title: Testing COVID-19 tests faces methodological challenges

text: Abstract In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, while the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, while others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fails to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.


title: Hypoalbuminaemia in COVID‐19 infection: a predictor of severity or a potential therapeutic target?

text: We read with interest the findings of Huang's et al.'s retrospective study which revealed an association between hypoalbuminaemia and mortality in COVID‐19. In response to their findings we have synthesised a structured summary of the literature in order to discuss conclusions that could be drawn collectively. Furthermore, the authors also discuss a potential therapeutic role for correction of this hypoalbuminaemia. We would like to consider the applicability and relevance of the existing literature concerning albumin infusion in acute respiratory distress syndrome (ARDS) and severe sepsis, the principal causes of mortality in COVID‐19. This article is protected by copyright. All rights reserved.


title: Coronary and structural heart disease interventions during COVID-19 pandemic: A road map for clinicians and health care delivery systems

text: BACKGROUND: Because of the COVID-19 pandemic, cath labs have had to modify their workflow for elective and urgent patients. METHODS: We surveyed 16 physicians across 3 hospitals in our healthcare system to address COVID-19 related concerns in the management of interventional and structural heart disease patients, and to formulate system wide criteria for deferring cases till after the pandemic. RESULTS: Our survey yielded common concerns centered on the need to protect patients, cath lab staff and physicians from unnecessary exposure to COVID-19; for COVID-19 testing prior to arrival to the cath lab; for clear communication between the referring physician and the interventionalist; but there was initial uncertainty among physicians regarding the optimal management of ST elevation myocardial infarction (STEMI; percutaneous coronary intervention versus thrombolytics). Patients with stable angina and hemodynamically stable acute coronary syndromes were deemed suitable for initial medical management, except when they had large ischemic burden. Most transcatheter aortic valve implantations (TAVI) were felt appropriate for postponement except in symptomatic patients with aortic valve area <0.5 cm(2) or recent hospitalization for heart failure (HF). Most percutaneous mitral valve repair (pMVR) procedures were felt appropriate for postponement except in patients with HF. All left atrial appendage closure (LAAC) and patent foramen ovale (PFO)/atrial septal defect (ASD) closure procedures were felt appropriate for postponement. CONCLUSION: Our survey of an experienced team of clinicians yielded concise guidelines to direct the management of CAD and structural heart disease patients during the initial phases of the COVID-19 pandemic.


title: University life and pandemic influenza: Attitudes and intended behaviour of staff and students towards pandemic (H1N1) 2009

text: BACKGROUND: In a pandemic young adults are more likely to be infected, increasing the potential for Universities to be explosive disease outbreak centres. Outbreak management is essential to reduce the impact in both the institution and the surrounding community. Through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (H1N1) 2009 at a major university in Sydney, Australia. METHODS: The survey was available online from 29 June to 30 September 2009. The sample included academic staff, general staff and students of the University. RESULTS: A total of 2882 surveys were completed. Nearly all respondents (99.6%, 2870/2882) were aware of the Australian pandemic situation and 64.2% (1851/2882) reported either "no anxiety" or "disinterest." Asian-born respondents were significantly (p < 0.001) more likely to believe that the pandemic was serious compared to respondents from other regions. 75.9% (2188/2882) of respondents had not made any lifestyle changes as a result of the pandemic. Most respondents had not adopted any specific behaviour change, and only 20.8% (600/2882) had adopted the simplest health behaviour, i.e. hand hygiene. Adoption of a specific behaviour change was linked to anxiety and Asian origin. Students were more likely to attend the university if unwell compared with staff members. Positive responses from students strongly indicate the potential for expanding online teaching and learning resources for continuing education in disaster settings. Willingness to receive the pandemic vaccine was associated with seasonal influenza vaccination uptake over the previous 3 years. CONCLUSIONS: Responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. Lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students.


Traqueobronquitis necrotizante con obstrucción del tubo endotraqueal en pacientes COVID-19


docid: yaeduwvb

title: Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait?

text: Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.


title: Expression of Lymphocytes and Lymphocyte Subsets in Patients with Severe Acute Respiratory Syndrome

text: In a cohort of 38 patients with severe acute respiratory syndrome (SARS), we observed leukopenia in 47% of patients, lymphopenia in 84%, and T lymphopenia in 95%. CD4(+) T lymphocyte levels were reduced in 100% of patients, CD8(+) T lymphocyte levels were reduced in 87%, B lymphocyte levels were reduced in 76%, and natural killer cell levels were reduced in 55%. Our data suggested that these patients' immune systems were impaired during the course of SARS. The absolute counts of lymphocyte subsets demonstrated a clinical significance for patients with SARS.


title: Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer

text: Abstract Cancer prevention and treatment using traditional Chinese medicines have attracted increasing interest. This study characterizes antioxidant activity and phenolic compounds of traditional Chinese medicinal plants associated with anticancer, comprising 112 species from 50 plant families. The improved ABTS•+ method was used to systematically assess the total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC) of the medicinal extracts. The TEAC values and total phenolic content for methanolic extracts of herbs ranged from 46.7 to 17,323 μmol Trolox equivalent/100 g dry weight (DW), and from 0.22 to 50.3 g of gallic acid equivalent/100 g DW, respectively. A positive, significant linear relationship between antioxidant activity and total phenolic content (all R 2 values≥0.95) showed that phenolic compounds were the dominant antioxidant components in the tested medicinal herbs. Major types of phenolic compounds from most of the tested herbs were preliminarily identified and analyzed, and mainly included phenolic acids, flavonoids, tannins, coumarins, lignans, quinones, stilbenes, and curcuminoids. These medicinal herbs exhibited far stronger antioxidant activity and contained significantly higher levels of phenolics than common vegetables and fruits. Traditional Chinese medicinal plants associated with anticancer might be potential sources of potent natural antioxidants and beneficial chemopreventive agents.


title: The effect of paramedic rapid sequence intubation on outcome in trauma patients

text: Study objectives: The objective of this study is to evaluate the effect of paramedic rapid sequence intubation (RSI) on trauma patient outcome. Methods: Consecutive major trauma patients were prospectively enrolled in 2 phases, the first before and the second after the implementation of a paramedic RSI program. Paramedics with experience in this mixed suburban and rural emergency medical services (EMS) system were eligible for RSI training. RSI training consisted of 6 hours of didactic and mannequin training. Operating room intubation experience is required for oral intubation clearance in the system but is not used for RSI training. All trauma patients with a Glasgow Coma Scale (GCS) score between 3 and 8 and for whom resuscitation was indicated were eligible for inclusion. Exclusion criteria included death in the field or ED and inability to obtain outcome information. For both phases, intubation was indicated for trauma patients with a GCS score of 3 to 8. For phase 2, oral intubation was attempted for all patients before RSI. Etomidate and succinylcholine were administered for RSI. RSI was not attempted for patients for whom the alternative airways, esophageal-tracheal twin-lumen airway device (Combitube), cricothyrotomy, or bag-valve-mask ventilation was judged not feasible. The Combitube was used as the primary salvage airway device. Method of airway control, intubation success rates, and survival to hospital discharge were determined. Results: There were 134 patients with outcomes in phase 1: 19 of 21 (90.5%) in arrest at presentation had a definitive airway established, and 19 had additional exclusion criteria, leaving 94 for analysis. There were 386 patients with outcomes in phase 2: 85 of 94 (90.4%) in arrest at presentation had a definitive airway established, and 65 had additional exclusion criteria, leaving 227 for analysis. The oral intubation success rate was improved for phase 2 study versus phase 1 control patients (53.3% versus 14.9%); total definitive airway rate was also greater (59.5% versus 40.4%). RSI was used in 112 patients; 11 were excluded. Oral intubation success for RSI patients was 87.5%; 91.1% had definitive airways established. Survival for patients with oral intubation without RSI was similar for both phases (42.4% versus 42.9%). Survival for study patients was improved during phase 2 (78.0% versus 67.3%). Survival for study RSI patients was 85.1%. Conclusion: EMS protocols for paramedic RSI resulted in improved intubation success rates and improved survival to hospital discharge.


docid: nglihgpx

title: Statins: Could an old friend help the fight against COVID‐19?

text: COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has overwhelmed Healthcare Systems requiring the rapid development of treatments, at least, to reduce COVID‐19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID‐19 patients based on evidence that they may target virus receptors, replication, degradation and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could act modulating virus entry, acting on the SARS‐CoV‐2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well‐known anti‐inflammatory properties of statins, by blocking several molecular mechanisms, including NF‐κB and NLRP3 inflammasome, could limit the “cytokine storm” in severe COVID‐19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improve COVID‐19 outcomes.


title: Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways

text: Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.


title: Healthcare simulation to prepare for the COVID-19 pandemic

text: • COVID-19 challenged providers and organization with unfamiliar and unprecedented scenarios. • We simulated anticipated airborne contagion scenarios to familiarize providers with safe practices. • COVID-19 procedures were safely examined in realistic situations and modified based on participant debriefings. • Simulation promoted interdisciplinary integration of our organizational response to COVID-19.


title: Porous gold nanoparticles for attenuating infectivity of influenza A virus

text: BACKGROUND: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations. MAIN BODY: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold–thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA. CONCLUSION: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.


title: Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition

text: Abstract Many viruses encode antagonists to prevent interferon (IFN) induction. Infection of fibroblasts with the murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) did not result in nuclear translocation of interferon-regulatory factor 3 (IRF3), a key transcription factor involved in IFN induction, and induction of IFN mRNA transcription. Furthermore, MHV and SARS-CoV infection could not prevent IFN induction by poly (I:C) or Sendai virus, suggesting that these CoVs do not inactivate IRF3-mediated transcription regulation, but apparently prevent detection of replicative RNA by cellular sensory molecules. Our data indicate that shielding of viral RNA to host cell sensors might be the main general mechanism for coronaviruses to prevent IFN induction.


title: Multiple Sclerosis Mechanisms of Disease and Strategies for Myelin and Axonal Repair

text: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system with a variety of presentations and unclear pathogenesis. Multiple sclerosis has been associated with the term autoimmunity as a surrogate for pathogenesis. Multiple sclerosis is an organ-specific disease with immune-mediated myelin destruction. Understanding the complex etiology of multiple sclerosis and the importance of axon integrity is critical for clinicians who treat the disease. This review discusses the immune and autoimmune aspects of multiple sclerosis based on the current published data and novel evidence of strategies that promote remyelination and protect axons.


title: Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

text: Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG(1) and IgG(2) antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ(+) lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible.


title: The coronavirus (COVID‐19) pandemic's impact on mental health

text: Throughout the world, the public is being informed about the physical effects of SARS‐CoV‐2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID‐19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID‐19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID‐19 outbreak on the mental health of people.


title: CFD simulation of airborne pathogen transport due to human activities

text: Abstract Computational Fluid Dynamics (CFD) is an increasingly popular tool for studying the impact of design interventions on the transport of infectious microorganisms. While much of the focus is on respiratory infections, there is substantial evidence that certain pathogens, such as those which colonise the skin, can be released into, and transported through the air through routine activities. In these situations the bacteria is released over a volume of space, with different intensities and locations varying in time rather than being released at a single point. This paper considers the application of CFD modelling to the evaluation of risk from this type of bioaerosol generation. An experimental validation study provides a direct comparison between CFD simulations and bioaerosol distribution, showing that passive scalar and particle tracking approaches are both appropriate for small particle bioaerosols. The study introduces a zonal source, which aims to represent the time averaged release of bacteria from an activity within a zone around the entire location the release takes place. This approach is shown to perform well when validated numerically though comparison with the time averaged dispersion patterns from a transient source. However, the ability of a point source to represent such dispersion is dependent on airflow regime. The applicability of the model is demonstrated using a simulation of an isolation room representing the release of bacteria from bedmaking.


title: α2-3- and α2-6- N-linked sialic acids allow efficient interaction of Newcastle Disease Virus with target cells

text: Receptor recognition and binding is the first step in the viral cycle. It has been established that Newcastle Disease Virus (NDV) interacts with sialylated molecules such as gangliosides and glycoproteins at the cell surface. Nevertheless, the specific receptor(s) that mediate virus entry are not well known. We have analysed the role of the sialic acid linkage in the early steps of the viral infection cycle. Pretreatment of ELL-0 cells with both α2,3 and α2,6 specific sialidases led to the inhibition of NDV binding, fusion and infectivity, which were restored after α2,3(N)- and α2,6(N)-sialyltransferase incubation. Moreover, α2,6(N)-sialyltransferases also restored NDV activities in α2-6-linked sialic acid deficient cells. Competition with α2-6 sialic acid-binding lectins led to a reduction in the three NDV activities (binding, fusion and infectivity) suggesting a role for α2-6- linked sialic acid in NDV entry. We conclude that both α2-3- and α2-6- linked sialic acid containing glycoconjugates may be used for NDV infection. NDV was able to efficiently bind, fuse and infect the ganglioside-deficient cell line GM95 to a similar extent to that of its parental MEB4, suggesting that gangliosides are not essential for NDV binding, fusion and infectivity. Nevertheless, the fact that the interaction of NDV with cells deficient in N-glycoprotein expression such as Lec1 was less efficient prompted us to conclude that NDV requires N-linked glycoproteins for efficient attachment and entry into the host cell. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10719-012-9431-0) contains supplementary material, which is available to authorized users.


title: Acquired Fusion Activity of a Murine Coronavirus MHV-2 Variant with Mutations in the Proteolytic Cleavage Site and the Signal Sequence of the S Protein

text: Abstract The spike (S) protein of a nonfusogenic murine coronavirus, MHV-2, was compared to the S protein of a variant with fusion activity, MHV-2f. Two amino acids differed between the S proteins of these viruses; one was located in the signal sequence and the other was in the putative cleavage site. The amino acid at position 12 in the signal sequence was S in MHV-2 and C in MHV-2f. The amino acid sequence of the cleavage site of MHV-2 was HRARS, while that of MHV-2f was HRARR, showing one amino acid replacement at position 757. In DBT cells infected with MHV-2, the S protein was not cleaved, while the S protein of MHV-2f was cleaved. The S protein of MHV-2f expressed in a transient vaccinia virus expression system was cleaved and was fusogenic in contrast to the nonfusogenic activity of uncleaved MHV-2 S protein. Because the signal sequence is assumed to be removed from the mature S protein soon after synthesis, and because the S protein of MHV-2 was expressed on the cell surface in the same way as the S protein of MHV-2f, the difference in the signal sequence seemed to have had little effect on the transportation and the fusion activity of the S protein. These results showed that MHV-2 does not fuse cells due to the lack of cleavage of its S protein. This conclusion differs from studies on the activity of syncytium formation by the S proteins of fusogenic MHV-JHM and -A59 strains. Possible reasons for these differences in fusion activity are discussed.


title: Potent Inhibition of Enterovirus D68 and Human Rhinoviruses by Dipeptidyl Aldehydes and α-Ketoamides

text: Enterovirus D68 (EV-D68) is an emerging pathogen responsible for mild to severe respiratory infections that occur mostly in infants, children and teenagers. EV-D68, one of more than 100 non-polio enteroviruses, is acid-labile and biologically similar to human rhinoviruses (HRV) (originally classified as HRV87). However, there is no approved preventive or therapeutic measure against EV-D68, HRV, or other enteroviruses. In this study, we evaluated the antiviral activity of series of dipeptidyl compounds against EV-D68 and HRV strains, and demonstrated that several peptidyl aldehyde and α-ketoamide peptidyl compounds are potent inhibitors of EV-D68 and HRV strains with high in-vitro therapeutic indices (>1000). One of the α-ketoamide compounds is shown to have favorable pharmacokinetics profiles, including a favorable oral bioavailability in rats. Recent successful development of α-ketoamide protease inhibitors against hepatitis C virus suggests these compounds may have a high potential for further optimization and development against emerging EV-D68, as well as HRV.


title: Mutation of the S and 3c genes in genomes of feline coronaviruses

text: Feline coronavirus (FCoV) is classified into two biotypes based on its pathogenicity in cats: a feline enteric coronavirus of low pathogenicity and a highly virulent feline infectious peritonitis virus. It has been suspected that FCoV alters its biotype via mutations in the viral genome. The S and 3c genes of FCoV have been considered the candidates for viral pathogenicity conversion. In the present study, FCoVs were analyzed for the frequency and location of mutations in the S and 3c genes from faecal samples of cats in an animal shelter and the faeces, effusions, and tissues of cats that were referred to veterinary hospitals. Our results indicated that approximately 95% FCoVs in faeces did not carry mutations in the two genes. However, 80% FCoVs in effusion samples exhibited mutations in the S and 3c genes with remainder displaying a mutation in the S or 3c gene. It was also suggested that mutational analysis of the 3c gene could be useful for studying the horizontal transmission of FCoVs in multi-cat environments.


title: In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19

text: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has led to a global public health crisis. In elderly individuals and those with comorbidities, COVID-19 is associated with high mortality, frequently caused by acute respiratory distress syndrome. We examine in situ expression of SARS-CoV-2 in airways and lung obtained at autopsy of individuals with confirmed COVID-19 infection. Seven autopsy cases (male, N = 5; female, N = 2) with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection and a median age of 66 years (range, 50–77 years) were evaluated using a rabbit polyclonal antibody against SARS Nucleocapsid protein in correlation with clinical parameters. The median time from symptom onset to death was 9 days (range, 6–31 days), from hospitalization 7 days (range, 1–21 days), from positive RT-PCR 7 days (range, 0–18 days), and from intensive care unit admission defining onset of respiratory failure 3 days (range, 1–18 days). Chest imaging identified diffuse airspace disease in all patients corresponding to acute and (N = 5) or organizing (N = 2) diffuse alveolar damage (DAD) on histologic examination. Among five patients with acute-phase DAD (≤7 days from onset of respiratory failure), SARS-CoV-2 was detected in pulmonary pneumocytes and ciliated airway cells (N = 5), and in upper airway epithelium (N = 2). In two patients with organizing DAD (>14 days from onset of respiratory failure), no virus was detected in lungs or airways. No endothelial cell infection was observed. The findings suggest that SARS-CoV-2 infection of epithelial cells in lungs and airways of patients with COVID-19 who developed respiratory failure can be detected during the acute phase of lung injury and is absent in the organizing phase.


docid: vcvhmqgg

title: A novel rabies vaccine based on infectious propagating particles derived from hybrid VEEV-Rabies replicon

text: BACKGROUND: Live attenuated vaccines (LAVs) can mimic natural infection and have advantages to stimulate a robust and sustained immune response as well as to confer long-term protection. However, safety concerns is one of the major obstacles for LAVs development. In an effort to achieve the optimal balance between immunogenicity and safety, researchers currently have taken different strategies for the development of LAVs. METHODS: We constructed a novel infectious self-propagating hybrid replicon particle (PRP), VEEV-RABV-G, through replacing the entire structural proteins of the Venezuelan equine encephalitis virus (VEEV) with the glycoprotein of rabies virus (RABV-G) as the single structural protein. We evaluated the potential of VEEV-RABV-G as a safe live attenuated vaccine in mice model. FINDINGS: We found that VEEV-RABV-G could self-propagate efficiently in cell culture and induce a robust humoral immunity and provide protection against virulent RABV challenge in immunized mice. Remarkably, VEEV-RABV-G is highly attenuated in both adult and sucking mice, causing much weaker inflammatory and apoptotic effects in the brains of infected adult mice and significantly lower weight loss and morbidity compared with the commonly used RABV-derived LAVs. INTERPRETATION: This study reveals the feasibility of developing novel rabies vaccines based on the self-replicating PRPs. FUNDING: This work was supported by the National Key Research and Development Program of China (2016YFD0500400).


title: Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active

text: Abstract Angiotensin-converting enzyme (ACE) is a metallopeptidase that converts angiotensin I into angiotensin II. ACE is crucial in the control of cardiovascular and renal homeostasis and fertility in mammals. In vertebrates, both transmembrane and soluble ACE, containing one or two active sites, have been characterized. So far, only soluble, single domain ACEs from invertebrates have been cloned, and these have been implicated in reproduction in insects. Furthermore, an ACE-related carboxypeptidase was recently characterized in Leishmania, a unicellular eukaryote, suggesting the existence of ACE in more distant organisms. Interestingly, in silico databank analysis revealed that bacterial DNA sequences could encode putative ACE-like proteins, strikingly similar to vertebrates' enzymes. To gain more insight into the bacterial enzymes, we cloned the putative ACE from the phytopathogenic bacterium, Xanthomonas axonopodis pv. citri, named XcACE. The 2 kb open reading frame encodes a 672-amino-acid soluble protein containing a single active site. In vitro expression and biochemical characterization revealed that XcACE is a functional 72 kDa dipeptidyl-carboxypeptidase. As in mammals, this metalloprotease hydrolyses angiotensin I into angiotensin II. XcACE is sensitive to ACE inhibitors and chloride ions concentration. Variations in the active site residues, highlighted by structural modelling, can account for the different substrate selectivity and inhibition profile compared to human ACE. XcACE characterization demonstrates that ACE is an ancestral enzyme, provoking questions about its appearance and structure/activity specialisation during the course of evolution.


title: Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis.

text: Background An ongoing outbreak of pneumonia caused by a novel coronavirus [severe acute respiratory syndrome coronavirus (SARS-CoV)-2], named COVID-19, hit a major city of China, Wuhan in December 2019 and subsequently spread to other provinces/regions of China and overseas. Several studies have been done to estimate the basic reproduction number in the early phase of this outbreak, yet there are no reliable estimates of case fatality rate (CFR) for COVID-19 to date. Methods In this study, we used a purely data-driven statistical method to estimate the CFR in the early phase of the COVID-19 outbreak. Daily numbers of laboratory-confirmed COVID-19 cases and deaths were collected from January 10 to February 3, 2020 and divided into three clusters: Wuhan city, other cities of Hubei province, and other provinces of mainland China. Simple linear regression model was applied to estimate the CFR from each cluster. Results We estimated that CFR during the first weeks of the epidemic ranges from 0.15% (95% CI: 0.12-0.18%) in mainland China excluding Hubei through 1.41% (95% CI: 1.38-1.45%) in Hubei province excluding the city of Wuhan to 5.25% (95% CI: 4.98-5.51%) in Wuhan. Conclusions Our early estimates suggest that the CFR of COVID-19 is lower than the previous coronavirus epidemics caused by SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).


Psychobiotics: An emerging alternative to ensure mental health amid the COVID-19 outbreak?


docid: ftzjdvfj

title: Experimental infection of adult axenic rats with Parker's Rat Coronavirus

text: The pathogenesis of Parker's Rat Coronavirus (PRCV) was studied in axenic CD rats. Three to four 9 to 10 week old rats were euthanized daily for eight days after intranasal inoculation. Rats remained free of clinical disease. Virus was recovered from the nasopharynx and trachea after twenty-four hours and from the lung by day three but was not detected in respiratory tract after seven days. Viral antigen was detected by indirect immunofluorescence in the mucosal epithelium of upper respiratory tract and in pulmonary alveolar septae from day two to six postinoculation. Acute rhinitis developed by day two and was associated with mild focal necrosis of respiratory mucosal epithelium. Mild nonsuppurative tracheitis and multifocal interstitial pneumonia appeared by day five and persisted through day eight. Dacryoadenitis did not occur, sialoadenitis was detected in only three rats and virus was recovered from only one submaxillary salivary gland. This experiment indicates that PRCV can be a primary pathogen for the respiratory system of adult rats. In contrast to sialodacryoadenitis (SDA) virus the tropism of PRCV for salivary and lacrimal glands is low.


title: On Determining the Age Distribution of COVID-19 Pandemic

text: Pandemics tend to have higher occurrence (morbidity) in younger individuals but higher mortality for the elderly. The higher rate of mortality of COVID-19 in elderly individuals has been discussed in many reports. However, this pandemic is a double-edged sword as this comment shows higher morbidity rates in elderly as well. This is shown by comparing the age distribution of cases in China and South Korea to the relative populations. In every case, the relative number of elderly contracting the virus is far higher than the proportion of elderly in the population. This is unlike past pandemics and shows that aging populations are at an even higher risk than the perceived age dependent rates may imply.


title: Synthesis and SAR studies on azetidine-containing dipeptides as HCMV inhibitors

text: Abstract SAR studies on an azetidine-containing dipeptide prototype inhibitor of HCMV are described. Three series of structurally modified analogues, involving substitutions at the N- and C-terminus, and at the C-terminal side-chain were synthesized and evaluated for antiviral activity. Aliphatic or no substituents at the C-carboxamide group, an aliphatic C-terminal side-chain, as well as a benzyloxycarbonyl moiety at the N-terminus were absolute requirements for anti-HCMV activity. The conformational restriction induced by the 2-azetidine residue into the dipeptide derivatives, identified by 1H NMR as a γ-type reverse turn, seems to have influence on the activity of these molecules.


title: Phage displayed peptides recognizing porcine aminopeptidase N inhibit transmissible gastroenteritis coronavirus infection in vitro

text: Abstract Porcine aminopeptidase N (pAPN) is a cellular receptor of transmissible gastroenteritis virus (TGEV), a porcine coronavirus. Interaction between the spike (S) protein of TGEV and pAPN initiates cell infection. Small molecules, especially peptides are an expanding area for therapy or diagnostic assays for viral diseases. Here, the peptides capable of binding the pAPN were, for the first time, identified by biopanning using a random 12-mer peptide library to the immobilized protein. Three chemically synthesized peptides recognizing the pAPN showed effective inhibition ability to TGEV infection in vitro. A putative TxxF motif was identified in the S protein of TGEV. Phages bearing the specific peptides interacted with the pAPN in ELISA. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays confirmed the protective effect of the peptides on cell infection by TGEV. Moreover, the excellent immune responses in mice induced by the identified phages provided the possibility to develop novel phage-based vaccines.


title: Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy

text: Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice. IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections.


title: SARS-CoV-2 Infection with Different Radiological Insights

text: Severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) is a novel viral infection characterized by several symptoms range from mild to severe clinical conditions that could lead to death. We report two different radiological findings on computed tomography (CT) in two patients affected by SARS-CoV-2: a lung acute embolism (APE) in the first case and a radiological picture of acute respiratory distress syndrome (ARDS) in the second case. This is an important issue to be identified in order to provide more specific therapy earlier, including both antiviral and anti-inflammatory drugs associated with anti anticoagulant therapy.


title: Effect of multiple intravenous injections of butaphosphan and cyanocobalamin on the metabolism of periparturient dairy cows 1

text: Abstract Numerous adjunct therapeutic agents have been investigated for the treatment or control of fat mobilization syndrome in periparturient dairy cows. The aim of this study was to determine the effects of multiple i.v. injections of 10% butaphosphan and 0.005% cyanocobalamin combination (Catosal, Bayer Animal Health, Leverkusen, Germany) between 1 and 2 wk antepartum (a.p.) on the metabolism and health of dairy cows. Forty-five late-gestation Holstein-Friesian cows (second pregnancy) were allocated randomly to 1 of 3 groups with 15 cows/group: group C6 (6 daily i.v. injections of butaphosphan at 10mg/kg of body weight (BW) and cyanocobalamin at 5μg/kg of BW in the last 2 wk of gestation); group C3 (3 daily i.v. injections of butaphosphan at 10mg/kg of BW and cyanocobalamin at 5μg/kg of BW in the last week of gestation); and group C0 (equivolume daily i.v. injections of 0.9% NaCl solution). Serum biochemical analysis was performed on jugular venous blood samples that were periodically obtained a.p. and postpartum (p.p.). Health status and milk production were monitored p.p. Serum cyanocobalamin concentration increased in groups C6 and C3 p.p. Multiple daily i.v. injections of Catosal before parturition increased p.p. glucose availability, as evaluated by p.p. serum glucose concentration, and decreased peripheral fat mobilization and ketone body formation, as evaluated by p.p. serum nonesterified fatty acid and β-OH butyrate concentrations. The number of puerperal infections in the first 5 d after calving was decreased in group C6, relative to group C0. We conclude that multiple injections of Catosal during the close-up period have a beneficial effect on the metabolism of periparturient dairy cows. Our results are consistent with the hypothesis that high-producing dairy cows in early lactation may have a relative or actual deficiency of cyanocobalamin.


title: Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus)

text: Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.


title: A diagnostic oligonucleotide microarray for simultaneous detection of grapevine viruses

text: Abstract At least 58 viruses have been reported to infect grapevines causing economic damage globally. Conventional detection strategies based on serological assays, biological indexing and RT-PCR targeting one or few viruses in each assay are widely used. Grapevines are prone to contain mixed infections of several viruses, making the use of these techniques time-consuming. A 70-mer oligonucleotide microarray able to detect simultaneously a broad spectrum of known viruses as well as new viruses by cross-hybridization to highly conserved probes is reported in the present study. The array contains 570 unique probes designed against highly conserved and species-specific regions of 44 plant viral genomes. In addition probes designed against plant housekeeping genes are also included. By using a random primed RT-PCR amplification strategy of grapevine double stranded RNA-enriched samples, viral agents were detected in single and mixed infections. The microarray accuracy to detect 10 grapevine viruses was compared with RT-PCR yielding consistent results. For this purpose, grapevine samples containing single or mixed infections of Grapevine leafroll-associated virus-1, -2, -3, -4, -7, -9, Grapevine fanleaf virus, Grapevine rupestris stem pitting-associated virus, Grapevine virus A, and Grapevine virus B were used. Genomic libraries containing complete viral genomes were also used as part of the validation process. The specific probe hybridization pattern obtained from each virus makes this approach a powerful tool for high throughput plant certification purposes and also for virus discovery if the new viral genomic sequences have partial similarity with the microarray probes. Three Closteroviridae members (Grapevine leafroll-associated virus -4, -7 and -9) were detected for the first time in Chilean grapevines using the microarray.


docid: pykihnup

text: Koh Y, Hegney D, Drury V. International Journal of Nursing Practice 2012; 18: 195–204 Nurses' perceptions of risk from emerging respiratory infectious diseases: A Singapore study The recent emergence of virulent respiratory infectious diseases such as Severe Acute Respiratory Syndrome (SARS) and Influenza A/H1N1 viruses predisposes nurses to occupational risks. This qualitative study investigated how Chinese Singaporean nurses perceived the risks of exposure to these infectious diseases and the factors that influenced this risk perception. Data were collected through face‐to‐face interviews and were analyzed using Braun and Clarke's process of thematic analysis. Three themes emerged: living with risk; the experience of SARS; and acceptance of risk. The nature of nursing work was perceived to place participants at risk of infection. Another significant finding of this study is that the government's, organizations' and nurses' perceptions of new emerging respiratory infectious diseases were influenced by their previous experience with SARS. Similar to previous studies, nurses working at the ‘front line’ believed that infection from these diseases was an unavoidable occupational hazard.


title: Faculty development in medical education: an environmental scan in countries within the Asia pacific region

text: PURPOSE: In recent years, faculty development (FD) research is more noticeable within an inter-professional context and in allied health education. However, there is a paucity of published literature on FD medical education programs in Asia. With the formation of the Asia Pacific Medical Education Network (APME-Net) in 2015, a scoping review of an environmental scan of FD medical education programs in main institutions in South East Asia and Australia in 2018 was conducted. METHODS: A survey was developed to collect data on FD in medical education after several rounds of discussion with APME-Net members. The representatives from nine countries in Asia and Australia were invited to partner in this research project. They sent the questionnaire to the Dean of all different medical schools after ethical clearance. The data collected was analyzed using descriptive statistics. RESULTS: Only institutions in four countries responded to the questionnaire. The medical/health professions education center/department/unit has been established in most educational institutions in these countries. These centers/departments/units mostly carry out FD programs to improve the teaching and learning skills of trained participants, particularly clinical teachers via workshops and seminars. Staffing issues and participant buy-in are the current key priorities of the center/department/unit in terms of FD. Lastly, research related FD program has not been well-supported in these countries, hence, the lack of publication in this area. CONCLUSION: Collaboration between countries to address key areas of interest and develop more standardized and productive FD medical education is required especially in research.


title: Prevalence of antibodies against transmissible gastroenteritis virus (TGEV) in Hungary

text: Abstract Transmissible gastroenteritis (TGE) is a highly contagious enteric disease of swine, which became infrequent with the appearance of porcine respiratory coronavirus (PRCV). TGE was last reported in Hungary in 2013 and the virus has not been found since, therefore a serological survey was planned to estimate the level of protection against it. 908 sera of sows from 93 farms were selected together with 174 archive samples from one farm covering a wider age group. All samples were screened with an indirect immunofluorescence (IF) test with a positive result of 15.42% and 17.82%, respectively. All IF-positive samples were examined with a commercial ELISA, revealing seropositivity against PRCV in almost all cases. These findings should serve as a recommendation to not omit TGE from the diagnostics of diarrhoea in swine.


title: Epidemiological characteristics of 2019-ncoV infections in Shaanxi, China by February 8, 2020

text: The patients confirmed with NCP in Shaanxi Province are mainly have the history of Wuhan contact, There are characteristics of family aggregation and concealment.


title: Enterovirus genotypes among patients with severe acute respiratory illness, influenza‐like illness, and asymptomatic individuals in South Africa, 2012‐2014

text: Enteroviruses can cause outbreaks of severe acute respiratory illness (SARI) and EV‐A, ‐B, ‐C, and ‐D species have different pathogenic profiles and circulation patterns. We aimed to characterize and determine the prevalence of enterovirus genotypes among South African patients with respiratory illness and controls during June 2012 to July 2014. Syndromic SARI and influenza‐like illness (ILI) surveillance was performed at two sentinel sites. At each site nasopharyngeal/oropharyngeal specimens were collected from SARI and ILI patients as well as controls. Specimens were tested for enterovirus by real‐time PCR. Positive specimens were further genotyped by sequencing a region of the VP1 gene. The prevalence of enterovirus was 5.8% (87/1494), 3.4% (103/3079), and 3.4% (46/1367) among SARI, ILI, and controls, respectively (SARI/controls, P = 0.002 and ILI/control, P = 0.973). Among the 101/236 (42.8%) enterovirus‐positive specimens that could be genotyped, we observed a high diversity of circulating enterovirus genotypes (a total of 33 genotypes) from all four human enterovirus species with high prevalence of Enterovirus‐B (60.4%; 61/101) and Enterovirus‐A (21.8%; 22/101) compared to Enterovirus‐C (10.9%; 11/101) and Enterovirus‐D (6.9%; 7/101) (P = 0.477). Of the enterovirus genotypes identified, Echovirus 30 (9.9%, 10/101), Coxsackie virus B5 (7.9%, 8/101) and Enterovirus‐D68 (6.9%, 7/101) were most prevalent. There was no difference in disease severity (SARI or ILI compared to controls) between the different enterovirus species (P = 0.167). We observed a high number of enterovirus genotypes in patients with respiratory illness and in controls from South Africa with no disease association of EV species with disease severity.


docid: vuonolxg

title: MERS, SARS and other coronaviruses as causes of pneumonia

text: Human coronaviruses (HCoVs) have been considered to be relatively harmless respiratory pathogens in the past. However, after the outbreak of the severe acute respiratory syndrome (SARS) and emergence of the Middle East respiratory syndrome (MERS), HCoVs have received worldwide attention as important pathogens in respiratory tract infection. This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS‐coronaviruses (CoV), MERS‐CoV and other HCoV infections.


title: Applications of gold nanoparticles in virus detection

text: Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications.


title: Virus detection and its association with symptoms during influenza‐like illness in a sample of healthy adults enrolled in a randomised controlled vaccine trial

text: Background Viral respiratory infections are associated with significant morbidity and mortality. Many new aetiological agents have been described recently. Objectives We looked for respiratory viruses in a population‐based sample of healthy adults with influenza‐like illness (ILI). We investigated host and spatio‐temporal associations with virus isolation and host, spatio‐temporal and virus associations with self‐reported symptoms. Patients/Methods We recruited 586 participants experiencing 651 illness episodes from a population of healthy adults enrolled in an influenza vaccine effectiveness trial. At ILI assessment visits, a respiratory swab was collected and tested for viruses using a combination of polymerase chain reaction (PCR) assays. Participants also completed a questionnaire detailing their clinical course in 336 episodes. Results Of 643 samples analysed, a virus was identified in 44%. Half were picornaviruses, with influenza and coronaviruses the next most common. Individuals with influenza were significantly less likely to have been immunised than the reference (virus negative) population (OR = 0·52 (0·31, 0·87) P = 0·01). The mean symptom score (95% CI) reported by individuals with influenza was significantly higher than in all other episodes [Influenza: 10·2 (9·4, 10·9); Other: 7·4 (7·2, 7·7); Difference (95% CI): 2·5 (1·5, 3·5); P < 0·001]. In an analysis restricted to influenza‐positive cases, the symptom score was not attenuated by vaccination. Conclusions Our findings indicate that a greater number of symptoms are displayed by individuals presenting with influenza confirmed ILI compared with other agents that cause ILI. While influenza vaccination reduced the probability of influenza virus detection, symptom score for influenza‐positive ILI was not attenuated.


title: Novel isoxazolidine analogues of homonucleosides and homonucleotides

text: Abstract Isoxazolidine analogues of homonucleos(t)ides were synthesized from nucleobase-derived nitrones 20a-20e (uracil, 5-fluorouracil, 5-bromouracil, thymine, adenine) employing 1,3-dipolar cycloadditions with allyl alcohol as well as with alkenylphosphonates (allyl-, allyloxymethyl- and vinyloxymethyl- and vinylphosphonate). Besides reactions with vinylphosphonate the additions proceeded regioselectively to produce mixtures of major cis and minor trans 3,5-disubstituted isoxazolidines (d.e. 28–82%). From vinylphosphonate up to 10% of 3,4-disubstituted isoxazolidines was additionally produced. Vicinal couplings, shielding effects and 2D NOE correlations were employed in configurational assignments as well as in conformational analysis to find out preferred conformations for several isoxazolidines and to observe anomeric effects (pseudoaxial orientation of phosphonylmethoxy groups) for those obtained from vinyloxymethylphosphonate. None of the tested compounds were endowed in vitro with antiviral activity against a variety of DNA and RNA viruses at subtoxic concentrations (up to 250 μM) nor exhibited antiproliferative activity towards L1210, CEM, and HeLa cells (IC50 = ≥100 μM).


title: Current and emerging diagnostic tests available for the novel COVID-19 global pandemic

text: On March 11, 2020 the World Health Organization (WHO) upgraded the status of the coronavirus disease 2019 (COVID-19) outbreak from epidemic to a global pandemic. This infection is caused by a novel coronavirus, SARS-CoV-2. Several rapid diagnostic tests have been developed at an astonishing pace; however, COVID-19 requires more highly specific rapid point-of-care diagnostic tests. This review describes the currently available testing approaches, as well as the available test assays including the Xpert® Xpress SARS-CoV-2 test (takes (~)45 min) and Abbott ID COVID-19 test (5 min) as easy to use point-of-care tests for diagnosis of novel COVID-19 that have so far received the US Food and Drug Administration emergency use authorizations clearance. This review is correct as of the date published and will be updated as more diagnostic tests come to light.


title: Aminoacyl-tRNA synthetases, therapeutic targets for infectious diseases

text: Abstract Despite remarkable advances in medical science, infection-associated diseases remain among the leading causes of death worldwide. There is a great deal of interest and concern at the rate at which new pathogens are emerging and causing significant human health problems. Expanding our understanding of how cells regulate signaling networks to defend against invaders and retain cell homeostasis will reveal promising strategies against infection. It has taken scientists decades to appreciate that eukaryotic aminoacyl-tRNA synthetases (ARSs) play a role as global cell signaling mediators to regulate cell homeostasis, beyond their intrinsic function as protein synthesis enzymes. Recent discoveries revealed that ubiquitously expressed standby cytoplasmic ARSs sense and respond to danger signals and regulate immunity against infections, indicating their potential as therapeutic targets for infectious diseases. In this review, we discuss ARS-mediated anti-infectious signaling and the emerging role of ARSs in antimicrobial immunity. In contrast to their ability to defend against infection, host ARSs are inevitably co-opted by viruses for survival and propagation. We therefore provide a brief overview of the communication between viruses and the ARS system. Finally, we discuss encouraging new approaches to develop ARSs as therapeutics for infectious diseases.


title: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; p(interaction)=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; p(interaction)=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.


COVID-19 outbreak and cancer patient management: viewpoint from radio-oncologists


Uniquely conserved immunosuppressive viral exoribonucleases


title: Selection of reference genes for expression analysis using RT-qPCR in the dissemination system of Heliothis virescens ascovirus 3 h (HvAV-3h)

text: Ascoviruses are double-stranded DNA viruses that mainly infect noctuid larvae, and are transmitted by the parasitoid wasp Microplitis similis Lyle. Ascovirus-parasitoids wasp-noctuid insects constitute the dissemination system. Selection of suitable reference genes for the dissemination system could play an important role in elucidating the pathogenic molecular mechanisms of ascovirus. Unfortunately, such studies on potential reference genes in the dissemination system of ascoviruses are lacking. In the present study, we evaluated 11 candidate reference genes: β-actin1 (ACT1), β-actin2 (ACT2), elongation factor 1 (EF1), elongation factor 2 (EF2), ribosomal protein L10 (L10), ribosomal protein L17A (L17A), superoxide dismutase (SOD), 28S ribosome (28S), Tubulin (TUB) and 18S ribosome (18S). The samples were originally from various virus concentrations and points-in-time of experimental treatments using RefFinder and four algorithms. The results showed that EF1 was the most stable internal gene in S. exigua and M. similis and that EF2 was the most stable in the IOZCAS-Spex-II-A cell line, and the stability of reference genes were confirmed via the expression levels of two inhibitor of apoptosis-like (iap-like) genes from Heliothis virescens ascovirus 3 h (HvAV-3h). This study provides a crucial basis for future research that explores the molecular mechanisms of the pathogenesis of ascoviruses.


title: Prevention and treatment of COVID‐19 disease by controlled modulation of innate immunity

text: The recent outbreak of coronavirus disease 2019 (COVID‐19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses an enormous threat to global public health and economies. Human coronaviruses normally cause no or mild respiratory disease but in the past two decades, potentially fatal coronavirus infections have emerged, causing respiratory tract illnesses such as pneumonia and bronchitis. These include severe acute respiratory syndrome coronavirus (SARS‐CoV), followed by the Middle East respiratory syndrome coronavirus (MERS‐CoV), and recently the SARS‐CoV‐2 coronavirus outbreak which emerged in Wuhan, China, in December 2019. Currently, most COVID‐19 patients receive traditional supportive care including breathing assistance. To halt the ongoing spread of the pandemic SARS‐CoV‐2 coronavirus and rescue individual patients, established drugs and new therapies are under evaluation. Since it will be some time until a safe and effective vaccine will be available, the immediate priority is to harness innate immunity to accelerate early antiviral immune responses. Secondly since excessive inflammation is a major cause of pathology, targeted anti‐inflammatory responses are being evaluated to reduce inflammation‐induced damage to the respiratory tract and cytokine storms. Here, we highlight prominent immunotherapies at various stages of development which aim for augmented anti‐coronavirus immunity and reduction of pathological inflammation. This article is protected by copyright. All rights reserved


title: Structural proteomics of the SARS coronavirus: a model response to emerging infectious diseases

text: A number of structural genomics/proteomics initiatives are focused on bacterial or viral pathogens. In this article, we will review the progress of structural proteomics initiatives targeting the SARS coronavirus (SARS-CoV), the etiological agent of the 2003 worldwide epidemic that culminated in approximately 8,000 cases and 800 deaths. The SARS-CoV genome encodes 28 proteins in three distinct classes, many of them with unknown function and sharing low similarity to other proteins. The structures of 16 SARS-CoV proteins or functional domains have been determined to date. Remarkably, eight of these 16 proteins or functional domains have novel folds, indicating the uniqueness of the coronavirus proteins. The results of SARS-CoV structural proteomics initiatives will have several profound biological impacts, including elucidation of the structure–function relationships of coronavirus proteins; identification of targets for the design of anti-viral compounds against SARS-CoV and other coronaviruses; and addition of new protein folds to the fold space, with further understanding of the structure–function relationships for several new protein families. We discuss the use of structural proteomics in response to emerging infectious diseases such as SARS-CoV and to increase preparedness against future emerging coronaviruses.


title: Gastrointestinal Complications in Critically Ill Patients With COVID-19

text: Supplemental Digital Content is available in the text


title: Formation of dioxins from triclosan with active chlorine: A potential risk assessment

text: Abstract Triclosan, a widely used antimicrobial agent, can increase colitis-associated colon tumorigenesis, and induce liver fibrosis and cancer in mice through mechanisms which may be relevant in humans. In this study, an analytical method using gas chromatography-mass spectrometry (GC–MS) and high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS) was developed to measure dioxins and chlorinated derivatives from triclosan in the presence of active chlorine in seawater matrix. Formation yields of dioxins and chlorinated triclosans were assessed at different initial precursor concentrations under dark and UV light irradiation conditions. Results showed that triclosan was rapidly transformed to its chlorinated derivatives, i.e. tetraclosans and pentaclosans, of which the formation yields peaked after 1 h of reaction. UV light was the key factor to promote the formation of dioxins. With the same initial triclosan/active chlorine ratio, the highest yield of dioxins was observed with lower initial concentrations of triclosan under UV irradiation. Five dioxins, including 2,8-DCDD, 1,2,8-TrCDD, 2,3,7-TrCDD, 1,2,3,8-TeCDD, and 2,3,7,8-TeCDD, were identified and quantified. 2,3,7,8-TeCDD, the most toxic dioxin, was firstly reported as the photo-transformation product of triclosan in aquatic solution. Results presented here are useful for a comprehensive understanding of the fate and toxicity of triclosan in contaminated waters.


title: The MultiBac Baculovirus/Insect Cell Expression Vector System for Producing Complex Protein Biologics

text: Multiprotein complexes regulate most if not all cellular functions. Elucidating the structure and function of these complex cellular machines is essential for understanding biology. Moreover, multiprotein complexes by themselves constitute powerful reagents as biologics for the prevention and treatment of human diseases. Recombinant production by the baculovirus/insect cell expression system is particularly useful for expressing proteins of eukaryotic origin and their complexes. MultiBac, an advanced baculovirus/insect cell system, has been widely adopted in the last decade to produce multiprotein complexes with many subunits that were hitherto inaccessible, for academic and industrial research and development. The MultiBac system, its development and numerous applications are presented. Future opportunities for utilizing MultiBac to catalyze discovery are outlined.


title: Evaluating the Mental Health Impacts of the COVID-19 Pandemic in Urban South Africa: Perceived Risk of COVID-19 Infection and Childhood Trauma Predict Adult Depressive Symptoms

text: South Africa’s national lockdown introduced serious threats to public mental health in a society where one in three individuals develop a psychiatric disorder during their life. We aimed to evaluate the mental health impacts of the COVID-19 pandemic using a mixed methods design. This longitudinal study drew from a preexisting sample of 957 adults living in Soweto, a major township near Johannesburg. Psychological assessments were administered across two waves: between August 2019-March 2020 and during the first six weeks of the lockdown (late March-early May 2020). Interviews on COVID-19 experiences were administered in the second wave. Multiple regression models examined relationships between perceived COVID-19 risk and depression. Full data on perceived COVID-19 risk, depression, and covariates were available in 221 adults. 14.5% of adults were at risk for depression. Higher perceived COVID-19 risk predicted greater depressive symptoms (p < 0.001) particularly among adults with histories of childhood trauma, though this effect was marginally significant (p = 0.062). Adults were two times more likely to experience significant depressive symptoms for every one unit increase in perceived COVID-19 risk (p = 0.016; 95% CI [1.14, 3.49]). Qualitative data identified potent experiences of anxiety, financial insecurity, fear of infection, and rumination. Higher perceived risk of COVID-19 infection is associated with greater depressive symptoms among adults with histories of childhood trauma during the first six weeks of quarantine. High rates of severe mental illness and low availability of mental healthcare amidst COVID-19 emphasize the need for immediate and accessible psychological resources in South Africa.


title: Community-based immunization in opportunistic social networks

text: Abstract Immunizing important nodes has been shown to be an effective solution to suppress the epidemic spreading. Most studies focus on the globally important nodes in a network, but neglect the locally important nodes in different communities. We claim that given the temporal community feature of opportunistic social networks (OSN), this strategy has a biased understanding of the epidemic dynamics, leading us to conjecture that it is not “the more central, the better” for the implementation of control strategy. In this paper, we track the evolution of community structure and study the effect of community-based immunization strategy on epidemic spreading. We first break the OSN traces down into different communities, and find that the community structure helps to delay the outbreak of epidemic. We then evaluate the local importance of nodes in communities, and show that immunizing nodes with high local importance can remarkably suppress the epidemic. More interestingly, we find that high local importance but non-central nodes play a big role in epidemic spreading process, removing them improves the immunization efficiency by 25% to 150% at different scenarios.


title: The Rapid Response to the COVID-19 Pandemic by the Arthroplasty Divisions at Two Academic Referral Centers

text: Abstract The COVID-19 pandemic has created widespread changes across all of healthcare. The impacts on the delivery of orthopaedic services has been challenged as a result. In order to ensure and provide for adequate health care resources in terms of hospital capacity, personnel and personal protective equipment (PPE), service lines such as adult reconstruction and lower limb arthroplasty have stopped or substantially limited elective surgeries and have been forced to re-engineer care processes for a high-volume of patients. Herein, we summarize the similar approaches by two arthroplasty divisions in high volume academic referral centers in 1) the cessation of elective surgeries, 2) workforce restructuring, 3) phased delivery of outpatient and inpatient care, and 4) educational restructuring.


docid: cadyykks

title: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature

text: Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.


docid: ffulkqrf

title: High Diagnostic Yield of Dedicated Pulmonary Screening before Hematopoietic Cell Transplantation in Children

text: Abstract Pulmonary complications are an important cause for treatment-related morbidity and mortality in hematopoietic cell transplantation (HCT) in children. The aim of this study was to investigate the yield of our pre-HCT pulmonary screening program. We also describe our management guidelines based on these findings and correlate them with symptomatic lung injury after HCT. Since 2008, all patients undergo a dedicated pulmonary screening consisting of pulmonary function test (PFT), chest high-resolution computed tomography (HRCT), and bronchial alveolar lavage (BAL) before HCT. We systematically evaluated the yield during the first 5 years of our screening program. We included 142 consecutive children. In 74% of patients, abnormalities were found. In 66% of patients, 1 or more PFT results were <80% of normal. Chest HRCT showed abnormalities in 55%; 19% of these abnormalities were considered “clinically significant.” BAL was abnormal in 43% of patients; respiratory viruses (PCR) were found in 35 patients, fungi (antigen or culture) in 21, and bacteria (culture) in 22. All 3 screening tests contributed separately to clinically relevant information regarding pulmonary status in these pre-HCT children. In 46 patients (33%), screening results had diagnostic and/or therapeutic implications. We found an association between pre-SCT HRCT findings and lung injury after transplantation. Pre-HCT screening with the combination of 3 modalities, reflecting different domains of respiratory status (function, structure, and microbial colonization), reveals important abnormalities in a substantial number of patients. Whether this improves patient outcome requires further investigation.


Sustaining Frontline ICU Healthcare Workers during the COVID-19 Pandemic and Beyond


title: The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial

text: BACKGROUND: An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids. OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients. METHODS: Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward. RESULTS: In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%. CONCLUSIONS: Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.


GPs call for cut in red tape to manage aftermath of covid-19


title: Glycan arrays lead to the discovery of autoimmunogenic activity of SARS-CoV

text: Using carbohydrate microarrays, we characterized the carbohydrate binding activity of SARS-CoV neutralizing antibodies elicited by an inactivated SARS-CoV vaccine. In these antibodies, we detected undesired autoantibody reactivity specific for the carbohydrate moieties of an abundant human serum glycoprotein asialo-orosomucoid (ASOR). This observation provides important clues for the selection of specific immunologic probes to examine whether SARS-CoV expresses antigenic structures that mimic the host glycan. We found that lectin PHA-L (Phaseolus vulgaris L.), which is specific for a defined complex carbohydrate of ASOR, stained the SARS-CoV-infected cells specifically and intensively. Taken together, we present immunologic evidence that a carbohydrate structure of SARS-CoV shares antigenic similarity with host glycan complex carbohydrates. The experimental approaches we applied in this study are likely applicable for the identification of immunologic targets of other viral pathogens.


Sex differences in the relationship between digit ratio (2D:4D) and national case fatality rates for COVID-19: A reply to Sahin


title: Porcine deltacoronavirus: histological lesions and genetic characterization

text: First identified in 2012 in a surveillance study in Hong Kong, porcine deltacoronavirus (PDCoV) is a proposed member of the genus Deltacoronavirus of the family Coronaviridae. In February of 2014, PDCoV was detected in pigs with clinical diarrheal symptoms for the first time in the USA. Since then, it has been detected in more than 20 states in the USA and in other countries, including Canada, South Korea, and mainland China. So far, histological lesions in the intestines of pigs naturally infected with PDCoV under field conditions have not been reported. In this report, we describe the characteristic histological lesions in the small intestine that were associated with PDCoV infection, as evidenced by detection of viral nucleic acid by RT-PCR. In addition, we performed genomic analysis to determine the genetic relationship of all PDCoV strains from the four countries. We found that PDCoV mainly caused histological lesions in the small intestines of naturally infected piglets. Sequence analysis demonstrated that the PDCoV strains of different countries are closely related and shared high nucleotide sequence similarity; however, deletion patterns in the spike and 3’ untranslated regions are different among the strains from mainland China, Hong Kong, the USA, and South Korea. Our study highlights the fact that continual surveillance is needed to trace the evolution of this virus.


Navigating “Down Time” During COVID-19


US Army joins hunt for SARS drug


title: Corporate report obfuscation: artefact or phenomenon?

text: Abstract Obfuscation is a type of writing that obscures the intended message. The presence of obfuscation is investigated in annual and interim reports and prospectuses, and is defined as the simultaneous use of writing with (a) low reading ease and (b) high readability variability. This is a new and more rigorous approach to the detection of obfuscation. This article offers one of three alternative explanations. Either management endorses the use of such a writing technique to permit deliberately a certain level of opacity from period to period so as to lessen investor anxiety about organizational impacts from environmental changes, or it seeks in some way to mislead by misrepresenting or concealing unpleasant facts; finally, obfuscation may occur because different people write different sections of corporate reports, or even different sections of one part of a report. There may of course be a mix of these explanations. The study examined external reporting documents of 60 Hong Kong public companies, and found reading ease to be difficult and variability to be pervasive. The study sought associations between obfuscation and corporate profitability, age, complexity and location of hardest to read passages. Management should note that obfuscation does occur in corporate communications, and that steps should be taken to eliminate or minimize any unintended writing of this nature.


title: Molecularly imprinted polymers for the selective extraction of glycyrrhizic acid from liquorice roots

text: Abstract A new Molecularly Imprinted Solid Phase Extraction (MISPE) protocol was developed for the selective extraction and purification of glycyrrhizic acid (GL) from liquorice roots. Non-covalent MIP were synthesized using methacrylic acid (MAA), 2-(dimethylamino)ethyl methacrilate (DMAEM) or 2-hydroxyethylmetacrylate (HEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. After the evaluation of the selectivity of the GL imprinted polymers, the performance of these materials as Solid Phase Extraction (SPE) sorbents was investigated. MIP having HEMA as functional monomer were found to be able to selectively extract almost 80% of GL content in liquorice roots. The proposed MISPE-HPLC procedure has good precision, thus it can be successfully used for the purification of GL from natural sources.


title: Detection of alpha and betacoronaviruses in multiple Iberian bat species

text: Bat coronaviruses (CoV) are putative precursors of the severe acute respiratory syndrome (SARS) CoV and other CoV that crossed the species barrier from zoonotic reservoirs into the human population. To determine the presence and distribution of CoV in Iberian bats, 576 individuals of 26 different bat species were captured in 13 locations in Spain. We report for the first time the presence of 14 coronaviruses in 9 Iberian bat species. Phylogenetic analysis of a conserved CoV genome region (RdRp gene) shows a wide diversity and distribution of alpha and betacoronavirus in Spain. Interestingly, although some of these viruses are related to other European BatCoV, or to Asian CoV, some of the viruses found in Spain cluster in new groups of α and β CoV.


title: The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds

text: BACKGROUND: Bovine respiratory syncytial virus (BRSV) and bovine corona virus (BCV) affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. METHODS: We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. RESULTS: Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001) bulk tank milk somatic cell count (BMSCC) compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01) of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. CONCLUSIONS: Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great importance and that herds can stay free from these infection transmission although virus is circulating in the area.


title: Housing influences tissue cytokine levels and the fecal bacterial community structure in rats

text: Abstract Immune measures and the fecal bacterial community were examined in female Biobreeding rats housed in wire bottom cages (wire) or in solid bottom cages containing hardwood chips (bedding). Housing did not affect food intake, weight gain, fecal output or fibre content, serum liver enzymes, or spleen and mesenteric lymph node immune cell populations. Bedding-housed rat feces were enriched in phylotypes aligning within the phylum Firmicutes (families Lactobacillaceae and Erysipelotrichaceae) and had a 2-fold lower content of phylotypes aligning within the phylum Bacteroidetes. Feces from bedding-housed rats also contained significantly more acetic acid and less propionic, isobutyric, valeric and isovaleric acids than those housed on wire. Bedding-housed rats had significantly higher splenic concentrations of interleukin-4 (P < 0.001). These results demonstrate that bedding can indirectly influence systemic and mucosal immune measures, potentially adding additional complexities and confounding results to nutrition studies investigating the health effects of dietary fibres.


docid: ifutobng

title: Les tests de diagnostic rapide des viroses respiratoires et des gastroentérites virales: intérêts et limites

text: Résumé Les tests de dépistage rapide (TDR) basés sur la technique d’immunochromatographie sont très répandus pour le diagnostic des maladies infectieuses. Dans le cadre des infections respiratoires virales, il s’agit essentiellement de tests pour le diagnostic de la grippe et des infections à virus respiratoire syncytial (VRS). Pour le diagnostic des gastroentérites virales, ce sont des tests de détection des rotavirus, adénovirus, norovirus et astrovirus qui peuvent être utilisés. Les TDR pour les infections à VRS et les gastroentérites sont utilisés essentiellement dans le cadre de la pathologie pédiatrique. Ces tests présentent généralement une spécificité élevée mais une sensibilité modeste par rapport aux techniques moléculaires. Ce sont donc surtout des tests de dépistages et leur négativité ne permet pas d’exclure le diagnostic. Summary Rapid diagnostic tests (RDT), based on immunochromatography, are widely used for the diagnosis of infectious diseases. For viral respiratory infections, RDT target infections by influenza viruses or respiratory syncytial virus (RSV). For diagnosis of gastroenteritis, RDT can be used for the detection of rotavirus, adenovirus, norovirus or astrovirus. RDT for RSV or gastroenteritis are mainly used in a pediatric context. RDT generally present a high specificity, however their sensitivity is only modest by comparison with molecular technics. Consequently, RDT are essentially considered as screening tests, and their negativity does not allow to exclude the diagnostic of respiratory or gastrointestinal viral infection.


title: Characterization of the norovirus 3C-like protease

text: Abstract The recombinant 3C-like protease of Chiba virus, a Norovirus, expressed in Escherichia coli cells was purified and characterized as to effects of pH, temperature, salt contents, and SH reagents on its proteolytic activity. The optimal pH and temperature of the 3C-like protease for the proteolytic activity were 8.6 and 37°C, respectively. Increased concentration (∼100mM) of monovalent cations such as Na+ and K+ was inhibitory to the activity. Hg2+ and Zn2+ remarkably inhibited the protease activity, while Mg2+ and Ca2+ had no virtual effect. Several sulfhydryl reagents such as p-chloromercuribenzoic acid, methyl methanethiosulfonate, N-ethylmaleimide and N-phenylmaleimide also blocked the activity, confirming the previous result that cysteine residue(s) were responsible for the proteolysis.


title: Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV Oligonucleotides

text: [Image: see text] The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. Here, a paper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregation is reported as an alternative to traditional colorimetric approaches. PNA probes are an attractive alternative to DNA and RNA probes because they are chemically and biologically stable, easily synthesized, and hybridize efficiently with the complementary DNA strands. The acpcPNA probe contains a single positive charge from the lysine at C-terminus and causes aggregation of citrate anion-stabilized silver nanoparticles (AgNPs) in the absence of complementary DNA. In the presence of target DNA, formation of the anionic DNA-acpcPNA duplex results in dispersion of the AgNPs as a result of electrostatic repulsion, giving rise to a detectable color change. Factors affecting the sensitivity and selectivity of this assay were investigated, including ionic strength, AgNP concentration, PNA concentration, and DNA strand mismatches. The method was used for screening of synthetic Middle East respiratory syndrome coronavirus (MERS-CoV), Mycobacterium tuberculosis (MTB), and human papillomavirus (HPV) DNA based on a colorimetric paper-based analytical device developed using the aforementioned principle. The oligonucleotide targets were detected by measuring the color change of AgNPs, giving detection limits of 1.53 (MERS-CoV), 1.27 (MTB), and 1.03 nM (HPV). The acpcPNA probe exhibited high selectivity for the complementary oligonucleotides over single-base-mismatch, two-base-mismatch, and noncomplementary DNA targets. The proposed paper-based colorimetric DNA sensor has potential to be an alternative approach for simple, rapid, sensitive, and selective DNA detection.


Governmental responses to COVID-19 and its economic impact: a brief Euro-Asian comparison