title: A randomized open-label trial on the use of budesonide/formoterol (Symbicort(®)) as an alternative reliever medication for mild to moderate asthmatic attacks

text: BACKGROUND: Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort(®), AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS: We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort(® )vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS: Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort(®). For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort(® )vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either "a little better" or "much better" on the 5-point Likert scale, with none reporting "no change" or getting worse. CONCLUSION: This study suggests that there is no statistical difference between using Symbicort(® )vs. nebulized salbutamol as the reliever for the first 15 min post-intervention.


title: Constrained optimal control applied to vaccination for influenza

text: Abstract The efficient time schedule and prioritization of vaccine supplies are important in mitigating impact of an influenza pandemic. In practice, there are restrictions associated with limited vaccination coverage and the maximum daily vaccine administration. We extend previous work on optimal control for influenza to reflect these realistic restrictions using mixed constraints on state and control variables. An optimal control problem is formulated with the aim of minimizing the number of infected individuals while considering intervention costs. Time-dependent vaccination is computed and analysed using a model incorporating heterogeneity in population structure under different settings of transmissibility levels, vaccine coverages, and time delays.


title: Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

text: Abstract Background: Multiple sclerosis (MS) afflicts more than 2.5 million individuals worldwide and this number is increasing over time. Within the past years, a great number of disease-modifying treatments have emerged; however, efficacious treatments and a cure for MS await discovery. Thymosins, soluble hormone-like peptides produced by the thymus gland, can mediate immune and non-immune physiological processes and have gained interest in recent years as therapeutics in inflammatory and autoimmune diseases. Methods: Pubmed was searched with no time constraints for articles using a combination of the keywords “thymosin/s” or “thymus factor/s” AND “multiple sclerosis”, mesh terms with no language restriction. Results: Here, we review the state-of-the-art on the effects of thymosins on MS and its experimental models. In particular, we describe what is known in this field on the roles of thymosin-α1 (Tα1) and -β4 (Tβ4) as potential anti-inflammatory as well as neuroprotective and remyelinating molecules and their mechanisms of action. Conclusion: Based on the data that Tα1 and Tβ4 act as anti-inflammatory molecules and as inducers of myelin repair and neuronal protection, respectively, a possible therapeutic application in MS for Tα1 and Tβ4 alone or combined with other approved drugs may be envisaged. This approach is reasonable in light of the current clinical usage of Tα1 and data demonstrating the safety, tolerability and efficacy of Tβ4 in clinical practice.


title: The otolaryngologist’s and anesthesiologist’s collaborative role in a pandemic: a large quaternary pediatric center’s experience with COVID-19 preparation and simulation

text: There has been a rapid global spread of a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which originated in Wuhan China in late 2019. A serious threat of nosocomial spread exists and as such, there is a critical necessity for well-planned and rehearsed processes during the care of the COVID-19 positive and suspected patient to minimize transmission and risk to healthcare providers and other patients. Because of the aerosolization inherent in airway management, the pediatric otolaryngologist and anesthesiologist should be intimately familiar with strategies to mitigate the high-risk periods of viral contamination that are posed to the environment and healthcare personnel during tracheal intubation and extubation procedures. Since both the pediatric otolaryngologist and anesthesiologist are directly involved in emergency airway interventions, both specialties impact the safety of caring for COVID-19 patients and are a part of overall hospital pandemic preparedness. We describe our institutional approach to COVID-19 perioperative pandemic planning at a large quaternary pediatric hospital including operating room management and remote airway management. We outline our processes for the safe and effective care of these patients with emphasis on simulation and pathways necessary to protect healthcare workers and other personnel from exposure while still providing safe, effective, and rapid care.


title: Immune function of an angiotensin-converting enzyme against Rice stripe virus infection in a vector insect

text: Abstract Angiotensin-converting enzyme (ACE) plays diverse roles in the animal kingdom. However, whether ACE plays an immune function against viral infection in vector insects is unclear. In this study, an ACE gene (LsACE) from the small brown planthopper was found to respond to Rice stripe virus (RSV) infection. The enzymatic activities of LsACE were characterized at different pH and temperature. Twenty planthopper proteins were found to interact with LsACE. RSV infection significantly upregulated LsACE expression in the testicle and fat body. When the expression of LsACE in viruliferous planthoppers was inhibited, the RNA level of the RSV SP gene was upregulated 2-fold in planthoppers, and all RSV genes showed higher RNA levels in the rice plants consumed by these planthoppers, leading to a higher viral infection rate and disease rating index. These results indicate that LsACE plays a role in the immune response against RSV transmission by planthoppers.


title: Pediatric Anesthesia Concerns and Management for Orthopedic Procedures

text: Anesthetic management of pediatric orthopedic patients is uniquely challenging. Approach to the pediatric patient must consider heightened preoperative anxiety and its postoperative behavioral and pain effects. Frequent respiratory infections can complicate timing of surgery and anesthetic care. Perioperative pain management usually involves a multimodal pharmacologic approach with the goal of minimizing opioid requirements. Regional anesthesia is valuable for postoperative pain control. Safety of its use in the pediatric population has been confirmed in recent studies. Included for discussion are fractures, slipped capital femoral epiphysis, club foot, and scoliosis.


title: Impact and clinical profiles of Mycoplasma pneumoniae co-detection in childhood community-acquired pneumonia

text: BACKGROUND: Increasing number of hospitalized children with community acquired pneumonia (CAP) is co-detected with Mycoplasma pneumoniae (Mp). The clinical characteristics and impact of Mp co-detected with other bacterial and/or viral pathogens remain poorly understood. The purpose of this study was to evaluate the demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection. METHODS: A total of 4148 hospitalized children with CAP were recruited from January to December 2017 at the Children’s Hospital of Hebei Province, affiliated to Hebei Medical University. A variety of respiratory viruses, bacteria and Mp were detected using multiple modalities. The demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection were recorded and analyzed. RESULTS: Among the 110 CAP children with Mp positive, 42 (38.18%) of them were co-detected with at least one other pathogen. Co-detection was more common among children aged ≤3 years. No significant differences were found in most clinical symptoms, complications, underlying conditions and disease severity parameters among various etiological groups, with the following exceptions. First, prolonged duration of fever, lack of appetite and runny nose were more prevalent among CAP children with Mp-virus co-detection. Second, Mp-virus (excluding HRV) co-detected patients were more likely to present with prolonged duration of fever. Third, patients co-detected with Mp-bacteria were more likely to have abnormal blood gases. Additionally, CAP children with Mp-HRV co-detection were significantly more likely to report severe runny nose compared to those with Mp mono-detection. CONCLUSION: Mp co-detection with viral and/or bacterial pathogens is common in clinical practice. However, there are no apparent differences between Mp mono-detection and Mp co-detections in terms of clinical features and disease severity.


title: Chapter Five Strategies for Characterization of Low-Abundant Intact or Truncated Low-Molecular-Weight Proteins From Human Plasma

text: Abstract Low-molecular-weight region (LMW, MW≤30kDa) of human serum/plasma proteins, including small intact proteins, truncated fragments of larger proteins, along with some other small components, has been associated with the ongoing physiological and pathological events, and thereby represent a treasure trove of diagnostic molecules. Great progress in the mining of novel biomarkers from this diagnostic treasure trove for disease diagnosis and health monitoring has been achieved based on serum samples from healthy individuals and patients and powerful new approaches in biochemistry and systems biology. However, cumulative evidence indicates that many potential LMW protein biomarkers might still have escaped from detection due to their low abundance, the dynamic complexity of serum/plasma, and the limited efficiency of characterization approaches. Here, we provide an overview of the current state of knowledge with respect to strategies for the characterization of low-abundant LMW proteins (small intact or truncated proteins) from human serum/plasma, involving prefractionation or enrichment methods to reduce dynamic range and mass spectrometry-based characterization of low-abundant LMW proteins.


title: Cytosol to Lysosome Transport of Intracellular Antigens During Immune Surveillance

text: The delivery of intracellular substrates such as misfolded proteins and damaged organelles from the cytosol to the lysosome for degradation is crucial for cell survival. Multiple transport pathways including bulk autophagy (microautophagy and macroautophagy) and chaperone‐mediated autophagy (CMA) have been identified to efficiently facilitate this transit of macromolecules from the cytoplasm to acidic vacuolar organelles. While autophagy plays a role in the general housekeeping of cells, it also functions in more specialized processes such as development and differentiation, responses to physiological stress and immunity. The presentation of both exogenous and endogenous antigens (Ag) by major histocompatibility complex (MHC) class II molecules to CD4(+) T lymphocytes is critical for the induction of tolerance to self Ag as well as the development of immunity against intracellular pathogens and tumors. Here, we discuss the class II‐mediated presentation of several endogenous Ag, dependent on either macroautophagy or CMA for their transport from the cytosol to endosomal/lysosomal compartments. Thus, the various pathways of autophagy as routes of cytoplasmic Ag delivery to lysosomes have significant implications for the MHC class II‐mediated immune response to intracellular pathogens and cancer.


title: Global Prevalence Estimates of Toxascaris leonina Infection in Dogs and Cats

text: Toxascaris leonina is an ascaridoid nematode of dogs and cats; this parasite affects the health of these animals. This study estimated the global prevalence of Ta. leonina infection in dogs and cats using random effects meta-analysis as well as subgroup, meta-regression and heterogeneity analyses. The data were stratified according to geographical region, the type of dogs and cats and environmental variables. A quantitative analysis of 135 published studies, involving 119,317 dogs and 25,364 cats, estimated prevalence rates of Ta. leonina in dogs and cats at 2.9% and 3.4%, respectively. Prevalence was highest in the Eastern Mediterranean region (7.2% for dogs and 10.0% for cats) and was significantly higher in stray dogs (7.0% vs. 1.5%) and stray cats (7.5% vs. 1.8%) than in pets. The findings indicate that, worldwide, ~26 million dogs and ~23 million cats are infected with Ta. leonina; these animals would shed substantial numbers of Ta. leonina eggs into the environment each year and might represent reservoirs of infection to other accidental or paratenic hosts. It is important that populations of dogs and cats as well as other canids and felids be monitored and dewormed for Ta. leonina and (other) zoonotic helminths.


title: Remote sensing of multiple vital signs using a CMOS camera-equipped infrared thermography system and its clinical application in rapidly screening patients with suspected infectious diseases

text: Summary Background Infrared thermography (IRT) is used to screen febrile passengers at international airports, but it suffers from low sensitivity. This study explored the application of a combined visible and thermal image processing approach that uses a CMOS camera equipped with IRT to remotely sense multiple vital signs and screen patients with suspected infectious diseases. Methods An IRT system that produced visible and thermal images was used for image acquisition. The subjects’ respiration rates were measured by monitoring temperature changes around the nasal areas on thermal images; facial skin temperatures were measured simultaneously. Facial blood circulation causes tiny color changes in visible facial images that enable the determination of the heart rate. A logistic regression discriminant function predicted the likelihood of infection within 10s, based on the measured vital signs. Sixteen patients with an influenza-like illness and 22 control subjects participated in a clinical test at a clinic in Fukushima, Japan. Results The vital-sign-based IRT screening system had a sensitivity of 87.5% and a negative predictive value of 91.7%; these values are higher than those of conventional fever-based screening approaches. Conclusions Multiple vital-sign-based screening efficiently detected patients with suspected infectious diseases. It offers a promising alternative to conventional fever-based screening.


SARS-CoV-2-induces acute and refractory relapse of systemic capillary leak syndrome (Clarkson's disease)


title: Family violence and COVID‐19: Increased vulnerability and reduced options for support

text: Family violence refers to threatening or other violent behaviour within families that may be physical, sexual, psychological, or economic, and can include child abuse and intimate partner violence (Peterman et al. 2020, van Gelder et al. 2020). Family violence during pandemics is associated with a range of factors including economic stress, disaster-related instability, increased exposure to exploitative relationships, and reduced options for support (Peterman et al. 2020). Due to the social isolation measures implemented across the globe to help reduce the spread of COVID-19, people living in volatile situations of family violence are restricted to their homes. Social isolation exacerbates personal and collective vulnerabilities while limiting accessible and familiar support options (van Gelder et al. 2020). In many countries, including Australia, we have already seen an increase in demand for domestic violence services and reports of increased risk for children not attending schools (Duncan, 2020); a pattern similar to previous episodes of social isolation associated with epidemics and pandemics (Boddy, Young & O'Leary 2020).


title: Turning Crisis into Opportunity: Nature of Science and Scientific Inquiry as Illustrated in the Scientific Research on Severe Acute Respiratory Syndrome

text: Interviews with key scientists who had conducted research on Severe Acute Respiratory Syndrome (SARS), together with analysis of media reports, documentaries and other literature published during and after the SARS epidemic, revealed many interesting aspects of the nature of science (NOS) and scientific inquiry in contemporary scientific research in the rapidly growing field of molecular biology. The story of SARS illustrates vividly some NOS features advocated in the school science curriculum, including the tentative nature of scientific knowledge, theory-laden observation and interpretation, multiplicity of approaches adopted in scientific inquiry, the inter-relationship between science and technology, and the nexus of science, politics, social and cultural practices. The story also provided some insights into a number of NOS features less emphasised in the school curriculum—for example, the need to combine and coordinate expertise in a number of scientific fields, the intense competition between research groups (suspended during the SARS crisis), the significance of affective issues relating to intellectual honesty and the courage to challenge authority, the pressure of funding issues on the conduct of research and the ‘peace of mind’ of researchers, These less emphasised elements provided empirical evidence that NOS knowledge, like scientific knowledge itself, changes over time. They reflected the need for teachers and curriculum planners to revisit and reconsider whether the features of NOS currently included in the school science curriculum are fully reflective of the practice of science in the 21st century. In this paper, we also report on how we made use of extracts from the news reports and documentaries on SARS, together with episodes from the scientists’ interviews, to develop a multimedia instructional package for explicitly teaching the prominent features of NOS and scientific inquiry identified in the SARS research.


title: Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

text: Abstract Streptococcus pneumoniae is the main cause of diseases such as meningitis, pneumoniae and sepsis, especially in children and old people. Due to costly antibiotic treatment, and increasing resistance of pneumococcus, developing high-efficient protective vaccine against this pathogen is an urgent need. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in children and adult groups, but the serotype replacement of S. pneumoniae strains causes the reduction in efficacy of such vaccines. For overcoming the aforesaid drawbacks epitope-based vaccines are introduced as the relevant alternative. In our previous research, the epitope vaccine was designed based on immunodominant epitopes from PspA, CbpA antigens as cellular stimulants and PhtD, PiuA as humoral stimulants. Because the low immunogenicity is the main disadvantage of epitope vaccine, in the current study, we applied coiled-coil self-assembled structures for developing our vaccine. Recently, self-assembled peptide nanoparticles (SAPNs) have gained much attention in the field of vaccine development due to their multivalency, self-adjuvanticity, biocompatibility, and size similarity to pathogen. In this regard, the final designed vaccine is comprised of cytotoxic T lymphocytes (CTL) epitopes from PspA and CbpA, helper T lymphocytes (HTL) epitopes from PhtD and PiuA, the pentamer and trimmer oligomeric domains form 5-stranded and 3-stranded coiled-coils as self-assembled scaffold, Diphtheria toxoids (DTD) as a universal T-helper, which fused to each other with appropriate linkers. The four different arrangements based on the order of above-mentioned compartments were constructed, and each of them were modeled, and validated to find the 3D structure. The structural, physicochemical, and immunoinformatics analyses of final vaccine construct represented that our vaccine could stimulate potent immune response against S. pneumoniae; however, the potency of that should be approved via various in vivo and in vitro immunological tests.


title: Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

text: Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes.


Balancing the need for rapid and rigorous scientific data during early phase of the COVID-19 pandemic: A further role for the Scientific Community


title: Recent Advances in Diagnostic Microbiology

text: The past decade has seen a surge in the development of a variety of molecular diagnostics designed to rapidly identify or characterize medically important microorganisms. We briefly review important advances in molecular microbiology, and then discuss specific assays that have been implemented in clinical microbiology laboratories throughout the country. We also discuss emerging methods and technologies that will soon be more widely used for the prompt and accurate detection of the agents of infectious diseases.


Antibody Testing For Covid-19: Can It Be Used As A Screening Tool In Areas With Low Prevalence?


title: Acylation of virol. spike glycoproteins: A feature of enveloped RNA viruses

text: Abstract The covalent attachment of fatty acids to the glycoproteins of orthomyxo-, paramyxo, alpha-, and coronavirus was studied. All enveloped viruses analyzed afford covalently bound fatty acid in at least one species of their spike glycoproteins. No internal components of the viruses studied including the hydrophobic M proteins of myxo- and rhabdoviruses contained fatty acid. Analysis of myxovirus particles devoid of the exposed portions of their spikes revealed that fatty acids are linked to the hydrophobic tail fragment of the glycoprotein which is associated with the viral lipid bilayer. With influenza virus hemagglutinin the fatty acid attachment site could be located at the cyanogen bromide peptide of the small subunit (HA2) which contains the membrane-embedded region of the polypeptide. The binding of fatty acids to viral glycoproteins occurs in a wide range of host cells including mammalian, avian, and insect cells.


Therapeutic RNA?


Considerations for performing immediate breast reconstruction during the COVID‐19 pandemic


docid: ubuwacxq

title: Disease Detection or Public Opinion Reflection? Content Analysis of Tweets, Other Social Media, and Online Newspapers During the Measles Outbreak in the Netherlands in 2013

text: BACKGROUND: In May 2013, a measles outbreak began in the Netherlands among Orthodox Protestants who often refuse vaccination for religious reasons. OBJECTIVE: Our aim was to compare the number of messages expressed on Twitter and other social media during the measles outbreak with the number of online news articles and the number of reported measles cases to answer the question if and when social media reflect public opinion patterns versus disease patterns. METHODS: We analyzed measles-related tweets, other social media messages, and online newspaper articles over a 7-month period (April 15 to November 11, 2013) with regard to topic and sentiment. Thematic analysis was used to structure and analyze the topics. RESULTS: There was a stronger correlation between the weekly number of social media messages and the weekly number of online news articles (P<.001 for both tweets and other social media messages) than between the weekly number of social media messages and the weekly number of reported measles cases (P=.003 and P=.048 for tweets and other social media messages, respectively), especially after the summer break. All data sources showed 3 large peaks, possibly triggered by announcements about the measles outbreak by the Dutch National Institute for Public Health and the Environment and statements made by well-known politicians. Most messages informed the public about the measles outbreak (ie, about the number of measles cases) (93/165, 56.4%) followed by messages about preventive measures taken to control the measles spread (47/132, 35.6%). The leading opinion expressed was frustration regarding people who do not vaccinate because of religious reasons (42/88, 48%). CONCLUSIONS: The monitoring of online (social) media might be useful for improving communication policies aiming to preserve vaccination acceptability among the general public. Data extracted from online (social) media provide insight into the opinions that are at a certain moment salient among the public, which enables public health institutes to respond immediately and appropriately to those public concerns. More research is required to develop an automatic coding system that captures content and user’s characteristics that are most relevant to the diseases within the National Immunization Program and related public health events and can inform official responses.


title: Positive RT-PCR tests among discharged COVID-19 patients in Shenzhen, China

text: Among all 209 discharged coronavirus 2019 patients in Shenzhen China between January 23 and February 21, 2020, there are 9 (4.3%) patients showed RT-PCR positive in throat swabs, 13 (6.2%) patients showed RT-PCR positive in anal swabs, and 22 (10.5%) positive in either type. The time between discharge and positive RT-PCR tests is 4.7 days on average. These numbers shed light on the viral dynamics of COVID-19.


title: Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry

text: BACKGROUND: Envelope (E) glycoprotein E2 of the hepatitis C virus (HCV) mediates binding of the virus to target cell receptors. Nevertheless, the precise role of E1 in viral entry remains elusive. METHODS: To understand the involvement of the fusion peptide-like domain positioned at residues 264 to 290 within envelope glycoprotein E1 in HCV infection, mutants with Ala and Asn substitutions for residues conserved between HCV and E proteins of flaviviruses or the fusion proteins of paramyxoviruses were constructed by site-directed mutagenesis and their effects on membrane fusion and viral infectivity were examined. RESULTS: None of these mutations affected the synthesis or cell surface expression of envelope proteins, nor did they alter the formation of a non-covalent E1-E2 heterodimer or E2 binding to the large extracellular loop of CD81. The Cys residues located at positions 272 and 281 were unlikely involved in intra- or intermolecular disulfide bond formation. With the exception of the G267A mutant, which showed increased cell fusion, other mutants displayed reduced or marginally inhibited cell fusion capacities compared to the wild-type (WT) E1E2. The G267A mutant was also an exception in human immunodeficiency virus type 1 (HIV-1)/HCV E1E2 pseudotyping analyses, in that it showed higher one-cycle infectivity; all other mutants exhibited greatly or partially reduced viral entry versus the WT pseudotype. All but the G278A and D279N mutants showed a WT-like profile of E1E2 incorporation into HIV-1 particles. Since C272A, C281A, G282A, and G288A pseudotypes bound to Huh7 cells as effectively as did the WT pseudotype, the reduced infectivity of these pseudotypes was due to their ability to inhibit cell fusion. CONCLUSION: Our results indicate that specific residues, but not the structure, of this fusion peptide-like domain are required for mediating cell fusion and viral entry.


title: SYSTEMS VIROLOGY: HOST-DIRECTED APPROACHES TO VIRAL PATHOGENESIS AND DRUG TARGETING

text: High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and adeeper understanding of how viruses cause disease. To realize these goals, pipets and petri dishes need to join forces with the powers of mathematics and computational biology.


title: To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections

text: CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bT(RM)). CD8 bT(RM) are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bT(RM) have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bT(RM) and discuss their roles in controlling viral infections of the brain.


title: A Practical Decontamination Framework for COVID-19 Front-line Workers Returning Home

text: Supplemental Digital Content is available in the text


title: Novel human astroviruses in pediatric respiratory samples: A one‐year survey in a Swiss tertiary care hospital

text: Although classical human astroviruses (HAstV) are known to be a leading cause of viral gastroenteritis, the pathogenesis and clinical manifestations of novel HAstV remain largely unknown. There is mounting evidence that, in contrast to classical astroviruses, novel HAstV exhibit tropism for the upper respiratory tract. This one‐year period prevalence screened all available clinical nasopharyngeal swab samples collected from pediatric patients aged ≤5 years for novel and classical HAstV using real‐time reverse transcription polymerase chain reaction. A total of 205 samples were tested; two novel HAstV cases were detected for a prevalence of 1.3%, with viral loads suggesting active upper respiratory tract replication. No classical HAstV was detected.


title: Phenotyping for drought resistance in bread wheat using physiological and biochemical traits

text: Abstract Drought is one of the most prominent limiting factors that negatively affect crop productivity by manipulating its physiological pathway. One hundred twenty diverse bread wheat genotypes were used in a pot experiment to explore the relationship among their fifteen physio-biochemical traits (PBT) by using multivariate analysis, heatmapping and stress tolerance index (STI) for grain yield as a marker trait to identify high yielding genotype with maximum stress tolerance capability. Increased proline and sugar accumulation were observed from control to moisture deficient environments by 159% and 122%, respectively. Moreover, leaf membrane stability index (LMSI), leaf relative water content (LRWC), relative dry weight (RDW), chlorophyll content, leaf surface area (LSA), Leaf succulence (LS), canopy temperature depression (CTD), relative excised leaf water loss (RELWL) and leaf osmotic potential (LOP) showed significantly decreasing trend in drought stress treatment as compared to well-watered plants by −21%, −21%, −34%, −22%, −38%, −37%, −46%, −18% and −35% respectively. Additionally, principal component analysis and genotype by trait biplot analysis showed that initial 7 principal components (PC1 to PC7) represented 77.27% and 79.02% of total cumulative variation under control and drought stress respectively. Genotypic-Phenotypic correlation revealed that most of the attributes were higher in case of genotypic correlation component (rg) as compared to the phenotypic correlation component (rp) indicating more genetic association between traits. The darker and lighter colour scale produced by heatmap exhibited contrasting nature of genotypes, as positive side with higher values represented drought resistance while values on the negative side with lower values showed susceptible performance of genotypes. Our results concluded that the studied PBT associated with STI for grain yield are the main factors which may contribute in improved productivity of wheat crop and if these traits show appropriate performance under stress condition the crop will show the more productive returns under changing climate.


docid: ewdfqktw

title: Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome

text: Summary Background Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. Methods The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). Findings Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. Interpretation The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.


title: Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

text: Abstract To determine differences in infection kinetics of two temporally and genetically different type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in vivo with and without concurrent porcine circovirus (PCV) type 2a or 2b infection, 62 pigs were randomly assigned to one of seven groups: negative controls (n =8); pigs coinfected with a 1992 PRRSV strain (VR-2385) and PCV2a (CoI-92-2a; n =9), pigs coinfected with VR-2385 and PCV2b (CoI-92-2b; n =9), pigs coinfected with a 2006 PRRSV strain (NC16845b) and PCV2a (CoI-06-2a; n =9), pigs coinfected with NC16845b and PCV2b (CoI-06-2b; n =9), pigs infected with VR-2385 (n =9), and pigs infected with NC16845b (n =9). Blood samples were collected before inoculation and at day post-inoculation (dpi) 3, 6, 9 and 12 and tested for the presence of PRRSV antibody and RNA, PCV2 antibody and DNA, complete blood counts, and interferon gamma (IFN-γ) levels. Regardless of concurrent PCV2 infection, VR-2385 initially replicated at higher levels and reached peak replication levels at dpi 6. Pigs infected with VR-2385 had significantly higher amounts of viral RNA in serum on both dpi 3 and dpi 6, compared to pigs infected with NC16845b. The peak of NC16845b virus replication occurred between dpi 9 and dpi 12 and was associated with a delayed anti-PRRSV antibody response in these pigs. PCV2 coinfection resulted in significantly more severe macroscopic and microscopic lung lesions and a stronger anti-PRRSV IgG response compared to pigs infected with PRRSV alone. This work further emphasizes in vivo replication differences among PRRSV strains and the importance of coinfecting pathogens.


title: Rethinking Urban Epidemiology: Natures, Networks and Materialities

text: How should we understand the relationship between urban environments and infectious diseases? This article addresses this question from three particular perspectives: that of the materialities of health, that of nature and that of networks. The first perspective analytically blends biological dynamics, environmental influence and social practice. The second perspective, mainly influenced by multispecies ethnographies, foregrounds the liveliness and unboundedness of cities. Finally, the third perspective analyses how health is drawn into the domain of security. The article argues that while globalization and urbanization are often discussed as having triggered the emergence and spread of pathogens, urban epidemics are not self‐evident and ‘natural' consequences of these pro‐cesses. They do not fall neatly into universal categories of space, modernity or risk; rather, they are produced and shaped by a range of social, political, biological and economic sites and scales. Accordingly, the emergence of pathogens depends on its articulation through specific analytical frameworks. This article suggests that a critical focus on how infectious diseases manifest themselves differently in different local contexts may not only provide insights into the manifold forms of urban life, but also into the multiple, complex and highly political constitution of health.


title: Chapter 8 Health Hazards of Medical Waste and its Disposal

text: Abstract Medical waste is a source of generation of hazardous biomedical waste. Medical waste generation and disposal is an important aspect, especially in countries with poor hygiene and high population. Medical centers including hospitals, clinics, and places where diagnosis and treatment are conducted generate wastes that are highly hazardous and put people under risk of fatal diseases. Policies should be framed to avoid spread of infections by providing specification for handling waste for generation, segregation, collection, storage, transportation, and treatment. Awareness should be created at all levels of society through various means of communication and education, so that the risks of spreading the health hazards could be minimized. This chapter deals with medical waste, principles of waste management program, categories of health-care waste, parameters to be monitored in health-care waste, finances to be managed, and national plans for health-care waste.


title: The Evolutionary Genetics of Viral Emergence

text: Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. Understanding the evolutionary basis to virus emergence is therefore a key research goal and many of the debates in this area can be considered within the rigorous theoretical framework established by evolutionary genetics. In particular, the respective roles played by natural selection and genetic drift in shaping genetic diversity are also of fundamental importance for understanding the nature of viral emergence. Herein, we discuss whether there are evolutionary rules to viral emergence, and especially whether certain types of virus, or those that infect a particular type of host species, are more likely to emerge than others. We stress the complex interplay between rates of viral evolution and the ability to recognize cell receptors from phylogenetically divergent host species. We also emphasize the current lack of convincing data as to whether viral emergence requires adaptation to the new host species during the early stages of infection, or whether it is largely a chance process involving the transmission of a viral strain with the necessary genetic characteristics.


title: Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset

text: IMPORTANCE: The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. OBJECTIVE: To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. DESIGN, SETTING, AND PARTICIPANTS: This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. MAIN OUTCOMES AND MEASURES: Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). RESULTS: We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 56 men and 44 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). CONCLUSIONS AND RELEVANCE: In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.


title: Epidemiologic characteristics of traumatic fractures in elderly patients during the outbreak of coronavirus disease 2019 in China

text: PURPOSE: This study aimed to describe the epidemiologic characteristics of fracture in the elderly during the COVID-19. METHODS: This was a retrospective multi-centre study, which included patients who sustained fractures between 20 January and 19 February 2020. The collected data included patients’ demographics (age and gender), injury-related (injury type, fracture location, injury mechanism, places where fracture occurred), and treatment modality. SPSS 23.0 was used to describe the data and perform some analysis. RESULTS: A total of 436 patients with 453 fractures were included; there were 153 males and 283 females, with an average age of 76.2 years (standard deviation, SD, 7.7 years; 65 to 105). For either males or females, 70–74 years was the most commonly involved age group. A total of 317 (72.7%) patients had their fractures occurring at home. Among 453 fractures, there were 264 (58.3%) hip fractures, accounting for 58.3%. Fall from standing height was the most common cause of fracture, making a proportion of 89.4% (405/453). Most fractures (95.8%, 434/453) were treated surgically, and 4.2% (19/453) were treated by plaster fixation or traction. Open reduction and internal fixation (ORIF) was the most used surgical method, taking a proportion of 49.2% (223/453). CONCLUSION: These findings highlighted the importance of primary prevention (home prevention) measures and could be used for references for individuals, health care providers, or health administrative department during the global pandemic of COVID-19.


title: Inhaled anti-infective chemotherapy for respiratory tract infections: Successes, challenges and the road ahead

text: One of the most common causes of illnesses in humans is from respiratory tract infections caused by bacterial, viral or fungal pathogens. Inhaled anti-infective drugs are crucial for the prophylaxis and treatment of respiratory tract infections. The benefit of anti-infective drug delivery via inhalation is that it affords delivery of sufficient therapeutic dosages directly to the primary site of infection, while minimizing the risks of systemic toxicity or avoiding potential suboptimal pharmacokinetics/pharmacodynamics associated with systemic drug exposure. This review provides an up-to-date treatise of approved and novel developmental inhaled anti-infective agents, with particular attention to effective strategies for their use, pulmonary pharmacokinetic properties and safety.


Potential Neurologic and Oncologic Implications of the Novel Coronavirus


title: ¿Cuáles son los conflictos éticos más frecuentes para los internistas españoles?

text: BACKGROUND AND OBJECTIVE: Clinicians face a multitude of ethical conflicts in their daily practice. There have been no studies on the types of ethical conflicts encountered most frequently and that are of most concern to clinicians in Spain. The aim of this study is to report the most common ethical conflicts faced by Spanish internists, as well as the importance that the practitioners attribute to each conflict. MATERIALS AND METHODS: Our observational cross-sectional study employed a voluntary and anonymous survey aimed at Spanish medical internists and distributed through an ad hoc platform of the Spanish Society of Internal Medicine. RESULTS: The most common and relevant ethical issues for Spanish internists are related to patients’ end of life (decisions limiting therapeutic effort, use of palliative treatments, the establishment of do-not-resuscitate orders), the conflicts arising within the doctor-patient/family relationship, and making decisions with noncompetent patients. These results are similar to those of other English and European series. The ethical problems further complicate the healthcare activity of clinicians who more often notice these problems (50.3%) than those who do not notice them (16%). CONCLUSIONS: The most common and relevant ethical conflicts among Spanish internists are related to managing patients’ end of life, followed by those related to the doctor-patient relationship and the management of noncompetent patients. It is essential that training programs be designed to better address and recognise these problems.


title: The Battle of RNA Synthesis: Virus versus Host

text: Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage.


Leading the Academic Department during the COVID‐19 Crisis


title: Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian hospitalised patients

text: Abstract Background Human respiratory coronavirus (hCoV) HKU1 infections were reported for the first time in 2005 in Hong Kong. Objective To investigate epidemiological, clinical, and diagnostic features of HKU1 infections. Study design Longitudinal, prospective study from November 2005 through May 2006 in a hospitalised patient population. Results Overall, 48/426 (11.3%) patients were found to be infected by hCoV acute respiratory tract infections (ARTI). Of these, 10 (19.2%) were caused by HKU1 (6 single infections and 4 coinfections) during the period January–May 2006. Diagnosis was made by using RT-PCR for all four hCoVs, and in parallel, in-house developed group-specific monoclonal antibodies (MAbs) for HKU1 and 229E. HKU1-specific MAb was able to retrospectively identify 8 of 10 HKU1 strains detected by RT-PCR. Phylogenetic analysis showed that four HKU1 strains were genotype A and six genotype B. In HKU1-infected patients, the predominant clinical symptom was rhinorrhea (nine patients). Within group II hCoV, HKU1-infected patients had a significantly lower rate of lower ARTI compared to OC43-infected patients. Conclusion HKU1 hCoV strains circulated in northern Italy during the winter–spring season 2005–2006. Both HKU1 genotypes were detected. HKU1-specific MAb may contribute to the rapid diagnosis of HKU1 infections currently performed by RT-PCR.


title: Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease

text: Abstract Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai’s cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.


title: Simple Respiratory Protection—Evaluation of the Filtration Performance of Cloth Masks and Common Fabric Materials Against 20–1000 nm Size Particles

text: A shortage of disposable filtering facepiece respirators can be expected during a pandemic respiratory infection such as influenza A. Some individuals may want to use common fabric materials for respiratory protection because of shortage or affordability reasons. To address the filtration performance of common fabric materials against nano-size particles including viruses, five major categories of fabric materials including sweatshirts, T-shirts, towels, scarves, and cloth masks were tested for polydisperse and monodisperse aerosols (20–1000 nm) at two different face velocities (5.5 and 16.5 cm s(−1)) and compared with the penetration levels for N95 respirator filter media. The results showed that cloth masks and other fabric materials tested in the study had 40–90% instantaneous penetration levels against polydisperse NaCl aerosols employed in the National Institute for Occupational Safety and Health particulate respirator test protocol at 5.5 cm s(−1). Similarly, varying levels of penetrations (9–98%) were obtained for different size monodisperse NaCl aerosol particles in the 20–1000 nm range. The penetration levels of these fabric materials against both polydisperse and monodisperse aerosols were much higher than the penetrations for the control N95 respirator filter media. At 16.5 cm s(−1) face velocity, monodisperse aerosol penetrations slightly increased, while polydisperse aerosol penetrations showed no significant effect except one fabric mask with an increase. Results obtained in the study show that common fabric materials may provide marginal protection against nanoparticles including those in the size ranges of virus-containing particles in exhaled breath.


title: Up-regulation of the expression of leucine-rich α2-glycoprotein in hepatocytes by the mediators of acute-phase response

text: Abstract Leucine-rich α2-glycoprotein (LRG) is a plasma protein in which leucine-rich repeats (LRRs) were first discovered. Although the physiological function of LRG is not known, increases in the serum level of LRG have been reported in various diseases. In this study, we found that LRG was induced by recombinant human IL-6 in human hepatoma HepG2 cells. The induction of LRG by IL-6 was up-regulated synergistically with either IL-1β or TNFα in a pattern similar to those for type 1 acute-phase proteins. We also found that lipopolysaccharide (LPS) administered intraperitoneally to mice enhanced dose-dependently the expression of LRG mRNA in the liver as well as those for mouse major acute-phase proteins. These results strongly suggest that LRG was a secretory type 1 acute-phase protein whose expression was up-regulated by the mediator of acute-phase response.


title: COVID-19: Changing Trends and Its Impact on Future of Dentistry

text: The outbreak of coronavirus disease 2019 (COVID-19) rapidly escalated into a worldwide pandemic, creating a global health and economic crisis. It is a novel virus which is distinct from SARS-CoV and MERS-CoV, with Chinese horseshoe bats being the most probable origin. Transmission occurs primarily through droplet spread or contact routes. Due to the characteristics of dental settings, the risk of cross infection between dental health care personnel (DHCP) and patients can be very high. This article provides a brief overview of the structure of the virus, modes of transmission, and clinical features of COVID-19 disease. The aim of this article is to recommend infection control strategies and patient management protocols to provide optimum dental care and simultaneously prevent nosocomial infection in dental settings.


docid: lxnrikmu

title: The utility of LASSO-based models for real time forecasts of endemic infectious diseases: A cross country comparison

text: Abstract Introduction Accurate and timely prediction for endemic infectious diseases is vital for public health agencies to plan and carry out any control methods at an early stage of disease outbreaks. Climatic variables has been identified as important predictors in models for infectious disease forecasts. Various approaches have been proposed in the literature to produce accurate and timely predictions and potentially improve public health response. Methods We assessed how the machine learning LASSO method may be useful in providing useful forecasts for different pathogens in countries with different climates. Separate LASSO models were constructed for different disease/country/forecast window with different model complexity by including different sets of predictors to assess the importance of different predictors under various conditions. Results There was a more apparent cyclicity for both climatic variables and incidence in regions further away from the equator. For most diseases, predictions made beyond 4 weeks ahead were increasingly discrepant from the actual scenario. Prediction models were more accurate in capturing the outbreak but less sensitive to predict the outbreak size. In different situations, climatic variables have different levels of importance in prediction accuracy. Conclusions For LASSO models used for prediction, including different sets of predictors has varying effect in different situations. Short term predictions generally perform better than longer term predictions, suggesting public health agencies may need the capacity to respond at short-notice to early warnings.


Reply to: “A Dermatologic Manifestation of COVID-19: Transient Livedo Reticularis”


title: Hyperactive Delirium Requires More Aggressive Management in Patients with COVID-19: Temporarily Rethinking “Low and Slow”

text: Delirium is a common symptom in patients admitted to our hospital with COVID-19, and in cases of hyperactive delirium we have frequently observed behaviors that pose a significant risk of disease transmission to health care providers. Managing this symptom has emerged as an important challenge, as our local health care system has been strained by providers becoming sick or quarantined. Preventative and non-pharmacologic interventions remain critical for managing delirium in such patients, though occasionally pharmacologic treatment is required. When use of an antipsychotic medication is indicated, we recommend that providers consider foregoing the lowest common dose and instead start with the next incrementally higher dose to more quickly and reliably ensure the safety of both patients and providers. We do not recommend initiating prophylactic treatment or escalating doses in a manner that conflicts with currently accepted guidelines without carefully considering the risks and benefits


title: In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B(4)

text: The lack of effective therapeutics for Coxsackievirus B(4) (CVB(4)) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB(4) infection was explored in vitro and in mice. Emodin reduced CVB(4) entry and replication on Hep-2 cells in a concentration- and time-dependent manner, with a 50% effective concentration (EC(50)) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB(4) entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB(4)-induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB(4) infection.


title: The role of self-reported smell and taste disorders in suspected COVID‑19

text: PURPOSE: The sudden onset of smell and taste loss has been reported as a symptom related to COVID-19. There is urgent need to provide insight to the pandemic and evaluate anosmia as a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions. METHODS: Systematic review of the PubMed/Medline, Cochrane databases and preprints up to May 3, 2020. Combined search terms included: “COVID-19”, “SARS-CoV-2”, “coronavirus”, “nose”, “anosmia”, “hyposmia”, “olfactory loss”, “smell loss”, “taste loss”, and “hypogeusia”. RESULTS: Our search identified 18 reviewed articles and 6 manuscript preprints, including a large epidemiological study, four observational case series, five case–controlled studies, five cross-sectional studies, five case series of anosmic patients and four electronic surveys. Great methodological differences were noted. A significant prevalence of anosmia is reported in COVID-19 patients. Controlled studies indicate that anosmia is more common in COVID-19 patients than in patients suffering from other viral infections or controls. Most of the studies reported either smell loss or smell plus taste loss. Less severe COVID-19 disease is related to a greater prevalence of anosmia. A quick recovery of the smell loss may be expected in most COVID-19 cases. CONCLUSION: Anosmia is more prevalent in COVID-19 patients than in patients suffering from other respiratory infections or controls.


title: Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model

text: Abstract Background The most common acute infections occur in the respiratory tract. Recent discoveries of several novel viruses have markedly increased the repertoire of agents understood to cause presentations of acute respiratory disease. Objectives Further understanding is needed of the relative importance of newly discovered pathogens in the clinical setting to provide clinicians with an indication of appropriate diagnostic and therapeutic targets. To address this, quantification of the disease burden of respiratory viruses in hospitalized patients was undertaken. Study design Disease burden caused by respiratory viruses in hospitalized patients was quantified using the World Health Organization endorsed DALY model. Diagnostic testing results from samples collected over three years for adenovirus (AdV), influenzas A and B, parainfluenza viruses 1, 2 and 3 (PIV-1, -2 and -3), respiratory syncytial virus (HRSV), and previously published retrospective screening for human metapneumovirus, rhinoviruses, and four respiratory coronaviruses were applied to the DALY model. Disability weights were calculated per 1000 hospitalized patients in age banded groups. Results Strikingly different disease burden profiles were observed in children and adults. Adenoviruses were among the leading cause of respiratory presentations in children but not adults. HRSV and influenza A were consistently one of the greatest causes of disease regardless of sampled population. Rhinoviruses and PIV-3 were significant pathogens in all groups except those aged 16–64 years. In immunocompromised patients rhinoviruses were the leading viral cause of disease. Conclusions These analyses provide a framework which can be used to identify where finite resources should be directed in respiratory therapeutics and vaccine development.


title: Effectiveness of Neuraminidase Inhibitors for Preventing Staff Absenteeism during Pandemic Influenza

text: We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies for neuraminidase inhibitors that would minimize absenteeism among healthcare workers. A pandemic with a basic reproductive number (R(0)) of 2.5 resulted in peak absenteeism of 10%. Treatment decreased peak absenteeism to 8%, while 8 weeks’ prophylaxis reduced it to 2%. For pandemics with higher R(0), peak absenteeism exceeded 20% occasionally and 6 weeks’ prophylaxis reduced peak absenteeism by 75%. Insufficient duration of prophylaxis increased peak absenteeism compared with treatment only. Earlier pandemic detection and initiation of prophylaxis may render shorter prophylaxis durations ineffective. Eight weeks’ prophylaxis substantially reduced peak absenteeism under a broad range of assumptions for severe pandemics (peak absenteeism >10%). Small investments in treatment and prophylaxis, if adequate and timely, can reduce absenteeism among essential staff.


title: Could Autism Spectrum Disorders be a Risk Factor for COVID-19?

text: The coronavirus SARS-CoV-2 pandemia is infecting millions of people and some studies relate conditions that might increase the risk of developing a fatal course for the disease, such as diabetes, cardiovascular diseases and obesity. In COVID-19 physiopathology, one of the main inflammation mechanisms is the “cytokine storm”, causing a pro-inflammatory state, related to cardiac and pulmonary damage. There is also a less effective role of lymphocyte B and T in the humoral immunity due to the reduction of their proliferative response. The physiopathology of ASD (Autism Spectrum Disorder) involves several modifications at the genetic and at the immune level, such as the increase of inflammatory cytokines and abnormal immune response in several levels. We hypothesize that ASD could be a risk-factor as the other conditions are.


docid: bumdpeyv

title: Update on the Cutaneous Manifestations of COVID 19()


docid: pqegqjyu

title: A short, animated video to improve good COVID-19 hygiene practices: a structured summary of a study protocol for a randomized controlled trial

text: OBJECTIVES: Entertainment-education (E-E) media can improve behavioral intent toward health-related practices. In the era of COVID-19, millions of people can be reached by E-E media without requiring any physical contact. We have designed a short, wordless, animated video about COVID-19 hygiene practices—such as social distancing and frequent hand washing—that can be rapidly distributed through social media channels to a global audience. The E-E video’s effectiveness, however, remains unclear. 1. Quantify people’s interest in watching a short, animated video about COVID-19 hygiene (abbreviated to CoVideo). 2. Establish the CoVideo’s effectiveness in increasing behavioural intent toward COVID-19 hygiene. 3. Establish the CoVideo’s effectiveness in improving COVID-19 hygiene knowledge. TRIAL DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of the CoVideo against an attention placebo control (APC) video or no video. The trial has an intervention arm (CoVideo), placebo arm (APC), and control arm (no video). Nested in each trial arm is a list experiment and questionnaire survey, with the following ordering. Arm 1: the CoVideo, list experiment, and questionnaire survey. Arm 2: the APC video, list experiment, questionnaire survey, and CoVideo. Arm 3: the list experiment, questionnaire survey, and CoVideo. For each list experiment, participants will be randomized to a control or treatment group. The control group will receive a list of five items and the treatment group will receive the same five items plus one item about COVID-19 hygiene. We will use the list experiment to reduce response bias associated with socially desirable answers to COVID-19 questions. The questionnaire survey will include items about the participant’s age, sex, country of residence, highest education, and knowledge of COVID-19 spread. After completing the list experiment and questionnaire survey, participants in Arms 2 and 3 will receive the CoVideo to ensure post-trial access to treatment. PARTICIPANTS: This will be an online study setting. We will use Prolific Academic (ProA: https://www.prolific.co) to recruit participants and host our study on the Gorilla™ platform (www.gorilla.sc). To be eligible, participants must be between the age of 18 and 59 years (male, female, or other) and have current residence in the United States, the United Kingdom, Germany, Spain, Mexico, or France. Participants will be excluded from the study if they cannot speak English, German, French, or Spanish (since the instructions and survey questions will be available in these 4 languages only). INTERVENTION AND COMPARATOR: The intervention is an E-E video about COVID-19 hygiene (CoVideo). Developed by our co-author (MA) for Stanford Medicine, the CoVideo is animated with sound effects, and has no words, speech, or text. The CoVideo shows how the novel coronavirus is spread (airborne, physical contact) and summarizes the public’s response to the COVID-19 outbreak. Key components of the CoVideo are the promotion of five hygiene practices: i) social distancing and avoiding group gatherings, ii) frequently washing hands with soap and water or sanitizer, iii) cleaning surfaces at home (e.g., kitchen counters), iv) not sharing eating utensils, and v) avoidance of stockpiling essential goods (such as toilet paper and face masks). The CoVideo, which was designed for universal reach and optimized for release on social media channels, can be viewed at https://www.youtube.com/watch?v=rAj38E7vrS8. The comparators are an APC video (Arm 2) or no video (Arm 3). The APC video is similar in style to the CoVideo; it is also animated with a duration of 2.30 minutes, has sound effects but no words, speech, or text. The video message is about how small choices become actions, which become habits, which become a way of life. It is available at https://www.youtube.com/watch?v=_HEnohs6yYw. Each list experiment will have a control list as the comparator. The control list is needed to measure the prevalence of behavioral intent toward COVID-19 hygiene. MAIN OUTCOMES: This study will measure primary and secondary outcomes related to COVID-19 hygiene. By hygiene, we mean the adoption of behaviors or practices that reduce the chances of being infected or spreading COVID-19. As our primary outcome, we will measure changes in behavioral intent toward five hygiene practices: social distancing, washing hands, cleaning household surfaces, not sharing eating utensils, and not stockpiling essential goods. As a secondary outcome, we will measure knowledge about behaviors that can prevent the spread of COVID-19. RANDOMIZATION: Using a web-based randomization algorithm, Gorilla will randomly allocate participants to the intervention (CoVideo), placebo (APC), or control (no video) arm (sequence generation) at a 1:1:1 ratio. Within each trial arm, Gorilla will randomly allocate participants at a 1:1 ratio to the control or treatment group. Items in the lists will be randomly ordered to avoid order effects. The presentation order of the list experiments will also be randomized. BLINDING: Because ProA handles the interaction between the study investigators and participants, the participants will be completely anonymous to the study investigators. The outcome measures will be self-reported and submitted anonymously. All persons in the study team will be blinded to the group allocation. NUMBERS TO BE RANDOMIZED: The Gorilla algorithm will randomize 6,700 participants to each trial arm, giving a total sample size of 20,100. TRIAL STATUS: The protocol version number is 1.0 and the date is 18 May 2020. Recruitment is expected to end by 22 June 2020. Thus far, the study investigators have recruited 2,500 participants on ProA. Of these participants, 800 have completed the study on the Gorilla platform. TRIAL REGISTRATION: The study and its outcomes were registered at the German Clinical Trials Register (www.drks.de) on May 12(th), 2020, protocol number: #DRKS00021582. The study was registered before any data was collected. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.


title: Respiratory infections during air travel

text: An increasing number of individuals undertake air travel annually. Issues regarding cabin air quality and the potential risks of transmission of respiratory infections during flight have been investigated and debated previously, but, with the advent of severe acute respiratory syndrome and influenza outbreaks, these issues have recently taken on heightened importance. Anecdotally, many people complain of respiratory symptoms following air travel. However, studies of ventilation systems and patient outcomes indicate the spread of pathogens during flight occurs rarely. In the present review, aspects of the aircraft cabin environment that affect the likelihood of transmission of respiratory pathogens on airplanes are outlined briefly and evidence for the occurrence of outbreaks of respiratory illness among airline passengers are reviewed. (Intern Med J 2005; 35: 50–55)


title: Clinical implications of exercise immunology

text: Abstract Maintaining leanness and a physically active lifestyle during adulthood reduces systemic inflammation, an underlying factor in multiple chronic diseases. The anti-inflammatory influence of near-daily physical activity in lowering C-reactive protein, total blood leukocytes, interleukin-6, and other inflammatory cytokines may play a key role in lowering risk of cardiovascular disease, certain types of cancer, type 2 diabetes, sarcopenia, and dementia. Moderate exercise training causes favorable perturbations in immunity and a reduction in incidence of upper respiratory tract infection (URTI). During each bout of moderate exercise, an enhanced recirculation of immunoglobulins, neutrophils, and natural killer cells occurs that persists for up to 3-h post-exercise. This exercise-induced surge in immune cells from the innate immune system is transient but improves overall surveillance against pathogens. As moderate exercise continues on a near-daily basis for 12–15 weeks, the number of symptoms days with URTI is decreased 25%–50% compared to randomized sedentary controls. Epidemiologic and animal studies support this inverse relationship between URTI risk and increased physical activity.


title: Epidemiology of Coronavirus COVID-19: Forecasting the Future Incidence in Different Countries

text: This paper forecasts the future spread of COVID-19 by exploiting the identified lead-lag effects between different countries. Specifically, we first determine the past relation among nations with the aid of dynamic time warping. This procedure allows an elastic adjustment of the time axis to find similar but phase-shifted sequences. Afterwards, the established framework utilizes information about the leading country to predict the Coronavirus spread of the following nation. The presented methodology is applied to confirmed Coronavirus cases from 1 January 2020 to 28 March 2020. Our results show that China leads all other countries in the range of 29 days for South Korea and 44 days for the United States. Finally, we predict a future collapse of the healthcare systems of the United Kingdom and Switzerland in case of our explosion scenario.


Influenza immunization among Chinese seniors: Urgent calling for improving vaccination coverage, education, and research


title: Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities

text: The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells. Thus, some health care providers and media sources have questioned the continued use of ACE inhibitors and ARBs. In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin–angiotensin–aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors. We propose that the application of RAAS inhibitors for COVID-19 patients with CVDs may be beneficial rather than harmful.


title: Development, implementation and preliminary evaluation of clinical dashboards in a department of anesthesia

text: Clinical dashboards summarize indicators of high-volume patient data in a concise, user-friendly visual format. There are few studies of the use of dashboards to improve professional practice in anesthesiology. The objective of the present study was to describe the user-centered development, implementation and preliminary evaluation of clinical dashboards dealing with anesthesia unit management and quality assessment in a French university medical center. User needs and technical requirements were identified in end user interviews and then synthesized. Several representations were then developed (according to good visualization practice) and submitted to end users for appraisal. Lastly, dashboards were implemented and made accessible for everyday use via the medical center’s network. After a period of use, end user feedback on the dashboard platform was collected as a system usability score (range 0 to 100). Seventeen themes (corresponding to 29 questions and 42 indicators) were identified. After prioritization and feasibility assessment, 10 dashboards were ultimately implemented and deployed. The dashboards variously addressed the unit’s overall activity, compliance with guidelines on intraoperative hemodynamics, ventilation and monitoring, and documentation of the anesthesia procedure. The mean (standard deviation) system usability score was 82.6 (11.5), which corresponded to excellent usability. We developed clinical dashboards for a university medical center’s anesthesia units. The dashboards’ deployment was well received by the center’s anesthesiologists. The dashboards’ impact on activity and practice after several months of use will now have to be assessed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00522-x) contains supplementary material, which is available to authorized users.


title: Comparative Genomics of Korean Infectious Bronchitis Viruses (IBVs) and an Animal Model to Evaluate Pathogenicity of IBVs to the Reproductive Organs

text: The K-I and nephropathogenic K-II genotypes of infectious bronchitis virus (IBV) have been isolated since 1995 and 1990, respectively, in Korea and commercial inactivated oil-emulsion vaccines containing KM91 (K-II type) and Massachusetts 41 strains have been used in the field. To date, genomic analyses of Korean IBV strains and animal models to test the pathogenicity of Korean IBVs to the reproductive organs have been rare. In the present study, comparative genomics of SNU8067 (K-I type) and KM91 IBVs was performed, and an animal model to test the pathogenicity of SNU8067 was established and applied to vaccine efficacy test. The genome sizes of SNU8067 (27,708 nt) and KM91 (27,626 nt) were slightly different and the nucleotide and amino acid identities of the S1 (79%, 77%), 3a (65%, 52%), and 3b (81%, 72%) genes were lower than those of other genes (94%–97%, 92%–98%). A recombination analysis revealed that SNU8067 was a recombinant virus with a KM91-like backbone except S1, 3a, and 3b genes which might be from an unknown virus. An SNU8067 infection inhibited formation of hierarchal ovarian follicles (80%) and oviduct maturation (50%) in the control group, whereas 70% of vaccinated chickens were protected from lesions.


title: Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

text: During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.


title: Invasion Science and the Global Spread of SARS-CoV-2

text: Abstract Emerging infectious diseases like COVID19 are driven by ecological and socioeconomic factors, and their rapid spread and devastating impacts mirror those of invasive species. Collaborations between biomedical researchers and ecologists, heretofore rare, are vital to limiting future outbreaks. Enhancing the cross-disciplinary framework offered by invasion science could achieve this goal.


title: Digital Transition by COVID‐19 Pandemic? The German Food Online Retail

text: The COVID‐19 pandemic has led to a sharp increase in online trade. This article examines the impact of the pandemic on online grocery retail in Germany. Here we follow and refine the multi‐level perspective by Geels, and examine to what extent and why the online grocery retail expanded during the pandemic. A particular focus is on the spatial expansion into rural areas. The study shows a general upswing in the grocery trade and disproportionately high growth in online grocery trade and identifies driving and limiting factors. While COVID‐19 has opened a window of opportunity, our results indicate little transition of grocery to e‐grocery. This finding can be explained by the sudden and temporary constellation at the level of the socio‐technical regime during the pandemic. As a result, we argue for a rethinking the temporality of windows of opportunities and the related vulnerability of the innovations which need them.


title: Coronavirus Disease 2019 (COVID-19): Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome

text: Abstract Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.


title: Manipulation of the infectious bronchitis coronavirus genome for vaccine development and analysis of the accessory proteins()

text: Infectious bronchitis coronavirus (IBV) is the cause of the single most economically costly infectious disease of domestic fowl in the UK—and probably so in many countries that have a developed poultry industry. A major reason for its continued dominance is its existence as many serotypes, determined by the surface spike protein (S), cross-protection being poor. Although controlled to some degree by live and inactivated vaccines, a new generation of IB vaccines is called for. Reverse genetic or ‘infectious clone’ systems, which allow the manipulation of the IBV genome, are key to this development. New vaccines would ideally be: genetically stable (i.e. maintain a stable attenuated phenotype); administered in ovo; and be flexible with respect to the source of the spike protein gene. Rational attenuation of IBV requires the identification of genes that are simultaneously not essential for replication and whose absence would reduce pathogenicity. Being able to modify a ‘core’ vaccine strain to make it applicable to a prevailing serotype requires a procedure for doing so, and the demonstration that ‘spike-swapping’ is sufficient to induce good immunity. We have demonstrated that four small IBV proteins, encoded by genes 3 and 5, are not essential for replication; failure to produce these proteins had little detrimental affect on the titre of virus produced. Our current molecularly cloned IBV, strain Beaudette, is non-pathogenic, so we do not know what effect the absence of these proteins would have on pathogenicity. That said, plaque size and composition of various gene 3/5 recombinant IBVs in cell culture, and reduced output and ciliostasis in tracheal organ cultures, shows that they are less aggressive than the wild-type Beaudette. Consequently these genes remain targets for rational attenuation. We have recently obtained evidence that one or more of the 15 proteins encoded by gene 1 are also determinants of pathogenicity. Hence gene 1 is also a target for rational attenuation. Replacing the S protein gene of Beaudette with that from the pathogenic M41 strain resulted in a recombinant virus that was still non-pathogenic but which did induce protection against challenge with M41. We have since made other ‘spike-swapped’ recombinants, including ones with chimaera S genes. Uniquely, our molecular clone of Beaudette is benign when administered to 18-day-old embryos, even at high doses, and induces immunity after this route of vaccination. Taken together, our results point to the creation of a new generation of IB vaccines, based on rational modification of the genome, as being a realisable objective.


title: Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak

text: The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.


title: Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses

text: The emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARSCoV-2-specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.


title: Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

text: Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl’s antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses. Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis.


title: Spectrum of Clinical Illness in Hospitalized Patients with “Common Cold” Virus Infections

text: The viruses associated most frequently with the “common cold” are rhinoviruses and coronaviruses. The first prospective cohort study to determine the prevalence of rhinovirus and coronavirus infections in patients of all ages hospitalized for acute respiratory illnesses is described. Hospital admissions for acute respiratory illnesses were identified, and cell culture for rhinovirus and serologic assays on paired sera for coronaviruses 229E and OC43 were performed. A total of 61 infections with rhinoviruses and coronaviruses were identified from 1198 respiratory illnesses (5.1%); in addition, 9 additional infections associated with ≥1 other respiratory viruses were identified. Of those infected with only rhinovirus or coronavirus, underlying cardiopulmonary diseases were present in 35% of the patients aged <5 years, in 93% aged between 5 and 35 years, and in 73% aged >35 years. The predominant clinical syndromes varied by age: pneumonia and bronchiolitis in children aged <5 years; exacerbations of asthma in older children and young adults; and pneumonia and exacerbations of chronic obstructive pulmonary disease and congestive heart failure in older adults. Therefore, rhinovirus and coronavirus infections in hospitalized patients were associated with lower respiratory tract illnesses in all age groups.


title: Allowing visitors back in the nursing home during the COVID-19 crisis – A Dutch national study into first experiences and impact on well-being

text: Abstract Objectives To prevent and control COVID-19 infections, nursing homes across the world have taken very restrictive measures, including a ban for visitors. These restrictive measures have an enormous impact on residents’ well-being and pose dilemmas for staff, although primary data are lacking. A Dutch guideline was developed to cautiously open nursing homes for visitors during the COVID-19 pandemic. This study reports the first findings on how the guideline was applied in the local context, the compliance to local protocols and the impact on well-being of residents, their family caregivers and staff. Design A mixed-methods cross-sectional study was conducted Setting and participants In total, 26 nursing homes were permitted to enlarge their possibilities for allowing visitors in their facility. These nursing homes were proportionally representative of the Netherlands as they were selected by their local Area Health Authority for participation. At each nursing home, a contact person was selected for participation in the current study. Methods A mixed-method cross-sectional study was conducted, consisting of questionnaire, telephone interviews, analyses of documentation (i.e. local visiting protocols) and a WhatsApp group. Results Variation in local protocols was observed, for example related to the use of personal protective equipment, location and supervision of visits. In general, experiences were very positive. All nursing homes recognized the added value of real and personal contact between residents and their loved ones and indicated a positive impact on well-being. Compliance with local guidelines was sufficient to good. No new COVID-19 infections were reported during this time. Conclusions and implications These results indicate the value of family visitation in nursing homes and positive impact of visits. Based on these results, the Dutch government has decided to allow all nursing homes in the Netherlands to cautiously open their homes using the guidelines. More research is needed on impact and long-term compliance.


title: Current research status of immunology in the genomic era

text: This review updates the current status of immunology research under the influence of genomics, both conceptually and technologically. It particularly highlights the advantages of employing the high-throughput and large-scale technology, the large genomic database, and bioinformatic power in the immunology research. The fast development in the fields of basic immunology, clinical immunology (tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy. We also speculate the future research directions of immunology in the era of genomics and post-genomics.


title: SYBR Green based real-time RT-PCR assay for detection and genotype prediction of bovine noroviruses and assessment of clinical significance in Norway

text: Abstract A novel SYBR Green based real-time RT-PCR assay for detection of genogroup III bovine noroviruses (BoNoV) was developed and the assay applied to 419 faecal samples from calves with and without diarrhoea. The samples were obtained from 190 Norwegian dairy and beef herds. BoNoV was detected in 49.6% of the samples from 61.1% of the herds indicating that BoNoV is ubiquitous in Norway. The overall prevalence was not significantly different in diarrhoea and non-diarrhoea samples. Analyses of polymerase gene sequences revealed both genotype III/1 and III/2 with genotype III/2 (Newbury2-like) being the most prevalent. Detected capsid sequences were restricted to Newbury2-like and the chimeric Bo/Thirsk10/00/UK strain. The RNA polymerase genotypes of the circulating BoNoVs in Norway were predicted by melting temperature analysis. Additional data from a challenge experiment suggest that a high proportion of young calves are shedding low levels of BoNoV for a prolonged time after recovering from the associated diarrhoea. The findings may explain some of the discrepancies in detection rates from previous studies and explain why some studies have failed to detect significant prevalence differences between calves with and without diarrhoea. It may also shed new light on some epidemiological aspects of norovirus infections.