title: Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi

text: The phytochemical investigation on the roots of Acanthopanax henryi (Araliaceae) resulted in the discovery of twenty compounds whose chemical structures were elucidated by the analysis of 1D-, 2D-NMR, mass spectrometry data, other physicochemical properties, and a comparison of the spectral data with the literature. They were identified as (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), 6-methoxy-7-hydroxycoumarin (5), behenic acid (6), 3-O-caffeoyl-quinic acid (7), 5-O-caffeoyl-quinic acid (8), 1,3-di-O-caffeoyl-quinic acid (9), 1,4-di-O-caffeoyl-quinic acid (10), 1,5-di-O-caffeoyl-quinic acid (11), (+)-threo-(7R,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (12), (+)-erythro-(7S,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (13), ferulic acid (14), caffeic acid (15), stigmasterol (16), β-sitosterol (17), adenosine (18), syringin (19), and trans-coniferin (20). Among these isolates, compound 3 showed inhibitory activity against lipopolysaccharide- (LPS-) induced nitric oxide (NO) and prostaglandin E2 (PGE(2)) production with IC(50) values of 2.22 ± 0.11 and 2.28 ± 0.23 μM, respectively. The effects of compound 3 were associated with the suppression of LPS-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Furthermore, compound 3 negatively regulated the production of interleukin- (IL-) 1β and tumor-necrosis factor- (TNF-) α at the transcriptional level in LPS-stimulated BV2 microglial cells. These antineuroinflammatory effects of compound 3 were mediated by p38 mitogen-activated protein kinase (MAPK).


title: A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications

text: Artificial manipulation of antibody genes has facilitated the production of several unique recombinant antibody formats, which have highly important therapeutic and biotechnological applications. Although bispecific antibodies (bsAbs) are not new, they are coming to the forefront as our knowledge of the potential efficacy of antibody-based therapeutics expands. The next generation of bsAbs is developing due to significant improvements in recombinant antibody technologies. This review focuses on recent advances with a particular focus on improvements in format and design that are contributing to the resurgence of bsAbs, and in particular, on innovative structures applicable to next generation point-of-care (POC) devices with applicability to low resource environments.


title: New method for comparing DNA primary sequences based on a discrimination measure

text: Abstract We introduce a new approach to compare DNA primary sequences. The core of our method is a new measure of pairwise distances among sequences. Using the primitive discrimination substrings of sequence S and Q, a discrimination measure DM(S, Q) is defined for the similarity analysis of them. The proposed method does not require multiple alignments and is fully automatic. To illustrate its utility, we construct phylogenetic trees on two independent data sets. The results indicate that the method is efficient and powerful.


title: Structural and functional similarities in bunyaviruses: Perspectives for pan‐bunya antivirals

text: The order of Bunyavirales includes numerous (re)emerging viruses that collectively have a major impact on human and animal health worldwide. There are no vaccines for human use or antiviral drugs available to prevent or treat infections with any of these viruses. The development of efficacious and safe drugs and vaccines is a pressing matter. Ideally, such antivirals possess pan‐bunyavirus antiviral activity, allowing the containment of every bunya‐related threat. The fact that many bunyaviruses need to be handled in laboratories with biosafety level 3 or 4, the great variety of species and the frequent emergence of novel species complicate such efforts. We here examined the potential druggable targets of bunyaviruses, together with the level of conservation of their biological functions, structure, and genetic similarity by means of heatmap analysis. In the light of this, we revised the available models and tools currently available, pointing out directions for antiviral drug discovery.


title: The Adaptation of Parliament's Multiple Roles to COVID-19

text: Legislatures are complex institutions that serve many purposes. While their overall roles vary in different political systems, they typically serve multiple functions, including representation, law making, scrutiny of government, public symbolism, and others. These inevitably overlap and sometimes collide; similarly, individual legislators must balance party, constituency, and personal factors in their decision making. Now, in a time of sudden and unexpected disruption amid the COVID-19 pandemic, the Parliament of Canada has been forced to rethink its complex activities under urgent and unexpected new conditions.


title: Real-time isothermal detection of Abalone herpes-like virus and red-spotted grouper nervous necrosis virus using recombinase polymerase amplification

text: Abstract Abalone herpes-like virus (AbHV) and Red-spotted grouper nervous necrosis virus (RGNNV) are two serious viruses that infect animal populations in aquaculture. Both viruses cause diseases associated with high mortality rates, resulting in dramatic economic losses in the aquaculture industry. There are currently no effective treatments for either of these two viral diseases. Thus, early, rapid, and accurate diagnosis plays a fundamental role in disease prevention and control in aquaculture. Traditional methods of diagnosis, such as virus culture, enzyme-linked immunoassay, and polymerase chain reaction (PCR), are either time consuming or require sophisticated temperature control devices. In this study, one sets of specific primers and probes were designed for the real-time quantitative recombinase polymerase amplification (qRPA) detection of AbHV and RGNNV separately. The sensitivity and specificity of detection were evaluated by comparison with detection by conventional PCR and quantitative PCR. The optimal reaction temperature and time for virus detection is 37°C for 20min. The detection limit is 100 copies per reaction, making this approach faster and more sensitive than qPCR in this study. In a field application, the detection percentage of qRPA was higher than that of qPCR for both AbHV and NNV. Additionally, good correlation was found between qRPA and qPCR detection (R2 >0.8). The methods presented here can be used as alternatives to qPCR for quick and quantitative detection of pathogens infecting aquaculture species.


title: Substrate specificity profiling of SARS-CoV-2 main protease enables design of activity-based probes for patient-sample imaging

text: In December 2019, the first cases of infection with a novel coronavirus, SARS-CoV-2, were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for coronavirus disease 2019 (COVID-19); therefore, research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 main protease constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position. We used it to determine the substrate preferences of the SARS-CoV and SARS-CoV-2 main proteases, using natural and a large panel of unnatural amino acids. On the basis of these findings, we designed and synthesized an inhibitor and two activity-based probes, for one of which we determined the crystal structure of its complex with the SARS-CoV-2 Mpro. Using this approach we visualized SARS-CoV-2 active Mpro within nasopharyngeal epithelial cells of a patient with active COVID-19 infection. The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.


title: Amino acids within hypervariable region 1 of avian coronavirus IBV (Massachusetts serotype) spike glycoprotein are associated with neutralization epitopes

text: Abstract The spike glycoprotein (S) gene of IBV codes for a precursor protein which is cleaved into the N-terminal S1 and C-terminal S2 glycopolypeptides. The S1 glycopolypeptide, which induces neutralizing antibody, comprises approximately 520 amino acid residues. We have determined the nucleotide sequence of S1 of seven strains of the Massachusetts (Mass) serotype and the first 337 bases of two additional Mass strains. Despite the fact that the strains had been isolated over three decades in Europe and the U.S.A. there was only 4% base and 6% amino acid variation within the group. Nearly one third of the 32 amino acid differences in S1 were in two hypervariable regions (HVRs 1 and 2) comprising residues 38–51 and 99–115, identified by Niesters et al. (1986), showing that HVRs 1 and 2 are a feature of the Mass serotype. Amino acid variation within HVRs 1 and 2 was 29% and 40% respectively. Five vaccine strains could be distinguished from each other by sequencing of the first 337 nucleotides. Variants of M41 which resisted neutralization by two monoclonal antibodies (A13 and A38) had the same, single base change at position 134, resulting in substitution of proline residue 45 by histidine. This indicates that residues within HVR 1 are associated with epitopes which induce neutralizing antibody.


title: COVID-19-induced visitor boom reveals the importance of forests as critical infrastructure

text: During the 2020 COVID-19 pandemic, countries around the globe have implemented a certain degree of lockdown, restricting citizens' freedom of movement and freedom of assembly. This article aims to illustrate the impact that the measures against the spread of COVID-19 have on forest recreation, building on a study in an urban context around Bonn (Germany) that was conducted between April 2019 and February 2020. The quantitative and qualitative data on urban forest visits from that study were supplemented with new census data supported by selected expert interviews. We found that visitor numbers since the inception of COVID-19 measures in March 2020 have more than doubled. Visitor patterns have drastically shifted, from an even distribution throughout the day with small peaks before and after office hours to a culmination in the late afternoon. Lastly, the interviewed forestry professionals have noted that a new set of visitors, i.e. young people, families with children and non-locals, has arrived to the forest. This influx of more and novice visitors poses challenges for forest managers and urban forest policy. It is, however, also a unique opportunity for a substantial engagement of forestry with society at large, that has implications for forest policy, especially in urban areas, possibly beyond the COVID-19 pandemic era.


title: Vaccine development for emerging virulent infectious diseases

text: Abstract The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. Clinical trial design for diseases with high mortality rates and/or high morbidity in the face of a global perception of immediate need and the factors that drive design in the face of a changing epidemiology are presented. Vaccines for EIDs thus present a unique paradigm to standard development precepts.


title: Hantavirus RNA in Saliva from Patients with Hemorrhagic Fever with Renal Syndrome

text: Hantaviruses cause 2 zoonotic diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome. Infection is usually initiated after inhalation of virus-contaminated rodent excreta. In addition to the zoonotic infection route, growing evidence suggests person-to-person transmission of Andes virus. For this reason, we studied whether saliva from HFRS patients contained hantavirus. During an outbreak in northern Sweden of nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, we collected saliva and plasma from 14 hospitalized NE patients with verified Puumala virus (PUUV) infection. PUUV RNA was detected in saliva from 10 patients (range 1,530–121,323 PUUV RNA copies/mL) by quantitative reverse transcription–PCR. The PUUV S-segment sequences from saliva and plasma of the same patients were identical. Our data show that hantavirus RNA could be detected in human saliva several days after onset of disease symptoms and raise the question whether interhuman transmission of hantavirus may occur through saliva.


title: Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

text: BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I(2) for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.


title: A critique of the Indian government’s response to the COVID-19 pandemic

text: The most destructive effects of Covid-19 in India have not been the result of the disease, but the nature of the government response. The most stringent lockdown in the world destroyed the economy and forced millions into poverty and hunger, but did not control virus transmission. The resurgence of disease as restrictions were lifted and the continued economic distress point to ten major features of state response that ensured these unfortunate outcomes.


title: Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology

text: Many viruses induce hepatitis in humans, highlighting the need to understand the underlying mechanisms of virus-induced liver pathology. The murine coronavirus, mouse hepatitis virus (MHV), causes acute hepatitis in its natural host and provides a useful model for understanding virus interaction with liver cells. The MHV accessory protein, ns2, antagonizes the type I interferon response and promotes hepatitis. We show that ns2 has 2’,5’-phosphodiesterase activity, which blocks the interferon inducible 2’,5’-oligoadenylate synthetase (OAS)-RNase L pathway to facilitate hepatitis development. Ns2 cleaves 2’, 5’-oligoadenylate, the product of OAS, to prevent activation of the cellular endoribonuclease RNase L and consequently block viral RNA degradation. An ns2 mutant virus was unable to replicate in the liver or induce hepatitis in wild type mice, but was highly pathogenic in RNase L deficient mice. Thus, RNase L is a critical cellular factor for protection against viral infection of the liver and the resulting hepatitis.


title: EIF4A2 interacts with the membrane protein of transmissible gastroenteritis coronavirus and plays a role in virus replication

text: Abstract Transmissible gastroenteritis coronavirus (TGEV) is enteropathogenic coronavirus that causes diarrhea in pigs, and is associated with high morbidity and mortality in sucking piglets. The TGEV membrane (M) protein is a decisive protein for the proliferation of viral proteins, and is associated with virus assembly and budding. To identify the cellular proteins that interact with the TGEV M protein, yeast two-hybrid screening was employed, and seven cellular proteins were identified M-binding partners. Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. Additionally, confocal microscopy revealed that EIF4A2 and M were colocalized in the cytoplasm. Furthermore, the function of EIF4A2 in intestinal cells during TGEV infection was examined. A knockdown of EIF4A2 by siRNA markedly decreased M protein proliferation and TGEV replication in target cells. Thus demonstrating that EIF4A2 plays a significant role in TGEV replication. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection.


title: Translational control of retroviruses

text: All replication-competent retroviruses contain three main reading frames, gag, pol and env, which are used for the synthesis of structural proteins, enzymes and envelope proteins respectively. Complex retroviruses, such as lentiviruses, also code for regulatory and accessory proteins that have essential roles in viral replication. The concerted expression of these genes ensures the efficient polypeptide production required for the assembly and release of new infectious progeny virions. Retroviral protein synthesis takes place in the cytoplasm and depends exclusively on the translational machinery of the host infected cell. Therefore, not surprisingly, retroviruses have developed RNA structures and strategies to promote robust and efficient expression of viral proteins in a competitive cellular environment.


Elderly nursing homes residents—are they a priority in national COVID-19 strategies?


title: Enzyme assays for synthesis and degradation of 2-5As and other 2′-5′ oligonucleotides

text: BACKGROUND: The 5′-triphosphorylated, 2′-5′-linked oligoadenylate polyribonucleotides (2-5As) are central to the interferon-induced antiviral 2-5A system. The 2-5As bind and activate the RNase L, an endoRNase degrading viral and cellular RNA leading to inhibition of viral replication. The 2-5A system is tightly controlled by synthesis and degradation of 2-5As. Whereas synthesis is mediated by the 2′-5′ oligoadenylate synthetase family of enzymes, degradation seems to be orchestrated by multiple enzyme nucleases including phosphodiesterase 12, the ectonucleotide pyrophosphatase/phosphodiesterase 1 and the A-kinase anchoring protein 7. RESULTS: Here we present assay tools for identification and characterization of the enzymes regulating cellular 2-5A levels. A procedure is described for the production of 2′-5′ oligoadenylates, which are then used as substrates for development and demonstration of enzyme assays measuring synthetase and nuclease activities, respectively. The synthetase assays produce only a single reaction product allowing for very precise kinetic assessment of the enzymes. We present an assay using dATP and the A(pA)(3) tetramer core as substrates, which requires prior isolation of A(pA)(3). A synthetase assay using either of the dNTPs individually together with NAD(+) as substrates is also presented. The nuclease reactions make use of the isolated 2′-5′ oligoadenylates in producing a mixture of shorter reaction products, which are resolved by ion-exchange chromatography to determine the enzyme activities. A purified human 2′-5′ oligoadenylate synthetase and a purified human phosphodiesterase 12 along with crude extracts expressing those proteins, are used to demonstrate the assays. CONCLUSIONS: This paper comprises an assay toolbox for identification and characterization of the synthetases and nucleases regulating cellular 2-5A levels. Assays are presented for both enzyme families. The assays can also be used to address a broader cellular role of the OAS enzymes, based on the multiple substrate specificity intrinsic to these proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12858-015-0043-8) contains supplementary material, which is available to authorized users.


title: Social Distancing against COVID-19: Implication for the Control of Influenza

text: Social distancing has been adopted as one of basic protective measures against coronavirus disease 2019 (COVID-19). During 2019–2020 season, influenza epidemic period was exceptionally short and epidemic peak was low in comparison with previous seasons in Korea. Influenza epidemic pattern was bimodal in 2016–2017 and 2018–2019 seasons, however, influenza viruses have rarely been circulating in spring, 2020 in Korea. Although multiple factors could affect the size of influenza epidemic, extensive application of nonpharmaceutical interventions including mask wearing and social distancing in response to COVID-19 seems to be a major factor of reduced influenza epidemic. Social distancing measures with high feasibility and high acceptability should be implemented even if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are developed in the future. Establishment of guideline for workplace social distancing is needed and it would contribute to reduce disease burden of influenza, especially in vaccine mismatch year.


title: Biochemical and functional characterization of the membrane association and membrane permeabilizing activity of the severe acute respiratory syndrome coronavirus envelope protein

text: Abstract A diverse group of cytolytic animal viruses encodes small, hydrophobic proteins to modify host cell membrane permeability to ions and small molecules during their infection cycles. In this study, we show that expression of the SARS-CoV E protein in mammalian cells alters the membrane permeability of these cells. Immunofluorescent staining and cell fractionation studies demonstrate that this protein is an integral membrane protein. It is mainly localized to the ER and the Golgi apparatus. The protein can be translocated to the cell surface and is partially associated with lipid rafts. Further biochemical characterization of the protein reveals that it is posttranslationally modified by palmitoylation on all three cysteine residues. Systematic mutagenesis studies confirm that the membrane permeabilizing activity of the SARS-CoV E protein is associated with its transmembrane domain.


title: A diagnostic reasoning and optimal treatment model for bacterial infections with fuzzy information

text: Summary This study proposes an optimization model for optimal treatment of bacterial infections. Using an influence diagram as the knowledge and decision model, we can conduct two kinds of reasoning simultaneously: diagnostic reasoning and treatment planning. The input information of the reasoning system are conditional probability distributions of the network model, the costs of the candidate antibiotic treatments, the expected effects of the treatments, and extra constraints regarding belief propagation. Since the prevalence of the pathogens and infections are determined by many site-by-site factors, which are not compliant with conventional approaches for approximate reasoning, we introduce fuzzy information. The output results of the reasoning model are the likelihood of a bacterial infection, the most likely pathogen(s), the suggestion of optimal treatment, the gain of life expectancy for the patient related to the optimal treatment, the probability of coverage associated with the antibiotic treatment, and the cost-effect analysis of the treatment prescribed.


title: Balkan Nephropathy: Evolution of Our Knowledge

text: Balkan endemic nephropathy (BEN), originally described in the late 1950s as a chronic tubulointerstitial kidney disease, is identified by its unique epidemiological features. The most remarkable characteristic of BEN is the focal topographical nature that characterizes its occurrence at the global, national, and even household level. BEN affects only certain endemic rural foci along tributaries of the Danube River in the Balkan countries of Bosnia, Bulgaria, Croatia, Romania, and Serbia. The spatial distribution has remained astonishingly unchanged with time because the disease affects the same endemic clusters as 50 years ago. The natural course of the disease is characterized by universal development of end-stage renal disease and the frequent development of upper urinary tract tumors, posing a substantial disease burden to the afflicted areas. The greatest challenge in the study of BEN has been the elucidation of its cause. The unique features of the disease, in particular its endemic nature and the long incubation period required for the disease to develop, have led to the proposal that BEN represents a unique environmental disease. The quest for the responsible environmental factor has been long and diverse, and although no definitive answer has been provided to date, converging lines of evidence support the theory that long-term consumption of food contaminated with aristolochic acid underlies the pathogenesis of BEN. The present review describes the evolution of our knowledge of BEN in relation to the development of the main theories for its pathogenesis.


title: Ambulant erworbene Pneumonie bei Erwachsenen

text: Die ambulant erworbene Pneumonie ist die häufigste ernste Infektionserkrankung in Deutschland. Die Mehrzahl der Fälle wird ambulant behandelt. Die Diagnose wird klinisch durch Zeichen der Infektion, respiratorischen Symptomen und dem Auskultationsbefund gestellt und durch den Nachweis eines pneumonischen Infiltrats in der Röntgenaufnahme bestätigt. Der mit Abstand häufigste Erreger bleibt Streptococcus pneumoniae, der in Deutschland unverändert hohe Penicillinempfindlichkeit zeigt. Daneben werden Haemophilus influenzae, Mykoplasmen, Legionellen und Influenza-Viren regelmäßig nachgewiesen. Eine mikrobiologische Diagnostik ist in der Praxis nicht routinemäßig erforderlich. Zur Einschätzung der Prognose und Entscheidung über die Notwendigkeit einer Hospitalisierung dient der CRB65-Score. Die Auswahl der kalkulierten Therapie richtet sich nach Schweregrad der Infektion und Vorliegen von Komorbiditäten. Aminopenicilline sind Mittel erster Wahl bei unkomplizierten Pneumonien. Bei Verdacht auf Mykoplasmen- und Legionelleninfektion ist ein Makrolid oder ein neueres Fluorchinolon indiziert. Wichtige präventive Maßnahmen sind die jährliche Influenzaimpfung und die Pneumokokkenimpfung.


title: Performance of the Luminex xTAG Respiratory Viral Panel Fast in a clinical laboratory setting

text: Abstract The aim of the study was to develop a real-time RT-PCR for the detection of enteroviruses (EVs) and rhinoviruses (RVs) and to assess the performance of the xTAG RVP Fast assay in comparison to a direct fluorescent assay (DFA), a real-time RT-PCR assay for the detection of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), and the EV/RV RT-PCR assay developed in this study. The performance of the RVP Fast assay was assessed in the analysis of 373 nasopharyngeal samples. For the viruses of the DFA panel, detection rates of 27.6% and 23.8% were obtained by RVP and DFA, respectively, in analysis of a set of 297 samples collected in 2009–2010. These results show statistically significant superiority of the RVP Fast assay (P =0.049). For RSV, hMPV, EV, and RV, detection rates of 48.0% and 45.2% were achieved by RVP and RT-PCR, respectively. For individual targets, increased detection of EV/RV (P =0.043) and decreased detection of influenza A virus (P =0.004) by RVP in comparison to real-time RT-PCR was observed. The results of the present study imply the need to adjust the InfA component of the RVP Fast assay to also cover the InfA(H1N1) 2009 virus.


title: New treatment regimes for virus-induced exacerbations of asthma

text: Abstract This review will focus on the role of viruses as causes of asthma exacerbations. The article will briefly review the current literature supporting this view, with a special focus on human rhinovirus (RV), the main virus associated with exacerbations of asthma. The review will then refer to possible strategies for treatment, and will include discussion on treatment with specific anti-viral therapy and type I interferon as a treatment for RV. The review will also include a discussion on current therapies for asthma, such as glucocorticosteroid and β 2 agonist therapy alone and in combination and why this may be relevant to virus-induced exacerbations of asthma. Finally, the potential for future anti-inflammatory/immunomodulatory therapies with a focus on NF-κB inhibition will be discussed.


title: Evaluation of the Human Host Range of Bovine and Porcine Viruses that may Contaminate Bovine Serum and Porcine Trypsin Used in the Manufacture of Biological Products

text: Current U.S. requirements for testing cell substrates used in production of human biological products for contamination with bovine and porcine viruses are U.S. Department of Agriculture (USDA) 9CFR tests for bovine serum or porcine trypsin. 9CFR requires testing of bovine serum for seven specific viruses in six families (immunofluorescence) and at least 2 additional families non-specifically (cytopathicity and hemadsorption). 9CFR testing of porcine trypsin is for porcine parvovirus. Recent contaminations suggest these tests may not be sufficient. Assay sensitivity was not the issue for these contaminations that were caused by viruses/virus families not represented in the 9CFR screen. A detailed literature search was undertaken to determine which viruses that infect cattle or swine or bovine or porcine cells in culture also have human host range [ability to infect humans or human cells in culture] and to predict their detection by the currently used 9CFR procedures. There are more viruses of potential risk to biological products manufactured using bovine or porcine raw materials than are likely to be detected by 9CFR testing procedures; even within families, not all members would necessarily be detected. Testing gaps and alternative methodologies should be evaluated to continue to ensure safe, high quality human biologicals.


title: BEI Resources: Supporting antiviral research

text: Abstract The Biodefense and Emerging Infections Research Resources Repository (BEI Resources) provides unique, quality-assured reagents to the scientific community for use in basic research and product development involving biodefense and emerging infectious diseases. These include microorganisms (up to Biosafety Level-3) on the National Institute of Allergy and Infectious Diseases (NIAID) and Centers for Disease Control and Prevention (CDC) lists of Category A, B and C priority pathogens. In addition to live microorganisms, related products such as polyclonal antisera, monoclonal antibodies, isolated nucleic acid preparations, overlapping peptide arrays, purified proteins, and assay kits are also available. Many of these materials have direct or indirect applications in antiviral research. These reagents are available free of charge to all registered investigators, regardless of funding source or affiliation. Acquisition of new reagents for the repository is one of the critically necessary and challenging tasks for BEI Resources. Therefore, investigators are encouraged to deposit relevant items, so as to provide access to materials, relief from the burden of distribution, protection of intellectual property rights, and secure storage. In addition, BEI Resources has the capability of contracting for the preparation of specific reagents. If there is a resource needed to advance a specific research area, contact an NIAID program officer or use the “suggest a reagent” option on the BEI Resources homepage, www.beiresources.org.


Ho Chi Minh City‐ the front line against COVID‐19 in Vietnam


title: Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV–infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.


title: Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia

text: Excessive host inflammatory responses negatively impact disease outcomes in respiratory infection. Host-pathogen interactions during the infective phase of influenza are well studied, but little is known about the host’s response during the repair stage. Here, we show that influenza infection stimulated the expression of angiopoietin-like 4 (ANGPTL4) via a direct IL6-STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated lung recovery and improved lung tissue integrity. ANGPTL4-deficient mice also showed reduced lung damage and recovered faster from influenza infection when compared to their wild-type counterparts. Retrospective examination of human lung biopsy specimens from infection-induced pneumonia with tissue damage showed elevated expression of ANGPTL4 when compared to normal lung samples. These observations underscore the important role that ANGPTL4 plays in lung infection and damage and may facilitate future therapeutic strategies for the treatment of influenza pneumonia.


title: Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage: Comparative analytical study of physicochemical quality attributes

text: COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has produced a serious emergency for global public health, placing enormous stress on national health systems in many countries. Several studies suggest that cytokine storms (interleukins) may play an important role in severe cases of COVID-19. Neutralizing key inflammatory factors in cytokine release syndrome (CRS) could therefore be of great value in reducing the mortality rate. Tocilizumab (TCZ) in its intravenous (IV) form of administration -RoActemra® 20 mg/mL (Roche)- is indicated for treatment of severe CRS patients. Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe, with several ongoing clinical trials. This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals, which has resulted in shortages. Here, we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion, at 6 mg/mL and 4 mg/mL, prepared from RoActeram® 20 mg/mL (IV form) and from RoActemra® 162 mg (0.9 mL solution pre-filled syringe, subcutaneous form), to evaluate the use of the latter for preparing clinical solutions required for IV administration, so that in a situation of shortage of the IV medicine, the SC form could be used to prepare the solutions for IV delivery of TCZ. It is important to remember that during the current pandemic all the medicines are used off-label, since none of them has yet been approved for the treatment of COVID-19.


title: Bovine herpesvirus-1-induced pharyngeal tonsil lesions in neonatal and weanling calves

text: Abstract The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by intranasal aerosol. Calves were monitored from days 1 to 5, and on day 6 (neonates) or 8 (weanlings) and, in a second trial at day 4·5, by histology, electron microscopy, immunocytochemistry and virus isolation. Mucosal lesions of neonates were similar to, but less extensive than, those of weanling calves. Loss of microvilli and goblet cells, with minimal epithelial erosions as early as day 1, progressed to necrosis of epithelium and adjacent lymphoid tissue, and leucocyte exudation. Lesions and clinical disease were progressive up to and including day 6 in neonates, but resolving in weanlings on days 5 and 8. By transmission electron microscopy, the physical characteristics of the phagocytic cells appeared similar in both age groups, and viral replication was not identified in leucocytes. Virus was isolated from, or found by immunocytochemistry in, the pharyngeal tonsil of all calves examined, except for two weanlings on days 1 and 8. Virus as detected by immunocytochemistry was restricted to epithelium and superficial lymphoid tissue in neonates, but was found in deep lymphoid tissue around germinal centres in weanlings. The study showed that the pharyngeal tonsil is readily infected with BHV-1 and may be an important lymphoid tissue for early anti-viral responses. The delayed inflammatory response and reduced viral clearance may contribute to the increased susceptibility of neonatal calves to fatal BHV-1 infections.


title: Structure and immune recognition of the porcine epidemic diarrhea virus spike protein

text: Porcine epidemic diarrhea virus is an alphacoronavirus responsible for significant morbidity and mortality in pigs. A key determinant of viral tropism and entry, the PEDV spike protein is a key target for the host antibody response and a good candidate for a protein-based vaccine immunogen. We used electron microscopy to evaluate the PEDV spike structure, as well as pig polyclonal antibody responses to viral infection. The structure of the PEDV spike reveals a configuration similar to that of HuCoV-NL63. Several PEDV protein-protein interfaces are mediated by non-protein components including a glycan at Asn264 and two bound palmitoleic acid molecules. The polyclonal antibody response to PEDV infection shows a dominance of epitopes in the S1 region. This structural and immune characterization provides new insights into coronavirus spike stability determinants and explores the immune landscape of viral spike proteins.


Covid-19: free resources to support radiographers


title: Responding to coronavirus disease 2019: LA County hospital experience

text: The coronavirus disease 2019 (COVID-19) has rapidly spread across the world since first being identified in Wuhan, China, in late 2019. In order to prepare for the surge of patients and the corresponding increase in radiology exams, clear and detailed policies need to be implemented by hospitals and radiology departments. In this article, we highlight the experiences and policies at LAC+USC Medical Center, the largest single provider of healthcare in LA County. Our policies aim to reduce the risk of transmission, guide patient management and workflow, preserve and effectively allocate resources, and be responsive to changing dynamics. We hope this communication may help other institutions in dealing with this pandemic as well as future outbreaks.


title: Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

text: BACKGROUND: The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. METHODS: Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. DISCUSSION: SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. TRIAL REGISTRATION: NCT03331991. Registered on November 6, 2017. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3444-7) contains supplementary material, which is available to authorized users.


title: Cloning, sequencing, expression, and purification of SARS-associated coronavirus nucleocapsid protein for serodiagnosis of SARS

text: Abstract A novel coronavirus has been associated with a worldwide outbreak of atypical pneumonia referred to as Severe Acute Respiratory Syndrome (SARS-CoV). SARS-CoV nucleocapsid (N) protein has been cloned sequenced and expressed in Escherichia coli strain. Purified N protein was used to measure the SARS-CoV specific IgG antibodies from 16 SARS-CoV infected patients’ sera and from 131 control subjects using ELISA assay. Specific antibody responses to the purified recombinant N protein after 10, 20, and 30 days of disease onset were observed in 13 of 16 (81.3%), 16 of 16 (100%) and 16 of 16 (100%) SARS patients sera, respectively. Comparison of detection results with a commercially available diagnostic kit coated with a mixture of SARS-CoV viral proteins showed 9 of 16 (56.3%), 13 of 16 (81.3%), and 15 of 16 (93.7%) positive responses, respectively. None of 131 control sera gave positive reaction in either assay. This data suggests that the N protein of SARS-CoV is immunodominant and this ELISA based test assay for detecting the SARS-CoV N antigen may hold a significant value for SARS diagnosis.


Acute kidney injury in hospitalized patients with coronavirus disease 2019 (COVID-19): a meta-analysis


title: Optical Imaging Paves the Way for Autophagy Research

text: Autophagy is a degradation process in eukaryotic cells that recycles cellular components for nutrition supply under environmental stress and plays a double-edged role in development of major human diseases. Noninvasive optical imaging enables us to clearly visualize various classes of structures involved in autophagy at macroscopic and microscopic dynamic levels. In this review, we discuss important trends of emerging optical imaging technologies used to explore autophagy and provide insights into the mechanistic investigation and structural study of autophagy in mammalian cells. Some exciting new prospects and future research directions regarding optical imaging techniques in this field are also highlighted.


title: MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

text: BACKGROUND: It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear. METHODS: The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)—dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined. RESULTS: MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3. CONCLUSION: MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.


title: Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a) and genotype II porcine reproductive and respiratory syndrome virus (PRRSV) induces CD4(+)CD25(+)FoxP3(+) T cells in vitro

text: Porcine circovirus associated disease (PCVAD) is currently one of the most economically important diseases in the global swine industry. Porcine circovirus type 2 (PCV2) is the primary causative agent, however co-infection with other swine pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV) is often required to induce the full spectrum of clinical PCVAD. While the specific mechanisms of viral co-infection that lead to clinical disease are not fully understood, immune modulation by the co-infecting viruses likely plays a critical role. We evaluated the ability of dendritic cells (DC) infected with PRRSV, PCV2 or both to induce regulatory T cells (T(regs)) in vitro. DCs infected with PCV2 significantly increased CD4(+)CD25(+)FoxP3(+) T(regs) (p<0.05) and DCs co-infected with PRRSV and PCV2 induced significantly higher numbers of T(regs) than with PCV2 alone (p<0.05). Cytokine analysis indicated that the induction of T(regs) by co-infected DCs may be dependent on TGF-β and not IL-10. Our data support the immunomodulatory role of PCV2/PRRSV co-infection in the pathogenesis of PCVAD, specifically via T(reg) mediated immunosuppression.


title: An Outbreak of Polygenic Scores for Coronary Artery Disease

text: [Figure: see text]


Herpes zoster in COVID‐19‐positive patients


title: Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

text: Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.


title: Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus

text: Abstract Diammonium glycyrrhizin (DG), a salt from glycyrrhizinate (GL) that is a major active component of licorice root extract with various pharmacological activities was investigated for its inhibitory effect on pseudorabies virus (PrV) infection. In parallel, lithium chloride (LiCl), a chemical reagent with potential antiviral activity was compared with DG for their inhibitory ability against PrV infection in vitro. Virus plaque-reduction assays, PCR and RT-PCR analysis indicated that both drugs inhibited cell infection by PrV. Moreover, addition of the drugs resulted in fewer apoptotic cells during PrV infection.


title: Rapid detection of infectious bovine Rhinotracheitis virus using recombinase polymerase amplification assays

text: BACKGROUND: Infectious bovine rhinotracheitis virus (IBRV) is a major pathogen in cattle and has led to significant economic losses to the dairy industry worldwide, and therefore a more optimal method for the rapid diagnosis of IBRV infection is highly needed. In this study, we described the development of a lateral flow dipstrip (LFD) of isothermal recombinase polymerase amplification (RPA) method for rapid detection of IBRV. METHODS: Distinct regions were selected as a candidate target for designing the LFD-RPA primers and probes. The analytical sensitivity of the RPA assay was determined using ten-fold serially diluted IBRV DNA. The specificity of the assay was assessed with other viral pathogens of cattle with similar clinic and other herpesviruses. The clinical performance was evaluated by testing 106 acute-phase high fever clinical specimens. RESULTS: RPA primers and probe were designed to target the specific conserved UL52 region fragment of IBRV. The detection could be completed at a constant temperature of 38 °C for 25 min, and the amplification products were easily visualized on a simple LFD. The detection limit of this assay was 5 copies per reaction of IBRV DNA and there was no cross-reactivity with other viruses causing bovine gastrointestinal and respiratory infections or other herpesviruses. The assay performance on acute-phase high fever clinical samples collected from cattle with no vaccine against IBRV, which were suspected to be infected with IBRV, was validated by detecting 24 fecal, 36 blood, 38 nasal swab and 8 tissue specimens, and compared with SYBR Green I based real-time PCR. The coincidence between IBRV LFD-RPA and real-time PCR was 100%. CONCLUSION: IBRV LFD-RPA was fast and much easier to serve as an alternative to the common measures used for IBRV diagnosis, as there is reduction in the use of instruments for identification of the infected animals. In addition, this assay may be the potential candidate to be used as point-of-care diagnostics in the field.


title: Colorimetric Detection of Dengue by Single Tube Reverse-Transcription-Loop-Mediated Isothermal Amplification

text: Dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. Several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. Hence, the loop-mediated isothermal amplification (LAMP) is potentially ideal to be used especially in resource limited environments. Serum was collected from healthy donors and patients diagnosed with dengue infection. RNA extracted from the serum samples were tested by reverse-transcription-LAMP assay developed based on 3′-NCR gene sequences for DENV 1–4. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. Sensitivity and specificity of RT-LAMP results were calculated and compared to qRT-PCR and ELISA. RT-LAMP is highly sensitive with the detection limit of 10 RNA copies for all serotypes. Dengue virus RNA was detected in all positive samples using RT-LAMP and none of the negative samples within 30–45 minutes. With continuing efforts in the optimization of this assay, RT-LAMP may provide a simple and reliable test for detecting DENV in areas where dengue is prevalent.


title: Non-animal replacement methods for veterinary vaccine potency testing: state of the science and future directions

text: Abstract NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the second in the series, provides recommendations for current and future use of non-animal methods and strategies for veterinary vaccine potency testing. Workshop participants recommended that future efforts to replace animal use give priority to vaccines (1) that use large numbers of animals per test and for which many serials are produced annually, (2) that involve significant animal pain and distress during procedures, (3) for which the functional protective antigen has been identified, (4) that involve foreign animal/zoonotic organisms that are dangerous to humans, and (5) that involve pathogens that can be easily spread to wildlife populations. Vaccines identified as the highest priorities were those for rabies, Leptospira spp., Clostridium spp., Erysipelas, foreign animal diseases (FAD), poultry diseases, and fish diseases. Further research on the identification, purification, and characterization of vaccine protective antigens in veterinary vaccines was also identified as a priority. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included (1) investigations into the relative impact of various adjuvants on antigen quantification assays, (2) investigations into extraction methods that could be used for vaccines containing adjuvants that can interfere with antigen assays, and (3) review of the current status of rabies and tetanus human vaccine in vitro potency methods for their potential application to the corresponding veterinary vaccines. Workshop participants recommended enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for veterinary vaccine potency testing that will benefit animal welfare and replace animal use while ensuring continued protection of human and animal health.


Comment on “The experience on coronavirus disease 2019 and cancer from an oncology hub institution in Milan, Lombardy Region” and reflections from the Italian Association of Oncology Nurses


title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine

text: The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process.


Jartti T, Kuusipalo H, Vuorinen T, Söderlund‐Venermo M, Allander T, Waris M, Hartiala J, Ruuskanen O. Allergic sensitization is associated with rhinovirus‐, but not other virus‐, induced wheezing in children. Pediatr Allergy Immunol 2010: 21: 1008–1014. © 2010 John Wiley & Sons A/S Background: Data on the link between atopy and viral wheeze are limited. Aim: To evaluate the association between IgE sensitization and viral infection in wheezing children. Methods: This is an observational study in hospitalized wheezing children (n = 247; median age 1.6 ; interquartile range 1.1, 2.9). Eighteen respiratory viral infections were studied using all available methods. A specific immunoglobulin E (IgE) sensitization for common food and aeroallergens and other atopy‐related variables including total IgE, blood and nasal eosinophils, exhaled nitric oxide, eczema and atopic eczema, parental allergy and asthma, number of wheezing episodes, positive asthma predictive index or asthma and use of inhaled corticosteroid were correlated with specific viral etiology. Results: Atopy was closely associated with sole rhinovirus etiology (n = 58) but not with sole respiratory syncytial virus, sole enterovirus, sole human bocavirus, sole other virus, mixed viral, or virus negative etiology. The number of sensitizations was particularly associated with sole rhinovirus etiology (odds ratio 4.59; 95% confidence interval 1.78, 11.8; adjusted to age and sex), followed by aeroallergen sensitization (respectively; 4.18; 2.00, 8.72), total IgE level (2.06; 1.32, 3.21), food allergen sensitization (2.02; 1.08, 3.78), and nasal eosinophil count (1.52; 1.08, 2.13). Conclusions: According to our data, allergic sensitization is positively linked to rhinovirus‐, but not other virus‐, associated wheezing and calls attention for studies to test rhinovirus‐associated wheezing as a part of asthma risk indices.


title: Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan

text: BACKGROUND: The effectiveness of inactivated influenza vaccine (IIV) against laboratory-confirmed influenza pneumonia in older adults remains to be established. METHODS: Pneumonia patients aged ≥65 years who visited a study hospital in Chiba, Japan, were prospectively enrolled from February 2012 to January 2014. Sputum samples were collected from participants and tested for influenza virus by polymerase chain reaction assays. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza pneumonia was estimated by a test-negative design. RESULTS: Among a total of 814 pneumonia patients, 42 (5.2%) tested positive for influenza: 40 were positive for influenza A virus, and two were positive for influenza B virus. The IVE against laboratory-confirmed influenza pneumonia was 58.3% (95% confidence interval, 28.8–75.6%). The IVE against influenza pneumonia hospital admission, severe pneumonia, and death was 60.2% (95% CI, 22.8–79.4%), 65.5% (95% CI, 44.3–78.7%), and 71% (95% CI, −62.9% to 94.8%), respectively. In the subgroup analyses, the IVE against influenza pneumonia was higher for patients with immunosuppressive conditions (85.9%; 95% CI, 67.4–93.9%) than for those without (48.7%; 95% CI, 2.7–73%) but did not differ by patients’ statin use status. CONCLUSION: IIV effectively reduces the risk of laboratory-confirmed influenza pneumonia in older adults.


title: Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages

text: Abstract Patients with severe burn injuries are extremely susceptible to infection, and the host's antibacterial responses are frequently suppressed by alternatively activated macrophages (M2Mϕ), commonly demonstrated in these patients. An immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral blood of thermally injured patients, has been described as an inducer of M2Mϕ. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mϕ generation stimulated by PMN-II was examined. M2Mϕ were generated from resident Mϕ (R-Mϕ, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2Mϕ were not generated from R-Mϕ when the same transwell cultures were performed in the presence of GL. M2Mϕ were not generated from R-Mϕ after cultivation with PMN-II previously treated with GL, while R-Mϕ previously treated with GL converted to M2Mϕ after they were cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II were shown to be effector molecules responsible for the generation of M2Mϕ. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2Mϕ generation through the inhibition of CCL2/interleukin-10 production by PMN-II.


title: Heroes of SARS: professional roles and ethics of health care workers

text: Summary Objectives. To examine the professional moral duty of health care workers (HCWs) in the outbreak of severe acute respiratory syndrome (SARS) in 2003. Methods. Descriptive discussion of media reports, analysis of ethical principles and political decisions discussed in the outbreak, with particular emphasis on the events in mainland China and Taiwan. Results. There were differences in the way that Taiwan and mainland China responded to the SARS epidemic, however, both employed techniques of hospital quarantine. After early policy mistakes in both countries HCWs were called heroes. The label ‘hero’ may not be appropriate for the average HCW when faced with the SARS epidemic, although a number of self-less acts can be found. The label was also politically convenient. Conclusions. A middle ground for reasonable expectations from HCW when treating diseases that have serious risk of infection should be expected. While all should act according to the ethic of beneficence not all persons should be expected to be martyrs for society.


title: Foreign Policy through Other Means: Hard Power, Soft Power, and China's Turn to Political Warfare to Influence the United States

text: Abstract The People's Republic of China increasingly has turned to political warfare and sharp power to influence U.S. policy toward China and on international issues that it considers important. This turn in part reflects the limited effectiveness of Beijing's much-increased hard power and its never-formidable and now-reduced soft power as means to achieve China's ends with the United States. China's political warfare and uses of sharp power pursue both direct influence on U.S. policy and indirect impact through affecting American attitudes toward China and China-related issues. China's efforts range across many sectors—including business, culture, media, education, and more—and they have prompted reactions and countermeasures. In China's view, the United States has long been engaged in something like political warfare or sharp power undertakings targeting China. If, or as, U.S.-China relations continue to become more adversarial, political warfare, uses of sharp power, and measures to counter them are likely to increase.


High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California


How To Maximize Trainee Education During the COVID-19 Pandemic: Perspectives from Around the World


title: A Retrospective Study of 286 Cases of Neurological Disorders of the Cat

text: Abstract Archive central nervous tissue from 286 cats with neurological disorders was reviewed for histological evidence of feline spongiform encephalopathy (FSE), which may have occurred before it was first recognized in 1990. The following six categories of disease were identified: congenital; degenerative; inflammatory; neoplastic; FSE; lesion-free. The largest category (inflammatory) contained 92 cats, of which 47 were considered to be consistent with infection by feline infectious peritonitis (FIP) virus. Six cats showed evidence of more than one disease process; thus, one cat with FIP also had toxocara infection of the lateral ventricles and five cats with FSE also showed perivascular cuffing suggestive of concurrent viral infection. In only two cases did the diagnosis on review differ significantly from the original interpretation. There was no evidence of FSE before the original case was recognized in April 1990.


title: Infectious Diseases and Mass Gatherings

text: PURPOSE OF REVIEW: Mass gatherings (MGs) are characterized by a high concentration of people at a specific time and location. Infectious diseases are of particular concern at MGs. The aim of this review was to summarize findings in the field of infectious diseases with a variety of pathogens associated with international MGs in the last 5 years. RECENT FINDINGS: In the context of Hajj, one of the largest religious MGs at Mecca, Saudi Arabia, respiratory tract infections are the leading cause of infectious diseases in pilgrims with a prevalence of 50–93%. The most commonly acquired respiratory viruses were human rhinovirus, followed by human coronaviruses and influenza A virus, in decreasing order. Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were the predominant bacteria. The prevalence of Hajj-related diarrhea ranged from 1.1 to 23.3% and etiologies included Salmonella spp., and Escherichia coli, with evidence of acquisition of antimicrobial-resistant bacteria. In other MGs such as Muslim, Christian, and Hindu religious events, sports events, and large-scale open-air festivals, outbreaks have been reported less frequently. The most common outbreaks at these events involved diseases preventable by vaccination, notably measles and influenza. Gastrointestinal infections caused by a variety of pathogens were also recorded. SUMMARY: Because social distancing and contact avoidance are difficult measures to implement in the context of many MGs, individual preventive measures including vaccination, use of face mask, disposable handkerchief and hand hygiene may be recommended. Nevertheless, the effectiveness of these measures has been poorly investigated in the context of MGs.


title: New Twists in Detecting mRNA Modification Dynamics

text: Modified nucleotides in mRNA are an essential addition to the standard genetic code of four nucleotides in animals, plants, and their viruses. The emerging field of epitranscriptomics examines nucleotide modifications in mRNA and their impact on gene expression. The low abundance of nucleotide modifications and technical limitations, however, have hampered systematic analysis of their occurrence and functions. Selective chemical and immunological identification of modified nucleotides has revealed global candidate topology maps for many modifications in mRNA, but further technical advances to increase confidence will be necessary. Single-molecule sequencing introduced by Oxford Nanopore now promises to overcome such limitations, and we summarize current progress with a particular focus on the bioinformatic challenges of this novel sequencing technology.


The Millennium Project: the positive health implications of improved environmental sustainability


title: Chapter 12 CSF in acute and chronic infectious diseases

text: Abstract Infections of the nervous system are an important and challenging aspect of clinical neurology. Immediate correct diagnosis enables to introduce effective therapy, in conditions that without diagnosis may leave the patient with severe neurological incapacitation and sometimes even death. The cerebrospinal fluid (CSF) is a mirror that reflects nervous system pathology and can promote early diagnosis and therapy. The present chapter focuses on the CSF findings in neuro-infections, mainly viral and bacterial. Opening pressure, protein and glucose levels, presence of cells and type of the cellular reaction should be monitored. Other tests can also shed light on the causative agent: serology, culture, staining, molecular techniques such as polymerase chain reaction. Specific examination such as panbacterial and panfungal examinations should be examined when relevant. Our chapter is a guide-text that combines clinical presentation and course with CSF findings as a usuaful tool in diagnosis of neuroinfections.


title: Pratique des explorations fonctionnelles respiratoires pendant l’épidémie COVID-19

text: Due to proven risks of hospital-acquired transmission and contamination of healthcare personnel, the COVID-19 outbreak significantly disrupts lung function and exercise testing facilities. This document reports proposals made by the "Respiratory Function" and "Alvéole" working groups of the French language respiratory society with regard to the completion of lung function testing at rest, cardiopulmonary exercise testing and the 6-minute walking test, in the current period of activity resumption following the lifting of the strict lockdown in force from March 17 to May 11, 2020.


title: Cell-type specific requirements for thiol/disulfide exchange during HIV-1 entry and infection

text: BACKGROUND: The role of disulfide bond remodeling in HIV-1 infection is well described, but the process still remains incompletely characterized. At present, the data have been predominantly obtained using established cell lines and/or CXCR4-tropic laboratory-adapted virus strains. There is also ambiguity about which disulfide isomerases/ reductases play a major role in HIV-1 entry, as protein disulfide isomerase (PDI) and/or thioredoxin (Trx) have emerged as the two enzymes most often implicated in this process. RESULTS: We have extended our previous findings and those of others by focusing on CCR5-using HIV-1 strains and their natural targets - primary human macrophages and CD4(+) T lymphocytes. We found that the nonspecific thiol/disulfide exchange inhibitor, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), significantly reduced HIV-1 entry and infection in cell lines, human monocyte-derived macrophages (MDM), and also phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Subsequent studies were performed using specific anti-PDI or Trx monoclonal antibodies (mAb) in HIV-1 envelope pseudotyped and wild type (wt) virus infection systems. Although human donor-to-donor variability was observed as expected, Trx appeared to play a greater role than PDI in HIV-1 infection of MDM. In contrast, PDI, but not Trx, was predominantly involved in HIV-1 entry and infection of the CD4(+)/CCR5(+) T cell line, PM-1, and PHA-stimulated primary human T lymphocytes. Intriguingly, both PDI and Trx were present on the surface of MDM, PM-1 and PHA-stimulated CD4(+) T cells. However, considerably lower levels of Trx were detected on freshly isolated CD4(+) lymphocytes, compared to PHA-stimulated cells. CONCLUSIONS: Our findings clearly demonstrate the role of thiol/disulfide exchange in HIV-1 entry in primary T lymphocytes and MDM. They also establish a cell-type specificity regarding the involvement of particular disulfide isomerases/reductases in this process and may provide an explanation for differences among previously published studies. More importantly, from an in vivo perspective, the preferential utilization of PDI may be relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4(+) cells, while the elevated levels of Trx reported in the chronic stages of HIV-1 infection may facilitate the virus entry in macrophages and help to sustain high viremia during the decline of T lymphocytes.


title: Ferrets as Sentinels of the Presence of Pathogenic Cryptococcus Species in the Mediterranean Environment

text: Cryptococcus gattii is a pathogenic environmental yeast that is considered to be emerging in different areas of the world including the Mediterranean Basin. Exposure to infection might be more likely in animals than in human beings, given their closer relationship with the natural habitat of the yeast, vegetation and soil. Thus, animals, and especially pets, can act as indicators of the presence of this yeast in a determined area. Domestic ferrets (Mustela putorius furo) have become common pets in the past 10–20 years. Their natural behavior of sniffing around and going inside narrow spaces makes them prone to contact with decaying organic matter and soil, the substrate for Cryptococcus species. This study describes two cases of cryptococcosis in ferrets in the Iberian Peninsula and Balearic Islands and documents a relationship of ferret cryptococcosis with environmental isolates in the same locations. Here, we emphasize the importance of how an adequate identification and environmental search of the yeast leads to a better understanding of the epidemiology of cryptococcosis and suggests ferrets may act as sentinels for this fungal disease.


title: Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice

text: BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8(+) T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.


title: Rethinking Biosafety in Research on Potential Pandemic Pathogens

text: If accidentally released, mammalian-transmissible influenza A/H5N1 viruses could pose a greater threat to public health than possibly any other infectious agent currently under study in laboratories, because of such viruses’ likely combination of transmissibility and virulence to humans. We advocate explicit risk-benefit assessments before work on such pathogens is permitted or funded, improvement of biosafety practices and enforcement, and harmonization of criteria for permitting such experiments across government agencies, as well as internationally. Such potential pandemic pathogens, as they have been called, jeopardize not only laboratory workers and their contacts, but also the wider population, who should be involved in assessments of when such risks are acceptable in the service of scientific knowledge that may itself bear major public health benefits.


title: Identification of Taiwan and China-like recombinant avian infectious bronchitis viruses in Taiwan

text: Abstract Infectious bronchitis virus (IBV) infections in poultry cause great economic losses to the poultry industry worldwide. The emergence of viral variants complicates disease control. The IBV strains in Taiwan were clustered into two groups, Taiwan group I and Taiwan group II, based on the S1 gene. A variant was previously identified and showed a distinct S1 gene homology with other local strains. This study investigated the 3′ 7.3kb genome of eight Taiwan strains isolated from 1992 to 2007. The genes of interest were directly sequenced. Sequence analyses were performed to detect any recombination event among IBVs. The results demonstrated that all of the examined viruses maintained the typical IBV genome organization as 5′-S-3a-3b-E-M-5a-5b-N-UTR-3′. In the phylogenetic analyses, various genes from one strain were clustered into separate groups. Moreover, frequent recombination events were identified in the Simplot analyses among the Taiwan and China CK/CH/LDL/97I-type strains. Putative crossover sites were located in the S1, S2, 3b, M genes and the intergenic region between the M and 5a genes. All of the recombinants showed chimeric IBV genome arrangements originated from Taiwan and China-like parental strains. Field IBVs in Taiwan undergo genetic recombination and evolution.


title: Continued use of IBV 793B vaccine needs reassessment after its withdrawal led to the genotype's disappearance

text: Abstract Over a period of almost two years, broilers chickens on several hundred Italian farms, were monitored for infectious bronchitis virus. Detections were genotyped using a hypervariable region of the gene coding for the S1 segment of the spike protein. A range of genotypes were detected which comprised QX, Q1, Mass, D274 and 793B. Sequences of 793B viruses detected in chickens, vaccinated with either of the two commonly used 793B type vaccines were almost identical to sequences of one or other of these vaccines. This strong indication of vaccine association led to the withdrawal of live 793B vaccine use on all of the farms of the study. Except for one sample collected soon after 793B vaccination ceased, it was no longer possible to detect 793B vaccine on these farms. It appears that field 793B strains have disappeared from the region of Italy tested thus obviating any need for current vaccine protection against 793B.


title: Rianimazione e influenza grave: pandemia influenzale A (H1N1)

text: Durante la pandemia influenzale A (H1N1) nel 2009-2010, il 20% dei pazienti ospedalizzati ha presentato delle forme gravi con trasferimento in rianimazione. L’età mediana di questi pazienti era di circa 30 anni, con una percentuale leggermente inferiore al 10% di donne gravide. Si riscontrava circa un 80% di comorbilità, essenzialmente malattie cardiorespiratorie e obesità. Il tempo mediano tra la comparsa della sindrome influenzale e il trasferimento in rianimazione era di un giorno. I test di diagnosi rapida sono realizzabili a partire da semplici campioni respiratori, ma la loro sensibilità rimane bassa. La durata mediana del ricovero in rianimazione era dell’ordine di 11 giorni. Circa il 70% dei pazienti ha richiesto una ventilazione meccanica (durata mediana di dieci giorni). Oltre il 95% di questi pazienti ha ricevuto un trattamento antivirale e oltre il 95% degli antibiotici, a fronte di un 20% soltanto di infezioni batteriche documentate, soprattutto da Streptococcus pneumoniae e Staphylococcus aureus. La mortalità globale a 28 giorni era del 17%. Il tempo mediano tra la comparsa della sindrome influenzale e il decesso era di 14 giorni. Fra questi decessi, la maggior parte dei pazienti aveva ricevuto un trattamento antivirale, ma non sempre nelle prime 48 ore, il che appare un fattore prognostico infausto. Così, il trattamento antivirale è consigliato nelle forme gravi; il virus pandemico A (H1N1) era sensibile ai due inibitori della neuraminidasi. Sono stati riscontrati dei casi sporadici di resistenza, il che spinge a sviluppare altre molecole attive sui virus influenzali.


Consensus Guidelines for Interventional Cardiology Services Delivery During COVID-19 Pandemic in Australia and New Zealand


title: Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease

text: A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 Å resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.


Data show companies switching giving strategies due to pandemic


title: Immunostimulatory Effect of Gold Nanoparticles Conjugated with Transmissible Gastroenteritis Virus

text: Animals were immunized with transmissible gastroenteritis virus conjugated with gold nanoparticles. The resultant antibodies had a higher titer than antibodies produced in response to native virus. Immunization with the antigen-colloidal gold complex led to a significant increase of the peritoneal macrophages respiratory activity and of plasma IFN-γ level in immunized animals.


title: The 2020 Covid-19 pandemic and global value chains

text: This paper considers the impact of the Covid-19 pandemic on firm strategies and, in particular, the configuration of firms’ global value chains (GVCs) once the pandemic has been brought under control. The merits of alternative location strategies (international diversification vs reshoring) are compared, as are the merits of different governance arrangements (internalization vs externalization) for GVC activities. The possibility of fire-sale foreign direct investment is raised, and the wider geopolitical context is emphasized. The widespread human tragedy is noted, as is the dilemma facing national governments around the world in balancing lives and livelihoods.


title: Arg(972) Insulin receptor substrate-1 is associated with decreased serum angiotensin-converting enzyme 2 levels in acute myocardial infarction patients: in vivo and in vitro evidence

text: BACKGROUND: Activation of the renin-angiotensin system (RAS) plays a critical role in the pathophysiology of myocardial infarction (MI) and the development of heart failure. Both angiotensin-converting enzyme 2 (ACE2) and insulin/insulin receptor substrate-1 (IRS-1) show cardioprotective effects after acute MI. The Arg(972) IRS-1 polymorphism is associated with diminished activity of insulin. In the present study, we explored the association among Arg(972) IRS-1, acute MI, and serum levels of ACE2. METHODS: A total of 711 subjects, including 351 subjects with first-time acute MI and 360 subjects without a history of MI were genotyped for Arg(972) IRS-1 polymorphism. Serum levels of ACE2 and MI severity scores were determined. Primary human cardiomyocytes with overexpression of wild type IRS-1 or Arg(972) IRS-1 or knockdown of endogenous IRS-1 were exposed to normoxia and hypoxia, and the expression levels of ACE2 were determined. RESULTS: The serum ACE2 level was significantly increased in acute MI patients compared with that of non-MI controls. Compared with wild type IRS-1 carriers, Arg(972) IRS-1 carriers exhibited decreased serum ACE2 levels and increased MI severity scores after MI. Our in vitro data demonstrate that impairment of insulin/IRS-1/PI3K signaling by overexpression of Arg(972)-IRS-1, knockdown of endogenous IRS-1, or PI3K inhibitor can abolish hypoxia-induced IRS-1-associated PI3K activity and ACE2 expression in human cardiomyocytes, which suggests a causal relationship between Arg(972)-IRS-1 and decreased serum ACE2 levels in acute MI patients. Our in vitro data also indicate that insulin/IRS-1/PI3K signaling is required for ACE2 expression in cardiomyocytes, and that hypoxia can enhance the induction effect of insulin/IRS-1/PI3K signaling on ACE2 expression in cardiomyocytes. CONCLUSIONS: This study provides the first evidence of crosstalk between insulin/IRS-1/PI3K signaling and RAS after acute MI, thereby adding fresh insights into the pathophysiology and treatment of acute MI.


title: A New Approach for Monitoring Ebolavirus in Wild Great Apes

text: BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.


title: Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged in the Middle East. Since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. Disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. We used the rhesus macaque model of mild MERS to investigate whether the immune response plays a role in the pathogenicity in relation to MERS-CoV shedding. Immunosuppressed macaques were inoculated with MERS-CoV and sampled daily for 6 days to assess their immune statues and to measure viral shedding and replication. Immunosuppressed macaques supported significantly higher levels of MERS-CoV replication in respiratory tissues and shed more virus, and virus disseminated to tissues outside of the respiratory tract, whereas viral RNA was confined to respiratory tissues in non-immunosuppressed animals. Despite increased viral replication, pathology in the lungs was significantly lower in immunosuppressed animals. The observation that the virus was less pathogenic in these animals suggests that disease has an immunopathogenic component and shows that inflammatory responses elicited by the virus contribute to disease.


title: An Economic Analysis of the Costs Associated with Pre-Weaning Management Strategies for Dairy Heifers

text: SIMPLE SUMMARY: Rearing of replacement female calves on a dairy farm is of critical importance to maintain herd sizes, improve the genetic quality of the herd, and remain economically sustainable. A 2-year investment period is needed for replacement female heifers to grow before entering the milking herd. The management of replacements over this 2-year period can vary greatly among operations, making it difficult to compare producers’ cost to benchmark. The objective of this project was to develop a model to calculate the cost of rearing a replacement heifer from birth to weaning under different housing, milk source, allotments, and labor and health management decisions to be used as a dairy farm decision support tool. We calculated the cost for management options with general cost values. We found that the average feed cost represented 46% of the total cost while labor, and fixed and variable costs represented 33%, 9%, and 12%, respectively. The total cost increased as milk allotment increased, but cost per Kg of gain decreased. The ranges in total cost within each management scenario often exceed the difference in cost from one scenario to the next. In conclusion, variable costs have the potential to vary among operations, playing a major role in the total cost of rearing replacements from birth to weaning. ABSTRACT: Dairy calves are raised in various housing and feeding environments on dairy farms around North America. The objective of this study was to develop a simulation model to calculate the cost of raising replacement dairy heifers using different inputs that reflect different management decisions and evaluate their influence on the total cost. In this simulation, 84 calves were modeled between 0–2 months of age to reflect a 1000 heifer herd. The decisions associated with housing, liquid diet source and allowance, labor utilization, and health were calculated. Costs and biological responses were reflective of published surveys, literature, and market conditions. A 10,000-iteration economic simulation was used for each management scenario using @Risk and PrecisionTree add-ons (Palisade Corporation, Ithaca, NY, USA) to account for variation in pre-weaning mortality rate, weaning age, and disease prevalence. As milk allotment increased, total feed cost increased. Feeding calves a higher allowance of milk resulted in a lower cost per kg of gain. Average feed cost percentage of the total cost was 46% (min, max: 33%, 59%) while labor, and fixed and variable cost represented 33% (20%, 45%), 9% (2%, 12%), and 12% (10%, 14%), respectively. Total pre-weaning costs ranged from $258.56 to $582.98 per calf across all management scenarios and milk allotments.


title: Restructuring an Academic Dermatology Practice During the COVID‐19 Pandemic

text: SARS‐COV‐2 is a highly virulent positive‐sense single stranded RNA virus that spreads rapidly via respiratory droplets, causing severe acute respiratory syndromes with significant mortality and morbidity. Currently 210 countries and territories are affected around the world with a reported 2.6 million confirmed cases.(1) The COVID 19 pandemic has changed the way patients attend their specialist appointments and receive medical care. Whilst some specialist clinics have closed we have implemented strategies and restructured our academic practice in Australia to minimize the spread of disease whilst treating patients who need urgent care. We hope to share these strategies in the hope they may be useful to the dermatology community. This article is protected by copyright. All rights reserved.


title: Evaluation of the rationale for concurrent use of N95 filtering facepiece respirators with loose-fitting powered air-purifying respirators during aerosol-generating medical procedures

text: The concurrent use of N95 filtering facepiece respirators with powered air-purifying respirators during aerosol-generating medical procedures in patients with severe respiratory pathogens has been promoted as offering additional protection against infectious agents. The purpose of this article is to examine the impact of this additional respiratory equipment upon protection and personal performance. The presumed additive protective effect of an N95 filtering facepiece respirator used concurrently with a powered air-purifying respirator has not been subjected to rigorous scientific investigation. The burden imposed by additional respiratory protective equipment should not be discounted, and the potentially minor contribution to protection may be offset by the negative impact on personal performance. Novel uses of protective equipment occasionally are spawned during crisis situations, but their generalized applicability to healthcare workers should ultimately be evidence-based.


title: Stem cell-based Lung-on-Chips: The best of both worlds?

text: Abstract Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models. Organs-on-Chips, which are microengineered bioinspired tissue systems, recapitulate the mechanochemical environment and physiological functions of human organs while concurrent advances in generating and differentiating human stem cells promise a renewable supply of patient-specific cells for personalized and precision medicine. Here, we discuss the challenges of modeling human lung pathophysiology in vitro, evaluate past and current models including Organs-on-Chips, review the current status of lung tissue modeling using human pluripotent stem cells, explore in depth how stem-cell based Lung-on-Chips may advance disease modeling and drug testing, and summarize practical consideration for the design of Lung-on-Chips for academic and industry applications.


Long-acting injectable antipsychotics treatment during COVID-19 pandemic – A new challenge


title: Using X-ray images and deep learning for automated detection of coronavirus disease

text: Coronavirus is still the leading cause of death worldwide. There are a set number of COVID-19 test units accessible in emergency clinics because of the expanding cases daily. Therefore, it is important to implement an automatic detection and classification system as a speedy elective finding choice to forestall COVID-19 spreading among individuals. Medical images analysis is one of the most promising research areas, it provides facilities for diagnosis and making decisions of a number of diseases such as Coronavirus. This paper conducts a comparative study of the use of the recent deep learning models (VGG16, VGG19, DenseNet201, Inception_ResNet_V2, Inception_V3, Resnet50, and MobileNet_V2) to deal with detection and classification of coronavirus pneumonia. The experiments were conducted using chest X-ray & CT dataset of 6087 images (2780 images of bacterial pneumonia, 1493 of coronavirus, 231 of Covid19, and 1583 normal) and confusion matrices are used to evaluate model performances. Results found out that the use of inception_Resnet_V2 and Densnet201 provide better results compared to other models used in this work (92.18% accuracy for Inception-ResNetV2 and 88.09% accuracy for Densnet201). Communicated by Ramaswamy H. Sarma