaca el uso de amoxicilina en una dosis diaria por 10 días. En sinusitis aguda, otitis media aguda y neumonía, la recomendación de tratamiento inicial lo constituye la amoxicilina a dosis de 80–100mg/kg/día. Se discuten algoritmos de manejo para cada una de estas patologías. Summary Respiratory infections are the main cause of consultation and hospitalization in children. Because viral respiratory infections do not require specific antiviral treatment (only in occasional exceptions), in this article we will refer to the management of bacterial respiratory infections: streptococcal pharyngitis, acute bacterial sinusitis, bacterial otitis media and bacterial community-acquired pneumonia. In the treatment of streptococcal pharyngitis, the use of amoxicillin (50mg/kg/day) in a daily dose for 10 days is a new recommendation. In acute sinusitis, acute otitis media and community-acquired pneumonia, the recommended initial treatment is amoxicillin in a dose of 80 –100mg/kg/day. Management algorithms for each of these conditions are discussed.


title: Novel SARS-like Betacoronaviruses in Bats, China, 2011

text: To clarify the evolutionary relationships among betavoronaviruses that infect bats, we analyzed samples collected during 2010–2011 from 14 insectivorous bat species in China. We identified complete genomes of 2 novel betacoronaviruses in Rhinolophus pusillus and Chaerephon plicata bats, which showed close genetic relationships with severe acute respiratory syndrome coronaviruses.


title: Antiviral Effect of Diammonium Glycyrrhizinate on Cell Infection by Porcine Parvovirus

text: Porcine parvovirus (PPV) can cause reproductive failure in swine, resulting in economic losses to the industry. Antiviral effects of diammonium glycyrrhizinate (DG) have been reported on several animal viruses; however, to date it has yet to be tested on PPV. In this study, the antiviral activity of DG on swine testis (ST) cell infection by PPV was investigated using an empirically determined, non-toxic concentration of DG and three different experimental designs: (1) pre-treatment of virus prior to infection; (2) pre-treatment of cells prior to infection; and (3) direct treatment of virus-infected cells. The results showed that DG possesses potent inhibitory effects on PPV when the virus was treated before incubation with ST cells and that virus infectivity decreased in a dose-dependent manner. Results were confirmed by indirect immunofluorescence assays and real-time quantitative PCR. In addition, deoxycholate was used as a control to exclude the possibility that DG acted as a detergent to inhibit PPV infectivity. The study clearly indicates that DG has a direct anti-PPV effect in vitro.


title: SARS-CoV-2 infection may result in appendicular syndrome: Chest CT scan before appendectomy

text: Abstract The initial clinical presentation of CoronaVirus Disease 2019 may be appendicular syndrome. An abdominal CT scan ruled out a diagnosis of appendicitis and a chest CT scan yielded a diagnosis of SARS-CoV-2 infection. CT scan is required before considering emergency surgery for acute appendicitis.


title: Chapter 404 Introduction The Clans and Families of Cysteine Peptidases

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 404 is Clans and Families of Cysteine Peptidases.


title: Evaluation of serological assays available in a biosafety level 2 laboratory and their application for survey of Middle East respiratory syndrome coronavirus among livestock in Ethiopia

text: A serological survey of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted among dromedary camels and herbivorous animals sharing the same pasturage in Ethiopia. The pseudotyped vesicular stomatitis virus coated with the spike protein of MERS-CoV was used in virus neutralization (VN) tests performed in a biosafety level (BSL)-2 laboratory. The results were similar to those obtained from the VN test using live MERS-CoV and were more sensitive than the ELISA performed using synthetic MERS S1 fragment as the antigen as well as the competitive ELISA performed using a monoclonal antibody against MERS-CoV. According to the comprehensive results of the four types of serodiagnosis methods, positive antibodies were detected only in dromedary camels and the remaining herbivorous animals were not infected with the virus. Moreover, using the present procedure, serological tests for MERS-CoV can be conducted even in BSL 2 laboratory.


title: Ultrasound-assisted extraction of five isoflavones from Iris tectorum Maxim

text: Abstract This study investigated the use of ultrasound-assisted extraction (UAE) to improve the extraction efficiency of the classical solvent extraction techniques such as maceration extraction (ME) and soxhlet extraction (SE) to extract five isoflavones (tectoridin, iristectorin B, iristectorin A, tectorigenin and iristectorigenin A) from Iris tectorum. The effects of various factors such as extraction solvent, solvent concentration, temperature, solvent to solid ratio, ultrasound power, extraction time and particle size on the yield of target components were investigated. The optimal UAE conditions found were: 70% (v/v) methanol solution, temperature 45°C, solvent to solid ratio 15ml/g, ultrasound power 150W, extraction time 45min and particle size 60–80 mesh. The results indicated that compared with ME at 18h and SE at 6h, UAE gave the highest extraction yields of tectoridin, iristectorin B, iristectorin A, tectorigenin, iristectorigenin A and total isoflavones at 45min. The results indicated that UAE was an alternative method for extracting isoflavones from I. tectorum.


title: Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial

text: OBJECTIVES: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below. TRIAL DESIGN: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial. INTERVENTION AND COMPARATOR: Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x10(6) cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics. MAIN OUTCOMES: The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO(2)/FiO(2) ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality. RANDOMISATION: After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC). TRIAL STATUS: REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as a COVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27(th) March 2020 and MHRA on 30(th) March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King’s College London, Guys and St Thomas’ Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT 03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017). FULL PROTOCOL: The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


title: Surgical management of head and neck tumours during the SARS-CoV (COVID-19) pandemic

text: Gestione chirurgica dei tumori testa e collo durante la pandemia da SARS-CoV (Covid-19).


title: Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks

text: PURPOSE: To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. METHODS: Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. DATA SOURCES: Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016. RESULTS: 226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28–34). Reported mortality was highest in South Asia (61% [95% CI 50–71]) and Sub-Saharan Africa (53% [95% CI 29–75]), in comparison to Western Europe (25% [95% CI 22–30]), North America (25% [95% CI 22–27]) and Australia (15% [95% CI 13–18]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24–30]), acute respiratory distress syndrome (37% [95% CI 32–44]), acute kidney injury (44% [95% CI 26–64]), and critically ill pregnant patients (10% [95% CI 5–19]). CONCLUSION: Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.


docid: bioaupeo

title: Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography

text: Abstract Patients with Coronavirus Disease 2019 (COVID-19) often have clinical characteristics, such as chest tightness and dyspnea. Continuous, unresolved dyspnea often indicates the progression of lung lesions. The mechanism that underlies the chest distress and dyspnea in patients with COVID-19 is still unclear. Chest CT has a higher sensitivity and can play an essential role in the diagnosis and treatment of the disease. However, our clinical observations showed that although some patients had significant chest distress and dyspnea, the lesions that were observed in the lungs during computed tomography were milder and not completely consistent with clinical symptoms. We analyzed the clinical characteristics, laboratory test results, and imaging findings of these patients. We found that extensive inflammation of the bilateral and respiratory bronchioles in patients with COVID-19 due to excessive activation of proinflammatory cytokines and chemotactic aggregation of T-lymphocytes at the site of inflammation are possible mechanisms underlying chest distress and dyspnea in patients with COVID-19. Short-time and lose-dose use of corticosteroid may be helpful to treat chest tightness and dyspnea in mild COVID-19 patients. Through this study, we aimed to improve our understanding of the pathogenesis of COVID-19.


docid: tclyhhwa

title: Bed bugs bite the hospitality industry? A framing analysis of bed bug news coverage

text: News coverage plays an important role in determining individuals' travel decisions and influencing the general tourism market. Bed bug infestation, as a growing crisis in the hospitality and tourism industry, has been featured in news coverage. This study conducted a framing analysis of news coverage that is pertinent to the bed bug crisis and to the hospitality and travel industry. Selected news articles, representing three different destinations, were retrieved from five national newspapers. Results showed that bed bug infestation has been framed as a typical health crisis, with aspects of consequence and seriousness featured. Findings further confirmed the hospitality and travel industry as frequently cited in the bed bug news coverage. A positive correlation existed between the mention of the hospitality and travel industry, and the use of either a thematic frame or the news frame consequence. Based on the findings, implications for tourism crisis management were discussed.


A time of reflection: a time for change


title: Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study

text: Summary Background Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR. Methods We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens. Findings Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001). Interpretation Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness. Funding University Hospital Clermont-Ferrand.


title: Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics

text: At the time of writing this commentary (February 2020), the coronavirus COVID‐19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS‐CoV‐2 virus may take many months. Moreover, vaccines based on viral‐encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS‐CoV‐2 virus infections. This idea is based on observations that the angiotensin‐converting enzyme 2 (ACE2) very likely serves as the binding site for SARS‐CoV‐2, the strain implicated in the current COVID‐19 epidemic, similarly to strain SARS‐CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS‐CoV‐2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.


title: An uneven pandemic

text: Coronavirus will play out very differently in the world's poorest nations


title: Determination of the Dependence of Thermal Diffusivity with Moringa Concentration by Thermal Lens as a Sensitive Experimental Technique

text: The use of photothermal techniques has become of special importance due to their versatile application in the thermal characterization of materials. Therefore, the thermal lens technique in the mismatched dual-beam mode is an alternative, sensitive and non-evasive tool that was used in this research to determine the thermal diffusivity of Moringa oleifera. The dual arrangement of the thermal lens technique is based on the use of an Ar(+)Xe excitation laser (422 nm) and a He–Ne laser (632 nm) test laser. Moringa solutions were prepared by green synthesis with different concentrations ranging from 1.56 mg·mL(−1), 3.12 mg·mL(−1), 6.25 mg·mL(−1) to 12.50 mg·mL(−1). Different optical techniques (UV–vis, FTIR, XPS and EDS) were used to characterize the Moringa leaf powders. Results showed that the increase of thermal diffusivity could be related to the presence of functional groups and metallic elements in Moringa elemental composition. In this work, it was found that the thermal diffusivity of Moringa increases with increasing concentration. This study will be useful for application in heat transport and drug release.


title: Biotinylated and radioactive cDNA probes in the detection by hybridization of bovine enteric coronavirus

text: Abstract cDNA, synthesized on bovine coronavirus (BCV) genomic RNA templates, could be used to detect very small quantities (i.e. 1 pg) of viral RNA by hybridization with either radioisotopic-labelled or biotinylated recombinant plasmids. Virus was optimally attached to nitrocellulose membranes when spotted in 1 × SSC, whereas 20 × SSC was superior for viral RNA. Denaturation and RNA fixation of both RNA, still encapsidated in virus particles and isolated genomic RNA, was achieved by baking of the blots in vacuum. Virus detection in the supernatant of infected HRT-18 cells was feasible, but improved significantly after proteinase K treatment. No homology was observed between virus cDNA with either plasmid DNA or nucleic acid isolated from non-infected HRT-18 cells. Hybridization with radioisotopic-labelled probes in higher formamide concentrations (up to 60%) increased the detection signals, possibly by reducing reassociation of the probe. Significant detection amplification (30–50 times) was achieved in the case of biotinylated probes by stimulation of hyperpolymer formation on already hybridized target sequences, by additional hybridization with biotinylated pUC-19. A detection amplification was also obtained when hybridization was done with two probes (pBC-52 and pBC-247), containing non-overlapping viral sequences. Although the detectability was surpassed by biotinylated probes, sensitivity was superior in radioisotopic virus detection.


title: Is conscientious objection incompatible with a physician’s professional obligations?

text: In response to physicians who refuse to provide medical services that are contrary to their ethical and/or religious beliefs, it is sometimes asserted that anyone who is not willing to provide legally and professionally permitted medical services should choose another profession. This article critically examines the underlying assumption that conscientious objection is incompatible with a physician’s professional obligations (the “incompatibility thesis”). Several accounts of the professional obligations of physicians are explored: general ethical theories (consequentialism, contractarianism, and rights-based theories), internal morality (essentialist and non-essentialist conceptions), reciprocal justice, social contract, and promising. It is argued that none of these accounts of a physician’s professional obligations unequivocally supports the incompatibility thesis.


Children with cancer in the time of COVID‐19: An 8‐week report from the six pediatric onco‐hematology centers in Lombardia, Italy


title: 2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations

text: The outbreak of pneumonia originating in Wuhan, China, has generated 830 confirmed cases, including 26 deaths, as of 24 January 2020. The virus (2019-nCoV) has spread elsewhere in China and to other countries, including South Korea, Thailand, Japan and USA. Fortunately, there has not yet been evidence of sustained human-to-human transmission outside of China. Here we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.37. However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.005. This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a large global epidemic.


title: COVID-19 and smoking: is nicotine the hidden link?

text: Nicotine via alpha7-nicotinic receptor induces ACE-2 overexpression in human bronchial epithelial cells (HBEpC) https://bit.ly/3eJ5b35


Mental wellbeing and burnout in surgical trainees: implications for the post‐COVID‐19 era


title: Forecasting the cumulative number of COVID-19 deaths in China: a Boltzmann function-based modeling study

text: The COVID-19 outbreak is ongoing in China. Here, Boltzmann function-based analyses reveal the potential total numbers of COVID-19 deaths: 3,260 (95% confidence interval [CI], 3187–3394) in China; 110 (95% CI, 109–112) in Hubei Province; 3,174 (95% CI, 3095–3270) outside Hubei; 2,550 (95% CI, 2494–2621) in Wuhan City; and 617 (95% CI, 607–632) outside Wuhan.


title: A predictive model and scoring system combining clinical and CT characteristics for the diagnosis of COVID-19

text: OBJECTIVES: To develop a predictive model and scoring system to enhance the diagnostic efficiency for coronavirus disease 2019 (COVID-19). METHODS: From January 19 to February 6, 2020, 88 confirmed COVID-19 patients presenting with pneumonia and 80 non-COVID-19 patients suffering from pneumonia of other origins were retrospectively enrolled. Clinical data and laboratory results were collected. CT features and scores were evaluated at the segmental level according to the lesions’ position, attenuation, and form. Scores were calculated based on the size of the pneumonia lesion, which graded at the range of 1 to 4. Air bronchogram, tree-in-bud sign, crazy-paving pattern, subpleural curvilinear line, bronchiectasis, air space, pleural effusion, and mediastinal and/or hilar lymphadenopathy were also evaluated. RESULTS: Multivariate logistic regression analysis showed that history of exposure (β = 3.095, odds ratio (OR) = 22.088), leukocyte count (β = − 1.495, OR = 0.224), number of segments with peripheral lesions (β = 1.604, OR = 1.604), and crazy-paving pattern (β = 2.836, OR = 2.836) were used for establishing the predictive model to identify COVID-19-positive patients (p < 0.05). In this model, values of area under curve (AUC) in the training and testing groups were 0.910 and 0.914, respectively (p < 0.001). A predicted score for COVID-19 (PSC-19) was calculated based on the predictive model by the following formula: PSC-19 = 2 × history of exposure (0–1 point) − 1 × leukocyte count (0–2 points) + 1 × peripheral lesions (0–1 point) + 2 × crazy-paving pattern (0–1 point), with an optimal cutoff point of 1 (sensitivity, 88.5%; specificity, 91.7%). CONCLUSIONS: Our predictive model and PSC-19 can be applied for identification of COVID-19-positive cases, assisting physicians and radiologists until receiving the results of reverse transcription–polymerase chain reaction (RT-PCR) tests. KEY POINTS: • Prediction of RT-PCR positivity is crucial for fast diagnosis of patients suspected of having coronavirus disease 2019 (COVID-19). • Typical CT manifestations are advantageous for diagnosing COVID-19 and differentiation of COVID-19 from other types of pneumonia. • A predictive model and scoring system combining both clinical and CT features were herein developed to enable high diagnostic efficiency for COVID-19.


Viral Etiology of Common Cold in Children, Finland


title: Development and Implementation of a Clinician-facing Prognostic Communication Tool for Patients with COVID-19 and Critical Illness

text: Abstract Effective prognostication for a novel disease presents significant challenges, especially given the stress induced during a pandemic. We developed a point-of-care tool to summarize outcome data for critically ill patients with COVID-19 and help guide clinicians through a thoughtful prognostication process. Two authors reviewed studies of outcomes of patients with critical illness due to COVID-19 and created a visual infographic tool based on available data. Survival data were supplemented by descriptions of best and worst-case clinical scenarios. The tool also included prompts for clinician reflection designed to enhance awareness of cognitive biases that may affect prognostic accuracy. This online, open source COVID-19 Prognostication Tool has been made available to all clinicians at our institution and is updated weekly to reflect evolving data. Our COVID-19 Prognostication Tool may provide a useful approach to promoting consistent and high-quality prognostic communication across a healthcare system.


docid: daiikgth

title: Public knowledge and preventive behavior during a large-scale Salmonella outbreak: results from an online survey in the Netherlands

text: BACKGROUND: Food-borne Salmonella infections are a worldwide concern. During a large-scale outbreak, it is important that the public follows preventive advice. To increase compliance, insight in how the public gathers its knowledge and which factors determine whether or not an individual complies with preventive advice is crucial. METHODS: In 2012, contaminated salmon caused a large Salmonella Thompson outbreak in the Netherlands. During the outbreak, we conducted an online survey (n = 1,057) to assess the general public’s perceptions, knowledge, preventive behavior and sources of information. RESULTS: Respondents perceived Salmonella infections and the 2012 outbreak as severe (m = 4.21; five-point scale with 5 as severe). Their knowledge regarding common food sources, the incubation period and regular treatment of Salmonella (gastro-enteritis) was relatively low (e.g., only 28.7% knew that Salmonella is not normally treated with antibiotics). Preventive behavior differed widely, and the majority (64.7%) did not check for contaminated salmon at home. Most information about the outbreak was gathered through traditional media and news and newspaper websites. This was mostly determined by time spent on the medium. Social media played a marginal role. Wikipedia seemed a potentially important source of information. CONCLUSIONS: To persuade the public to take preventive actions, public health organizations should deliver their message primarily through mass media. Wikipedia seems a promising instrument for educating the public about food-borne Salmonella.


title: Transgene Pflanzen als orale Impfstoffe Grüne Revolution in der Medizin?: Grüne Revolution in der Medizin?

text: With the methods of molecular biotechnology it is possible today to produce therapeutical effectiv proteins in plants. So called edible vaccines can be used for active immunization as well as for passive immunization. For an efficient production of recombinant proteins a procedure was developed, in which only the leaves are treated with genetically modified bacteria instead of the time consuming regeneration of transgenic plants. With an orally applicated vaccine a complete systematic immune response can be induced, but in comparison to a parenteral injection, a 100 times higher dosis of the antigen is necessary. The immunogenity of antigens produced in plants was confirmed in several animal experiments. Clinical studies with recombinant antibodies of transgenic plants against the caries pathogen Streptococcus mutans were successful. Future studies will focus on improved production rates, the search for suitable plant species and the phenomenon of oral tolerance.


title: Electrophoretic fractionation of creatine kinase isoenzymes and macroenzymes in clinically healthy dogs and cats and preliminary evaluation in central neurologic disease

text: Background: Information about the electrophoretic distribution of CK‐MM, CK‐MB, and CK‐BB, serum creatine kinase (CK) isoenzymes that are indicators of skeletal muscle, cardiac muscle, and brain lesions, respectively, and CK macroenzymes (macro‐CK1 and macro‐CK2) in dogs and cats with and without central neurologic disease is scant and equivocal. Objectives: The objectives of this study were to describe the electrophoretic distribution of CK isoenzymes and macroenzymes in healthy dogs and cats and to provide a preliminary assessment of the utility of CK enzymatic electrophoresis in dogs and cats with central neurologic disease. Methods: Electrophoretic separation of serum CK isoenzymes and macroenzymes was performed on freeze‐thawed serum samples from 20 healthy dogs and 3 dogs with central neurologic disease and from 14 healthy cats and 6 cats with neurologic feline infectious peritonitis (FIP). Electrophoretic separation was also performed on supernatants of homogenized brain, skeletal muscle, and cardiac muscle from both species, to assess the tissue distribution of isoenyzmes in dogs and cats. Results: CK‐MM was the predominant isoenzyme in the serum of healthy dogs and cats, followed by macro‐CK2 and CK‐BB in dogs and by both macroenzymes in cats. In dogs, CK‐MB was essentially absent from both serum and homogenized hearts. CK‐BB increased in dogs with neurologic disease. In cats, CK‐BB was essentially absent from serum, but was present in brain homogenates. Two of 6 cats with FIP had increased macro‐CK1 and increased CK‐BB activity. Conclusions: This study identified the electophoretic distribution of CK isoenzymes and macroenzymes of dogs and cats and provided encouraging data about the possible use of CK‐BB as a biomarker for canine neurologic disorders, but not for FIP.


title: Introduction of SARS in France, March–April, 2003

text: We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription–polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22–23. Timely detection, isolation of probable cases, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France.


title: Theoretical conditions for the coexistence of viral strains with differences in phenotypic traits: a bifurcation analysis

text: We investigate the dynamics of a wild-type viral strain which generates mutant strains differing in phenotypic properties for infectivity, virulence and mutation rates. We study, by means of a mathematical model and bifurcation analysis, conditions under which the wild-type and mutant viruses, which compete for the same host cells, can coexist. The coexistence conditions are formulated in terms of the basic reproductive numbers of the strains, a maximum value of the mutation rate and the virulence of the pathogens. The analysis reveals that parameter space can be divided into five regions, each with distinct dynamics, that are organized around degenerate Bogdanov–Takens and zero-Hopf bifurcations, the latter of which gives rise to a curve of transcritical bifurcations of periodic orbits. These results provide new insights into the conditions by which viral populations may contain multiple coexisting strains in a stable manner.


title: Diabetes and metabolic syndrome as risk factors for COVID-19

text: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.


title: Comparison of viral replication and IFN response in alpaca and bovine cells following bovine viral diarrhea virus infection

text: Abstract Alpacas develop diminished disease following bovine viral diarrhea virus (BVDV) infection compared to cattle. We hypothesized that alpaca and bovine cells have differential permissiveness and responses to BVDV infection. To characterize alpaca testicular (AT) and bovine turbinate (BT) cells BVDV infection permissiveness, viral replication and interferon (IFN) synthesis was evaluated. BVDV replicated 3–4 logs lower in AT cells with diminished antigen deposition compared to BT cells. BVDV infection inhibited IFN response in both AT and BT cells. Compared to BT cells, BVDV-infected AT cells had a 2–5 fold increase in IFN synthesis following dsRNA stimulation. The greater IFN response of AT cells compared to BT cells following poly I:C stimulation with or without ncp BVDV infection, may be the basis for the decreased BVDV permissiveness of AT cells and may contribute to the clinical differences following BVDV infection of alpacas and cattle.


title: OCCUPATIONAL DISEASES | Overview

text: This overview describes the main categories of specific occupational disorders and it covers also how work exposures are potential determinants of common respiratory conditions. Acute inhalation injuries may present as inhalation fever or as acute tracheobronchitis and pneumonitis. Occupational asthma is the most frequent work-related respiratory disease. It may be caused by allergic sensitization to macromolecules of biologic origin or to chemicals of low molecular weight, as well as by (heavy) exposure to workplace irritants. The pneumoconioses are caused by the accumulation of dust particles or fibres in the lungs. They include silicosis, coal workers’ pneumoconioses, asbestosis and other less common pneumoconioses. Chronic beryllium disease is caused by a cell-mediated sensitization to beryllium and resembles sarcoidosis. Hard-metal lung disease is caused by sensitivity to cobalt and resembles hypersensitivity pneumonitis. Extrinsic allergic alveolitis or hypersensitivity pneumonitis is generally caused by sensitization to aerosolized biological antigens. Several types of infections may be related more or less specifically to work. Chronic obstructive lung disease is mainly caused by cigarette smoking, but exposure to dusts and gases contribute to its incidence. Similarly, bronchopulmonary cancer is not only caused by smoking, but also by occupational agents, most notably asbestos. Asbestos is also a cause of nonmalignant and malignant pleural disease.


title: Predictive symptoms and comorbidities for severe COVID-19 and intensive care unit admission: a systematic review and meta-analysis

text: OBJECTIVES: COVID-19 has a varied clinical presentation. Elderly patients with comorbidities are more vulnerable to severe disease. This study identifies specific symptoms and comorbidities predicting severe COVID-19 and intensive care unit (ICU) admission. METHODS: A literature search identified studies indexed in MEDLINE, EMBASE and Global Health before 5th March 2020. Two reviewers independently screened the literature and extracted data. Quality appraisal was performed using STROBE criteria. Random effects meta-analysis identified symptoms and comorbidities associated with severe COVID-19 or ICU admission. RESULTS: Seven studies (including 1813 COVID-19 patients) were included. ICU patients were older (62.4 years) than non-ICU (46 years), with a greater proportion of males. Dyspnoea was the only symptom predictive for severe disease (pOR 3.70, 95% CI 1.83–7.46) and ICU admission (pOR 6.55, 95% CI 4.28–10.0). COPD was the strongest predictive comorbidity for severe disease (pOR 6.42, 95% CI 2.44–16.9) and ICU admission (pOR 17.8, 95% CI 6.56–48.2), followed by cardiovascular disease and hypertension. CONCLUSIONS: Dyspnoea was the only symptom predictive for severe COVID-19 and ICU admission. Patients with COPD, cardiovascular disease and hypertension were at higher risk of severe illness and ICU admission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00038-020-01390-7) contains supplementary material, which is available to authorized users.


title: Seroprevalence of Rodent Pathogens in Wild Rats from the Island of St. Kitts, West Indies

text: SIMPLE SUMMARY: The role of rodents in the transmission of many diseases is widely known. Wild rats abundant in urban environments may transmit diseases to humans and other animals, including laboratory rodents used for biomedical research in research facilities, possibly compromising research data. In order to gather information about the various diseases present around such facilities, it is important to conduct routine surveillance of wild rodents in the area. In this pilot study, we surveyed 22 captured wild rats (Rattus norvegicus and Rattus rattus) from the Caribbean island of St. Kitts for 19 microorganisms. Information gained from such surveillance data would be beneficial in assessing regional public health risks and when implementing routine laboratory rodent health monitoring protocols. ABSTRACT: A pilot seroprevalence study was conducted to document exposure to selected pathogens in wild rats inhabiting the Caribbean island of St. Kitts. Serum samples collected from 22 captured wild rats (Rattus norvegicus and Rattus rattus) were tested for the presence of antibodies to various rodent pathogens using a rat MFI2 serology panel. The samples were positive for cilia-associated respiratory bacillus (13/22; 59.1%), Clostridium piliforme (4/22; 18.2%), Mycoplasma pulmonis (4/22; 18.2%), Pneumocystis carinii (1/22; 4.5%), mouse adenovirus type 2 (16/22; 72.7%), Kilham rat virus (15/22; 68.2%), reovirus type 3 (9/22; 40.9%), rat parvovirus (4/22; 18.2%), rat minute virus (4/22; 18.2%), rat theilovirus (2/22; 9.1%), and infectious diarrhea of infant rats strain of group B rotavirus (rat rotavirus) (1/22; 4.5%). This study provides the first evidence of exposure to various rodent pathogens in wild rats on the island of St. Kitts. Periodic pathogen surveillance in the wild rat population would be beneficial in assessing potential regional zoonotic risks as well as in enhancing the current knowledge when implementing routine animal health monitoring protocols in facilities with laboratory rodent colonies.


title: Lung ultrasound in a Singapore COVID-19 intensive care unit patient and a review of its potential clinical utility in pandemic

text: Background: Point-of-care bedside lung ultrasound is a diagnostic adjunct in the management of respiratory diseases We describe the clinical progress and lung ultrasound findings of a Singaporean COVID-19 intensive care unit patient who was diagnosed with COVID-19 infection Methods: The clinical course of one COVID-19 patient managed in the intensive care unit was traced The patient was diagnosed with COVID-19 virus infection and intubated after developing respiratory failure Serial point-of-care bedside lung ultrasound was performed by the managing intensivist daily, and correlated with the clinical progress and chest X-ray imaging done for the patient Results: The patient exhibited lung ultrasound findings consistent with that described for viral pneumonias This included numerous B-lines and subpleural consolidations with disrupted pleural lines distributed symmetrically, predominantly in bilateral upper BLUE points, and lower BLUE points bilaterally Coalescing B-lines leading on to the development of bilateral "white lung" were associated with worsening acute respiratory distress syndrome An increased density or reduction of the B-lines was associated with clinical improvement or deterioration, respectively Conclusions: Trained clinicians, who are familiar with point-of-care lung ultrasonography, may consider point-of-care bedside ultrasound as an important adjunct to history and physical examination for the diagnosis and management of COVID-19 when advanced imaging is not available because of logistical reasons or infectious control This applies in particular to cases where resources are limited, and patient transfers to facilities offering such services may prove hazardous Background: Point-of-care bedside lung ultrasound is a diagnostic adjunct in the management of respiratory diseases We describe the clinical progress and lung ultrasound findings of a Singaporean COVID-19 intensive care unit patient who was diagnosed with COVID-19 infection Methods: The clinical course of one COVID-19 patient managed in the intensive care unit was traced The patient was diagnosed with COVID-19 virus infection and intubated after developing respiratory failure Serial point-of-care bedside lung ultrasound was performed by the managing intensivist daily, and correlated with the clinical progress and chest X-ray imaging done for the patient Results: The patient exhibited lung ultrasound findings consistent with that described for viral pneumonias This included numerous B-lines and subpleural consolidations with disrupted pleural lines distributed symmetrically, predominantly in bilateral upper BLUE points, and lower BLUE points bilaterally Coalescing B-lines leading on to the development of bilateral “white lung” were associated with worsening acute respiratory distress syndrome An increased density or reduction of the B-lines was associated with clinical improvement or deterioration, respectively Conclusions: Trained clinicians, who are familiar with point-of-care lung ultrasonography, may consider point-of-care bedside ultrasound as an important adjunct to history and physical examination for the diagnosis and management of COVID-19 when advanced imaging is not available because of logistical reasons or infectious control This applies in particular to cases where resources are limited, and patient transfers to facilities offering such services may prove hazardous


title: Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: An in silico investigation

text: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an in silico approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve Clerodendrum species against the imperative spike protein, main protease enzyme M(pro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski’s rule of five and Veber’s rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol in vitro and in vivo towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19. Communicated by Ramaswamy H. Sarma


title: Laboratory-Acquired Infections

text: Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most common causes. Infections due to the bloodborne pathogens (hepatitis B virus, hepatitis C virus, and human immunodeficiency virus) remain the most common reported viral infections, whereas the dimorphic fungi are responsible for the greatest number of fungal infections. Because of the increasing attention on the role of the laboratory in bioterrorism preparation, I discuss the risk of laboratory-acquired infection with uncommon agents, such as Francisella tularensis and Bacillus anthracis. Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the importance of alerting the laboratory if infection with a high-risk agent is suspected.


title: Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: a meta-analysis approach

text: BACKGROUND: The availability of gene expression data that corresponds to pig immune response challenges provides compelling material for the understanding of the host immune system. Meta-analysis offers the opportunity to confirm and expand our knowledge by combining and studying at one time a vast set of independent studies creating large datasets with increased statistical power. In this study, we performed two meta-analyses of porcine transcriptomic data: i) scrutinized the global immune response to different challenges, and ii) determined the specific response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection. To gain an in-depth knowledge of the pig response to PRRSV infection, we used an original approach comparing and eliminating the common genes from both meta-analyses in order to identify genes and pathways specifically involved in the PRRSV immune response. The software Pointillist was used to cope with the highly disparate data, circumventing the biases generated by the specific responses linked to single studies. Next, we used the Ingenuity Pathways Analysis (IPA) software to survey the canonical pathways, biological functions and transcription factors found to be significantly involved in the pig immune response. We used 779 chips corresponding to 29 datasets for the pig global immune response and 279 chips obtained from 6 datasets for the pig response to PRRSV infection, respectively. RESULTS: The pig global immune response analysis showed interconnected canonical pathways involved in the regulation of translation and mitochondrial energy metabolism. Biological functions revealed in this meta-analysis were centred around translation regulation, which included protein synthesis, RNA-post transcriptional gene expression and cellular growth and proliferation. Furthermore, the oxidative phosphorylation and mitochondria dysfunctions, associated with stress signalling, were highly regulated. Transcription factors such as MYCN, MYC and NFE2L2 were found in this analysis to be potentially involved in the regulation of the immune response. The host specific response to PRRSV infection engendered the activation of well-defined canonical pathways in response to pathogen challenge such as TREM1, toll-like receptor and hyper-cytokinemia/ hyper-chemokinemia signalling. Furthermore, this analysis brought forth the central role of the crosstalk between innate and adaptive immune response and the regulation of anti-inflammatory response. The most significant transcription factor potentially involved in this analysis was HMGB1, which is required for the innate recognition of viral nucleic acids. Other transcription factors like interferon regulatory factors IRF1, IRF3, IRF5 and IRF8 were also involved in the pig specific response to PRRSV infection. CONCLUSIONS: This work reveals key genes, canonical pathways and biological functions involved in the pig global immune response to diverse challenges, including PRRSV infection. The powerful statistical approach led us to consolidate previous findings as well as to gain new insights into the pig immune response either to common stimuli or specifically to PRRSV infection.


title: Complete genome analysis of a SARS-like bat coronavirus identified in the Republic of Korea

text: Bats have been widely known as natural reservoir hosts of zoonotic diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) caused by coronaviruses (CoVs). In the present study, we investigated the whole genomic sequence of a SARS-like bat CoV (16BO133) and found it to be 29,075 nt in length with a 40.9% G+C content. Phylogenetic analysis using amino acid sequences of the ORF 1ab and the spike gene showed that the bat coronavirus strain 16BO133 was grouped with the Beta-CoV lineage B and was closely related to the JTMC15 strain isolated from Rhinolophus ferrumequinum in China. However, 16BO133 was distinctly located in the phylogenetic topology of the human SARS CoV strain (Tor2). Interestingly, 16BO133 showed complete elimination of ORF8 regions induced by a frame shift of the stop codon in ORF7b. The lowest amino acid identity of 16BO133 was identified at the spike region among various ORFs. The spike region of 16BO133 showed 84.7% and 75.2% amino acid identity with Rf1 (SARS-like bat CoV) and Tor2 (human SARS CoV), respectively. In addition, the S gene of 16BO133 was found to contain the amino acid substitution of two critical residues (N479S and T487 V) associated with human infection. In conclusion, we firstly carried out whole genome characterization of the SARS-like bat coronavirus discovered in the Republic of Korea; however, it presumably has no human infectivity. However, continuous surveillance and genomic characterization of coronaviruses from bats are necessary due to potential risks of human infection induced by genetic mutation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01668-w) contains supplementary material, which is available to authorized users.


docid: sceioxhq

title: Recommendations for Treatment of Nail Lichen Planus During the COVID‐19 Pandemic


title: Outlining the keyword co-occurrence trends in Shuanghuanglian injection research: A bibliometric study using CiteSpace III

text: Abstract Objective To explore the evolvement and new trends in the use of Shuanghuanglian injection (SHLI). Methods China National Knowledge Infrastructure (CNKI), PubMed, and Embase were extensively searched using the search terms “Shuanghuanglian injection” and “Shuanghuanglian fenzhen” to retrieve articles relevant to SHLI (1992–2020). Retrieved articles were further investigated by two authors to exclude those unrelated to SHLI. The bibliographical references of the included articles were exported as raw data and then treated using the CiteSpace tool to visualize the mapping of the SHLI research domain. Essential clusters and highly frequent keywords were quantified for further analysis. The clusters were automatically labeled by the algorithm of tf*idf for objective analysis. Basic bibliometric features, including article types and yearly trend in article numbers were also determined and discussed. Results The modules of the keywords of interest presented clear boundaries with a high modularity score (Q = 0.73). High-confidence clusters were identified, including bioactivity fingerprint (S = 0.99), equal pupils (S = 0.91), drug preparation department (S = 0.87), difficulty in respiration (S = 0.85), peristalsis (0.88), and Danshen powder injection (S = 0.94). The characteristic keywords in terms of frequency and burstiness were Shuanghuanglian powder for injection (F = 235, B = 5.22), SHLI (F = 112, B = 11.39), and adverse drug reactions (ADRs; F = 104, B = 7.35). Conclusion In the field of SHLI study, there are five major topic categories: bioactivity fingerprint; ADR mechanism and cause detection; proper preparation; clinical evidence accumulation; and efficacy in diseases with no effective treatment and combination usage. The trend for using modern methodologies from a science-based perspective to study SHLI will continue to exist. The causes of multi-factorial ADRs may be an important topic for future studies.


title: Course of Illness after Viral Infection in Indian Children with Cystic Fibrosis

text: OBJECTIVE: To study the clinical impact of respiratory viral infection in children with cystic fibrosis (CF). DESIGN: Retrospective cohort study. SETTING: Tertiary care referral centre for CF in India. PARTICIPANTS/PATIENTS: Children with CF attending a pediatric chest clinic. METHODS: Case records of the children with CF who had a pulmonary exacerbation with documented acute respiratory viral infection between October 2013 and December 2014 (Group I) and an equal number of controls (Group II) with pulmonary exacerbation in absence of acute respiratory viral infection were reviewed. OUTCOME MEASURES: The two groups were compared for the following outcomes over a period of 12–18 months: bacterial colonization, antibiotics usage, pulmonary exacerbations, numbers of outpatient visits, hospitalization and oxygen therapy and spirometric parameters. RESULTS: In total, 46 children [23 each with viral infection (Group I) and without viral infection (Group II)] of age 7–264 months were enrolled; baseline clinical status and pulmonary function tests were comparable. Mean (SD) follow-up duration in those who had viral infection and who had no viral infection was 15.7 (7.1) and 17.5 (5.4) months, respectively. On follow-up, children with viral infection (Group I) had adverse outcome in form of greater worsening of Shwachman clinical scores, number of pulmonary exacerbations requiring antibiotic usage [4 (2.1%)] and [2.8 (1.7%)], need for intravenous antibiotics 30.4% vs. 8.7%, hospitalization rates 31.8% vs. 4.3% and mortality 30.4% vs. 4.7%, respectively. CONCLUSION: Acute viral infection in children with CF affected course of illness on follow-up, including frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12–18 months.


title: Combination of IMOD™ and Arbidol to increase their immunomodulatory effects as a novel medicine to prevent and cure influenza and some other infectious diseases

text: Abstract Viral diseases such as influenza, which are easily transferable from person to person or even country to country, pose one of the biggest threats to health today. Viruses such as avian influenza viruses (N1H5 and H9N1) have been reported to spread in the present decade and, very recently, the novel coronavirus that has caused many life-threatening illnesses and deaths all around the world has received much attention. To prevent these highly contagious viral infections, we have proposed the combination of IMOD™ and Arbidol to increase their immunomodulatory effects as a novel medicine to prevent and cure influenza and some other infectious diseases such as hepatitis B and C. On the one hand, IMOD™ within the last few years has been proven to safely and effectively increase the life expectancy for human immunodeficiency virus (HIV)-infected individuals by increasing CD4 lymphocytes. On the other hand, Arbidol, an antiviral agent has been used safely and effectively in the past two decades to prevent and cure all types of influenza and flu. Therefore, the combination of both in a single dosage to further increase CD4 lymphocytes and interferon gamma (IFN-γ) could be a better choice for treatment of viral infections. This proposal tries to provide enough support and background for approval of a randomized clinical trial by a relevant team of investigators.


title: Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

text: Approximately 4.4% of the human genome is comprised of endogenous retroviral sequences, a record of an evolutionary battle between man and retroviruses. Much of what we know about viral immunity comes from studies using mouse models. Experiments using the Friend virus (FV) model have been particularly informative in defining highly complex anti-retroviral mechanisms of the intrinsic, innate and adaptive arms of immunity. FV studies have unraveled fundamental principles about how the immune system controls both acute and chronic viral infections. They led to a more complete understanding of retroviral immunity that begins with cellular sensing, production of type I interferons, and the induction of intrinsic restriction factors. Novel mechanisms have been revealed, which demonstrate that these earliest responses affect not only virus replication, but also subsequent innate and adaptive immunity. This review on FV immunity not only surveys the complex host responses to a retroviral infection from acute infection to chronicity, but also highlights the many feedback mechanisms that regulate and counter-regulate the various arms of the immune system. In addition, the discovery of molecular mechanisms of immunity in this model have led to therapeutic interventions with implications for HIV cure and vaccine development.


title: Changes in nucleolar morphology and proteins during infection with the coronavirus infectious bronchitis virus

text: The nucleolus is a dynamic subnuclear structure involved in ribosome subunit biogenesis, cell cycle control and mediating responses to cell stress, among other functions. While many different viruses target proteins to the nucleolus and recruit nucleolar proteins to facilitate virus replication, the effect of infection on the nucleolus in terms of morphology and protein content is unknown. Previously we have shown that the coronavirus nucleocapsid protein will localize to the nucleolus. In this study, using the avian infectious bronchitis coronavirus, we have shown that virus infection results in a number of changes to the nucleolus both in terms of gross morphology and protein content. Using confocal microscopy coupled with fluorescent labelled nucleolar marker proteins we observed changes in the morphology of the nucleolus including an enlarged fibrillar centre. We found that the tumour suppressor protein, p53, which localizes normally to the nucleus and nucleolus, was redistributed predominately to the cytoplasm.


title: Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19

text: The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID‐19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID‐19 patients. We investigated 43 adult patients with COVID‐19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin‐6 (IL‐6), d‐dimer (d‐D), glucose, thrombin time, fibrinogen, and C‐reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL‐6 were 24.3 and 0.795 µg/L, respectively, while those of d‐D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL‐6 combined with d‐D was 0.840. The specificity of predicting the severity of COVID‐19 during IL‐6 and d‐D tandem testing was up to 93.3%, while the sensitivity of IL‐6 and d‐D by parallel test in the severe COVID‐19 was 96.4%. IL‐6 and d‐D were closely related to the occurrence of severe COVID‐19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID‐19 patients, which has important clinical value.


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title: Current targeted therapeutics against COVID-19: based on first-line experience in china

text: Abstract SARS-CoV-2 is a novel strain, causing a global pandemic since the end of 2019. The majority of patients showed nonspecific symptoms such as fever, dry cough, and fatigue. Most patients have a good prognosis while some with severe conditions could rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and even die. The exacerbation of the patient's condition may be due to a cytokine storm in the body. Effective targeted therapies including antiviral and immunization are urgently needed. Although many clinical trials are already underway and the majority of patients have received antiviral therapy based on medication experience with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and preliminary results from some clinical trials, there are no antiviral drugs proven to be effective currently. We summarize the current therapeutic medicines used in the clinic, hope to be able to provide some implications for clinical medication.


title: Evaluation of porcine epidemic diarrhea virus transmission and the immune response in growing pigs

text: Clinical disease associated with porcine epidemic diarrhea virus (PEDV) infection in naïve pigs is well chronicled; however, information on endemic PEDV infection is limited. To characterize chronic PEDV infection, the duration of infectious virus shedding and development of protective immunity was determined. On Day 0 (D0), a growing pig was challenged with PEDV and 13 contacts were commingled. On D7, 9 contact pigs (principal virus group (PG)), were selected, moved to a separate room and commingled with one sentinel pig (S1). This process was repeated weekly with S2, S3 and S4. The PG was PEDV-positive by PCR from D3-11, with some pigs intermittently positive to D42. Pigs S1 and S2 were PEDV-positive within 24 hours of commingling. Antibodies were detected in all PG by D21 and by 7 days post-contact in S1 and S2. Pigs S3 and S4 were PCR and antibody negative following commingling. To evaluate protective immunity, 5 naïve pigs (N) and the PG were challenged (N/C, PG/C) with homologous virus on D49. All N/C pigs were PEDV PCR-positive by D52 with detection out to D62 in 3/5 N/C pigs. All PG/C pigs were PEDV PCR-negative post-challenge. By D63, all N/C seroconverted. Although PEDV RNA was demonstrated in pigs after primary infection until D42, infectious PEDV capable of horizontal transmission to naïve pigs was only shed 14–16 days after infection to age-matched pigs. Homologous re-challenge 49 days post initial PEDV exposure did not result in re-infection of the pigs. This demonstrates potential for an effective PEDV vaccine.


title: Successful recovery from COVID-19 pneumonia after receiving baricitinib, tocilizumab, and remdesivir. A case report: Review of treatments and clinical role of computed tomography analysis

text: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic, threatening global public health. In the current paper, we describe our successful treatment of one COVID-19 pneumonia patient case with high mortality risk factors. Our experience underlines the importance of the use of a multidisciplinary therapeutic approach in order to achieve a favorable clinical outcome. Further, enhancing the capability of the COVID-19 diagnosis with the use of the chest imaging modalities is discussed.


title: Particulate Production and Composite Dust during Routine Dental Procedures. A Systematic Review with Meta-Analyses

text: Composite dust generation is most likely a continuous and daily procedure in dental practice settings. The aim of this systematic review was to identify, compile and evaluate existing evidence on interventions and composite material properties related to the production of aerosolized dust during routine dental procedures. Seven electronic databases were searched, with no limits, supplemented by a manual search, on 27 April 2020 for published and unpublished research. Eligibility criteria comprised of studies of any design, describing composite dust production related to the implementation of any procedure in dental practice. Study selection, data extraction and risk of bias (RoB) assessment was undertaken independently either in duplicate, or confirmed by a second reviewer. Random effects meta-analyses of standardized mean differences (SMD) with associated 95% confidence intervals (CIs) were employed where applicable. A total of 375 articles were initially identified, resulting in 13 articles being included in the qualitative synthesis, of which 5 contributed to meta-analyses overall. Risk of bias recordings ranged between low and high, pertaining to unclear/raising some concerns, in most cases. All types of composites, irrespective of the filler particles, released significant amounts of nano-sized particles after being ground, with potentially disruptive respiratory effects. Evidence supported increased % distribution of particles < 100 nm for nanocomposite Filtek Supreme XTE compared to both conventional hybrid Z100MP (SMD: 1.96, 95% CI: 0.85, 3.07; p-value; 0.001) and nano- hybrid Tetric EvoCeram (SMD: 1.62, 95% CI: 0.56, 2.68; p-value: 0.003). For cytotoxicity considerations of generated aerosolized particles, both nanocomposites Filtek Supreme XTE and nanohybrid GradiO revealed negative effects on bronchial epithelial cell viability, as represented by % formazan reduction at 330–400 μg/mL for 24 hours, with no recorded differences between them (SMD: 0.19; 95% CI: −0.17, 0.55; p-value: 0.30). Effective and more rigorous management of dental procedures potentially liable to the generation of considerable amounts of aerosolized composite dust should be prioritized in contemporary dental practice. In essence, protective measures for the clinician and the practices’ personnel should also be systematically promoted and additional interventions may be considered in view of the existing evidence.


title: COVID-19 Outbreak in Malaysia

text: In 2020 a significant threat to public health emerged. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic outbreak emerged in December 2019 from Wuhan City, Hubei Province, China and spread to the rest of the world. This disease was named COVID-19 by World Health Organization. To date (17(th) April 2020) a total of 2,230,439 cases of COVID-19; 150,810 cases of deaths and 564,210 recovered cases have been reported worldwide. In this review the SARS-CoV-2 morphology, pathogenic mechanism, similarities and differences between SARS-CoV and Middle East Respiratory Syndrome and severe acute respiratory syndrome, transmission mode, diagnosis, treatment, and preventive measures were investigated. The outbreak of COVID-19 from a Malaysian perspective was explored and mental health care during the COVID-19 outbreak was explored. To date, there is no vaccine or no specific treatment for COVID-19. Therefore, preventive measures are very important to prevent and control the rapid spread of the SARS-CoV-2 virus. Preparedness should be a priority for future pandemic outbreaks.


title: Impact of COVID-19 on U.S. and Canadian neurologists’ therapeutic approach to multiple sclerosis: a survey of knowledge, attitudes, and practices

text: OBJECTIVE: To report the understanding and decision-making of neuroimmunologists and their treatment of patients with multiple sclerosis (MS) during the early stages of the SARS-CoV-2 (COVID-19) outbreak. METHODS: A survey instrument was designed and distributed online to neurologists in April 2020. RESULTS: There were 250 respondents (response rate 21.8%). 243 saw > = 10 MS patients in the prior 6 months (average 197 patients) and were analyzed further (92% USA, 8% Canada; average practice duration 16 years; 5% rural, 17% small city, 38% large city, 40% highly urbanized). Patient volume dropped an average of 79% (53–11 per month). 23% were aware of patients self-discontinuing a DMT due to fear of COVID-19 with 43% estimated to be doing so against medical advice. 65% of respondents reported deferring > = 1 doses of a DMT (49%), changing the dosing interval (34%), changing to home infusions (20%), switching a DMT (9%), and discontinuing DMTs altogether (8%) as a result of COVID-19. Changes in DMTs were most common with the high-efficacy therapies alemtuzumab, cladribine, ocrelizumab, rituximab, and natalizumab. 35% made no changes to DMT prescribing. 98% expressed worry about their patients contracting COVID-19 and 78% expressed the same degree of worry about themselves. > 50% believed high-efficacy DMTs prolong viral shedding of SARS-CoV-2 and that B-cell therapies might prevent protective vaccine effects. Accelerated pace of telemedicine and practice model changes were identified as major shifts in practice. CONCLUSIONS: Reported prescribing changes and practice disruptions due to COVID-19 may be temporary but could have a lasting influence on MS care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-10045-9) contains supplementary material, which is available to authorized users.


title: A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus

text: Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative-control construct Flagellin-SAPN or a buffer control. The immunized chickens were challenged with 5x10(4.7) EID50 IBV M41 strain. High antibody responses were detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN immunized chickens had a significantly higher stimulation index than that of PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV-Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser tracheal lesion scores than did negative control chickens. The data demonstrated that the IBV-Flagellin-SAPN holds promise as a vaccine for IBV.


title: Exploring the Key Antecedents Influencing Consumer’s Continuance Intention toward Bike-Sharing Services: Focus on China

text: This study investigates the key antecedents affecting consumers’ continuance intention toward bike-sharing services in China. The theoretical framework clarifies the role of perceived value and trust in a service provider in enhancing customer’s continuance intention toward bike-sharing services. Perceived usefulness, perceived ease of use, and perceived enjoyment are considered vital factors in forming perceived value and trust in a service provider. Financial risk and privacy risk serve as inhibitors to consumers’ continuance intention. Our research model is validated using data from 224 bike-sharing consumers in China. Both perceived value and trust in a service have a significant impact on consumers’ continuance intention. However, financial risk significantly affects customer’s continuance intention, although privacy risk does not have a significant impact on it. The analysis results show that perceived usefulness has no significant effect on both perceived value and trust in a service provider. The results demonstrate that perceived ease of use and perceived enjoyment play a significant role in enhancing both perceived value and trust in a service provider. Our results are expected to provide academic and practical implications for bike-sharing services.


title: Revisiting the equity debate in COVID-19: ICU is no panacea

text: Throughout March and April 2020, debate raged about how best to allocate limited intensive care unit (ICU) resources in the face of a growing COVID-19 pandemic. The debate was dominated by utility-based arguments for saving the most lives or life-years. These arguments were tempered by equity-based concerns that triage based solely on prognosis would exacerbate existing health inequities, leaving disadvantaged patients worse off. Central to this debate was the assumption that ICU admission is a valuable but scarce resource in the pandemic context. In this paper, we argue that the concern about achieving equity in ICU triage is problematic for two reasons. First, ICU can be futile and prolong or exacerbate suffering rather than ameliorate it. This may be especially true in patients with COVID-19 with emerging data showing that most who receive access to a ventilator will still die. There is no value in admitting patients with poor prognostic indicators to ICU to meet an equity target when intensive critical care is contrary to their best interests. Second, the focus on ICU admission shifts focus away from important aspects of COVID-19 care where there is greater opportunity for mitigating suffering and enhancing equitable care. We propose that the focus on equity concerns during the pandemic should broaden to include providing all people who need it with access to the highest possible standard of end-of-life care. This requires attention to culturally safe care in the following interlinked areas: palliative care, communication and decision support and advanced care planning.


title: Full-Genome Sequence of Human Betacoronavirus 2c Jordan-N3/2012 after Serial Passage in Mammalian Cells

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiologic agent of a highly lethal pneumonia. Here, we report the full-genome sequence of the Jordan-N3/2012 strain after serial passage in two distinct mammalian cell lines. The genome exhibits noteworthy stability, which may inform the development of vaccines and therapeutics used to treat infection with this virus.


title: Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

text: Kawasaki disease (KD) is an acute febrile systemic vasculitis that occurs in children and is characterized by elevated levels of proinflammatory cytokines. Toll-like receptors (TLRs) serve as the sensor arm of the innate immune system and induce proinflammatory cytokine expressions. We recruited a total of 18 paired KD patients, before intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, 18 healthy controls, and 18 febrile controls. For TLR genes and their cytosine-phosphate-guanine (CpG) markers, we used Affymetrix GeneChip(®) Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip to evaluate gene expression levels and methylation patterns, respectively. KD patients demonstrated a significantly differential expression of TLR mRNA levels compared to both the healthy and febrile controls, with only TLR 3 and 7 not differing between the KD patients and the controls. After patients underwent IVIG treatment, the TLR mRNA levels, except for TLR3, decreased significantly in KD patients. In contrast, the methylation status of the CpG sites of TLR1, 2, 4, 6, 8, and 9 demonstrated an opposite tendency between the two stages of both the KD samples and the controls. TLRs, particularly TLR1, 2, 4, 6, 8, and 9, may stimulate the immunopathogenesis of KD. These results are among the first to use TLRs to prove that a bacterial inflammatory response may trigger KD.


title: Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

text: During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonu- clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3’ UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.