title: It Takes a Community to Raise the Prevalence of a Zoonotic Pathogen

text: By definition, zoonotic pathogens are not strict host-species specialists in that they infect humans and at least one nonhuman reservoir species. The majority of zoonotic pathogens infect and are amplified by multiple vertebrate species in nature, each of which has a quantitatively different impact on the distribution and abundance of the pathogen and thus on disease risk. Unfortunately, when new zoonotic pathogens emerge, the dominant response by public health scientists is to search for a few, or even the single, most important reservoirs and to ignore other species that might strongly influence transmission. This focus on the single “primary” reservoir host species can delay biological understanding, and potentially public health interventions as species important in either amplifying or regulating the pathogen are overlooked. Investigating the evolutionary and ecological strategy of newly discovered or emerging pathogens within the community of potential and actual host species will be fruitful to both biological understanding and public health.


title: Notfällige Neurointerventionen, Covid-19 und Thorax-CT: SOP und Literaturübersicht

text: BACKGROUND AND PURPOSE: To analyze standard operating procedures (SOP) of acute stroke imaging and interventions during COVID-19 pandemic with special emphasis on chest CT within a multimodal stroke protocol. METHODS: A questionnaire was distributed via email to members of the Professional Organization of German Neuroradiologists (Berufsverband Deutscher Neuroradiologen e.V.). RESULTS: Answers were received from 25 units: eleven of them acquire chest CT, three in any patient and eight, when COVID-19 is suspected due to body temperature increase, patient’s history or when the latter cannot be sufficiently obtained. Preliminary data indicate a high sensitivity and moderate negative predictive value. CONCLUSION: Different SOP reflect an uncertainty whether chest CT should be acquired as part of a multimodal stroke protocol. Accuracy of low dose chest CT cannot be determined yet. The strengths and limitations of chest CT are discussed.


docid: prnpojgb

title: Houttuynia cordata, a novel and selective COX-2 inhibitor with anti-inflammatory activity

text: Abstract Ethnopharmacological relevance Houttuynia cordata Thunb. (Saururaceae; HC) has been long used in traditional oriental medicine for the treatment of inflammation diseases. Modern research has implicated inducible cyclooxygenase-2 (COX-2) as a key regulator of the inflammatory process. Aim of the study In the present study, we aimed to investigate the effect of HC on COX-2. We examined the effects of HC on lipopolysaccharide (LPS)-induced prostaglandin (PG) E2 production, an indirect indicator of COX-2 activity, and COX-2 gene and protein expression in mouse peritoneal macrophages. Materials and methods LPS-induced mouse peritoneal macrophages were employed as an in vitro model system. LPS-induced PGE2 production was assessed by enzyme-linked immunosorbant assay and COX-2 protein expression was assessed by Western blot assay. Results The results showed that HC was able to inhibit the release of LPS-induced PGE2 from mouse peritoneal macrophages (IC50 value: 44.8μg/mL). Moreover, the inhibitory activity of HC essential oil elicited a dose-dependent inhibition of COX-2 enzyme activity (IC50 value: 30.9μg/mL). HC was also found to cause reduction in LPS-induced COX-2 mRNA and protein expression, but did not affect COX-1 expression. The non-steroidal anti-inflammatory drug (NSAID) and specific COX-2 inhibitor NS398 functioned similarly in LPS-induced mouse peritoneal macrophages. Conclusion Taken together, our data suggest HC mediates inhibition of COX-2 enzyme activity and can affect related gene and protein expression. HC works by a mechanism of action similar to that of NSAIDs. These results add a novel aspect to the biological profile of HC.


title: COVID-19 and Picotechnology: Potential Opportunities

text: Humanity's challenges are becoming increasingly difficult, and as these challenges become more advanced, the need for effective and intelligent action becomes more apparent. Meanwhile, the novel coronavirus disease (COVID-19) pandemic, which has plagued the world, could be considered as an opportunity to take a step toward the need for atomic engineering, compared to molecular engineering, as well as to accelerate this type of research. This approach, which can be expressed in terms of picotechnology, makes it possible to identify living cell types or in general, chemical and biological surfaces using their atomic arrays, and applied for early diagnosis even treatment of the disease.


title: Do citation trends reflect epidemiologic patterns? Assessing MRSA, emerging and re-emerging pathogens, 1963–2014

text: BACKGROUND: A rapid rise in PubMed citations on methicillin-resistant Staphylococcus aureus (MRSA) occurred after 2000, but the relationship of trends in citation to epidemiologic trends for infectious disease is not known. METHODS: We queried PubMed(R), for citations to the following: MRSA, HIV/AIDS, Staphylococcus aureus, severe acute respiratory syndrome, Lyme disease, avian influenza, West Nile virus, Chikungunya, Ebola virus and Middle Eastern respiratory syndrome. Incidence or mortality data were tabulated. RESULTS: We identified 560,225 citations in 1963–2014. There were two distinct qualitative citation patterns. Type I pathogens showed a decade of initial exponential growth. Type II pathogens showed a sudden spike in citations in a year or two, followed by a relative decline. MRSA most closely resembled a Type I pathogen. CONCLUSIONS: The Type I pattern pathogens had varied trends in disease incidence in the years following the exponential growth and subsequent decline in the number of citations. Their differing epidemiologic patterns did not correlate with their pattern of citations. We conclude that citation trends on MRSA cannot be used to determine past epidemiologic trends and also that the citation trend for MRSA in 1995–2011 most closely resembled that for HIV in 1981–1998.


title: Soft-shelled turtle iridovirus enters cells via cholesterol-dependent, clathrin-mediated endocytosis as well as macropinocytosis

text: Ranaviruses are nucleoplasmic large DNA viruses that can cause major economic losses in the aquaculture industry and pose a severe threat to global ecological diversity. The available literature demonstrates that classifiable members of the genus Ranavirus enter cells via multiple and complicated routes. Here, we demonstrated the underlying cellular entry mechanism of soft-shelled turtle iridovirus (STIV) using green fluorescence tagged recombinant virus. Treatment with chlorpromazine, sucrose, ethyl-isopropyl amiloride, chloroquine or bafilomycin A1 all significantly decreased STIV infection, suggesting that STIV uses clathrin-mediated endocytosis and macropinocytosis to enter cells via a pH-dependent pathway. Depletion of cellular cholesterol with methyl-β-cyclodextrin significantly inhibited STIV entry, but neither filipin III nor nystatin did, suggesting that STIV entry was cholesterol dependent but caveola independent. Treatment with dynasore, genistein, ML-7 or cytochalasin D all significantly inhibited STIV infection, indicating that Rac GTPase and myosin II activity were required for the macropinocytosis-like pathway as well as actin polymerization. Our findings suggest that the molecular events involved in STIV entry are not identical to those of other ranavirus isolates. Our results also extend our understanding of the molecular mechanism of iridovirus entry and pathogenesis.


title: The porcine deltacoronavirus replication organelle comprises double membrane vesicles and zippered endoplasmic reticulum with double membrane spherules

text: Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in 2012 from samples taken from pigs in 2009. PDCoV was subsequently identified in the USA in 2014 in pigs with a history of severe diarrhea and the virus has now been detected in pigs in several countries around the world. Following the development of tissue culture adapted strains of PDCoV, it is now possible to begin to address questions regarding virus-host cell interactions for this genera of coronavirus. Here we present a detailed study of PDCoV induced replication organelles. All positive strand RNA viruses induce the rearrangement of cellular membranes during virus replication to support viral RNA synthesis, forming the replication organelle. Replication organelles for the Alpha-, Beta- and Gammacoronavirus genera have been characterized. However the structures induced by deltacoronaviruses, in particular the presence of convoluted membranes or double membrane spherules, are unknown. Initially, the dynamics of PDCoV strain OH-FD22 replication were assessed with the onset of viral RNA synthesis, protein synthesis and progeny particle release determined. Subsequently, virus induced membrane rearrangements were identified in infected cells by electron microscopy. As has been observed for all other coronaviruses studied to date, PDCoV replication was found to induce the formation of double membrane vesicles. Significantly however, PDCoV replication was also found to induce the formation of regions of zippered endoplasmic reticulum and small associated tethered vesicles, double membrane spherules. These structures strongly resemble the replication organelle induced by avian Gammacoronavirus infectious bronchitis virus.


title: An in vitro system for the leader-primed transcription of coronavirus mRNAs.

text: We have developed an in vitro transcription system which can utilize exogenous leader RNA for mouse hepatitis virus (MHV) 'leader-primed' mRNA transcription. Cytoplasmic extracts containing viral proteins and template RNA were prepared by lysolecithin permeabilization of MHV-infected cells. Synthetic leader RNA which differed in sequence from the endogenous leader RNA was added to the extracts and demonstrated to be incorporated into MHV mRNAs. Irrespective of the size of leader RNAs added, the exogenous leader RNA was joined to the endogenous mRNA at the same site, which corresponds to a UCUAA pentanucleotide repeat region. Only leader RNAs containing the pentanucleotide sequences could be utilized for transcription. Mismatches between the intergenic site and the exogenous leader sequence within the pentanucleotide repeat region were corrected in the in vitro system. This in vitro system thus established a novel mechanism of leader-primed transcription using exogenous RNA in trans, and suggests the involvement of a specific ribonuclease activity during coronavirus mRNA synthesis.


Should Schools Reopen Early or Late? – Transmission Dynamics of COVID-19 in Children


title: Canine coronavirus in Australian dogs

text: Objective To estimate the frequency of serum antibodies (IgG and IgM) to canine coronavirus (CCV) in the Australian dog population and evaluate the role of CCV as a causative agent of gastroenteritis. Design A serological survey of antibodies to CCV among different dog populations. Procedure The development and characterisation of an indirect ELISA for the detection of antibodies (IgG and IgM) to CCV was undertaken. Sera collected from both diarrhoeal and non‐diarrhoeal dogs from various populations throughout Australia were tested for these antibodies to CCV. Results Serum samples (1396) collected from 1984 to 1998 were tested for the presence of IgG antibodies to CCV. Samples were divided into two categories on the basis of the number of dogs housed together. The groups were either an open population containing dogs housed as groups of three or less, or kennel populations. Sera from 15.8% of the open population and 40.8% of kennelled dogs were positive for CCV antibodies. The prevalence of antibodies varied from zero to 76% in kennelled dogs. About 23% of 128 dogs positive for IgG antibodies to CCV were also positive for IgM antibodies to CCV, indicating recent CCV infection. Of those dogs that were presented with clinical signs of gastroenteritis such as diarrhoea and vomiting(n = 29), 85% were positive in the IgM ELISA and 85.7% in the IgG ELISA for antibodies to CCV. In comparison, for those dogs presented without any history of gastroenteritis only 15% were positive for IgM and 30% positive for IgG. Conclusion Serological evidence indicates that infection with CCV in dogs is widespread throughout the Australian mainland. The prevalence of antibodies varies greatly among different populations, with an average of 40.8% positive in kennelled populations and 15.8% in the open population.


title: Improvement in the Reproducibility of a Paper-based Analytical Device (PAD) Using Stable Covalent Binding between Proteins and Cellulose Paper

text: Paper-based analytical devices (PADs) have been widely used in many fields because they are affordable and portable. For reproducible quantitative analysis, it is crucial to strongly immobilize proteins on PADs. Conventional techniques for immobilizing proteins on PADs are based on physical adsorption, but proteins can be easily removed by weak physical forces. Therefore, it is difficult to ensure the reproducibility of the analytical results of PADs using physical adsorption. To overcome this limitation, in this study, we showed a method of covalent binding of proteins to cellulose paper. This method consists of three steps, which include periodate oxidation of paper, the formation of a Schiff base, and reductive amination. We identified aldehyde and imine groups formed on paper using FT-IR analysis. This covalent bonding approach enhanced the binding force and binding capacity of proteins. We confirmed the activity of an immobilized antibody through a sandwich immunoassay. We expect that this immobilization method will contribute to the commercialization of PADs with high reproducibility and sensitivity.


title: Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

text: OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval –10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


title: Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding

text: Guinea fowl coronavirus (GfCoV) causes fulminating enteritis that can result in a daily death rate of 20% in guinea fowl flocks. Here, we studied GfCoV diversity and evaluated its phenotypic consequences. Over the period of 2014 to 2016, affected guinea fowl flocks were sampled in France, and avian coronavirus presence was confirmed by PCR on intestinal content and immunohistochemistry of intestinal tissue. Sequencing revealed 89% amino acid identity between the viral attachment protein S1 of GfCoV/2014 and that of the previously identified GfCoV/2011. To study the receptor interactions as a determinant for tropism and pathogenicity, recombinant S1 proteins were produced and analyzed by glycan and tissue arrays. Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Interestingly, recombinant GfCoV/2014 S1 has an increased affinity for these glycans compared to that of GfCoV/2011 S1, which was in agreement with the increased avidity of GfCoV/2014 S1 for gastrointestinal tract tissues. Enzymatic removal of receptors from tissues before application of spike proteins confirmed the specificity of S1 tissue binding. Overall, we demonstrate that diversity in GfCoV S1 proteins results in differences in glycan and tissue binding properties. IMPORTANCE Avian coronaviruses cause major global problems in the poultry industry. As causative agents of huge economic losses, the detection and understanding of the molecular determinants of viral tropism are of ultimate importance. Here, we set out to study those parameters and obtained in-depth insight into the virus-host interactions of guinea fowl coronavirus (GfCoV). Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls.


title: Rhinovirus C and Respiratory Exacerbations in Children with Cystic Fibrosis

text: To investigate a possible role for human rhinovirus C in respiratory exacerbations of children with cystic fibrosis, we conducted microbiologic testing on respiratory specimens from 103 such patients in São Paulo, Brazil, during 2006–2007. A significant association was found between the presence of human rhinovirus C and respiratory exacerbations.


title: Review article: genetic factors that modify the outcome of viral hepatitis

text: BACKGROUND: Genetic factors can play an important role for treatment response and disease progression in chronic viral hepatitis. AIM: To review the influence of host genetic factors on the clinical course as well as on treatment response in patients with viral hepatitis. METHODS: Review of the literature. RESULTS: A landmark genome‐wide association study (GWAS) identified polymorphisms in the IL28B gene on chromosome 19 (19q13.13) associated with response to therapy with pegylated interferon‐α (PEG‐IFN) and ribavirin (RBV) and spontaneous viral clearance in acute hepatitis C. Furthermore, IL28B genotype is associated with changes of lipid metabolism and insulin resistance. A further GWAS demonstrated that ITPA genetic variants protect HCV genotype 1 patients from RBV‐induced anaemia. Another polymorphism in the patatin‐like phospholipase domain containing 3 (PNPLA3) is associated with hepatic steatosis. Difficult‐to‐treat hepatitis C patients homozygous for GG had an up to five‐fold lower chance of viral clearance on PEG/RBV than non‐GG patients. In chronic hepatitis B patients treated with PEG‐IFN several retrospective analyses of IL28B rs12980275 and rs12979860 genotypes yielded conflicting results which can be explained by the heterogeneity between the study populations. Some variants of the HLA‐DP locus (HLA‐DPA1 A allele and HLA‐DPB1) protect against progression of chronic hepatitis B infection. CONCLUSIONS: The determination of IL28B polymorphisms may be useful to individualise treatment options when using PEG/RBV based therapies for chronic hepatitis C infection. In contrast, so far identified genetic factors play only a minor role in chronic hepatitis B infection.


neuroRAD 2020 Virtual


title: Pulmonary DNA vaccination: Concepts, possibilities and perspectives

text: Abstract Mucosal immunity establishes the first line of defence against pathogens entering the body via mucosal surfaces. Besides eliciting both local and systemic immunity, mucosal vaccination strategies that are non-invasive in nature may increase patient compliance and reduce the need for vaccine application by trained personnel. A relatively new concept is mucosal immunization using DNA vaccines. The advantages of DNA vaccines, such as the opportunity to combine the genetic information of various antigen epitopes and stimulatory cytokines, the enhanced stability and ease of production make this class of vaccines attractive and suitable for mucosal application. In contrast to the area of intranasal vaccination, only a few recent studies have focused on pulmonary immunization and the involvement of the pulmonary immune system in eliciting protective immune responses against inhaled pathogens. This review focuses on DNA vaccine delivery to the lung as a promising approach to prevent pulmonary-associated diseases caused by inhaled pathogens. Attractive immunological features of the lung as a site for immunization, the mechanisms of action of DNA vaccines and the pulmonary application of such vaccines using novel delivery systems will be discussed. We also examine pulmonary diseases prone to prevention or therapeutical intervention by application of DNA vaccines.


title: Transitioning to high efficiency air conditioning in Saudi Arabia: A benefit cost analysis for residential buildings

text: Abstract This paper assesses the benefits of transitioning to high efficiency air conditioning (AC) equipment for existing units specific to the residential building stock in the Kingdom of Saudi Arabia (KSA). The analysis is based on a calibrated residential building stock model for Saudi Arabia supported by national statistics regarding the characteristics of AC systems. Various housing prototypes, vintages, and locations are included in the analysis. Specifically, the analysis considers the scaling up of the government's High Efficiency AC (HEAC) program which offers 900 Saudi Riyals (240 USD) per unit to consumers for up to 6 split system units with an energy efficiency rating (EER) of 13.0 or more per household. The main findings of the study suggest that upgrading the existing old stock of window units and split systems currently in place to the requirements of HEAC program would generate a reduction in electricity consumption of around 33 TWh/year and 24 million tons of CO2. Due to the effect of the HEAC consumer subsidy, purchasing a high efficiency unit has a simple payback period for the consumer of 5 years which is faster than less efficient AC options. This would come at a cost to the government of approximately 6 Billion USD resulting in an annual income of 3.0 Billion USD from the sale of avoided fuel associated with the saved electricity consumption.


title: Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective

text: In this report, updated information and future perspectives about the use of saliva as a sample for laboratory analysis of the Covid-19 are highlighted. Saliva can be used for the direct detection of the SARS-CoV-2 virus, the quantification of the specific immunoglobulins produced against it, and for the evaluation of the non-specific, innate immune response of the patient. Moreover, a deeper knowledge of potential changes in the saliva proteome in this disease may allow the identification of new diagnostic and prognostic biomarkers, or even help our understanding of the mechanisms associated with the disease. With the development of appropriate sample collection and processing methods and the use of adequate assays, saliva can provide useful clinical information about the disease and could be potentially included in guidelines for sample collection for the diagnosis, disease management, and control of Covid-19.


title: Large artery ischaemic stroke in severe acute respiratory syndrome (SARS)

text: Of the 206 patients who contracted Severe Acute Respiratory Syndrome (SARS) in Singapore five developed large artery cerebral infarctions. Four patients were critically-ill and three died. Intravenous immunoglobulin was given to three patients. An increased incidence of deep venous thrombosis and pulmonary embolism was also observed among the critically-ill patients. We believe our experience warrants an increased vigilance against stroke and other thrombotic complications among critically-ill SARS patients in future outbreaks, especially if treatment such as intravenous immunoglobulin, that increases pro-thrombotic tendency, is contemplated.


Persistent Environmental Contamination and Prolonged Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea


title: We urgently need guidelines for managing COVID‐19 in children with comorbidities

text: I read with great interest the systematic review by Ludvigsson on the coronavirus disease 2019 (COVID-19) (1). The author needs to be complimented for a well-timed, rigorous and rapid synthesis of the evidence from the rather scant data available on how the virus affects children. The review, which focused on all papers published up to 19 March, drew important conclusions that have significant practical implications for those involved in providing acute care for children suffering from this disease.


title: Efficacy and safety of an attenuated live QX-like infectious bronchitis virus strain as a vaccine for chickens

text: The attenuation of infectious bronchitis (IB) QX-like virus strain L1148 is described. The virus was passaged multiple times in embryonated specific pathogen free (SPF) chicken eggs, and at different passage levels samples were tested for safety for the respiratory tract and kidneys in 1-day-old SPF chickens. There was a clear decrease in pathogenicity for the respiratory tract and kidneys when the virus had undergone a large number of passages. Passage level 80 was investigated for safety for the reproductive tract in 1-day-old and 7-day-old SPF chickens. In 1-day-old chickens, 12.5% of the vaccinated birds had macroscopic lesions. No lesions were observed if the chickens had been vaccinated at 7 days of age. Passage level 80 was investigated for its ability to spread from vaccinated to non-vaccinated chickens and for dissemination in the body. The virus was able to spread from vaccinated chickens to groups of non-vaccinated chickens, and in the vaccinated birds the virus was found frequently in oro-pharyngeal and cloacal swabs. A fragment of the hypervariable region of the S1 protein of passage level 80 was sequenced and revealed nucleotide changes resulting in two amino acid substitutions. Passage level 80 was given additional passages to levels 82 and 85. Both passage levels were tested for efficacy in SPF chickens and passage level 85 was tested for efficacy in commercial chickens with maternally derived antibodies (MDA) against a challenge with QX-like strain IB D388. In both SPF chickens and chickens with MDA, the vaccines based on strain IB L1148 were efficacious against challenge.


Assessing the Evidence Supporting Fruit Bats as the Primary Reservoirs for Ebola Viruses


title: Validation of a digital pathology system including remote review during the COVID-19 pandemic

text: Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3–42 in.; resolution, 1280 × 800–3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm(2). Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.


title: Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

text: Viral genomes have high gene densities and complex transcription strategies rendering transcriptome analysis through short-read RNA-seq approaches problematic. Adenovirus transcription and splicing is especially complex. We used long-read direct RNA sequencing to study adenovirus transcription and splicing during infection. This revealed a previously unappreciated complexity of alternative splicing and potential for secondary initiating codon usage. Moreover, we find that most viral transcripts tend to shorten polyadenylation lengths as infection progresses. Development of an open reading frame centric bioinformatics analysis pipeline provided a deeper quantitative and qualitative understanding of adenovirus’s genetic potential. Across the viral genome adenovirus makes multiple distinctly spliced transcripts that code for the same protein. Over 11,000 different splicing patterns were recorded across the viral genome, most occurring at low levels. This low-level use of alternative splicing patterns potentially enables the virus to maximise its coding potential over evolutionary timescales.


title: The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy

text: Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.


title: Autoinhibition of Bcr-Abl through Its SH3 Domain

text: Abstract Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt oligomerization, but restored by an SH3 point mutation that blocks ligand binding or a complementary mutation at the intramolecular SH3 binding site defined in c-Abl. Phosphorylation of tyrosines in the activation loop of the catalytic domain and the linker between the SH2 and catalytic domains (SH2-CD linker) is dependent on oligomerization and required for leukemogenesis. These results suggest that Bcr-Abl has a monomeric, unphosphorylated state with the SH3 domain engaged intramolecularly to Pro1124 in the SH2-CD linker, the form that is sensitive to the inhibitor imatinib (STI-571). The sole function of the coiled-coil domain is to disrupt the autoinhibited conformation through oligomerization and intermolecular autophosphorylation.


title: More awareness is needed for severe acute respiratory syndrome coronavirus 2019 transmission through exhaled air during non-invasive respiratory support: experience from China

text: Non-invasive respiratory support plays an essential role in the treatment of COVID-19. More awareness is needed of viral transmission through exhaled air. http://bit.ly/39kNrrF


title: Preventive Behavioral Responses to the 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in Korea

text: This study examined the public’s preventive behavioral responses during the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea and the influencing factors. Two cross-sectional telephone surveys were conducted by Gallup Korea using random digit dialing in June 2015 (n = 2004). The main outcome variables were nonpharmaceutical preventive measures (survey (1): Measures for reducing transmission (handwashing, face masks); and survey (2): Measures for avoiding contact with others). Multiple logistic regression was used to identify the factors influencing preventive behaviors. In survey (1), 60.3% of respondents reported more frequent handwashing and 15.5% reported wearing face masks at least once due to the MERS-CoV epidemic. In survey (2), 41–56% of respondents reported practicing avoidance measures. The concerned group was more likely to practice reducing transmission measures (odds ratio (OR) 4.5; 95% confidence interval (CI) 3.3–6.1) and avoidance measures (OR = 9.6; 95% CI, 6.4–14.4). The respondents who had low trust in president or ruling party had a higher practice rate of reducing transmission measures (OR = 1.7; 95% CI, 1.2–2.6) and avoidance measures (OR = 2.1; 95% CI, 1.2–3.5). Cooperative prevention measures need appropriated public concern based on effective risk communication.


title: Inferring who-infected-whom-where in the 2016 Zika outbreak in Singapore—a spatio-temporal model

text: Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector—Aedes aegypti—Zika had the potential to become endemic, like dengue. Guillain–Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e. who-infected-whom-where) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the ‘vector’ infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country.


title: Biochemical Microarrays for Studying Chemical Biology Interaction: DiscoveryDot(TM) Technology

text: DiscoveryDot(TM) is a novel solution‐phase technology for chemical compound microarrays which has been validated for several targets (e.g. serine proteases, cysteine proteases, metalloproteinases, histone deacetylases, phosphatases and various kinases) of significance for drug discovery. The historical context of microarrays and the advantages of the DiscoveryDot(TM) technology are highlighted. The success of this chemical microarray technology will provide unprecedented possibility and capability for parallel functional analysis of hundreds of thousands of chemical compounds.


title: THORACIC RADIOGRAPHIC CHARACTERISTICS OF CANINE INFLUENZA VIRUS IN SIX DOGS

text: Canine influenza virus is an emerging, highly contagious, respiratory pathogen that has not previously been radiographically described. In this retrospective case series study, we describe the thoracic radiographic appearance of confirmed canine influenza virus in six dogs. Radiographic findings varied, but included abnormal unstructured interstitial (one) and unstructured interstitial and alveolar (five) pulmonary patterns, which were distributed cranioventral (four), diffuse (one), and caudodorsal (one). The right middle (five), left cranial (five), and right cranial (four) lung lobes were most commonly affected. Additionally, mild pleural effusion was present in one dog. Intrathoracic lymphadenopathy and cranial mediastinal widening/fluid accumulation were not detected in any dog. Canine influenza virus should be considered as a differential diagnosis for canine patients with respiratory signs and a cranioventral unstructured interstitial to alveolar pulmonary pattern.


title: Processing and antigenicity of entire and anchor-free spike glycoprotein S of coronavirus TGEV expressed by recombinant baculovirus

text: Abstract The S gene of transmissible gastroenteritis virus (TGEV) was inserted into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV) using the transfer plasmid pVL941. Infection of Sf9 insect cells with the recombinant virus resulted in the synthesis of a 175K polypeptide which was able to trimerize and was transported to the cell surface as is the authentic TGEV S protein. Despite the lack of complete carbohydrate processing, the recombinant S protein exhibited antigenic properties similar to TGEV S and induced high levels of neutralizing antibodies in immunized rats. Engineering a deletion (70 amino acids) into the carboxy-terminus containing the membrane anchor of the polypeptide allowed its secretion. The oligomerization process and the antigenic profile of the anchor-free S protein were shown to be partially altered.


title: Synergistic effect of ribavirin and vaccine for protection during early infection stage of foot-and-mouth disease

text: In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after vaccination, research and development on antiviral agents is being conducted to induce protection until immunological competence is produced. This study tested whether well-known chemicals used as RNA virus treatment agents had inhibitory effects on FMD viruses (FMDVs) and demonstrated that ribavirin showed antiviral effects against FMDV in vitro/in vivo. In addition, it was observed that combining the administration of the antiviral agents orally and complementary therapy with vaccines synergistically enhanced antiviral activity and preserved the survival rate and body weight in the experimental animals. Antiviral agents mixed with an adjuvant were inoculated intramuscularly along with the vaccines, thereby inhibiting virus replication after injection and verifying that it was possible to induce early protection against viral infection prior to immunity being achieved through the vaccine. Finally, pigs treated with antiviral agents and vaccines showed no clinical signs and had low virus excretion. Based on these results, it is expected that this combined approach could be a therapeutic and preventive treatment for early protection against FMD.


title: A Sabin 1 poliovirus-based vaccine vector transfects Vero cells with high efficiency

text: Over the past 40 years, live oral poliovirus (PV) vaccines have contributed to the eradication of wild PV in most countries. These live vaccine strains have a high safety record and can stimulate both cellular and humoral immune responses. As both of these factors are critical characteristics of a good vaccine, we aimed to modify the oral PV vaccines to create a powerful vaccine vector for extraneous antigen expression. In this study, we amplified three separate fragments from the Sabin 1 virus genome by RT-PCR and cloned them into the pGEM-TEasy vector. A cassette containing engineered protease cleavage sites and a polylinker was introduced into one of these fragments (f1) in front of the translation start site. This construction facilitated the insertion of foreign genes into the vector and the subsequent release of their co-translated antigens after digestion by endogenous protease. We also placed a ribozyme (Rz) sequence between the T7 promoter and viral genomic DNA so that in vitro transcription and Rz cleavage recreated the authentic 5′ end of the PV genome RNA. Poly(A)(40) tails were added to the 3′ end of the genome to stabilize the transcribed RNA. The three PV genome fragments and their derivatives were cloned into various types of vectors that were transfected into Vero cells. Virus rescue experiments demonstrated that both the Rz and poly(A)(40 )elements were required for high transfection efficiency of the vector-derived RNAs.


title: Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism

text: Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.


title: Recent Advances in the Development of Antimicrobial Nanoparticles for Combating Resistant Pathogens

text: The rapid growth of harmful pathogens and their multidrug‐resistance poses a severe challenge for health professionals and for the development of new healthcare products. Various strategies are exploited for the development of effective antimicrobial agents, and nanoparticles are a particularly promising class of materials in this respect. This review summarizes recent advances in antimicrobial metallic, polymeric, and lipid‐based nanoparticles such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers. The latter materials in particular are engineered for antimicrobial agent delivery and act by encapsulation, receptor‐based binding, and disruption of microbial adherence to cellular substrates. Potential strategies for the design of multifunctional antimicrobial nanocarriers, combining material chemistry and biological interface science, are also discussed.


title: Predicting receptor functionality of signaling lymphocyte activation molecule for measles virus hemagglutinin by docking simulation

text: Predicting susceptibility of various species to a virus assists assessment of risk of interspecies transmission. Evaluation of receptor functionality may be useful in screening for susceptibility. In this study, docking simulation was conducted for measles virus hemagglutinin (MV‐H) and immunoglobulin‐like variable domain of signaling lymphocyte activation molecule (SLAM‐V). It was observed that the docking scores for MV‐H and SLAM‐V correlated with the activity of SLAM as an MV receptor. These results suggest that the receptor functionality may be predicted from the docking scores of virion surface proteins and cellular receptor molecules.


title: COVID ‐19 and the state of African neurology

text: Expectations of Africa having high rates of infection and death from COVID‐19 have, as yet, not materialised. At the time of writing, all 54 countries have officially reported COVID‐19 cases; 123,724 people have tested positive for the disease and 3,668 people have died. The reasons for such low levels may be due, in part, to countries rapid responses: South Africa declared a national state of disaster and implemented a nationwide lockdown before even its first death was reported and likewise Uganda suspended all public gatherings before the country reported its first case. In Ethiopia—where the first case was reported March 13—the office of the Prime Minister announced that schools, sporting events, and public gatherings should be suspended for 15 days, on March 16. In Addis Ababa, on April 8, the Council of Ministers declared a 5‐month long state of emergency.


docid: ykzsoafe

title: Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus

text: Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.


title: Prevention and control strategies for emergency, limited-term, and elective operations in pediatric surgery during the epidemic period of COVID-19

text: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 100 countries. Children approved to be susceptible to SARS-CoV-2 infection. Preventing and controlling the epidemic while ensuring orderly flows of pediatric surgery clinical work has proven to be a big challenge for both patients and clinicians during the epidemic. Based on the transmission characteristics of SARS-CoV-2 and the requirements for prevention and control of COVID-19, the authors proposed some concrete measures and practical strategies of managing emergency, limited-term, and elective pediatric surgeries during the epidemic period.


title: Distribution of Patients at Risk for Complications Related to COVID-19 in the United States: Model Development Study

text: BACKGROUND: Coronavirus disease (COVID-19) has spread exponentially across the United States. Older adults with underlying health conditions are at an especially high risk of developing life-threatening complications if infected. Most intensive care unit (ICU) admissions and non-ICU hospitalizations have been among patients with at least one underlying health condition. OBJECTIVE: The aim of this study was to develop a model to estimate the risk status of the patients of a nationwide pharmacy chain in the United States, and to identify the geographic distribution of patients who have the highest risk of severe COVID-19 complications. METHODS: A risk model was developed using a training test split approach to identify patients who are at high risk of developing serious complications from COVID-19. Adult patients (aged ≥18 years) were identified from the Walgreens pharmacy electronic data warehouse. Patients were considered eligible to contribute data to the model if they had at least one prescription filled at a Walgreens location between October 27, 2019, and March 25, 2020. Risk parameters included age, whether the patient is being treated for a serious or chronic condition, and urban density classification. Parameters were differentially weighted based on their association with severe complications, as reported in earlier cases. An at-risk rate per 1000 people was calculated at the county level, and ArcMap was used to depict the rate of patients at high risk for severe complications from COVID-19. Real-time COVID-19 cases captured by the Johns Hopkins University Center for Systems Science and Engineering (CSSE) were layered in the risk map to show where cases exist relative to the high-risk populations. RESULTS: Of the 30,100,826 adults included in this study, the average age is 50 years, 15% have at least one specialty medication, and the average patient has 2 to 3 comorbidities. Nearly 28% of patients have the greatest risk score, and an additional 34.64% of patients are considered high-risk, with scores ranging from 8 to 10. Age accounts for 53% of a patient’s total risk, followed by the number of comorbidities (29%); inferred chronic obstructive pulmonary disease, hypertension, or diabetes (15%); and urban density classification (5%). CONCLUSIONS: This risk model utilizes data from approximately 10% of the US population. Currently, this is the most comprehensive US model to estimate and depict the county-level prognosis of COVID-19 infection. This study shows that there are counties across the United States whose residents are at high risk of developing severe complications from COVID-19. Our county-level risk estimates may be used alongside other data sets to improve the accuracy of anticipated health care resource needs. The interactive map can also aid in proactive planning and preparations among employers that are deemed critical, such as pharmacies and grocery stores, to prevent the spread of COVID-19 within their facilities.


COVID‐19 and Its Impact on Management Research and Education: Threats, Opportunities and a Manifesto


title: Nanodiagnostics in Microbiology and Dentistry

text: This chapter presents a general overview of nanodiagnostics in microbiology and dentistry. Nanodiagnostics uses biosensor technology which is one of the most promising, compact systems consisting of a composite analysis of biological recognition element. Detecting an analyte (glucose, antibiotics, etc.) using a transducer element or detector element to quantify the amount of analyte is the working principle of biosensors. The transducer or the detector element transforms the signal resulting from the interaction of the analyte with the biological element into another signal that can be more easily measured and quantified. Nanobiotechnology scientists have also successfully produced microchips that are coated with biological molecules. The chip is designed to emit an electrical impulse signal when the molecules detect signs of a disease. Special sensor nanobots can be inserted into the blood under the skin where they can check blood contents and warn of any possible diseases. They can also be used to monitor the sugar level in the blood. Advantages of using such nanobots are that they are very cheap to produce and are easily portable.


title: Chapter 29 Rapid detection of organophosphates, Ochratoxin A, and Fusarium sp. in durum wheat via screen printed based electrochemical sensors

text: Publisher Summary Most of the inhibition bioassays or biosensors for organophosphate and carbamate pesticides are based on the amperometric detection of the enzymatic product of the reaction. Applications of amperometric biosensing strategies for pesticide detection in real or spiked food samples have been recently reported. Most of the applications have been developed for vegetable matrices. Different formats of biosensors have been used: disposable screenprinted choline oxidase biosensors using acetylcholinesterase (AChE) in solution were utilized to detect pesticides. Screen-printed sensor developed using photolithographic conducting copper track, graphite–epoxy composite, and either AChE or butirrylcholinesterase was also used in the analysis of spiked (paraoxon and carbofuran) samples of tap water and fruit juices at sub-nanomolar concentration. Additionally, the developed device, which consists of the hand-held potentiostat, the multiplexer for eight-channel control and a dedicated software, can be used to detect organophosphates pesticides, such as dichlorvos and pirimiphos methyl at contamination level below the maximum residue limit settled by the European Union and also amplified DNA of F. culmorum.


The Enigma of Health Literacy and COVID-19 Pandemic


title: Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study

text: Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear–nose–throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32–57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear–nose–throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear–nose–throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear–nose–throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02379-z) contains supplementary material, which is available to authorized users.


title: Clinical Signs and Diagnostic Tests in Acute Respiratory Infections

text: OBJECTIVES: To evaluate clinical manifestations of acute respiratory system infectious diseases and specific tests for causative agents in pediatric patients. METHODS: The authors evaluated children aged 0–16 y with clinical symptoms of acute respiratory tract infections who were administered rapid strep A test and/or throat culture test and/or respiratory viral panel test, from February 2012 through January 2013 at pediatric department of Acıbadem Maslak Hospital, Turkey. RESULTS: A total of 1654 patients were evaluated; 45.9 % were girls, 54.1 % were boys. Absence of cough and presence of headache were higher in the patients >6 y of age (p 0.0001, p 0.002 respectively). Positive respiratory viral panel test was higher in the patients <2 y of age (p 0.002). Both positive rapid strep A test and positive throat culture test were higher in the patients >6 y of age (p 0.0001). Positivity of rapid strep A or throat culture test were not observed in children <2 y of age. CONCLUSIONS: A clinician should mostly consider viral infections in the etiology of acute respiratory infections in children under 2 y of age and there is no need to rush for the use antibiotherapy. Bacterial etiology should be frequently considered after 6 y of age and rapid use of antibiotheraphy is essential to avoid the complications.


title: Prediction of Intrinsic Disorder in MERS-CoV/HCoV-EMC Supports a High Oral-Fecal Transmission

text: A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations.


title: Psychometric Properties of the Greek Version of FCV-19S

text: As COVID-19 delivered a devastating blow around Europe, unprecedented mental health issues have arisen. This study outlines the Greek translation and validation of the Fear of COVID-19 Scale (FCV-19S) in the general population. A sample of 3029 Greek-speaking individuals completed the FCV-19S, as part of a large online survey reporting on the aftermath of the coronavirus on the psychological health of Greeks. A total of 2970 participants completed all items without missing values, and their responses were included in the statistical analysis. The confirmatory factor analysis suggested an acceptable model fit. The internal consistency measured by Cronbach’s alpha = .87 for the whole scale. All hypothesized correlations were as expected, confirming the construct validity of the scale. The results of the analyses suggest that the psychometric properties of the Greek FCV-19S are sufficient.


title: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic

text: ABSTRACT Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.


title: Managing Severe Aortic Stenosis in the COVID-19 Era

text: Abstract The novel coronavirus-19 (COVID-19) pandemic has created uncertainty in the management of patients with severe aortic stenosis (AS). This population experiences high mortality from delays in treatment of valve disease but is largely overlapping with the population of highest mortality from COVID-19. We present strategies for managing patients with severe AS in the COVID-era. We suggest transitions to virtual assessments and consultation, careful pruning and planning of necessary testing, as well as fewer and shorter hospital admissions. These strategies center on minimizing patient exposure to COVID-19 and expenditure of human and health-care resources without significant sacrifice to patient outcomes during this public health emergency. Areas of innovation to improve our care during this time include increased use of wearable and remote devices to assess patient performance and vital signs, devices for facile cardiac assessment, and widespread use of clinical protocols for expedient discharge with virtual physical therapy and cardiac rehabilitation options.


title: Clones of cells from a human embryo lung: Their growth and susceptibility to respiratory viruses

text: Colonies of cells were obtained from human fetal lung tissue and exposed to recently isolated respiratory viruses. There was a considerable variation in the number of rounded cells found in different colonies exposed to rhinovirus types 2 and 9 (RV2 and 9), human coronavirus 229 E (HCV), adenovirus type 3 (Ad3) and respiratory syncytial virus (RSV). Smaller colonies had more rounded cells than larger colonies. Clones were established from 9 out of 11 colonies. They varied in their rate of growth and the pattern formed on a plastic surface. They varied also in their virus susceptibility particularly to “difficult” rhinoviruses such as RV9 and SF 1340. One cell clone (HL1/77 Clone 8), was highly susceptible to all these viruses. All cultures were more sensitive to RSV when maintained in F 12K medium than in MEM, whereas there was no difference for rhinoviruses. Influenza A and B and parainfluenza 3 viruses sometimes produced cytopathic effect, and always produced haemadsorption, but unlike the previous strains could not be passed serially and presumably produced little infections virus. All clones were rather insusceptible to Ad3; but the virus could be passed, whereas coxsackie virus B3 produced no CPE. Substantial yields of coronavirus and rhinovirus were obtained in gelatin sponge cultures. Two “very difficult” respiratory viruses which had just been adapted to tissue culture; namely, HS rhinovirus and JK coronavirus grew in 7 of 9 and in 6 of 9 clones respectively.


title: Decoding the global outbreak of COVID-19: the nature is behind the scene

text: The sudden emergence of SARS-CoV-2 causing the global pandemic is a major public health concern. Though the virus is considered as a novel entity, it is not a completely new member. It is just a new version of previously emerged human SARS corona virus. The rapid evolving nature by changing host body environment and extreme environmental stability, collectively makes SARS-CoV-2 into an extremely virulent genetic variant. The evolution of the virus has been occurred by the continuous process of molecular genetic manipulation, through mutation, deletion and genetic recombinationevents. Different host body environment acts as the supportive system for the pathogen which creates extreme selective pressure. By the process of genetic evolution the pathogen developes new characters. Then the new version of the virus has been naturally selected by susceptible human host and adapt itself inside the host body causing deadly effect. Moreover, extreme environmental stability helps in the process of viral survival outside the host and its transmission. Thus both the host body or internal environment and the external environment performs equally as a source, responsible for shaping the genetic evolution of the SARS-CoV-2 towards theCOVID-19 disease fitness in nature in a pandemic form.


The Scientific Response to a Pandemic


title: Enhanced Induction of SARS-CoV Nucleocapsid Protein-Specific Immune Response Using DNA Vaccination followed by Adenovirus Boosting in BALB/c Mice

text: OBJECTIVE: To investigate immunogenicity in the induction of humoral and cellular immune responses to genetic vaccines of the recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-N gene expressing the same protein plasmid, pcDNA3.1-N, and replication-defective adenoviral vector, rAd-N, in a pcDNA3.1-N prime-rAd-N boost regimen and the reverse sequence in a rAd-N prime-pcDNA3.1-N boost regimen. METHOD: After the mice had been immunized intramuscularly and/or intraperitoneally with pcDNA3.1-N and rAd-N in prime-triple boost immunization, humoral and cellular immune responses were detected. RESULTS: After detection, different levels of anti-N humoral and cellular responses are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen and the reverse sequence of heterogeneous combinations. There is a significant difference between heterogeneous and homologous vaccinations. However, the cytotoxic T lymphocyte (CTL) response was not significantly altered by the different prime-boost immunizations or the recombinant adenovirus of pcDNA3.1-N prime-rAd-N boost regimen alone, but lymphoproliferation and interferon-γ (IFN-γ) secretion were all enhanced by heterologous combination immunizations compared to homologous combinations. For the reverse sequence immunization regimen, lymphoproliferation, IFN-γ and CTL responses were all significantly weaker compared with pcDNA3.1-N prime-rAd-N boost regimen. CONCLUSION: Taken together, of all the combinations, the prime-triple boost immunization of pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N can effectively induce SARS-CoV-N-specific and strong humoral and cellular immune responses in mice. The present results suggest that DNA immunization followed by recombinant adenovirus boosting could be used as a potential SARS-CoV vaccine in the induction of an enhanced humoral and cellular immune response.


title: Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection

text: Bovine respiratory disease complex (BRDC) is the major cause of serious respiratory tract infections in calves. The disease is multifactorial, with either stress or reduced immunity allowing several pathogens to emerge. We investigated the susceptibility of bovine airway epithelial cells (BAEC) to infection by the three major viruses associated with the BRDC: bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza virus type 3 (BPIV3). For this purpose, two culture systems for well-differentiated BAEC were used: the air-liquid interface (ALI) system, where filter-grown BAEC differentiate into a pseudostratified respiratory epithelium and precision-cut lung slices (PCLS) where BAEC are maintained in the original tissue organisation. Comparative infection studies demonstrated that entry and release of BPIV3 occurred specifically via the apical membrane with ciliated cells being the major target cells. By contrast, airway epithelial cells were largely resistant to infection by BHV-1. When the epithelial barrier was abolished by opening tight junctions or by injuring the cell monolayer, BHV-1 infected mainly basal cells. Respiratory epithelial cells were also refractory to infection by BRSV. However, this virus infected neither differentiated epithelial cells nor basal cells when the integrity of the epithelial barrier was destroyed. In contrast to cells of the airway epithelium, subepithelial cells were susceptible to infection by BRSV. Altogether, these results indicate that the three viruses of the same disease complex follow different strategies to interact with the airway epithelium. Possible entry mechanisms are discussed.


title: EMMPRIN/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: novel propositions

text: Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with ‘S’ receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs.


AkzoNobel Shows Profitability Improvement for First Quarter despite COVID-19 Impacts


title: Campesin, a thermostable antifungal peptide with highly potent antipathogenic activities

text: Abstract An 9.4-kDa antifungal peptide designated as campesin was isolated from seeds of the cabbage Brassica campestris. The isolation procedure involved affinity chromatography on Affi-gel blue gel, ion exchange chromatography on Q-Sepharose and Mono S, and gel filtration on Superdex 75 and Superdex Peptide. The peptide was adsorbed on the first three chromatographic media. It exerted an inhibitory action on mycelial growth including Fusarium oxysporum and Mycosphaerella arachidicola, with an IC50 of 5.1 μM and 4.4 μM, respectively. The peptide was characterized by remarkable thermostability and pH stability. It inhibited proliferation of HepG2 and MCF cancer cells with an IC50 of 6.4 μM and 1.8 μM, and the activity of HIV-1 reverse transcriptase with an IC50 of 3.2 μM. It demonstrated lysolecithin binding activity.


docid: cmeszahl

title: Intravenous Immunoglobulins: Evolution of Commercial IVIG Preparations

text: Since its first use in 1952, human immunoglobulin has been used to treat people who have inherited antibody deficiencies. This article summarizes IVIG clinical development in primary immunodeficient patients and manufacturing improvements introduced over time. Manufacturing improvements include purification procedures that have reduced the incidence of adverse events and improved clinical efficacy, as well as virus inactivation and removal steps that have increased safety from blood-borne infections. Current manufacturing procedures, IVIG production trends, and recent clinical trial results are also reviewed.


title: Infecciones respiratorias por metapneumovirus en lactantes hospitalizados

text: Antecedentes El metapneumovirus humano es un virus de reciente descripción al que se atribuyen infecciones respiratorias que afectan fundamentalmente a la población infantil. Objetivos Conocer la incidencia de infecciones por metapneumovirus en lactantes hospitalizados, así como sus características clínicas y la posible presencia de coinfecciones con otros agentes virales. Pacientes y métodos Estudio prospectivo realizado de septiembre a junio de 2003 en todos los niños menores de 2 años ingresados en la Unidad de Lactantes del Hospital Severo Ochoa de Leganés (Madrid), por infección respiratoria. La detección de agentes virales se realizó mediante recogida de aspirado nasofaríngeo y realización de inmunofluorescencia directa y/o reacción en cadena de la polimerasa-transcripción inversa (RT-PCR). Descripción de las características clínicas y epidemiológicas de los procesos respiratorios de los pacientes con detección positiva para metapneumovirus humano. Resultados Ingresaron 200 lactantes con patología respiratoria durante el período mencionado, de los cuales en 18 se detectó infección por metapneumovirus humano (9% de los pacientes). El metapneumovirus humano supuso un 13,8% de los aislamientos virales positivos. El 100 % de estos niños ingresaron en marzo-abril. La edad media fue de 6,7 ± 6,1 meses. El 38,8 % desarrolló una bronquiolitis y en el 55,5 % se objetivó un episodio recurrente de sibilancias. El 55,5 % de los niños precisó oxigenoterapia durante el ingreso. Se encontraron coinfecciones con otros agentes virales en el 33,3 % de estos pacientes. Conclusiones El metapneumovirus humano es un agente viral muy frecuente en los lactantes afectados de enfermedad respiratoria, causando fundamentalmente bronquiolitis y episodios recurrentes de sibilancias. Es más frecuente en primavera y tiene una alta tendencia a la coinfección con otros virus. Background Human metapneumovirus (hPMV) is a recently identified virus that is recognized as a cause of respiratory tract illness in the pediatric population. Objectives To determine the incidence of respiratory tract infections caused by hPMV in hospitalized infants and to describe the clinical characteristics and possible presence of coinfection with other viral agents. Patients and methods We performed a prospective study from September to June 2003 in all children aged less than 24 months who were admitted to the Severo Ochoa Hospital (Leganés, Madrid) with a respiratory tract infection. Virological diagnosis was made with a direct immunofluorescent assay and/or reverse transcriptase-polymerase chain reaction on specimens obtained from nasopharyngeal washing. Demographic and clinical data from patients with an hPMV respiratory tract infection were analyzed. Results During the study period, 200 infants were admitted with a respiratory tract infection, of which 18 (9 %) had an hPMV infection. HPMV was the viral agent isolated in 13.8% of positive nasopharyngeal washings. All patients were admitted between March and April. The mean age was 6.7 ± 6.1 months. The most common diagnoses were recurrent wheezing (55.5 %) and bronchiolitis (38.8%). Oxygen therapy was required by 55.5 % of infants during hospitalization. Coinfection with other respiratory viruses was confirmed in 33.3% of the patients. Conclusions Human metapneumovirus is a major cause of respiratory tract illness in hospitalized infants. This virus causes mainly bronchiolitis and recurrent wheezing and is more frequent in spring. Coinfection with other respiratory viruses is frequent.


title: COVID-19 Pandemic and Beyond: Considerations and Costs of Telehealth Exercise Programs for Older Adults With Functional Impairments Living at Home—Lessons Learned from a Pilot Case Study

text: OBJECTIVE: The purpose of this study was to describe the process and cost of delivering a physical therapist–guided synchronous telehealth exercise program appropriate for older adults with functional limitations. Such programs may help alleviate some of the detrimental impacts of social distancing and quarantine on older adults at-risk of decline. METHODS: Data were derived from the feasibility arm of a parent study, which piloted the telehealth program for 36 sessions with 1 participant. The steps involved in each phase (ie, development, delivery) were documented, along with participant and program provider considerations for each step. Time-driven activity-based costing was used to track all costs over the course of the study. Costs were categorized as program development or delivery and estimated per session and per participant. RESULTS: A list of the steps and the participant and provider considerations involved in developing and delivering a synchronous telehealth exercise program for older adults with functional impairments was developed. Resources used, fixed and variable costs, per-session cost estimates, and total cost per person were reported. Two potential measures of the “value proposition” of this type of intervention were also reported. Per-session cost of $158 appears to be a feasible business case, especially if the physical therapist to trained assistant personnel mix could be improved. CONCLUSIONS: The findings provide insight into the process and costs of developing and delivering telehealth exercise programs for older adults with functional impairments. The information presented may provide a “blue print” for developing and implementing new telehealth programs or for transitioning in-person services to telehealth delivery during periods of social distancing and quarantine. IMPACT: As movement experts, physical therapists are uniquely positioned to play an important role in the current COVID-19 pandemic and to help individuals who are at risk of functional decline during periods of social distancing and quarantine. Lessons learned from this study’s experience can provide guidance on the process and cost of developing and delivering a telehealth exercise program for older adults with functional impairments. The findings also can inform new telehealth programs, as well as assist in transitioning in-person care to a telehealth format in response to the COVID-19 pandemic.


title: Syphilis in China: results of a national surveillance programme

text: Summary Background After a massive syphilis epidemic in the first half of the 20th century, China was able to eliminate this infection for 20 years (1960–80). However, substantial changes in Chinese society have been followed by a resurgent epidemic of sexually transmitted diseases. Sporadic reports have provided clues to the magnitude of the spread of syphilis, but a national surveillance effort is needed to provide data for planning and intervention. Methods We collected and assessed case report data from China's national sexually transmitted disease surveillance system and sentinel site network. Findings In 1993, the reported total rate of cases of syphilis in China was 0·2 cases per 100 000, whereas primary and secondary syphilis alone represented 5·7 cases per 100 000 persons in 2005. The rate of congenital syphilis increased greatly with an average yearly rise of 71·9%, from 0·01 cases per 100 000 livebirths in 1991 to 19·68 cases per 100 000 livebirths in 2005. Interpretation The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.


title: Protracted bacterial bronchitis: The last decade and the road ahead

text: Cough is the single most common reason for primary care physician visits and, when chronic, a frequent indication for specialist referrals. In children, a chronic cough (>4 weeks) is associated with increased morbidity and reduced quality of life. One common cause of childhood chronic cough is protracted bacterial bronchitis (PBB), especially in children aged <6 years. PBB is characterized by a chronic wet or productive cough without signs of an alternative cause and responds to 2 weeks of appropriate antibiotics, such as amoxicillin‐clavulanate. Most children with PBB are unable to expectorate sputum. If bronchoscopy and bronchoalveolar lavage are performed, evidence of bronchitis and purulent endobronchial secretions are seen. Bronchoalveolar lavage specimens typically reveal marked neutrophil infiltration and culture large numbers of respiratory bacterial pathogens, especially Haemophilus influenzae. Although regarded as having a good prognosis, recurrences are common and if these are frequent or do not respond to antibiotic treatments of up to 4‐weeks duration, the child should be investigated for other causes of chronic wet cough, such as bronchiectasis. The contribution of airway malacia and pathobiologic mechanisms of PBB remain uncertain and, other than reduced alveolar phagocytosis, evidence of systemic, or local immune deficiency is lacking. Instead, pulmonary defenses show activated innate immunity and increased gene expression of the interleukin‐1β signalling pathway. Whether these changes in local inflammatory responses are cause or effect remains to be determined. It is likely that PBB and bronchiectasis are at the opposite ends of the same disease spectrum, so children with chronic wet cough require close monitoring. Pediatr Pulmonol. 2016;51:225–242. © 2015 Wiley Periodicals, Inc.


The Argentine Society of Laparoscopic Surgery (SACIL) letter on Covid-19


title: Predictors of protective behaviors among American travelers to the 2009 Hajj

text: BACKGROUND Respiratory-borne infectious diseases can spread rapidly at mass gatherings. The 2009 Hajj took place during the influenza A (H1N1) pandemic. This study investigates factors associated with compliance with recommended influenza A (H1N1)-related health practices and behaviors among American pilgrims to the 2009 Hajj: receiving seasonal influenza vaccinations, receiving influenza A (H1N1) vaccinations, and behaviors intended to mitigate respiratory illness. METHODS American residents from Minnesota and Michigan completed anonymous surveys prior to and following travel to the 2009 Hajj. Surveys assessed demographics; knowledge, attitudes and practices (KAP) related to influenza A (H1N1); seasonal and H1N1 vaccinations; health-seeking behaviors; sources of health information; and protective behaviors during the Hajj. RESULTS Pre- and post-travel surveys were completed by 186 participants. Receiving seasonal influenza vaccination was reported by 138 (63%) respondents, and 80 (36%) reported receiving an influenza A (H1N1) vaccine. One hundred forty-four (79%) respondents reported engaging in protective behaviors during the Hajj to prevent illness. In multivariable models, greater perceived severity of influenza A (H1N1) before traveling was associated with: seasonal influenza vaccination (OR=1.74, 95% CI=1.14-2.62, p=.01), influenza A (H1N1) vaccination (OR=2.02, 95% CI=1.35-3.02, p=.001), and engaging in protective behaviors during the Hajj (OR=1.62, 95% CI=1.00-2.63, p=.003). CONCLUSIONS This study found that accurate knowledge of influenza A (H1N1) symptoms, transmission, and prevention was associated with greater perceived severity of influenza A (H1N1); and perceived influenza A (H1N1) severity was associated with engaging in recommended protective health practices. Understanding the barriers to and facilitators of compliance with recommended behaviors can help guide the development of tailored outreach strategies to mitigate the impact and spread of respiratory disease.


title: Preventing transfer of infectious agents

text: Abstract Xenotransplantation using pig cells, tissues and organs may be associated with the transfer of porcine infectious agents, which may infect the human recipient and in the worst case induce a disease (zoonosis). To prevent this, a broad screening program of the donor animals for putative zoonotic microorganisms, including bacteria, viruses, fungi and others, using sensitive and specific detection methods has to be performed. As long as it is still unknown, which microorganism represents a real risk for the recipient, experience from allotransplantation should be brought in. Due to the fact that pigs can be screened long before the date of transplantation, xenotransplantation will become eventually safer compared with allotransplantation. Screening and selection of animals free of potential zoonotic microorganisms, Caesarean section, vaccination and/or treatment with chemotherapeutics are the strategies of choice to obtain donor animals not transmitting microorganisms. In the case of porcine endogenous retroviruses (PERVs) which are integrated in the genome of all pigs and which cannot be eliminated this way, selection of animals with low virus expression and generation of genetically modified pigs suppressing PERV expressions may be performed.


title: Respiratory syncytial virus: The virus, the disease and the immune response

text: Abstract RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30–35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD4- and CD8-specific as well as Th1- and Th2-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th1 vs. Th2, IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1–S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.


The COVID-19 pandemic: a systemic analysis


title: Expression of the COVID‐19 receptor ACE2 in the human conjunctiva

text: SARS‐CoV‐2 is assumed to use angiotensin‐converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory‐confirmed SARS‐CoV‐2, and there has been speculation that SARS‐CoV‐2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high‐throughput RNA sequencing to assess mRNA expression of the SARS‐CoV‐2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS‐CoV‐2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median 0.0 transcripts per million (TPM), min 0.0 TPM, max 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS‐CoV‐2 via these mediators unlikely. This article is protected by copyright. All rights reserved.


Being (more) Human in a Digitized World


title: Lessons from SARS‐CoV‐2 screening in a Brazilian organ transplant unit

text: Protecting immunosuppressed patients during infectious disease outbreaks is crucial. During this novel coronavirus disease 2019 pandemic, preserving “clean areas” in hospitals assisting organ transplant recipients is key to protect them and to preserve transplantation activity. Evidence suggests that asymptomatic carriers might transmit the SARS‐CoV‐2, challenging the implementation of transmission preventive strategies. We report a single‐center experience using universal SARS‐CoV‐2 screening for all inpatients and newly admitted patients to an Organ Transplant Unit located in a region with significantly high community‐based transmission.


Aerosol or droplet: critical definitions in the COVID‐19 era


title: First detection of bovine noroviruses and detection of bovine coronavirus in Australian dairy cattle

text: BACKGROUND AND OBJECTIVE: Noroviruses have been recognised as a significant cause of neonatal enteritis in calves in many countries, but there has been no investigation of their occurrence in Australian cattle. This study aimed to establish whether bovine noroviruses could be detected in faecal samples from Australian dairy cattle. It also sought to determine whether bovine coronaviruses, also associated with neonatal enteritis in calves, could be detected in the same faecal samples. METHODS: A selection of faecal samples that were negative for rotaviruses from dairy farms located in three geographically distinct regions of Victoria were pooled and tested by reverse transcription‐PCR for the presence of noroviruses (genogroup III), neboviruses and bovine coronaviruses. RESULTS AND CONCLUSION: Genetically distinct genogroup III noroviruses were detected in two sample pools from different geographic regions and bovine coronavirus was detected in a third pool of samples. This is the first report of bovine norovirus infection in Australian cattle and suggests that future work is required to determine the significance of these agents as a cause of bovine enteric disease in Australia.


title: Porcine Circovirus Type 2 and Porcine Circovirus‐Associated Disease

text: Porcine circovirus type 2 (PCV2) belongs to the viral family Circoviridae and to the genus Circovirus. Circoviruses are small, single‐stranded nonenveloped DNA viruses that have an unsegmented circular genome. PCV2 is the primary causative agent of several syndromes collectively known as porcine circovirus‐associated disease (PCVAD). Many of the syndromes associated with PCVAD are a result of coinfection with PCV2 virus and other agents such as Mycoplasma and porcine reproductive and respiratory syndrome virus. PCV2 infection is present in every major swine‐producing country in the world, and the number of identified cases of PCVAD is rapidly increasing. In the United States, the disease has cost producers an average of 3–4 dollars per pig with peak losses ranging up to 20 dollars per pig. The importance of this disease has stimulated investigations aimed at identifying risk factors associated with infection and minimizing these risks through modified management practices and development of vaccination strategies. This paper provides an overview of current knowledge relating to PCV2 and PCVAD with an emphasis on information relevant to the swine veterinarian.


title: Is lithium a potential treatment for the novel Wuhan (2019-nCoV) coronavirus? A scoping review

text: The current rapid spread of the novel coronavirus (2019-nCoV) originating from Wuhan, China, calls for a rapid response from the research community Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity This brief review took a systematic approach to identify five in vitro studies reporting on the influence of lithium on coronaviral infections We propose that in the case of urgent need, lithium be explored as a potential treatment or prophylaxis for the novel Wuhan coronavirus (2019-nCoV)


title: Detection of Signature Sequences in Overlapping Genes and Prediction of a Novel Overlapping Gene in Hepatitis G Virus

text: In viruses an increased coding ability is provided by overlapping genes, in which two alternative open reading frames (ORFs) may be translated to yield two distinct proteins. The identification of signature sequences in overlapping genes is a topic of particular interest, since additional out-of-frame coding regions can be nested within known genes. In this work, a novel feature peculiar to overlapping coding regions is presented. It was detected by analysis of a sample set of 21 virus genomic sequences and consisted in the repeated occurrence of a cluster of basic amino acid residues, encoded by a frame, combined to a stretch of acidic residues, encoded by the corresponding overlapping frame. A computer scan of an additional set of virus sequences demonstrated that this feature is common to several other known overlapping ORFs and led to prediction of a novel overlapping gene in hepatitis G virus (HGV). The occurrence of a bifunctional coding region in HGV was also supported by its extremely lower rate of synonymous nucleotide substitutions compared to that observed in the other gene regions of the HGV genome. Analysis of the amino acid sequence that was deduced from the putative overlapping gene revealed a high content of basic residues and the presence of a nuclear targeting signal; these characteristics suggest that a core-like protein may be expressed by this novel ORF.


title: Membrane technology could play a part in finding a cure for HIV

text: Scientists in Australia have completed initial research on specially designed ceramic membranes that have the potential to remove viruses from water, air and blood. They say, as this brief feature shows, that membrane technology could play an important role in saving the lives of millions of people.


The COVID-19 Pandemic: A Patient-Centered Model of Systemic Shock and Cancer Care Adherence