title: Bioenergy in China: Evaluation of domestic biomass resources and the associated greenhouse gas mitigation potentials

text: Abstract As bioenergy produces neutral or even negative carbon emissions, the assessment of biomass resources and associated emissions mitigation is a key step toward a low carbon future. However, relevant comprehensive estimates lack in China. Here, we measure the energy potential of China's domestic biomass resources (including crop residues, forest residues, animal manure, municipal solid waste and sewage sludge) from 2000 to 2016 and draw the spatial-temporal variation trajectories at provincial resolution. Scenario analysis and life cycle assessment are also applied to discuss the greenhouse gas mitigation potentials. Results show that the collectable potential of domestic biomass resources increased from 18.31 EJ in 2000 to 22.67 EJ in 2016 with overall uncertainties fluctuating between (−26.6%, 39.7%) and (−27.6%, 39.5%). Taking energy crops into account, the total potential in 2016 (32.69 EJ) was equivalent to 27.6% of China's energy consumption. If this potential can be realized in a planned way to displace fossil fuels during the period 2020–2050, cumulative greenhouse gas emissions mitigation would be in the range of 1652.73–5859.56 Mt CO2-equivalent, in which the negative greenhouse gas emissions due to the introduction of bioenergy with carbon capture and storage would account for 923.78–1344.13 Mt CO2-equivalent. Contrary to increasing bioenergy potentials in most provinces, there are declining trends in Tibet, Beijing, Shanghai and Zhejiang. In addition, Yunnan, Sichuan and Inner Mongolia would have the highest associated greenhouse gas mitigation potentials. This study can provide valuable guidance on the exploitation of China's untapped biomass resources for the mitigation of global climate change.


title: Displacement ventilation with radiant panel for hospital wards: Measurement and prediction of the temperature and contaminant concentration profiles

text: Abstract Displacement ventilation (DV) is known to provide high air quality and ventilation efficiency. With DV, a contaminant interface is formed in a room, and the air quality in the occupant zone below the contaminant interface height can be kept clean. This paper proposes a DV system to solve the serious odor problem in hospital wards. A vertical radiant panel that can be controlled individually is suggested as a complementary heating system. In order to study the influence of the panel on the displacement ventilated room, the temperature and contaminant concentration profiles were examined under different panel conditions: the distance between the panel and bed, height of the panel, surface temperature of the panel, and supply airflow rate. When the radiant panel was heated, it created a stronger plume than the human body, which produced contaminated air. When there was space between the radiant panel and bed, the contaminated air was locked up before reaching the ceiling. Personal exposure of a standing person was also investigated because the contaminated interface is generally lower than the breathing zone of a standing person with DV. The zonal model and improved zonal model were validated by a comparison of their results with the measured contaminant concentrations.


title: Characterization of the Mechanical Unfolding of RNA Pseudoknots

text: Abstract The pseudoknot is an important RNA structural element that provides an excellent model system for studying the contributions of tertiary interactions to RNA stability and to folding kinetics. RNA pseudoknots are also of interest because of their key role in the control of ribosomal frameshifting by viral RNAs. Their mechanical properties are directly relevant to their unfolding by ribosomes during translation. We have used optical tweezers to study the kinetics and thermodynamics of mechanical unfolding and refolding of single RNA molecules. Here we describe the unfolding of the frameshifting pseudoknot from infectious bronchitis virus (IBV), three constituent hairpins, and three mutants of the IBV pseudoknot. All four pseudoknots cause −1 programmed ribosomal frameshifting. We have measured the free energies and rates of mechanical unfolding and refolding of the four frameshifting pseudoknots. Our results show that the IBV pseudoknot requires a higher force than its corresponding hairpins to unfold. Furthermore, its rate of unfolding changes little with increasing force, in contrast with the rate of hairpin unfolding. The presence of Mg2+ significantly increases the kinetic barriers to unfolding the IBV pseudoknot, but has only a minor effect on the hairpin unfolding. The greater mechanical stability of pseudoknots compared to hairpins, and their kinetic insensitivity to force supports the hypothesis that −1 frameshifting depends on the difficulty of unfolding the mRNA.


Viral Infections, an Overview with a Focus on Prevention of Transmission


Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A Perpetual Challenge


title: Association of low serum TGF-β level in hantavirus infected patients with severe disease

text: BACKGROUND: Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection. RESULTS: We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction. CONCLUSION: High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.


title: CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation?

text: CD9 belongs to the tetraspanin superfamily. Depending on the cell type and associated molecules, CD9 has a wide variety of biological activities such as cell adhesion, motility, metastasis, growth, signal transduction, differentiation, and sperm–egg fusion. This review focuses on CD9 expression by hematopoietic cells and its role in modulating cellular processes involved in the regulation of inflammation. CD9 is functionally very important in many diseases and is involved either in the regulation or in the mediation of the disease. The role of CD9 in various diseases, such as viral and bacterial infections, cancer and chronic lung allograft dysfunction, is discussed. This review focuses also on its interest as a biomarker in diseases. Indeed CD9 is primarily known as a specific exosome marker however, its expression is now recognized as an anti-inflammatory marker of monocytes and macrophages. It was also described as a marker of murine IL-10-competent Breg cells and IL-10-secreting CD9(+) B cells were associated with better allograft outcome in lung transplant patients, and identified as a new predictive biomarker of long-term survival. In the field of cancer, CD9 was both identified as a favorable prognostic marker or as a predictor of metastatic potential depending on cancer types. Finally, this review discusses strategies to target CD9 as a therapeutic tool. Because CD9 can have opposite effects depending on the situation, the environment and the pathology, modulating CD9 expression or blocking its effects seem to be a new promising therapeutic strategy.


title: The A–Z of Zika drug discovery

text: Despite the recent outbreak of Zika virus (ZIKV), there are still no approved treatments, and early-stage compounds are probably many years away from approval. A comprehensive A–Z review of the recent advances in ZIKV drug discovery efforts is presented, highlighting drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets are also described and discussed, as well as targets belonging to the host cell, as new opportunities for ZIKV drug discovery. All this knowledge is not only crucial to advancing the fight against the Zika virus and other flaviviruses but also helps us prepare for the next emerging virus outbreak to which we will have to respond.


title: Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset

text: The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.


title: BCG vaccine-induced protection from COVID-19 infection, wishful thinking or a game changer?

text: A series of epidemiological explorations have suggested a negative association between national BCG vaccination policy and the prevalence and mortality of COVID-19. Nevertheless, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for the potential biological basis of BCG cross-protection from severe COVID-19 and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density and age structure). Results fail to confirm the null hypothesis of no-association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.


title: Assessing hospital emergency management plans: A guide for infection preventionists

text: BACKGROUND: Hospital emergency management plans are essential and must include input from an infection preventionist (IP). Multiple hospital planning documents exist, but many do not address infection prevention issues, combine them with noninfection prevention issues, or are disease/event specific. An all-encompassing emergency management planning guide for IPs is needed. METHODS: A literature review and Internet search were conducted in December 2008. Data from relevant sources were extracted. A spreadsheet was created that delineated hospital emergency management plan components of interest to IPs. RESULTS: Of the sources screened, 49 were deemed relevant. Eleven domains were identified: (1) having a plan; (2) assessing hospital readiness; (3) having infection prevention policies and procedures; (4) having occupational health policies and procedures; (5) conducting surveillance and triage; (6) reporting incidents, having a communication plan, and managing information; (7) having laboratory support; (8) addressing surge capacity issues; (9) having anti-infective therapy and/or vaccines; (10) providing infection prevention education; and (11) managing physical plant issues. CONCLUSION: Infection preventionists should use this article as an assessment tool for evaluating their hospital emergency management plan and for developing policies and procedures that will decrease the risk of infection transmission during a mass casualty event.


title: Recommendations of the Spanish Society of Otolaryngology and Head and Neck Surgery for performing tracheotomies in patients infected by the coronavirus, Covid-19

text: Abstract The recent COVID-19 (coronavirus) pandemic is causing an increase in the number of patients who, due to their pulmonary ventilatory status, may require orotracheal intubation. COVID-19 infection has demonstrated a high rate of transmissibility, especially via the respiratory tract and by droplet spread. The Spanish Society of Otolaryngology and Head and Neck Surgery, based on the article by Wei et al. of 2003 regarding tracheotomies performed due to severe acute respiratory syndrome (SARS), has made a series of recommendations for the safe performance of tracheotomies.


title: An epidemiological investigation of porcine circovirus 3 infection in dogs in the Guangxi Province from 2015 to 2017, China

text: Abstract Porcine circovirus type 3 (PCV3) is an emerging circovirus species associated with several diseases. The study aimed to investigate the frequency of porcine circovirus 3 (PCV3) and its coinfection with canine parvovirus type 2 (CPV-2) in dogs in the Guangxi province from 2015 to 2017, China, and to examine the genome diversity of PCV3. Using polymerase chain reaction (PCR) amplification and sequencing, 96 of 406 (23.6%)samples were positive for PCV3, 38 out of 406 (9.4%) samples were coinfected with both PCV3 and CPV-2. The CPV-positive rate was significantly higher in the PCV3-positive samples than in the non-PCV3 samples, and the difference was extremely significant (P < 0.01). The complete genome (n=4) and ten capsid genes (n=10) of PCV3 were sequenced. Multiple sequence alignment results showed that these sequences shared 98.5–100% nucleotide similarity with the reference genome sequence and 97.5–100% nucleotide similarity with the reference capsid gene sequence. PCV3 was classified into two different genotypes, according to phylogenetic analysis based on the whole genome. These strains were clustered in PCV3a, showing a close relationship with PCV3-US/SD2016. Surprisingly, we separately analyzed these PCV3 strains from the Guangxi province and found that the dog and pig PCV3 are from different branches. In summary, this was the first seroprevalence and genetic investigation of PCV3 in dogs in the Guangxi province, China, and the first complete genome PCV3 from dogs obtained in the world. The results provide insights into the epidemiology and pathogenesis of this important virus.


title: Identification of porcine alveolar macrophage glycoproteins involved in infection of porcine respiratory and reproductive syndrome virus

text: The aim of this study was to identify the receptor(s) for PRRSV on porcine alveolar macrophages (PAMs) by producing monoclonal antibodies (MAbs) against these cells. Hybridoma supernatants were selected for their ability to block PRRSV infection. Four MAbs, 1-8D2, 9.4C7, 9.9F2, and 3-3H2 inhibited infection and recognised cell surface, PAM-specific antigens as shown by immunofluorescence and immunoperoxidase monolayer assay. These MAbs were then used to identify cellular proteins involved in PRRSV infection by radioimmunoprecipitation assays (RIPAs). MAbs 1-8D2 and 9.9F2 each recognised a 150 kDa-polypeptide doublet, while MAbs 9.4C7 and 3-3H2 both recognised a 220 kDa-polypeptide. Glycosidase treatment demonstrated all these polypeptides to be N-glycosylated. Thus, multiple glycoproteins appear to be involved in infection of PAMs by PRRSV.


title: Antiviral Natural Products and Herbal Medicines

text: ABSTRACT Viral infections play an important role in human diseases, and recent outbreaks in the advent of globalization and ease of travel have underscored their prevention as a critical issue in safeguarding public health. Despite the progress made in immunization and drug development, many viruses lack preventive vaccines and efficient antiviral therapies, which are often beset by the generation of viral escape mutants. Thus, identifying novel antiviral drugs is of critical importance and natural products are an excellent source for such discoveries. In this mini-review, we summarize the antiviral effects reported for several natural products and herbal medicines.


title: Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study

text: BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. AIM: We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. METHODS: Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012–9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. FINDINGS: Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. CONCLUSION: Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.


title: Chikungunya Virus

text: For chikungunya virus (CHIKV), the long-term sequelae from infection are yet ill-defined. The prolonged debilitating arthralgia associated with CHIKV infection has tremendous potential for impacting the global economy and should be considered when evaluating the human burden of disease and the allocation of resources. There is much still unknown about CHIKV and the illnesses that it causes. Developing a better understanding of the pathogenesis of CHIKV infection is a priority and forms the basis for developing effective strategies at infection prevention and disease control.


title: Fidelity Variants and RNA Quasispecies

text: By now, it is well established that the error rate of the RNA-dependent RNA polymerase (RdRp) that replicates RNA virus genomes is a primary driver of the mutation frequencies observed in RNA virus populations—the basis for the RNA quasispecies. Over the last 10 years, a considerable amount of work has uncovered the molecular determinants of replication fidelity in this enzyme. The isolation of high- and low-fidelity variants for several RNA viruses, in an expanding number of viral families, provides evidence that nature has optimized the fidelity to facilitate genetic diversity and adaptation, while maintaining genetic integrity and infectivity. This chapter will provide an overview of what fidelity variants tell us about RNA virus biology and how they may be used in antiviral approaches.


title: Radiotherapy Workflow and Protection Procedures During the Coronavirus Disease 2019 (COVID-19) Outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China

text: Abstract The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis.


title: Microbe Hunting in Laboratory Animal Research

text: Recent advances in nucleic acid diagnostic technologies have revolutionized microbiology by facilitating rapid, sensitive pathogen surveillance and differential diagnosis of infectious diseases. With the expansion and dissemination of genomic sequencing technology scientists are discovering new microbes at an accelerating pace. In this article we review recent progress in the field of pathogen surveillance and discovery with a specific focus on applications in the field of laboratory animal research. We discuss the challenges in proving a causal relationship between the presence of a candidate organism and disease. We also discuss the strengths and limitations of various assay platforms and describe a staged strategy for viral diagnostics. To illustrate the complexity of pursuing pathogen discovery research, we include examples from our own work that are intended to provide insights into the process that led to the selection of particular strategies.


title: An immunochromatography assay for rapid antemortem diagnosis of dogs suspected to have canine distemper

text: Abstract A new assay was developed for rapid and antemortem diagnosis of canine distemper (CD). This immunochromatography (IC)-based assay, which employs two monoclonal anti-CDV antibodies, was compared with nested PCR. When serial dilutions of purified CDV were tested, the CDV detection limits of the nested PCR and IC assays were 2×102 TCID50/ml and 5×102 TCID50/ml, respectively. Nasal irrigation fluid, conjunctival swabs, and blood lymphocytes from 66 dogs suspected to have CD were tested. Preliminary IC experiments revealed that the optimal sample volume and reaction time were 100μl and 5min, respectively. Relative to nested PCR, the sensitivity and specificity of the IC assay was maximal (100% and 100%, respectively) when conjunctival swabs were tested. This is significant because conjunctival swab specimens are easy to obtain in the early phase of CD infection. However, with blood lymphocytes and nasal samples, the IC assay was slightly less sensitive (89.7% and 85.7%, respectively) and specific (94.6% and 100%, respectively) than nested PCR. Since this novel IC assay does not require special instruments, it is a simple enough for dog owners to use. Since early detection of CD would allow appropriate treatment and quarantine to be instituted quickly, such a test would help reduce the morbidity and mortality associated with CD help to prevent its spread to other animals.


title: Radiologic chest CT findings from COVID‐19 in Orleans Parish, Louisiana

text: Orleans Parish in Louisiana is in the midst of an exponentially increasing number of patient admissions with COVID‐19 and respiratory symptoms. Patients have been described having CT findings most consistent with an early‐stage (<7 days from symptoms onset) or an advanced stage (8‐14 days from symptoms onset). We describe and illustrate those early and advanced stage CT findings from patients with documented COVID‐19 who have been admitted to University Medical Center in New Orleans, Louisiana.


title: Porcine transmissible gastroenteritis virus inhibits NF-κB activity via nonstructural protein 3 to evade host immune system

text: BACKGROUND: Transmissible gastroenteritis virus (TGEV), a member of the family Coronaviridae, causes lethal watery diarrhea in piglets. Previous studies have revealed that the coronaviruses develop various strategies to evade the host innate immunity through the inhibition of nuclear factor kappa B (NF-κB) signaling pathway. However, the ability of TGEV to inhibit the host innate immune response by modulating the NF-κB signaling pathway is not clear. METHODS: In this study, a dual luciferase reporter assay was used to confirm the inhibition of NF-κB by TGEV infection and to identify the major viral proteins involved in the inhibition of NF-κB signaling. Real-time quantitative PCR was used to quantify the mRNA expression of inflammatory factors. The deubiquitination of Nsp3 domains and its effect on IκBα and p65 were analyzed by western blotting. The ubiquitination level of IκBα was analyzed by immunoprecipitation. RESULTS: In ST and IPEC-J2 cells, TGEV exhibited a dose-dependent inhibition of NF-κB activity. Individual TGEV protein screening revealed the high potential of non-structural protein 3 (Nsp3) to inhibit NF-κB signaling, and leading to the downregulation of the NF-κB-induced cytokine production. We demonstrated that the inhibitory effect of Nsp3 was mainly mediated through the suppression of IκBα degradation as well as the inhibition of p65 phosphorylation and nuclear translocation. Furthermore, the amino acid residues at positions 590–1,215 in Nsp3 were demonstrated to inhibit the degradation of IκBα by inhibiting the IκBα ubiquitination. CONCLUSION: TGEV infection can inhibit the activation of the NF-κB signaling pathway, which is mainly mediated by Nsp3 through the canonical pathway. The amino acid residues at positions 590–1,215 in Nsp3 compose the critical domain that mediates NF-κB inhibition. We speculate that this inhibitory effect is likely to be related to the structure of PLP2 with deubiquitinating enzyme activity of the amino acid residues at positions 590–1,215 in Nsp3. Our study provides a better understanding of the TGEV-mediated innate immune modulation and lays the basis for studies on the pathogenesis of coronavirus.


title: The COVID 19 novel coronavirus pandemic 2020: seaweeds to the rescue? Why does substantial, supporting research about the antiviral properties of seaweed polysaccharides seem to go unrecognized by the pharmaceutical community in these desperate times?

text: Presently, there is lack of a vaccine that would lead to immunization against the virus COVID-19, but here are some of the characteristics that various seaweeds have and which may provide a glimpse into potential solutions of this global health problem in the near future and possibly forearm us for any future such pandemics. Many species of marine algae contain significant quantities of complex structural sulphated polysaccharides that have been shown to inhibit the replication of enveloped viruses. Other compounds, both of red algae (e.g., the lectin griffithsin and the phycocolloid carrageenan), and other sulphated polysaccharides extracted from green algae (i.e., ulvans) and brown algae (i.e., fucoidans) could be potential antiviral therapeutic agents against SARS-CoV-2.


title: α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment

text: [Image: see text] The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued a structure-based design of peptidomimetic α-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease–inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the α-ketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclohexylmethyl), display low-micromolar EC(50) values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against the Middle East Respiratory Syndrome coronavirus.


title: Investment, Depreciation and Obsolescence of R&D

text: Abstract Time-varying depreciation rates are estimated for research and development of the United States aggregate economy and innovation-intensive industries. Mean annual R&D depreciation rates are 31.5% for software, 41% for pharmaceuticals, 42% for semiconductors, and 30.4% for aggregate economy during 1978-2014. R&D depreciation rates vary across industries. R&D investment demand has separate elasticities in time-varying depreciation, interest rate and price growth, allowing for different rates of technology shifts across industries. Software R&D investment has the same magnitude of elasticities to depreciation, interest rate and price, supporting a user cost to apply. For pharmaceuticals and semiconductors, depreciation leads to more R&D investment that implies the effect of scale. For aggregate economy, depreciation reduces R&D investment more than interest rate, indicating obsolescence. Forecasting of R&D investment is improved at both industry and aggregate level. Forecastable time-varying depreciation, interest rate and price growth predict R&D investment based on the estimated demand function. The in-sample forecast comparison for 2015-2019 confirms the superiority to the alternative methods. Out-of-sample forecasts of R&D investment are carried out through 2025, and R&D capital stocks are constructed across industries and aggregate U.S. economy.


The use of gowns and masks to control respiratory illness in pediatric hospital personnel


title: Synthesis of empty capsid-like particles of Asia I foot-and-mouth disease virus in insect cells and their immunogenicity in guinea pigs

text: Abstract The assembly of foot-and-mouth disease virus (FMDV) requires the cleavage of the P12A polyprotein into individual structural proteins by protease 3C. In this study, we constructed a recombinant baculovirus that simultaneously expressed the genes for the P12A and 3C proteins of Asia I FMDV from individual promoters. The capsid proteins expressed in High Five™ insect cells were processed by viral 3C protease, as shown by Western blotting, and were antigenic, as revealed by their reactivity in an indirect sandwich-ELISA, and by immunofluorescent assay. The empty capsid-like particles were similar to authentic 75S empty capsids from FMDV in terms of their shape, size and sedimentation velocity, as demonstrated by sucrose gradient centrifugation. Both empty capsid-like particles and some small-sized particles (about 10nm in diameter) were also observed using immunoelectron microscopy. Furthermore, the empty capsid-like particles or intermediates induced high levels of FMDV-specific antibodies in guinea pigs following immunization, and neutralizing antibodies were induced in the second week after vaccination. These recombinant, non-infectious, FMDV empty capsids are potentially useful for the development of new diagnostic techniques and vaccines.


title: Design and Development of a Portable Disinfectant Device

text: With over 7 million people infected globally and over 5 lakh deaths reported worldwide by COVID-19 virus, World Health Organization (WHO) has declared it as a pandemic. India is also suffering badly because of the current crisis, with more than 4 lakh people infected and 13000 deaths reported as on 20th June 2020. There is no respite in sight as of now as the numbers continue to increase exponentially with each passing day. The only possible control to the virus is the availability of a vaccine, which will take a few months to be available to masses. Till then, the global economy has to start reopening slowly with several precautionary measures in place as advised by the WHO, such as mandatory wearing of masks in public places, frequent hand washing, practising good personal hygiene, and social distancing. Recently, the government of India (GoI) has also opened its economy with all the precautionary measures in place. Disinfecting of places of work, modes of transport, hospitals, and common areas is emerging as a mammoth challenge. With the objective of arresting the spread of COVID-19 virus and providing an efficient solution to the above problem, a portable disinfectant device is designed. Undertaken as an Industry-academia collaboration, it is a joint initiative between Technopark@iitk (IIT Kanpur Research and Technology Park) and Industry. The novelty of this device lies in its innovative design that combines spraying of sanitising liquid and UV light-based disinfection methodologies. For this, the device uses two separate disinfection systems: (1) the pump-nozzle assembly for spraying the disinfectant, and (2) UV-C radiations to increase the virus kill efficiency.


title: A model for epidemic dynamics in a community with visitor subpopulation

text: Abstract With a five dimensional system of ordinary differential equations based on the SIR and SIS models, we consider the dynamics of epidemics in a community which consists of residents and short-stay visitors. Taking different viewpoints to consider public health policies to control the disease, we derive different basic reproduction numbers and clarify their common/different mathematical natures so as to understand their meanings in the dynamics of the epidemic. From our analyses, the short-stay visitor subpopulation could become significant in determining the fate of diseases in the community. Furthermore, our arguments demonstrate that it is necessary to choose one variant of basic reproduction number in order to formulate appropriate public health policies.


title: Processing of virus-specific glycoproteins of varicella zoster virus

text: Abstract Monoclonal antibodies to varicella zoster virus (VZV) glycoproteins were used to study the processing of three glycoproteins with molecular weights of 83K–94K (gp 2), 64K (gp 3), and 55K (gp 5). Immunoprecipitation experiments performed with VZV-infected cells, pulse labeled with [3H]glucosamine in the presence of tunicamycin, suggest that O-linked oligosaccharide is present on the glycoprotein of gp 2. Use of the enzyme endo-β-N-acetylglucosaminidase H revealed that the fully processed form of gp 3 had high-mannose type and that of gp 5 had only complex type of N-linked oligosaccharides. Experiments with monensin suggest that the precursor form (116K) of gp 3 is cleaved during the processing from Golgi apparatus to cell surface membrane. The extension of O-linked oligosaccharide chain and the complex type of N-linked oligosaccharide chains also occurs during this processing.


Fatal alcohol immersion during the SARS epidemic in Taiwan


title: Xylem's supports community-based responses to Covid-19

text: Xylem has extended its Partner Community Grants Program to support community-level responses to Covid-19.


title: Bioinformatics analysis of SARS coronavirus genome polymorphism

text: BACKGROUND: We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP), insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. RESULTS: The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with "regular" isolates (no insertions / deletions except for 5' and 3' ends), the B-group of isolates with "long insertions", and the C-group of isolates with "many individual" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH). The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates) are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones). Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. CONCLUSIONS: The comparative study of SARS-CoV isolates provides essential information for genome polymorphism, indication of strain differences and variants evolution. It may help with the development of effective treatment.


title: Lectins with Anti-HIV Activity: A Review

text: Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.


title: Aromatic N-oxide bridged copper(II) coordination polymers: Synthesis, characterization and magnetic properties

text: Abstract The complexes [Cu2(o-NO2–C6H4COO)4(PNO)2] (1), [Cu2(C6H5COO)4(2,2′-BPNO)] n (2), [Cu2(C6H5COO)4(4,4′-BPNO)] n (3), [Cu(p-OH–C6H4COO)2(4,4′-BPNO)2·H2O] n (4), (where PNO=pyridine N-oxide, 2,2′-BPNO=2,2′-bipyridyl-N,N′-dioxide, 4,4′-BPNO=4,4′-bipyridyl-N,N′-dioxide) are prepared and characterized and their magnetic properties are studied as a function of temperature. Complex 1 is a discrete dinuclear complex while complexes 2–4 are polymeric of which 2 and 3 have paddle wheel repeating units. Magnetic susceptibility measurements from polycrystalline samples of 1–4 revealed strong antiferromagnetic interactions within the {Cu2}4+ paddle wheel units and no discernible interactions between the units. The complex 5, [Cu(NicoNO)2·2H2O] n ·4nH2O, in which the bridging ligand to the adjacent copper(II) ions is nicotinate N-oxide (NicoNO) the transmitted interaction is very weakly antiferromagnetic.


title: Emerging respiratory agents: New viruses for old diseases?

text: Abstract The recent advances in molecular technology have enabled the detection of several new viral agents in specimens collected from the human respiratory tract. Human metapneumovirus was first described in 2001, and is a significant respiratory pathogen, particularly of children. Following the identification of severe acute respiratory syndrome (SARS) associated coronavirus, two other newly detected coronaviruses, NL63 and HKU1, have been linked to respiratory disease in humans. However, identifying a new virus as the causative agent of a specific disease is difficult, and ideally would involve satisfying Koch's postulates. The recently described human bocavirus and polyomaviruses KI and WU have been detected in samples collected from humans with acute respiratory infection, but as yet, have not been conclusively proven to be agents of human disease. We review the new viral agents that have been detected in respiratory samples since 2001, and examine their contribution as agents of human disease.


title: Why the lower reported prevalence of asthma in patients diagnosed with COVID-19 validates repurposing EDTA solutions to prevent and manage treat COVID-19 disease

text: There currently is no specific antiviral drug or a vaccine for SARS-CoV-2/COVID-19 infections; now exceeding 3,500,000 infections worldwide. In the absence of animal models to test drugs, we need to find molecular explanations for any unforeseen peculiarities in clinical data, especially the recent reports describing an unexpected asthma paradox. Asthma is considered a high medical risk factor for susceptibility to SARS-CoV-2/COVID-19 infection, yet asthma is not on the list of top 10 chronic health problems suffered by people who died from SARS-CoV-2/COVID-19. Resolving this paradox requires looking beyond the binary model of a viral receptor-binding domain (RBD) attaching to the ACE-2 receptor. A pBlast analysis revealed that the SARS-CoV-2 surface spike protein contains two calcium-dependent fusion domains that were recently discovered SARS-CoV-1. These viral calcium-dependent binding domains can facilitate membrane fusion only after cleavage by the host surface protease TMPRSS2. Importantly, TMPRSS2 also requires calcium for its SRCR (scavenger receptor cysteine-rich) domain and its LDLRA (LDL receptor class A) domain. Thus, the presence of EDTA excipients in nebulized β(2)-agonist medicines can disrupt SARS-CoV-2/COVID-19 infection and can explain the asthma paradox. This model validates repurposing EDTA in nebulizer solutions from a passive excipient to an active drug for treating COVID-19 infections. Repurposed EDTA delivery to respiratory tissues at an initial target dose of 2.4 mg per aerosol treatment is readily achievable with standard nebulizer and mechanical ventilator equipment. EDTA warrants further investigation as a potential treatment for SARS-CoV-2 /COVID-19 in consideration of the new calcium requirements for virus infection and the regular presence of EDTA excipients in common asthma medications such as Metaproterenol. Finally, the natural history of Coronavirus diseases and further analysis of the fusion loop homologies between the Betacorona SARS-CoV-2 virus and the less pathogenic Alphacorona HC0V-229E virus suggest how to engineer a hybrid virus suitable for an attenuated alpha-beta SARS-CoV-2/COVID-19 vaccine. Thus, replacing SARS-CoV-2 fusion loops (amino acids 816-855) with the less pathogenic HCoV-229E fusion loop (amino acids 923-982) may provide antigenicity of COVID-19, but limit the pathogenicity to the level of HCoV-229E.


title: Live bacterial vaccines – a review and identification of potential hazards

text: The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.


title: The biological characteristics of SARS-CoV-2 Spike protein Pro330-Leu650

text: SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7,426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.


title: Preparations and limitations for prevention of severe acute respiratory syndrome in a tertiary care centre of India

text: Summary This short-term observational study of infection control practice was performed in the medical emergency outpatient department (EMOPD) of a tertiary-care hospital in India when threatened by an outbreak of severe acute respiratory syndrome (SARS). An investigator attended the lobby daily to screen patients with symptoms for SARS. Patient/attendant load, patient flow, medical staff working practices and position in the EMOPD were observed. Infection control measures such as fumigation and cleaning were noted, as was the EMOPD laboratory function, use of personnel protection and display of information on infectious diseases. A total of 162 (7.4%) of the 2165 patients surveyed had respiratory symptoms but no cases of SARS were found. The flow of patients and their attendants was not systematic. No laboratory tests for SARS were available, and no educational material on SARS was displayed. The EMOPDs in key hospitals need be able to screen for infectious diseases, especially in view of the threats from SARS and Avian influenza.


docid: iugtmdtk

title: Comparative effects of in ovo versus subcutaneous administration of the Marek's disease vaccine and pre-placement holding time on the processing yield of Ross 708 broilers,,

text: Effects of the in ovo (i.o.) or subcutaneous (s.c.) method of administration (moa) of the Marek's disease (MD) vaccine and 4 or 18 h pre-placement holding time (pht) on the processing yield of male broilers through 49 d of age (doa) were investigated. Ross 708 broiler hatching eggs (3,900) were either i.o.-vaccinated at 18 d of incubation or chicks from eggs that were not i.o.-vaccinated were s.c.-vaccinated at hatch. The i.o. injections (50 μL) were delivered by a commercial multi-egg injector and s.c. injections (200 μL) were delivered by an automatic pneumatic s.c. injector. The pht was imposed on chicks after vaccination. Sixteen birds were initially assigned to each of 15 replicate floor pens belonging to each of the moa and pht combination groups and were grown out through 48 doa. At 48 doa, 6 birds were randomly selected from each replicate pen and were weighed and fasted for 16 h before being processed. At 49 doa, whole carcass, fat pad, breast muscle, and tenders muscles weights were recorded. Whole carcass weight as a percentage of live BW, and fat pad, breast muscle, and tenders muscles weights as percentages of both live and whole carcass weights were calculated. Upon subjection of the data to a 2 × 2 factorial analysis, only a main effect due to moa was observed for tenders muscles weight as a percentage of live and whole carcass weights. Tenders muscles weight as a percentage of both live (P ≤ 0.010) and whole carcass (P ≤ 0.004) weight was higher in birds hatched from eggs that received i.o. rather than s.c. vaccinations. In conclusion, in comparison to s.c. vaccination, i.o. vaccination increased relative tenders weight yield, whether or not broilers were held for 4 or 18 h prior to placement. Therefore, with regard to broiler processing yield, i.o. and s.c. vaccinations were safe for the administration of the MD vaccine, with i.o. vaccination displaying a slight potential advantage.


title: Aircraft engine exhaust emissions and other airport-related contributions to ambient air pollution: A review

text: Abstract Civil aviation is fast-growing (about +5% every year), mainly driven by the developing economies and globalisation. Its impact on the environment is heavily debated, particularly in relation to climate forcing attributed to emissions at cruising altitudes and the noise and the deterioration of air quality at ground-level due to airport operations. This latter environmental issue is of particular interest to the scientific community and policymakers, especially in relation to the breach of limit and target values for many air pollutants, mainly nitrogen oxides and particulate matter, near the busiest airports and the resulting consequences for public health. Despite the increased attention given to aircraft emissions at ground-level and air pollution in the vicinity of airports, many research gaps remain. Sources relevant to air quality include not only engine exhaust and non-exhaust emissions from aircraft, but also emissions from the units providing power to the aircraft on the ground, the traffic due to the airport ground service, maintenance work, heating facilities, fugitive vapours from refuelling operations, kitchens and restaurants for passengers and operators, intermodal transportation systems, and road traffic for transporting people and goods in and out to the airport. Many of these sources have received inadequate attention, despite their high potential for impact on air quality. This review aims to summarise the state-of-the-art research on aircraft and airport emissions and attempts to synthesise the results of studies that have addressed this issue. It also aims to describe the key characteristics of pollution, the impacts upon global and local air quality and to address the future potential of research by highlighting research needs.


title: Genetic variation of nucleocapsid genes of porcine epidemic diarrhea virus field strains in China

text: Porcine epidemic diarrhea virus (PEDV) poses a great threat to the Chinese swine industry. During 2006–2011, 74.0 % (94/127) of samples from 32 swine-raising farms in 15 provinces were positive for PEDV by reverse transcription nested polymerase chain reaction (RT-nested PCR). The sequences of nucleocapsid (N) genes of 32 representative field strains were determined, and the open reading frames (ORFs) of these N genes were 1326 nucleotides long. The N gene sequences were found to be more than 95 % identical to each other. The number of potential phosphorylation sites in the N protein varied from 5 to 12. A phylogenetic tree based on the N genes showed that the 32 Chinese field strains formed three groups.


Physiology in Perspective: In a World of Social Distancing


title: Mechanism of Membrane Fusion by Viral Envelope Proteins

text: Publisher Summary Enveloped viruses enter cells by fusing their lipid bilayer membrane with a cellular membrane. Most viral fusion proteins require priming by proteolytic processing, either of the fusion protein itself or of an accompanying protein. The priming step, which often occurs during transport of the fusion protein to the cell surface but may also occur extracellularly, then prepares the fusion protein for triggering by events that accompany attachment and uptake. Two classes of viral fusion proteins have been identified so far by structural studies. The fusion of two bilayers that these proteins catalyze is likely to proceed by the same pathway in both cases. That is, these proteins are like enzymes that have different structures but that still catalyze the same chemical reaction. It is found that bilayer fusion reaction is common to all the enveloped viral entry pathways. It is believed to pass through an intermediate known as a “hemifusion stalk.”


title: Scarcity in the Covid‐19 Pandemic

text: As we write, U.S. cities and states with extensive community transmission of Covid‐19 are in harm's way—not only because of the disease itself but also because of prior and current failures to act. During the 2009 influenza pandemic, public health agencies and hospitals developed but never adequately implemented preparedness plans. Focused on efficiency in a competitive market, health systems had few incentives to maintain stockpiles of essential medical equipment. Just‐in‐time economic models resulted in storage of only those supplies needed then. At the same time, global purchasing in search of lower prices reduced the number of U.S. suppliers, with hospitals dependent on foreign companies. There is still a possibility that the pandemic will be manageably bad rather than unmanageably catastrophic in this country. Immediate, powerful, and sustained federal action could make the difference.


title: PLEOMORPHIC VIRUS-LIKE PARTICLES IN HUMAN FÆCES

text: Abstract Pleomorphic fringed particles bearing some resemblance to orthomyxoviruses and coronaviruses were seen in 90% of stools from south Indian children and adults but not in stools from neonates. This finding may be related to the abnormalities of intestinal structure and function common in this region of India.


title: Identification and characterization of a long non-coding RNA up-regulated during HIV-1 infection

text: Abstract Long non-coding RNAs (lncRNAs) are rapidly emerging as important regulators of a diverse array of cellular functions. Here, we describe a meta-analysis of two independent RNA-seq studies to identify lncRNAs that are differentially expressed upon HIV-1 infection. Only three lncRNA genes exhibited altered expression of ≥ 2-fold in HIV-1-infected cells. Of these, the uncharacterized lncRNA LINC00173 was chosen for further study. Both transcript variants of LINC00173 (lnc173 TSV1 and 2) could be detected by qPCR, localized predominantly to the nucleus and were reproducibly up-regulated during infection. Knock-out of the LINC00173 locus did not have detectable effects on HIV-1 replication. Interestingly, however, stimulation of Jurkat T cells with PMA/ionomycin resulted in a decrease of lnc173 expression, and Jurkat cells deficient for lnc173 on average expressed higher levels of specific cytokines than control cells. These data suggest that lnc173 may have a role in the regulation of cytokines in T cells.


title: Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma

text: BACKGROUND: Severe acute respiratory syndrome (SARS) is a new infectious disease caused by the SARS virus. Current first‐line treatments are experimental, and their effectiveness remains open to question. For more effective treatment and prevention of SARS, human SARS hyperimmune globulins for intravenous (IV) injection were purified in this study. STUDY DESIGN AND METHODS: A combination of cold ethanol precipitation and ion‐exchange chromatography was used to process pooled SARS convalescent plasma samples. Virus inactivation and removal approaches were taken to ensure safety. RESULTS: The purified hyperimmune globulins were formulated as a 5 percent solution, with an antibody titer specifically against the SARS virus of 1:83, 1:1600, and 1:200, as determined by enzyme‐linked immunosorbent assay, immunofluorescence assay, and neutralizing antibody test, respectively. The purity of the SARS hyperimmune globulins was 99.0 percent, and the monomer and dimer content was 100 percent. Other variables analyzed met the Chinese Requirements of Biologics for IV immune globulin. The SARS hyperimmune globulins prepared were subsequently approved for clinical evaluation by the Chinese National Institute for the Control of Pharmaceutical & Biological Products. CONCLUSION: IV‐injectable, purified, and concentrated human SARS hyperimmune globulins were prepared from pooled convalescent plasma samples, which are ready to be further evaluated.


title: What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review

text: Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.


title: Viral detection using a multiplex polymerase chain reaction–based assay in outpatients with upper respiratory infection

text: Abstract We evaluated a commercial multiplex polymerase chain reaction (PCR) assay in a cross-sectional study among 81 adult and pediatric outpatients—40 cases with upper respiratory infection symptoms and 41 asymptomatic controls—from February to April 2008. Two specimens (throat swab and nasal swab) from each participant were tested using the EraGen MultiCode-PLx Respiratory Virus Panel that detects 17 viral targets. Throat swabs were also tested for Group A Streptococcus (GAS) by PCR. Respiratory viruses were detected in 22/40 (55%) cases and in 3/41 (7%) controls (P < 0.001). GAS was detected in 10 (25%) cases; GAS and respiratory virus co-infection was found in 4 (10%). Agreement between nasal and throat swabs for viral detection was 69% in cases and 95% in controls. Of 22 cases with a detectable virus, 12 (54%) were picked up by only 1 (throat or nasal) specimen, and the detection rate was increased by combining results of nasal and throat swab testing.


title: Recurrent Positive Reverse Transcriptase–Polymerase Chain Reaction Results for Coronavirus Disease 2019 in Patients Discharged From a Hospital in China

text: This case series examines patients with coronavirus disease 2019 (COVID-19) who were discharged from the hospital and had recurrent positive reverse transcriptase–polymerase chain reaction (RT-PCR) results.


title: Complex formation between influenza virus polymerase proteins expressed in Xenopus oocytes

text: Abstract All three influenza virus polymerase (P) proteins were expressed in Xenopus oocytes from microinjected in vitro transcribed mRNA analogs, with yields of up to 100 ng per oocyte. To examine the functional state of the Xenopus-expressed P proteins, the polypeptides were tested for their ability to form stable complexes with each other. As seen in virus-infected cells, all three P proteins associated into an immunoprecipitable complex, suggesting that the system has considerable promise for the reconstruction of an active influenza RNA polymerase. Examination of the ability of paired combinations of the P proteins to associate indicated that PB1 contained independent binding sites for PB2 and PA, and so probably formed the backbone of the complex. Sedimentation analysis of free and complexed P proteins indicated that PB1 and PB2 did not exist as free monomers, and that similarly, complexes of all three P proteins did not simply consist of one copy of each protein. The heterodisperse sedimentation rate seen for complexes of all three P proteins did not appear to result from their binding to RNA, suggesting the incorporation of additional polypeptides polymerase complex.


title: Comparative evaluation of the seegene seeplex RV15 and real‐time PCR for respiratory virus detection

text: Respiratory virus infections contribute substantially both to hospitalizations of young children, and to morbidity in immunocompromised patients such as those with hematological malignancies. Their rapid and accurate diagnosis is essential to patient management. To evaluate the prospective utility of Seeplex® DPO technology in respiratory virus diagnosis, a panel of 99 respiratory samples positive by real‐time RT‐PCR for one or more viruses was assayed by the Seegene Seeplex® RV12 system. As well as being able to detect all 10 viruses in the real‐time RT‐PCR system with the exception of enteroviruses, RV12 can also distinguish between the two subgroups of RSV and detect two subgroups of coronaviruses. Seven of the nine viruses in common with the RT‐PCR were detected reliably by RV12. Eleven samples RT‐PCR‐positive for Metapneumovirus and five samples positive for influenza B were not detected by RV12. Seegene developed a second‐generation system, RV15, which not only allowed detection of three additional viruses, but also addressed the potential problems with RV12 specificity. To address these concerns, 84 respiratory samples positive for a range of viruses by real‐time PCR were assayed with RV15. The results of this evaluation improved significantly upon those seen with RV12. The high throughput capabilities and potential lower technical requirements afforded by the Seeplex® system may offer an alternative to real‐time RT‐PCR systems. J. Med. Virol. 83:1469–1475, 2011. © 2011 Wiley‐Liss, Inc.


title: The seven sins of hunting tourism

text: In a review of situational pressures on tourists, we identify seven sins or risk zones that induce moral disengagement and allow for behaviour that would be considered unethical by the same people when not on holiday. The context of hunting tourism reveals the following sins act cumulatively on the hunting tourist: “The Pay Effect”, “The Tourist Bubble”, “Last Chance Tourism”, “The Bucket List”, “When in Rome”, “The False Display”, and “The Saviour”. Identifying these sins and the way hunting tourists draw from them to neutralize eco-guilt are argued to be a first step on the call to set standards and practices within consumptive wildlife tourism consistent with the Precautionary Principle in tourism planning.


title: Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study

text: BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.


The Economics of Infectious Disease, Trade and Pandemic Risk


title: Description of COVID‐19 cases along with the measures taken on prevention and control in Zhejiang, China

text: Under the outbreak of COVID‐19, it was urgent to analyze the cases from clinical features and epidemiological factors, as well as understand the effectiveness of measures taken on disease prevent and control. A retrospective study was applied for descriptive analysis of clinical features and epidemiological factors of confirmed cases in four cities of Zhejiang. The Onset‐admission interval was calculated and plotted as well. The provincial measures regarding the response of COVID‐19 were summed up and sorted out. The distribution and sex and age were under normality distribution, and the age of 20 to 80 were all in risk of developing the disease. Clinical features of fever and cough were found mostly happen on patients. More than half of the patients had image changed on chest from reported data. The factor of closely contacted with confirmed cases was the most cause to the disease. The median onset‐admission interval was 6 days in Zhejiang province. As of the efficient health system, COVID‐19 had been successfully prevented and controlled in Zhejiang. Males and females were all vulnerable to COVID‐19. Preventing contact with confirmed cases could largely avoid the disease to happen. The government should take emergent and effective measures to prevent and treatment of the pandemic disease.


title: Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China

text: An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18–29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.


title: Contact chains of cattle farms in Great Britain

text: Network analyses can assist in predicting the course of epidemics. Time-directed paths or ‘contact chains' provide a measure of host-connectedness across specified timeframes, and so represent potential pathways for spread of infections with different epidemiological characteristics. We analysed networks and contact chains of cattle farms in Great Britain using Cattle Tracing System data from 2001 to 2015. We focused on the potential for between-farm transmission of bovine tuberculosis, a chronic infection with potential for hidden spread through the network. Networks were characterized by scale-free type properties, where individual farms were found to be influential ‘hubs' in the network. We found a markedly bimodal distribution of farms with either small or very large ingoing and outgoing contact chains (ICCs and OCCs). As a result of their cattle purchases within 12-month periods, 47% of British farms were connected by ICCs to more than 1000 other farms and 16% were connected to more than 10 000 other farms. As a result of their cattle sales within 12-month periods, 66% of farms had OCCs that reached more than 1000 other farms and 15% reached more than 10 000 other farms. Over 19 000 farms had both ICCs and OCCs reaching more than 10 000 farms for two or more years. While farms with more contacts in their ICCs or OCCs might play an important role in disease spread, farms with extensive ICCs and OCCs might be particularly important by being at higher risk of both acquiring and disseminating infections.


title: OUR COMMON ENEMY: COMBATTING THE WORLD'S DEADLIEST VIRUSES TO ENSURE EQUITY HEALTH CARE IN DEVELOPING NATIONS

text: In a previous issue of Zygon (Carvalho 2007), I explored the role of scientists—especially those engaging the science‐religion dialogue—within the arena of global equity health, world poverty, and human rights. I contended that experimental biologists, who might have reduced agency because of their professional workload or lack of individual resources, can still unite into collective forces with other scientists as well as human rights organizations, medical doctors, and political and civic leaders to foster progressive change in our world. In this article, I present some recent findings from research on three emerging viruses—HIV, dengue, and rotavirus—to explore the factors that lead to the geographical expansion of these viruses and the increase in frequency of the infectious diseases they cause. I show how these viruses are generating problems for geopolitical stability, human rights, and equity health care for developing nations that are already experiencing a growing poverty crisis. I suggest some avenues of future research for the scientific community for the movement toward resolution of these problems and indicate where the science‐religion field can be of additional aid.


title: Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency

text: Abstract Interferon lambda 4 (IFNλ4) has been recently known and studied for its role in hepatitis C virus (HCV) infection, but its clinical potential is significantly hampered due to its poor expression in vitro. Our study reports the successful production of IFNλ4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFNλ4, guided by structural analysis, and produced IFNλ4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFNλ4, the model structure of the IFNλ4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFNλ4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFNλ4 (eIFNλ4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFNλ4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFNλ4.


docid: pntezzct

title: Plasmon-Enhanced Fluorescence Biosensors: a Review

text: Surfaces of metallic films and metallic nanoparticles can strongly confine electromagnetic field through its coupling to propagating or localized surface plasmons. This interaction is associated with large enhancement of the field intensity and local optical density of states which provides means to increase excitation rate, raise quantum yield, and control far field angular distribution of fluorescence light emitted by organic dyes and quantum dots. Such emitters are commonly used as labels in assays for detection of chemical and biological species. Their interaction with surface plasmons allows amplifying fluorescence signal (brightness) that accompanies molecular binding events by several orders of magnitude. In conjunction with interfacial architectures for the specific capture of target analyte on a metallic surface, plasmon-enhanced fluorescence (PEF) that is also referred to as metal-enhanced fluorescence (MEF) represents an attractive method for shortening detection times and increasing sensitivity of various fluorescence-based analytical technologies. This review provides an introduction to fundamentals of PEF, illustrates current developments in design of metallic nanostructures for efficient fluorescence signal amplification that utilizes propagating and localized surface plasmons, and summarizes current implementations to biosensors for detection of trace amounts of biomarkers, toxins, and pathogens that are relevant to medical diagnostics and food control.


docid: gezlsgyh

title: Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms

text: Abstract The biliary glycoprotein (BGP)-encoding gene is a member of the human carcinoembryonic antigen (CEA) gene family. We have now cloned several mouse Bgp cDNAs from an outbred CDR-1 mouse colon cDNA library, as well as by reverse transcription-PCR amplification of colon RNA. The distinguishing features of the deduced Bgp protein isoforms are found in the two divergent N-terminal domains, the highly conserved internal C2-set immunoglobulin domains, and an intracytoplasmic domain of either 10 or 73 amino acids (aa). The cDNA structures suggest that these mRNAs are produced through alternative splicing of a Bgp gene and the usage of multiple transcriptional terminators. The Bgp deduced aa sequences are highly homologous to several well characterized rat hepatocyte proteins such as the cell CAM105/ecto-ATPase/ppl20/HA4 proteins. Oligodeoxyribonucleotide probes representing the various cDNA isoform domains revealed predominant transcripts of 1.8, 3.1 and 4.0 kb on Northern analyses of mouse colon RNA; some of these bands are actually composed of several co-migrating transcripts. The transcripts encoding the long intracytoplasmic-tailed Bgp proteins are expressed at one-tenth the relative abundance of the shorter-tailed species. We have previously demonstrated that several mouse Bgp cDNAs, when transfected into eukaryotic cells, express BGP proteins at the cell surface and function in vitro as cell adhesion molecules, much like their human and rat counterparts. The expression of the many Bgp isoforms at the surface of epithelial cells, such as colon, suggests that these proteins play a determinant role, through self- or heterologous contact, in renewal and/or differentiation of their epithelia.


title: Severe Acute Respiratory Syndrome Coronavirus Infection in Vaccinated Ferrets

text: Background. Development of vaccines to prevent severe acute respiratory syndrome (SARS) is limited by the lack of well-characterized animal models. Previous vaccine reports have noted robust neutralizing antibody and inflammatory responses in ferrets, resulting in enhanced hepatitis. Methods. We evaluated the humoral immune response and pathological end points in ferrets challenged with the Urbani strain of SARS-associated coronavirus (SARS-CoV) after having received formalin-inactivated whole-virus vaccine or mock vaccine. Results. Humoral responses were observed in ferrets that received an inactivated virus vaccine. Histopathological findings in lungs showed that infection of ferrets produced residual lung lesions not seen in both mock and vaccinated ferrets. SARS-CoV infection demonstrated bronchial and bronchiolar hyperplasia and perivascular cuffing in ferret lung tissue, as seen previously in infected mice. No evidence of enhanced disease was observed in any of the ferrets. All of the ferrets cleared the virus by day 14, 1 week earlier if vaccinated. Conclusions. The vaccine provided mild immune protection to the ferrets after challenge; however, there was no evidence of enhanced liver or lung disease induced by the inactivated whole-virus vaccine. The ferret may provide another useful model for evaluating SARS vaccine safety and efficacy.


Coinfections with SARS-CoV-2 and other respiratory pathogens


Overreliance on China and dynamic balancing in the shift of global value chains in response to global pandemic COVID-19: an Australian and New Zealand perspective


title: Coagulopathie associée au COVID-19: les éléments essentiels pour l’anesthésiste-réanimateur

text: Résumé Les perturbations de la coagulation sont fréquemment observées chez les patients atteints de COVID-19 ainsi que les événements cliniques thrombotiques. Ces évènements augmentent le risque de décès au cours de la maladie. Parmi les évènements biologiques on observe une augmentation des D Dimères (>3µg/L) et du fibrinogène (> 8g/L) et une thrombopénie, qui caractérisent le syndrome et sont associées à un mauvais pronostic. Ces marqueurs devraient être surveillés régulièrement au cours de l’hospitalisation des patients en réanimation. Le diagnostic d’embolie pulmonaire peut être difficile dans le contexte mais doit être évoqué en cas d’aggravation inexpliquée de l’hypoxémie ou d’insuffisance cardiaque droite. Le risque thrombo-embolique doit être stratifié pour adapter la thrombo-prophylaxie en prenant en compte la fonction rénale et le surpoids des patients. Summary Coagulation disorders are commonly reported in patients suffering from COVID-19 pneumonia. There are associated to an increased incidence of thrombotic disorders associated with an increased mortality rate. D-Dimers concentrations >3μg/L, fibrinogen >8g/L and decreased platelets count are associated with an increased thrombotic risk. These biological markers have to be closely monitored during ICU stay. The diagnosis of pulmonary embolism could be difficult in this setting. However, it has to be evoked in case of worsening hypoxemia unexplained by other reason and/or right ventricular failure. The thrombotic risk can be scored to adapt the thromboprophylactic treatment, impaired renal function and overweight making it even more difficult


OUTBREAK OF HUMAN METAPNEUMOVIRUS INFECTION IN ELDERLY INPATIENTS IN JAPAN


title: Neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐C‐reactive protein ratio in patients with severe coronavirus disease 2019 (COVID‐19): A meta‐analysis

text: Since March 11, 2020, the World Health Organization (WHO) defined Coronavirus disease 2019 (COVID-19) as a pandemic, with a series of confirmed cases that currently exceeded 300,000 people worldwide and with approximately 14,500 deaths. Accumulated evidence suggests that a subgroup of patients with severe COVID-19 could have a dysregulation of the immune response that allows the development of viral hyperinflammation. Thus, all patients with severe COVID-19 should be screened for hyperinflammation using laboratory parameters in order to improve mortality. Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-C-reactive protein ratio (LCR) are established inflammation markers that reflect systemic inflammatory response, and both are available in almost all laboratories. In this study, a meta-analysis was performed to investigate whether NLR and LCR values can help predict clinical severity in patients with COVID-19. This article is protected by copyright. All rights reserved.


title: Porcine plasma ficolin binds and reduces infectivity of porcine reproductive and respiratory syndrome virus (PRRSV) in vitro

text: Abstract Ficolins are collagenous lectins that bind N-acetylated glycans and participate in innate immune responses, including phagocytosis and complement activation. Related collagenous lectins such as mannan binding lectin (MBL) and surfactant proteins A and D possess antiviral activity, but this activity has not been demonstrated for ficolins. In these studies, we used purified porcine plasma ficolin α and recombinant ficolin α to assess their ability to bind and neutralize porcine reproductive and respiratory virus (PRRSV) in various assays. Recombinant ficolin α was designed with a C-terminal 6-histidine tag using a pcDNA3.1 expression vector system in CHO K1 cells. Plasma-purified and recombinant ficolin α reduced cytopathic effect of PRRSV-infected Marc-145 cells in neutralization assays and inhibited replication of infectious viral particles in a GlcNAc-dependent manner. In vitro replication determined by plaque assay was inhibited in the presence of plasma-purified ficolin α and recombinant ficolin. Immunoreactive plasma ficolin α and recombinant ficolin α also bound PRRSV-coated wells in a GlcNAc-dependent manner. These studies indicate that porcine ficolin can bind and neutralize a common arterivirus that is a major pathogen of swine.


title: First detection and molecular diversity of Brazilian bovine torovirus (BToV) strains from young and adult cattle

text: Abstract Bovine torovirus (BToV) is an established enteric pathogen of cattle, but its occurrence in Brazilian cattle had not been reported until now. This article describes a survey on BToV in Brazil carried out on 80 fecal samples from diarrheic young and adult cattle, using a nested-RT-PCR targeting the nucleocapsid (N) gene. BToV was detected in 6.25% (5/80) of stool samples from three different geographic regions. Sequences analysis showed that Brazilian BToVs have a high degree of identity with European and Japanese BToVs and a lower degree of identity with North American Breda 1 strain. These results show that, albeit its low frequency and the scarce number of research on the field, BToV is still present amongst cattle populations.


title: Discovery of a novel swine enteric alphacoronavirus (SeACoV) in southern China

text: Abstract Outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), have been recorded in a pig farm in southern China since February 2017. Isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named SeACoV) related to the bat coronavirus HKU2 identified in the same region a decade ago. Specific fluorescence signal was detected in Vero cells infected with SeACoV by using a positive sow serum collected in the same farm, but not by using TGEV-, PEDV- or PDCoV-specific antibody. Electron microscopy observation demonstrated that the virus particle with surface projections was 100–120nm in diameter. Complete genomic sequencing and analyses of SeACoV indicated that the extreme amino-terminal domain of the SeACoV spike (S) glycoprotein structurally similar to the domain 0 of the alphacoronavirus NL63, whereas the rest part of S structurally resembles domains B to D of the betacoronavirus. The SeACoV-S domain 0 associated with enteric tropism had an extremely high variability, harboring 75-amino-acid (aa) substitutions and a 2-aa insertion, compared to that of HKU2, which is likely responsible for the extended host range or cross-species transmission. The isolated virus was infectious in pigs when inoculated orally into 3-day-old newborn piglets, leading to clinical signs of diarrhea and fecal virus shedding. These results confirmed that it is a novel swine enteric coronavirus representing the fifth porcine coronavirus.


COVID‐19: its impact on dental schools in Italy, clinical problems in endodontic therapy and general considerations


title: A Brief Telephone Severity Scoring System and Therapeutic Living Centers Solved Acute Hospital-Bed Shortage during the COVID-19 Outbreak in Daegu, Korea

text: With the epidemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2, the number of infected patients was rapidly increasing in Daegu, Korea. With a maximum of 741 new patients per day in the city as of February 29, 2020, hospital-bed shortage was a great challenge to the local healthcare system. We developed and applied a remote brief severity scoring system, administered by telephone for assigning priority for hospitalization and arranging for facility isolation (“therapeutic living centers”) for the patients starting on February 29, 2020. Fifteen centers were operated for the 3,033 admissions to the COVID-19 therapeutic living centers. Only 81 cases (2.67%) were transferred to hospitals after facility isolation. We think that this brief severity scoring system for COVID-19 worked safely to solve the hospital-bed shortage. Telephone scoring of the severity of disease and therapeutic living centers could be very useful in overcoming the shortage of hospital-beds that occurs during outbreaks of infectious diseases.


Pakistanis’ Mental Health during the COVID-19


title: Predicting geographic location from genetic variation with deep neural networks

text: Most organisms are more closely related to nearby than distant members of their species, creating spatial autocorrelations in genetic data. This allows us to predict the location of origin of a genetic sample by comparing it to a set of samples of known geographic origin. Here, we describe a deep learning method, which we call Locator, to accomplish this task faster and more accurately than existing approaches. In simulations, Locator infers sample location to within 4.1 generations of dispersal and runs at least an order of magnitude faster than a recent model-based approach. We leverage Locator’s computational efficiency to predict locations separately in windows across the genome, which allows us to both quantify uncertainty and describe the mosaic ancestry and patterns of geographic mixing that characterize many populations. Applied to whole-genome sequence data from Plasmodium parasites, Anopheles mosquitoes, and global human populations, this approach yields median test errors of 16.9km, 5.7km, and 85km, respectively.


docid: csxyayof

title: Pandemie- und Seuchengeschichte als Pflegegeschichte?

text: This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. In the current COVID 19 pandemic, the importance of professional nursing is widely recognized. In German-speaking and international research, the history of nursing during pandemics and epidemics is largely unwritten. This paper gives an overview of questions and results in this research area and discusses the potential of a pandemic nursing history.


title: Assessing health burden risk and control effect on dengue fever infection in the southern region of Taiwan

text: BACKGROUND: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. OBJECTIVES: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. MATERIALS AND METHODS: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R(0))–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. RESULTS: We showed that R(0) and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323 (267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. CONCLUSION: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan.


docid: egyfzgwv

title: Acute Enteritis or Gastroenteritis in Young Dogs as a Predisposing Factor for Intestinal Intussusception: a Retrospective Study

text: Various types of intestinal intussusception were diagnosed in 29 of 220 young dogs with acute enteritis or gastroenteritis, due to canine parvovirus (85 cases) or presumably to other infectious agents, inflammation or less common hypermotility and metabolic derangements (135 cases). As the other causes of the disease were excluded, acute enteritis or gastroenteritis was considered to be the most likely predisposing factor for the intestinal intussusception. The most common type of intussusception was found to be the ileocolic. Of the 21 dogs that underwent surgical resection and anastomosis of the intestine, 18 dogs recovered completely and three died due to complications. The high survival rate was due to the effective pre‐operative, surgical and post‐operative therapy.


title: Adult outpatient experience of the 2009 H1N1 pandemic: Clinical course, pathogens, and evaluation of case definitions

text: Summary Objectives The aim was to describe causative agents and clinical characteristics in adult outpatients with upper airway symptoms during the 2009 H1N1 pandemic and to evaluate case definitions that are used in clinical practice. Methods From August through December 2009, 964 symptomatic adult outpatients were included. RT-PCR was used to detect the following pathogens: influenza A (H1N1) and B, parainfluenza 1–4, adenovirus, respiratory syncytial virus, human rhinovirus, human metapneumovirus, human coronavirus (OC43, 229E, NL63), Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella species. The Dutch GHOR, American CDC and WHO, and British HPA case definitions were evaluated. Results A respiratory pathogen was detected in 41% of tested patient samples; influenza A (H1N1) and human rhinovirus were both detected in 16%. Clinical presentation of influenza cases was significantly more serious when compared to rhinovirus or negative-tested cases. Test characteristics were almost similar for all 4 case definitions, with an average sensitivity of 66%, specificity of 70%, positive predictive value of 34% and negative predictive value of 90%. Conclusions Influenza A (H1N1) and human rhinovirus were the major pathogens responsible for respiratory disease. The 2009 H1N1 pandemic in Amsterdam followed a mild course. Test characteristics of 4 different clinical case definitions seemed comparable but rather useless.


title: Research progress on theaflavins: efficacy, formation, and preparation

text: Background: Theaflavins (TFs) are a category of natural compounds characterized with the benzotropolone skeleton. The prominent benefits of TFs have been well documented. Amount of research were conducted and excellent achievements were disclosed during the past years. However, as far as we know, there is no comprehensive review about TFs. Scope and approach: This review summarized the recent research progress. The activity of TFs on anti-oxidation, anti-mutagenicity, hypolipidemic, anti-inflammatory, anti-cancer, anti-viral effect as well as the epidemiological cure were sorted. Converging pioneer literature and deduction, the underlying formation mechanism of TFs was proposed. Subsequently, acquisition of TFs was pointed out to be the fundament for further research. Accelerated by enzyme, bio-synthesis of TFs were reviewed simultaneously. At the end, employing modern analysis instrument and technology, isolations of TFs were enumerated. Key findings and conclusions: Structure of the skeleton as well as functional groups were paramount related with the bio-activity of TFs. Meanwhile, oxidation pathway of two catechin molecules to form TFs were hypothesized. Also, ascertainment of the several therapeutic efficiency of the family members of TFs would be the next step in the future.


title: Development and biochemical and immunological characterization of early passage and immortalized bovine intestinal epithelial cell lines from the ileum of a young calf

text: The intestinal epithelium is a major site of interaction with pathogens. In bovine intestinal epithelial cells (BIECs), Toll-like receptors (TLRs) play an important role in innate immune responses against enteric pathogens. This study is aimed at establishing a stable bovine intestinal epithelial cell line that can be maintained by a continuous passage so that studies on innate immune responses against various enteric pathogens can be performed. The main goal was to establish pure cultures of primary and immortalized bovine intestinal epithelial cells from the ileum and then characterize them biochemically and immunologically. Mixed epithelial and fibroblast bovine ileal intestinal cultures were first established from a 2-day old calf. Limiting dilution method was used to obtain a clone of epithelial cells which was characterized using immunocytochemistry (ICC). The selected clone BIEC-c4 was cytokeratin positive and expressed low levels of vimentin, confirming the epithelial cell phenotype. Early passage BIEC-c4 cells were transfected with either simian virus 40 (SV40) large T antigen or human telomerase reverse transcriptase (hTERT), or human papillomavirus (HPV) type 16E6/E7 genes to establish three immortalized BIEC cell lines. The expression of SV40, hTERT and HPV E6/E7 genes in immortalized BIECs was confirmed by a polymerase chain reaction (PCR). Immunocytochemistry and immunofluorescence assays also confirmed the expression of SV40, hTERT and HPV E6 proteins. The immortalized BIECs were cytokeratin positive and all except HPV-BIECs expressed low levels of vimentin. A growth kinetics study indicated that there were no significant differences in the doubling time of immortalized BIECs as compared to early passage BIEC-c4 cells. All four BIEC types expressed TLR 1-10 genes, with TLR 3 and 4 showing higher expression across all cell types. These newly established early passage and immortalized BIEC cell lines should serve as a good model for studying infectivity, pathogenesis and innate immune responses against enteric pathogens.