title: Bacteria, viruses, and parasites in an intermittent stream protected from and exposed to pasturing cattle: Prevalence, densities, and quantitative microbial risk assessment

text: Abstract Over 3500 individual water samples, for 131 sampling times, targeting waterborne pathogens/fecal indicator bacteria were collected during a 7-year period from 4 sites along an intermittent stream running through a small livestock pasture system with and without cattle access-to-stream restriction measures. The study assessed the impact of cattle pasturing/riparian zone protection on: pathogen (bacterial, viral, parasite) occurrence, concentrations of fecal indicators, and quantitative microbial risk assessments (QMRA) of the risk of Cryptosporidium, Giardia and Escherichia coli O157:H7 infection in humans. Methodologies were developed to compute QMRA mean risks on the basis of water samples exhibiting potentially human infectious Cryptosporidium and E. coli based on genotyping Crytosporidium, and E. coli O157:H7 presence/absence information paired with enumerated E. coli. All Giardia spp. were considered infectious. No significant pasturing treatment effects were observed among pathogens, with the exception of Campylobacter spp. and E. coli O157:H7. Campylobacter spp. prevalence significantly decreased downstream through pasture treatments and E. coli O157:H7 was observed in a few instances in the middle of the unrestricted pasture. Densities of total coliform, fecal coliform, and E. coli reduced significantly downstream in the restricted pasture system, but not in the unrestricted system. Seasonal and flow conditions were associated with greater indicator bacteria densities, especially in the summer. Norovirus GII was detected at rates of 7–22% of samples for all monitoring sites, and rotavirus in 0–7% of samples for all monitoring sites; pasture treatment trends were not evident, however. Seasonal and stream flow variables (and their interactions) were relatively more important than pasture treatments for initially stratifying pathogen occurrence and higher fecal indicator bacteria densities. Significant positive associations among fecal indicator bacteria and Campylobacter spp. detection were observed. For QMRA, adjusting for the proportion of Cryptosporidium spp. detected that are infectious for humans reduces downstream risk estimates by roughly one order of magnitude. Using QMRA in this manner provides a more refined estimate of beneficial management practice effects on pathogen exposure risks to humans.


docid: irwzzhar

title: Trials and tribulations of young residents fighting COVID‐19

text: No one could foresee that an unknown novel virus far away in Asia eventually would end up as world's largest disaster. As days went by, COVID-19 soon began gaining international attention with its significant infectiousness, rapidly deteriorating course and mortality, even in young people.


title: Clinical metagenomics

text: Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.


Standing on your Foot and Ankle during COVID-19: Perspectives from a Singaporean Orthopaedic Foot and Ankle surgery unit


title: Glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetylneuraminic acid exhibits selective activities in vivo and altered tissue distribution

text: In order to study the effect of glycosylation on its biological activities and to develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with C9 spacer was chemically coupled to human recombinant IL-1α. NeuAc-coupled IL-1α (NeuAc-IL-1α) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1α. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1α exhibited a marked reduction in the activity to up-regulate serum IL-6, moderate reduction in the activities to up-regulate serum amyloid A and NOx. However, it exhibited comparable activities as IL-1α to down-regulate serum glucose and to improve the recovery of peripheral white blood cells from myelosuppression in 5-fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1α was high compared to IL-1α. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.


title: Redundancy and methodological issues in articles on COVID‐19

text: Despite the seriousness of the current pandemic, logical and critical thinking, common sense and method remain the mainstay of biomedicine. Unfortunately, the panic caused by the disease has led many to abandon those principles. Some scientists have used the situation to publish substandard articles that would never get published in normal times as journals publish quickly (and gain citations), without proper review and level of criticism. This situation has been used by medical equipment manufacturers and pharmaceutical industry as well, to promote publication of biased sponsored articles.


title: SEROEPIDEMIOLOGIC STUDIES OF CORONAVIRUS INFECTION IN ADULTS AND CHILDREN(1)

text: McIntosh, K. A. Z. Kapikian, H. C Turner, J. W. Hartley, R. H. Parrott and R. M. Chanock. (Lab. of Infectious Diseases, NIAID, NIH, Bethesda, Md. 20014) Sero-epidemiologic studies of coronavirus infection in adults and children. Amer. J. Epid., 1970, 97: 585–592-A seroepidemiologic study of infection by coronavirus strains 229E, OC38, OC43, and mouse hepatitis virus (MHV) strain A-59, is described. In adults with upper respiratory disease, two “outbreaks” of coronavirus infection occurred, one during the winter of 1965–1966 associated with complement fixing (CF) antibody responses to OC38, OC43 and MHV, and the other during the following winter associated with CF antibody responses to 229E. In hospitalized children, infection with 229E was rare; infection with OC38, OC43, and MHV occurred less often in hospitalized children with lower respiratory tract disease (3.5%) than in a control group with non-respiratory tract disease (8.2%). The limitations of the CF test using available coronavirus antigens are discussed.


title: Human Rhinovirus B and C Genomes from Rural Coastal Kenya

text: Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the sensitivity of local molecular diagnostics.


title: Intubation Containment System for Improved Protection From Aerosolized Particles During Airway Management

text: Objectives: Worldwide efforts to protect front line providers performing endotracheal intubation during the COVID-19 pandemic have led to innovative devices. Authors evaluated the aerosol containment effectiveness of a novel intubation aerosol containment system (IACS) compared with a recently promoted intubation box and no protective barrier. Methods: In a simulation center at the authors’ university, the IACS was compared to no protective barrier and an intubation box. Aerosolization was simulated using a commercial fog machine and leakage of aerosolize mist was visually assessed. Results: The IACS appeared to contain the aerosolized mist, while the intubation box allowed for mist to contact the laryngoscopist and contaminate the clinical space through arm port holes and the open caudal end. Both devices protected the laryngoscopist better than no protective barrier. Discussion: The IACS with integrated sleeves and plastic drape appears to offer superior protection for the laryngoscopist and assistant providers from aerosolized particles.


title: Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic

text: The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.


title: Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease

text: We have recently developed a transmissible vaccine to immunize rabbits against myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein [Bárcena et al. Horizontal transmissible protection against myxomatosis and rabbit haemorragic disease using a recombinant myxoma virus. J. Virol. 2000;74:1114–23]. Administration of the recombinant virus protects rabbits against lethal RHDV and MV challenges. Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations. However, potential risks must be extensively evaluated before considering its field use. In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions. Results indicated that vaccine administration is safe even at a 100-fold overdose. No undesirable effects were detected upon administration to immunosuppressed or pregnant rabbits. The recombinant virus maintained its attenuated phenotype after 10 passages in vivo.


title: Self-collection: an appropriate alternative during the SARS-CoV-2 pandemic

text: Abstract Objectives To evaluate the reliability of self-collection for SARS-CoV-2 and other respiratory viruses because swab collections for SARS-CoV-2 put health workers at risk of infection and require use of personal protective equipment (PPE). Methods In a prospective study, patients from two states in Australia attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) throat and nasal swabs (SCNT) prior to health worker collect (HC) using throat and nasal swabs (Site 1) or throat and nasopharyngeal swabs (Site 2). Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen's kappa (κ) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load. Results Of 236 patients sampled by HC and SC, 25 had SARS-CoV-2 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 y SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT. Conclusions Self-collection of throat and nasal swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other respiratory viruses and provides patients with easier access to testing, reduces exposure of the community and health workers to those being tested and reduces requirement for PPE.


title: Hormonal Regulation of Physiology, Innate Immunity and Antibody Response to H1N1 Influenza Virus Infection During Pregnancy

text: In 2009, the H1N1 swine flu pandemic highlighted the vulnerability of pregnant women to influenza viral infection. Pregnant women infected with influenza A virus were at increased risk of hospitalization and severe acute respiratory distress syndrome (ARDS), which is associated with high mortality, while their newborns had an increased risk of pre-term birth or low birth weight. Pregnant women have a unique immunological profile modulated by the sex hormones required to maintain pregnancy, namely progesterone and estrogens. The role of these hormones in coordinating maternal immunotolerance in uterine tissue and cellular subsets has been well researched; however, these hormones have wide-ranging effects outside the uterus in modulating the immune response to disease. In this review, we compile research findings in the clinic and in animal models that elaborate on the unique features of H1N1 influenza A viral pathogenesis during pregnancy, the crosstalk between innate immune signaling and hormonal regulation during pregnancy, and the role of pregnancy hormones in modulating cellular responses to influenza A viral infection at mid-gestation. We highlight the ways in which lung architecture and function is stressed by pregnancy, increasing baseline inflammation prior to infection. We demonstrate that infection disrupts progesterone production and upregulates inflammatory mediators, such as cyclooxygenase-2 (COX-2) and prostaglandins, resulting in pre-term labor and spontaneous abortions. Lastly, we profile the ways in which pregnancy alters innate and adaptive cellular immune responses to H1N1 influenza viral infection, and the ways in which these protect fetal development at the expense of effective long-term immune memory. Thus, we highlight advancements in the field of reproductive immunology in response to viral infection and illustrate how that knowledge might be used to develop more effective post-infection therapies and vaccination strategies.


title: Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay

text: BACKGROUND: There is widespread interest in the use of innate immune modulators as a defense strategy against infectious pathogens. Using rotavirus as a model system, we developed a cell-based, moderate-throughput screening (MTS) assay to identify compounds that reduce rotavirus infectivity in vitro, toward a long-term goal of discovering immunomodulatory agents that enhance innate responses to viral infection. RESULTS: A natural product library consisting of 280 compounds was screened in the assay and 15 compounds that significantly reduced infectivity without cytotoxicity were identified. Time course analysis of four compounds with previously characterized effects on inflammatory gene expression inhibited replication with pre-treatment times as minimal as 2 hours. Two of these four compounds, α-mangostin and 18-β-glycyrrhetinic acid, activated NFκB and induced IL-8 secretion. The assay is adaptable to other virus systems, and amenable to full automation and adaptation to a high-throughput format. CONCLUSION: Identification of several compounds with known effects on inflammatory and antiviral gene expression that confer resistance to rotavirus infection in vitro suggests the assay is an appropriate platform for discovery of compounds with potential to amplify innate antiviral responses.


title: Should we unstress SARS-CoV-2 infected cells?

text: [Figure: see text]


title: The Lung, the Heart, the Novel Coronavirus, and the Renin-Angiotensin System; The Need for Clinical Trials

text: Angiotensin-converting enzyme 2 (ACE2) is the receptor for COVID-19 (SARs-CoV-2). ACE2 protects the lung and heart from acute respiratory distress syndrome (ARDS) and acute myocarditis and arrhythmias, because it breaks down Angiotensin II, which has inflammatory effects in the lung and heart as well as in the kidney. When SARS-CoV-2 binds to ACE2, it suppresses it, so this protective action of ACE2 is lost. Death from COVID-19 is due to ARDS and also heart failure and acute cardiac injury. Drugs that prevent the inflammatory actions of Angiotensin II (i.e., Angiotensin receptor blockers, ARBs) prevent acute lung injury caused by SARS-CoV. Clinical trials are underway to test the risks and benefits of ARBs and angiotensin-converting enzyme inhibitors (ACEIs) in COVID-19 patients requiring hospitalization. Other potential treatments are also discussed.


title: Iron-rich air pollution nanoparticles: an unrecognised environmental risk factor for myocardial mitochondrial dysfunction and cardiac oxidative stress

text: Exposure to particulate air pollution is a major environmental risk factor for cardiovascular mortality and morbidity, on a global scale. Both acute and chronic cardiovascular impacts have so far been attributed to particulate-mediated oxidative stress in the lung and/or via ‘secondary’ pathways, including endothelial dysfunction, and inflammation. However, increasing evidence indicates the translocation of inhaled nanoparticles to major organs via the circulation. It is essential to identify the composition and intracellular targets of such particles, since these are likely to determine their toxicity and consequent health impacts. Of potential major concern is the abundant presence of iron-rich air pollution nanoparticles, emitted from a range of industry and traffic-related sources. Bioreactive iron can catalyse formation of damaging reactive oxygen species, leading to oxidative stress and cell damage or death. Here, we identify for the first time, in situ, that exogenous nanoparticles (∼15 – 40 nm diameter) within myocardial mitochondria of young, highly-exposed subjects are dominantly iron-rich, and co-associated with other reactive metals including aluminium and titanium. These rounded, electrodense nanoparticles (up to ∼ 10 x more abundant than in lower-pollution controls) are located within abnormal myocardial mitochondria (e.g. deformed cristae; ruptured membranes). Measurements of an oxidative stress marker, PrP(C) and an endoplasmic reticulum stress marker, GRP78, identify significant ventricular up-regulation in the highly-exposed vs lower-pollution controls. In shape/size/composition, the within-mitochondrial particles are indistinguishable from the iron-rich, combustion- and friction-derived nanoparticles prolific in roadside/urban environments, emitted from traffic/industrial sources. Incursion of myocardial mitochondria by inhaled iron-rich air pollution nanoparticles thus appears associated with mitochondrial dysfunction, and excess formation of reactive oxygen species through the iron-catalyzed Fenton reaction. Ventricular oxidative stress, as indicated by PrP(C) and GRP78 up-regulation, is evident even in children/young adults with minimal risk factors and no co-morbidities. These new findings indicate that myocardial iron overload resulting from inhalation of airborne, metal-rich nanoparticles is a plausible and modifiable environmental risk factor for cardiac oxidative stress and cardiovascular disease, on an international scale.


title: Serological prevalence of canine respiratory coronavirus

text: Abstract Canine respiratory coronavirus (CRCoV) has recently been detected in dogs; it is a group 2 coronavirus showing similarity to bovine coronavirus (BCoV) but is distinct from canine enteric coronavirus (CECoV). CRCoV may play an important role in canine infectious respiratory disease (CIRD) either by predisposing to further and potentially more serious viral and bacterial infections or possibly as a primary pathogen. The prevalence of serum antibodies to CRCoV, in a population of dogs in the south east of England, has been shown previously to be 30.1% on the first day of entry to a rehoming kennel [Erles, K., Toomey, C., Brooks, H.W., Brownlie, J., 2003. Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease. Virology 310, 216–223]. The purpose of this study was to establish the prevalence of CRCoV in the general canine population within as well as outside the UK. An ELISA, used to test for the presence of antibodies to CRCoV in canine serum samples, identified seropositive dogs in UK, USA, Canada, Republic of Ireland and Greece. The development of an ELISA based on CRCoV antigen and immunofluorescence assay are described here. 54.7% (547/1000) of North American and 36.0% (297/824) of United Kingdom dogs were seropositive for CRCoV. The age and geographical distribution of seropositive dogs was also assessed. The cross-reactivity demonstrated between CRCoV antibodies from different countries and a UK viral isolate suggests immunological similarity. The overall prevalence of this virus in both North America and the UK suggests that CRCoV has international significance and that further epidemiological studies are required.


docid: kuwargnp

title: Thoughts on What Chemists Can Contribute to Fighting SARS‐CoV‐2 – A Short Note on Hand Sanitizers, Drug Candidates and Outreach

text: The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three‐pronged approach is proposed.


title: Equine rotaviruses—Current understanding and continuing challenges

text: Abstract Equine rotaviruses were first detected in foals over 30 years ago and remain a major cause of infectious diarrhoea in foals. During this time, there has been substantial progress in the development of sensitive methods to detect rotaviruses in foals, enabling surveillance of the genotypes present in various horse populations. However, there has been limited epidemiological investigation into the significance of these circulating genotypes, their correlation with disease and the use of vaccination in these animal populations. Our knowledge of the pathogenesis of rotavirus infection in foals is based on a limited number of studies on a small number of foals and, therefore, most of our understanding in this area has been extrapolated from studies in other species. Questions such as the concentrations of rotavirus particles shed in the faeces of infected foals, both with and without diarrhoea, and factors determining the presence or absence of clinical disease remain to be investigated, as does the relative and absolute efficacy of currently available vaccines. The answer to these questions may help direct research into the development of more effective control measures.


title: Atypical Presentation of COVID-19 Incidentally Detected at (18)F-FDG PET/CT in an Asymptomatic Oncological Patient

text: The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at (18)F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an (18)F-FDG–avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a “far-from-COVID-19” finding at PET/CT.


title: The development of chronic cough in children following presentation to a tertiary paediatric emergency department with acute respiratory illness: study protocol for a prospective cohort study

text: BACKGROUND: Acute respiratory illness, a leading cause of cough in children, accounts for a substantial proportion of childhood morbidity and mortality worldwide. In some children acute cough progresses to chronic cough (>4 weeks duration), impacting on morbidity and decreasing quality of life. Despite the importance of chronic cough as a cause of substantial childhood morbidity and associated economic, family and social costs, data on the prevalence, predictors, aetiology and natural history of the symptom are scarce. This study aims to comprehensively describe the epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children presenting to a tertiary paediatric emergency department. METHODS/DESIGN: A prospective cohort study of children aged <15 years attending the Royal Children’s Hospital Emergency Department, Brisbane, for a respiratory illness that includes parent reported cough (wet or dry) as a symptom. The primary objective is to determine the prevalence and predictors of chronic cough (≥4 weeks duration) post presentation with acute respiratory illness. Demographic, epidemiological, risk factor, microbiological and clinical data are completed at enrolment. Subjects complete daily cough dairies and weekly follow-up contacts for 28(±3) days to ascertain cough persistence. Children who continue to cough for 28 days post enrolment are referred to a paediatric respiratory physician for review. Primary analysis will be the proportion of children with persistent cough at day 28(±3). Multivariate analyses will be performed to evaluate variables independently associated with chronic cough at day 28(±3). DISCUSSION: Our protocol will be the first to comprehensively describe the natural history, epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children. The results will contribute to studies leading to the development of evidence-based clinical guidelines to improve the early detection and management of chronic cough in children during and after acute respiratory illness.


title: Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir

text: Abstract Until recently, there were no effective drugs available blocking coronavirus (CoV) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Müller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C., Müller, M.A., Stellberger, T., von Dall’Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Züst, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-Weßels, C., Pöhlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches.


title: Another triple-spanning envelope protein among intracellularly budding RNA viruses: The torovirus E protein

text: Abstract The nucleotide sequence of the Berne virus envelope (E) protein gene was determined and its 26.5K translation product was identified by in vitro transcription and translation. Computer analysis of the protein sequence revealed the characteristics of a class III membrane protein lacking a cleaved signal sequence but containing three successive transmembrane α-helices in the N-terminal half, much the same as the coronavirus membrane (M) protein. The disposition of the E protein in the membrane was studied by in vitro translation in the presence of microsomes and by subsequent proteinase K digestion. Only small portions of either end of the polypeptide were found to be exposed on opposite sides of the vesicle membranes. Experiments with a hybrid E protein (EM) containing the C-terminal tail of a coronavirus M protein, to which an anti-peptide serum was available, showed that this C-terminus was present at the cytoplasmic side of the membrane, which is another similarity to the coronavirus M protein. Immunofluorescence experiments indicated that the EM protein, expressed by a recombinant vaccinia virus, accumulated in intracellular membranes, predominantly those of the endoplasmic reticulum. The common features of the torovirus E and the coronavirus M protein support our hypothesis that an evolutionary relationship exists between these groups of intracellularly budding viruses.


title: Molecular Beacons: A Novel Optical Diagnostic Tool

text: As a result of the efforts of the Human Genome Project and the rise in demand for molecular diagnostic assays, the development and optimization of novel hybridization probes have focused on speed, reliability, and accuracy in the identification of nucleic acids. Molecular beacons (MBs) are single-stranded, fluorophore-labeled nucleic acid probes that are capable of generating a fluorescent signal in the presence of target, but are dark in the absence of target. Because of the high specificity and sensitivity characteristics, MBs have been used in variety of fields. In this review, MBs are introduced and discussed as diagnostic tools in four sections: several technologies of MBs will be illustrated primarily; the limitation of MBs next; the third part is new fashions of MBs; and the last one is to present the application of MBs in disease diagnosis.


Maternal death in pregnancy due to COVID‐19


title: Molecular mechanisms of severe acute respiratory syndrome (SARS)

text: Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.


title: Feasibility of Tocilizumab in ICU patients with COVID‐19

text: Severe COVID‐19 causes cytokine release syndrome and is associated with high mortality. In this retrospective case series, all patients diagnosed with COVID‐19 by semi quantitative RT‐PCR and hyperinflammatory markers were treated with tocilizumab. The use of tocilizumab was associated with rapid apyrexia, improvement of respiratory, biological parameters and short length of hospitalization (11 days). Moreover, no adverse effect attributed to the treatment was noticed. Tocilizumab seems to be a promising and safe therapy in severe patients. This article is protected by copyright. All rights reserved.


SARS-CoV-2 as potential cause of cardiac inflammation and heart failure. Is it the virus, hyperinflammation, or MODS?


title: Viruses and Sialic Acids: Rules of Engagement

text: Viral infections are initiated by specific attachment of a virus particle to receptors at the surface of the host cell. For many viruses, these receptors are glycans that are linked to either a protein or a lipid. Glycans terminating in sialic acid and its derivatives serve as receptors for a large number of viruses, including several human pathogens. In combination with glycan array analyses, structural analyses of complexes of viruses with sialylated oligosaccharides have provided insights into the parameters that underlie each interaction. Here, we compare the currently available structural data on viral attachment proteins in complex with sialic acid and its variants. The objective is to define common parameters of recognition and to provide a platform for understanding the determinants of specificity. This information could be of use for the prediction of the location of sialic acid binding sites in viruses for which structural information is still lacking. An improved understanding of the principles that govern the recognition of sialic acid and sialylated oligosaccharides would also advance efforts to develop efficient antiviral agents.


docid: tltdzujk

title: Translation of viral mRNAs that do not require eIF4E is blocked by the inhibitor 4EGI-1

text: Abstract High throughput screening has rendered new inhibitors of eukaryotic protein synthesis. One such molecule, 4EGI-1 has been reported to selectively block the initiation factor eIF4E. We have investigated the action of this inhibitor on translation directed by several viral mRNAs which, in principle, do not utilize eIF4E. We found that 4EGI-1 inhibits translation directed by poliovirus IRES, in rabbit reticulocyte lysates, to a similar extent as capped mRNA. Moreover, 4EGI-1 inhibits translation driven by poliovirus IRES, both in vitro and in cultured cells, despite cleavage of eIF4G by picornavirus proteases. Finally, translation of vesicular stomatitis virus mRNAs and Sindbis virus subgenomic mRNA is blocked by 4EGI-1 in infected cells to a similar extent as cellular mRNAs. These findings cast doubt on the selective action of this inhibitor, and suggest that this molecule may affect other steps in protein synthesis unrelated to cap recognition by eIF4E.


title: A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV

text: Abstract In response to SARS-CoV infection, neutralizing antibodies are generated against the Spike (S) protein. Determination of the active regions that allow viral escape from neutralization would enable the use of these antibodies for future passive immunotherapy. We immunized mice with UV-inactivated SARS-CoV to generate three anti-S monoclonal antibodies, and established several neutralization escape mutants with S protein. We identified several amino acid substitutions, including Y442F and V601G in the S1 domain and D757N and A834V in the S2 region. In the presence of each neutralizing antibody, double mutants with substitutions in both domains exhibited a greater growth advantage than those with only one substitution. Importantly, combining two monoclonal antibodies that target different epitopes effected almost complete suppression of wild type virus replication. Thus, for effective passive immunotherapy, it is important to use neutralizing antibodies that recognize both the S1 and S2 regions.


title: Polycyclic peptide and glycopeptide antibiotics and their derivatives as inhibitors of HIV entry

text: Abstract Antiviral activity and other biological properties of two groups of polycyclic peptides are discussed. Antibiotics of the complestatin–kistamycin group have a structural motif similar to that of the peptide core of antibacterial antibiotics of the vancomycin–teicoplanin group though no amino acid component in the chloropeptin–kistamicin antibiotics is identical to an amino acid incorporated in the peptide core of the antibiotics of the vancomycin–teicoplanin group. Chloropeptins and the hydrophobic several derivatives of antibacterial antibiotics are inhibitors of HIV and some other viruses. They interfere with the viral (i.e. HIV) entry process. Chemical modifications of natural glycopeptide antibiotics led to the compounds with antiviral properties whereas antibacterial properties were lost. These glycopeptide aglycons derivatives can be envisaged as potential lead compounds for application as microbicides against sexual HIV transmission.


title: Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China

text: Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7–12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.


AIT und Covid-19 - Empfehlung von DGAKI und AeDA


title: Identification of a novel canine norovirus

text: Abstract By screening a collection of fecal samples from young dogs from different European countries, noroviruses (NoVs) were found in 13/294 (4.4%) animals with signs of enteritis whilst they were not detected in healthy dogs (0/42). An informative portion of the genome (3.4kb at the 3′ end) was generated for four NoV strains. In the capsid protein VP1 region, strains 63.15/2015/ITA and FD53/2007/ITA were genetically related to the canine GVI.2 strain C33/Viseu/2007/PRT (97.4–98.6% nt and 90.3–98.6% aa). Strain FD210/2007/ITA displayed the highest identity to the GVI.1 canine strain Bari/91/2007/ITA (88.0% nt and 95.0% aa). Strain 5010/2009/ITA displayed only 66.6–67.6% nt and 75.5–81.6% aa identities to the GVI.1 canine strains FD210/2007/ITA and Bari/91/2007/ITA and the GVI feline strain M49-1/2012/JPN. Identity to the other canine/feline NoVs strains in the VP1 was lower than 67.6% nt and 62.7% aa. Based on the full-length VP1 amino acid sequence and the criteria proposed for distinction of NoV genotypes, the canine NoV 5010/2009/ITA could represent the prototype of a third GVI genotype, thus providing further evidence for the genetic heterogeneity of NoVs in carnivores.


title: Zorgelijke ontwikkelingen: dreiging van SARS-epidemie, vogelpest treft mensen

text: Bij outbreaks van infectieziekten wordt een netwerk geactiveerd om verspreiding tegen te gaan, de Landelijke Coördinatiestructuur Infectieziektenbestrijding. Dit netwerk kreeg dit jaar eerst te maken met het vogelpestvirus (aviaire influenza A/H7). Het bureau lci nam maatregelen voor preventie en behandeling, onder meer vaccinatie van direct betrokkenen tegen humaan influenzavirus, dit wegens het risico van gelijktijdige besmetting met het aviaire en humane influenzavirus hetgeen een nieuwe virusvariant zou kunnen opleveren. Bij 89 mensen werd het A/H7-virus aangetoond, eenmaal met fatale afloop. De tweede bedreiging betrof – vrijwel tegelijkertijd – het sars-virus. Verspreiding vond wereldwijd plaats, vooral in ziekenhuizen waar sars-patiënten waren opgenomen. In Nederland is het virus niet aangetroffen, maar het bureau lci was in hoogste staat van paraatheid en zorgde voor verspreiding van actuele informatie onder professionals en de ontwikkeling van draaiboeken voor het geval ook Nederland getroffen zou worden. Beide uitbraken zijn door de lci aangegrepen als leerervaring om draaiboeken en protocollen verder aan te scherpen. Daarbij wordt ook rekening gehouden met de mogelijkheid van bioterrorisme. Zeer belangrijk blijft de alertheid van de arts(en) aan wie de patiënt met potentieel een ernstige infectieziekte wordt gepresenteerd. Er wordt gewerkt aan een wettelijke basis (Infectieziektewet, Quanrantainewet) om snel en adequaat ingrijpen door het bureau lci in toekomstige uitbraken van bijvoorbeeld sars mogelijk te maken.


Perioperative preparations for COVID -19 -The Pediatric Cardiac Team Perspective


title: Bioproduction of ribavirin by green microbial biotransformation

text: Abstract Ribavirin is an antiviral compound widely used in Hepatitis C Virus therapy. Biotransformation of this nucleoside analogue using Escherichia coli ATCC 12407 as biocatalyst is herein reported. Reaction parameters such as microorganism amounts, substrate ratio and temperature were optimized reaching conversion yields of 86%. Biocatalyst stability was enhanced by immobilization in agarose matrix. This immobilized biocatalyst was able to be reused for more than 270h and could be stored during more than 4 months without activity loss. Batch and packed-bed reactors based on a stabilized biocatalyst were assayed for bioprocess scale-up. A continuous sustainable bioprocess was evaluated using a prototype packed-bed reactor, which allowed to produce 95mg of ribavirin. Finally, in this work an efficient green bioprocess for ribavirin bioproduction using a stabilized biocatalyst was developed.


Genomic Sequencing of a SARS Coronavirus Isolate That Predated the Metropole Hotel Case Cluster in Hong Kong


docid: vhrikgpi

title: General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic

text: BACKGROUND: Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress. METHOD: Between September 1(st )and 30(th), 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28. RESULTS: More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008). CONCLUSIONS: A significant proportion of HCWs experienced moderately high anxiety about the pandemic, and their degree of worry was an independent correlate of psychological distress. Since perceived sufficiency of information about the A/H1N1 influenza prognosis was associated with reduced degree of worry, hospital managers and consultation-liaison psychiatry services should try to provide for HCWs' need for information, in order to offer favourable working conditions in times of extreme distress, such as the current and future pandemics.


Misinterpreting data in lipidology in the era of COVID-19


title: Closing coronavirus spike glycoproteins by structure-guided design

text: The recent spillover of SARS-CoV-2 in the human population resulted in the ongoing COVID-19 pandemic which has already caused 4.9 million infections and more than 326,000 fatalities. To initiate infection the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface, determining host and tissue tropism, and fusion of the viral and host membranes. Although SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design, its stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a prefusion SARS-CoV-2 S ectodomain trimer construct covalently stabilized in the closed conformation. Structural and antigenicity analysis showed we successfully shut S in the closed state without otherwise altering its architecture. Finally, we show that this engineering strategy is applicable to other β-coronavirus S glycoproteins and might become an important tool for vaccine design, structural biology, serology and immunology studies.


title: Glycyrrhizic acid derivatives as Dengue virus inhibitors

text: Abstract Dengue virus (DENV) is one of the most geographically distributed pathogenic flaviviruses transmitted by mosquitoes Aedes sps. In this study, the structure-antiviral activity relationships of Glycyrrhizic acid (GL) derivatives was evaluated by the inhibitory assays on the cytopathic effect (CPE) and viral infectivity of DENV type 2 (DENV2) in Vero E6 cells. GL (96% purity) had a low cytotoxicity to Vero E6 cells, inhibited DENV2-induced CPE, and reduced the DENV-2 infectivity with the IC50 of 8.1 μM. Conjugation of GL with amino acids or their methyl esters and the introduction of aromatic acylhydrazide residues into the carbohydrate part strongly influenced on the antiviral activity. Among compounds tested GL conjugates with isoleucine 13 and 11-aminoundecanoic acid 17 were found as potent anti-DENV2 inhibitors (IC50 1.2–1.3 μM). Therefore, modification of GL is a perspective way in the search of new antivirals against DENV2 infection.


title: Viral Precursor Polyproteins: Keys of Regulation from Replication to Maturation

text: Many viruses use a replication strategy involving the translation of a large polyprotein, which is cleaved by viral and/or cellular proteases. Several of these viruses severely impact human health around the globe, including HIV, HCV, Dengue virus, and West Nile virus. This method of genome organization has many benefits to the virus such as condensation of genetic material, as well as temporal and spatial regulation of protein activity depending on polyprotein cleavage state. The study of polyprotein precursors is necessary to fully understand viral infection, and identify possible new drug targets; however, few atomic structures are currently available. Presented here are structures of four recent polyprotein precursors from viruses with a positive sense RNA genome.


title: Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b

text: Abstract Feline coronaviruses (FCoVs) encode five accessory proteins termed 3a, 3b, 3c, 7a and 7b of unknown function. These proteins are dispensable for viral replication in vitro but are supposed to play a role in virulence. In the current study, we produced and characterized 7b-specific monoclonal antibodies (mAbs). A recombinant form of the 7b protein was expressed as a fusion protein in Escherichia coli, purified by immobilized metal affinity chromatography and used as immunogen. Two hybridoma lines, 5B6 and 14D8, were isolated that expressed mAbs that recognized 7b proteins of both FCoV serotypes. Using an extensive set of N- and C-terminally truncated 7b proteins expressed in E. coli and a synthetic peptide, the binding sites of mAbs 5B6 and 14D8 were mapped to an 18-residue region that comprises the only potential N-glycosylation site of the FCoV 7b protein. The two mAbs were suitable to detect a 24-kDa protein, which represents the nonglycosylated form of 7b in FCoV-infected cells. We speculate that glycosylation of 7b is part of the viral evasion strategy to prevent an immune response against this antigenic site.


title: Impact of pantoprazole on absorption and disposition of hydroxychloroquine, a drug used in Corona Virus Disease-19 (Covid-19): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes). TRIAL DESIGN: Single centre, open-label, parallel group, two-arm, phase I drug-drug interaction trial. PARTICIPANTS: Healthy volunteers (18-60 years old) are treated in the Clinical Pharmacological Trial Center of Heidelberg University Hospital, Germany. INTERVENTION AND COMPARATOR: • Participants are randomized in a group to either receive a nine-day course of pantoprazole, or to a control group without pantoprazole. All participants receive a single dose of HCQ 400 mg. • Additionally, CYP3A4 and CYP2D6 phenotyping with microdosed probe drugs is performed using midazolam and yohimbine as enzyme activity markers, respectively. MAIN OUTCOMES: Primary endpoint: Area under the curve (AUC)(0-72 h) and maximum concentration (C(max)) of a single oral dose of 400 mg HCQ with and without pantoprazole (changes in these two values describe relevant aspects of exposure to HCQ with and without administration of pantoprazole). Secondary endpoints: • AUC(2-4 h), AUC(0-6 h) and C(max) of midazolam and yohimbine. • Correlation of HCQ concentrations in whole blood with concentrations in plasma and peripheral blood mononuclear cells (PBMC). RANDOMISATION: Participants are assigned to treatment groups by using a randomisation list (1:1, block size = 4) and consecutive enrolment. BLINDING (MASKING): The trial is an open-label trial, participants and investigators are not blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 24 participants (12 per group) are planned to be randomised. TRIAL STATUS: Protocol version 2.1 dated 24/04/2020, first patient first visit. April 30th, 2020, recruitment ongoing, anticipated end of study June 30th, 2020. TRIAL REGISTRATION: EudraCT Number: 2020-001470-30, registered on 31 March 2020 German Clinical trials register number / International Clinical Trials Registry Platform: DRKS00021573, registered on 27 April 2020 FULL PROTOCOL: The full trial protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full trial protocol. The trial protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


title: A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples

text: In 5–40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA) that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3′-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18). The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6). Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material.


FIS Abstract


title: Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant

text: BACKGROUND: There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxins are the major contributing factors to the morbidity and mortality observed in acute anthrax infections. METHODS: Using recombinant B. anthracis protective antigen (PA83), covalently coupled to a novel non-toxic muramyl dipeptide (NT-MDP) derivative we hyper-immunized goats three times over the course of 14 weeks. Goats were plasmapheresed and the IgG fraction (not affinity purified) and F(ab')(2 )derivatives were characterized in vitro and in vivo for protection against lethal toxin mediated intoxication. RESULTS: Anti-PA83 IgG conferred 100% protection at 7.5 μg in a cell toxin neutralization assay. Mice exposed to 5 LD(50 )of Bacillus anthracis Ames spores by intranares inoculation demonstrated 60% survival 14 d post-infection when administered a single bolus dose (32 mg/kg body weight) of anti-PA83 IgG at 24 h post spore challenge. Anti-PA83 F(ab')(2 )fragments retained similar neutralization and protection levels both in vitro and in vivo. CONCLUSION: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-exposure, symptomatic human anthrax patients following a bioterrorism event. These results also indicate that recombinant PA83 coupled to NT-MDP is a potent inducer of neutralizing antibodies and suggest it would be a promising vaccine candidate for anthrax. The ease of production, ease of covalent attachment, and immunostimulatory activity of the NT-MDP indicate it would be a superior adjuvant to alum or other traditional adjuvants in vaccine formulations.


title: Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeutics

text: Abstract Recombinant protein containing one heptad-repeat 1 (HR1) segment and one HR2 segment of the HIV-1 gp41 (HR1–HR2) has been shown to fold into thermally stable six-helix bundle, representing the fusogenic core of gp41. In this study, we have used the fusogenic core as a scaffold to design HIV-1 fusion inhibitory proteins by linking another HR1 to the C terminus of HR1–HR2 (HR121) or additional HR2 to the N terminus of HR1–HR2 (HR212). Both recombinant proteins could be abundantly and solubly expressed and easily purified, exhibiting high stability and potent inhibitory activity on HIV-1 fusion with IC50 values of 16.2±2.8 and 2.8±0.63nM, respectively. These suggest that these rationally designed proteins can be further developed as novel anti-HIV-1 therapeutics.


title: Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians

text: Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. OBJECTIVES: This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. DESIGN, SETTING, AND PARTICIPANTS: Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. MEASUREMENTS AND MAIN RESULTS: Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0–10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. CONCLUSIONS: This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.


title: Virus disinfection mechanisms: the role of virus composition, structure, and function

text: Drinking waters are treated for enteric virus via a number of disinfection techniques including chemical oxidants, irradiation, and heat, however the inactivation mechanisms during disinfection remain elusive. Owing to the fact that a number of significant waterborne virus strains are not readily culturable in vitro at this time (e.g. norovirus, hepatitis A), the susceptibility of these viruses to disinfection is largely unknown. An in-depth understanding of the mechanisms involved in virus inactivation would aid in predicting the susceptibility of non-culturable virus strains to disinfection and would foster the development of improved disinfection methods. Recent technological advances in virology research have provided a wealth of information on enteric virus compositions, structures, and biological functions. This knowledge will allow for physical/chemical descriptions of virus inactivation and thus further our understanding of virus disinfection to the most basic mechanistic level.


title: Hyposialylated α1-acid glycoprotein inhibits phagocytosis of feline neutrophils

text: Abstract Feline α1-acid glycoprotein (fAGP) modifies both its serum concentration and its glycan moiety during diseases. fAGP is hyposialylated in cats with feline infectious peritonitis (FIP), but not in clinically healthy cats or in cats with other diseases. This study was aimed to determine whether hyposialylated fAGP influences phagocytosis. A flow cytometric method based on ingestion of fluoresceinated bacteria and adapted to feline blood was used to assess phagocytosis of leukocytes incubated with ‘non-pathological’ fAGP (purified from sera with normal concentrations of AGP) and ‘pathological’ fAGP (purified from sera with >1.5mg/mL hyposialylated AGP). The flow cytometric method provided repeatable results for neutrophils (coefficients of variations, CVs <15%) but not for monocytes (CVs>20%) which had also a high individual variability. Compared with saline solution and with non-pathological fAGP, pathological fAGP significantly decreased phagocytosis in neutrophils and monocytes. This study demonstrated that hyposialylated fAGP down-regulates the phagocytic activity of feline neutrophils.


title: Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System

text: With the continuing coronavirus disease 2019 (COVID-19) pandemic coupled with phased reopening, it is critical to identify risk factors associated with susceptibility and severity of disease in a diverse population to help shape government policies, guide clinical decision making, and prioritize future COVID-19 research. In this retrospective case-control study, we used de-identified electronic health records (EHR) from the University of California Los Angeles (UCLA) Health System between March 9(th), 2020 and June 14(th), 2020 to identify risk factors for COVID-19 susceptibility (severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) PCR test positive), inpatient admission, and severe outcomes (treatment in an intensive care unit or intubation). Of the 26,602 individuals tested by PCR for SARS-CoV-2, 992 were COVID-19 positive (3.7% of Tested), 220 were admitted in the hospital (22% of COVID-19 positive), and 77 had a severe outcome (35% of Inpatient). Consistent with previous studies, males and individuals older than 65 years old had increased risk of inpatient admission. Notably, individuals self-identifying as Hispanic or Latino constituted an increasing percentage of COVID-19 patients as disease severity escalated, comprising 24% of those testing positive, but 40% of those with a severe outcome, a disparity that remained after correcting for medical comorbidities. Cardiovascular disease, hypertension, and renal disease were premorbid risk factors present before SARS-CoV-2 PCR testing associated with COVID-19 susceptibility. Less well-established risk factors for COVID-19 susceptibility included pre-existing dementia (odds ratio (OR) 5.2 [3.2–8.3], p=2.6 × 10(−10)), mental health conditions (depression OR 2.1 [1.6–2.8], p=1.1 × 10(−6)) and vitamin D deficiency (OR 1.8 [1.4–2.2], p=5.7 × 10(−6)). Renal diseases including end-stage renal disease and anemia due to chronic renal disease were the predominant premorbid risk factors for COVID-19 inpatient admission. Other less established risk factors for COVID-19 inpatient admission included previous renal transplant (OR 9.7 [2.8–39], p=3.2×10(−4)) and disorders of the immune system (OR 6.0 [2.3, 16], p=2.7×10(−4)). Prior use of oral steroid medications was associated with decreased COVID-19 positive testing risk (OR 0.61 [0.45, 0.81], p=4.3×10(−4)), but increased inpatient admission risk (OR 4.5 [2.3, 8.9], p=1.8×10(−5)). We did not observe that prior use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers increased the risk of testing positive for SARS-CoV-2, being admitted to the hospital, or having a severe outcome. This study involving direct EHR extraction identified known and less well-established demographics, and prior diagnoses and medications as risk factors for COVID-19 susceptibility and inpatient admission. Knowledge of these risk factors including marked ethnic disparities observed in disease severity should guide government policies, identify at-risk populations, inform clinical decision making, and prioritize future COVID-19 research.


title: Effect of Filtration Conditions On Removal of Emerging waterborne pathogens

text: This study evaluated removal of live emerging waterborne pathogens by pilot‐scale conventional treatment with alum coagulation, flocculation, sedimentation, and filtration. The microbes tested were Cryptosporidium parvum oocysts, Encephalitozoon intestinalis spores, enteropathogenic Escherichia coli O157:H7, Aeromonas hydrophila, and bacteriophage MS2. The study showed the effects of filter run time, alternative loading rates, alternative filter media, and pH on pathogen removal. Results indicated that turbidity breakthrough was accompanied by breakthrough of all pathogens tested in this study. Results also suggest that the breakthrough of A. hydrophila and E. coli O157:H7 occurred more rapidly than that of turbidity. In general, filtration rate or alternative filter media configurations had no apparent effect on pathogen removal.


docid: xsuialnn

title: Glycosyltransferase complexes in eukaryotes: long-known, prevalent but still unrecognized

text: Glycosylation is the most common and complex cellular modification of proteins and lipids. It is critical for multicellular life and its abrogation often leads to a devastating disease. Yet, the underlying mechanistic details of glycosylation in both health and disease remain unclear. Partly, this is due to the complexity and dynamicity of glycan modifications, and the fact that not all the players are taken into account. Since late 1960s, a vast number of studies have demonstrated that glycosyltransferases typically form homomeric and heteromeric complexes with each other in yeast, plant and animal cells. To propagate their acceptance, we will summarize here accumulated data for their prevalence and potential functional importance for glycosylation focusing mainly on their mutual interactions, the protein domains mediating these interactions, and enzymatic activity changes that occur upon complex formation. Finally, we will highlight the few existing 3D structures of these enzyme complexes to pinpoint their individual nature and to emphasize that their lack is the main obstacle for more detailed understanding of how these enzyme complexes interact and function in a eukaryotic cell.


title: Clinical evaluation of multiplex real‐time PCR panels for rapid detection of respiratory viral infections

text: Respiratory viral infections are one of the leading causes of morbidity and mortality, particularly in children, the elderly and immunocompromised persons. Rapid identification of viral etiology is critical in ruling out non‐viral infections, initiating antiviral treatment and limiting the spread of the infection. Multiplex assays of more than one viral gene target in a single tube have the advantage of rapid screening of a large number of potential viral pathogens in a short time. A multiplex real‐time PCR assay was used in this study for detection of respiratory RNA and DNA viral infections in 728 specimens received from 585 adult and pediatric patients comprised of symptomatic and asymptomatic organ transplant recipients and non‐recipients for diagnosis of respiratory illnesses and for routine clinical monitoring. Multiplex PCR was more sensitive than the multiplex immunofluoresence culture assay (R‐mix) and also detected additional respiratory viruses that were not covered by the R‐mix panel. The number of respiratory viruses detected in symptomatic patients was significantly higher than asymptomatic patients in both adult and pediatric patients. Herpesviral infections were the predominant cause of lower respiratory tract infection in the organ transplant recipients, whereas respiratory syncytial virus was the most common pathogen in non‐transplant patients particularly children. Multiplex real‐time PCR for detection of respiratory viruses has the potential for rapid identification of viral pathogens. In this era of emerging viral infections, addition of newer viral targets to the multiplex PCR panels will be beneficial in determining both patient management and public health epidemiology. J. Med. Virol. 84:162–169, 2011. © 2011 Wiley Periodicals, Inc.


title: Hygienic and cosmetic care habits in polish women during COVID‐19 pandemic

text: BACKGROUND: COVID‐19 pandemic influences a lot of aspects of human life. Particularly, hygienic habits are affected. OBJECTIVES: Changes in washing and cosmetic standards during the pandemic toward the past are in the focus of our interest. MATERIAL AND METHODS: The questionnaire study was conducted anonymously in 140 women. The examination concerned pre‐ and during‐pandemic routine hygiene activities such as hands washing, hair washing, bathing, the use of disinfectants, and use of specific type of cosmetics. RESULTS AND DISCUSSION: Compared were data before and during pandemic. Responders declared increased handwashing and taking shower after coming back home and after using local city transportation. We found also that increased use of disinfectants during COVID‐19 pandemic. In contrary to that, number of people washing their hair decreased slightly. Work documents that profile of used cosmetics was changed; increasing hand cream use and decreasing in makeup cosmetics. Nearly, half of the respondents declare that they will maintain new habits also after the pandemic has ended.


title: The rise and evolution of COVID-19

text: Abstract Coronaviridae (CoV) is a large family of zoonotic viruses linked to a range of diseases from the common cold to the severe SARS-CoV and MERS-CoV epidemics. In 2019, a novel virus emerged from Wuhan, China characterized by a marked worldwide outbreak of respiratory illness. Prevention and containment became the prioritized intervention against COVID-19, coupled with a continued search for hallmarks of the disease which would allow early detection and provide insight to management and triage. Cutaneous findings associated with COVID include diffuse maculopapular rashes, livedo reticularis, and acro-ischemic ‘COVID toes’. These skin findings occurred anywhere from days before respiratory symptom onset to weeks after recovery, and predominantly in the child and adolescent population. The role of dermatologists can be expanded during this COVID-19 pandemic to help identify disease through cutaneous presentations.


Togaviridae


title: Social and environmental risk factors in the emergence of infectious diseases

text: Fifty years ago, the age-old scourge of infectious disease was receding in the developed world in response to improved public health measures, while the advent of antibiotics, better vaccines, insecticides and improved surveillance held the promise of eradicating residual problems. By the late twentieth century, however, an increase in the emergence and re-emergence of infectious diseases was evident in many parts of the world. This upturn looms as the fourth major transition in human–microbe relationships since the advent of agriculture around 10,000 years ago. About 30 new diseases have been identified, including Legionnaires' disease, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently, severe acute respiratory syndrome (SARS) and avian influenza. The emergence of these diseases, and resurgence of old ones like tuberculosis and cholera, reflects various changes in human ecology: rural-to-urban migration resulting in high-density peri-urban slums; increasing long-distance mobility and trade; the social disruption of war and conflict; changes in personal behavior; and, increasingly, human-induced global changes, including widespread forest clearance and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS) further compound the risks. The use and misuse of medical technology also pose risks, such as drug-resistant microbes and contaminated equipment or biological medicines. A better understanding of the evolving social dynamics of emerging infectious diseases ought to help us to anticipate and hopefully ameliorate current and future risks.


title: Multigroup, Adaptively Randomized Trials Are Advantageous for Comparing Coronavirus Disease 2019 (COVID-19) Interventions

text: In this commentary, the authors explain and call for a broader use of outcome-adaptive randomization when designing clinical trials to test multiple COVID-19 interventions. This design potentially reduces the number of deaths or other adverse outcomes incurred during a trial.


title: Coronavirus envelope protein: current knowledge

text: BACKGROUND: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. MAIN BODY: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. CONCLUSIONS: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.


title: What Have We Learned from the Novel Influenza A (H1N1) Pandemic in 2009 for Strengthening Pandemic Influenza Preparedness?

text: We need to apply lessons learned from previous influenza pandemics to continuously update preparedness and response plans. It has become evident that strengthening networks of international referral laboratories coupled with scaling-up efforts to expand epidemiological surveillance networks is critical for responding and mitigating the impact of influenza pandemics. The current swine-related influenza A (H1N1) pandemic has also shown that international collaboration remains a critical component to effectively respond to influenza pandemics in the current globalized world.


title: Evaluation of patients undergoing emergency surgery in a COVID-19 pandemic hospital: a cross-sectional study

text: BACKGROUND: The COVID-19 pandemic is threatening healthcare systems and hospital operations on a global scale Treatment algorithms have changed in general surgery clinics, as in other medical disciplines providing emergency services, with greater changes seen especially in pandemic hospitals OBJECTIVES: To evaluate the follow-up of patients undergoing emergency surgery in our hospital during the COVID-19 pandemic DESIGN AND SETTING: Cross-sectional study conducted in a tertiary-level public hospital METHODS: The emergency surgeries carried out between March 11 and April 2, 2020, in the general surgery clinic of a tertiary-care hospital that has also taken on the functions of a pandemic hospital, were retrospectively examined RESULTS: A total of 25 patients were included, among whom 20 were discharged without event, one remained in the surgical intensive care unit, two are under follow-up by the surgery service and two died Upon developing postoperative fever and shortness of breath, two patients underwent thoracic computed tomography (CT), although no characteristics indicating COVID-19 were found The discharged patients had no COVID-19 positivity at follow-up CONCLUSION: The data that we obtained were not surgical results from patients with COVID-19 infection They were the results from emergency surgeries on patients who were not infected with COVID-19 but were in a hospital largely dealing with the pandemic Analysis on the cases in this study showed that both the patients with emergency surgery and the patients with COVID infection were successfully treated, without influencing each other, through appropriate isolation measures, although managed in the same hospital In addition, these successful results were supported by 14-day follow-up after discharge


title: Covid-19 and asset management in EU: a preliminary assessment of performance and investment styles

text: The likelihood of pandemics has been perceived very low till very recently. Therefore, the exponential spread of Covid-19 was a major surprise that has resulted in a global rout of financial markets. In this study, we document some preliminary evidence of performance and investment styles of European funds during the evolution of Covid-19. We assess the period between January and May 2020 and categorized the spread of contagion in three phases. The results document that Social Entrepreneurship funds demonstrated positive returns across the three phases, while most of the other subcategories plunged into negative zone. Our findings on style analysis suggest that fund managers have been drifting from high risk option to low risk in terms of size and investment strategy. Similarly, there has been a switch from high risk to relatively less sensitive sectors and a transition of investment from countries with higher to those with lower number of cases.


title: Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

text: Impaired biosynthetic processing of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel, constitutes the most common cause of CF. Recently, we have identified a distinct category of mutation, caused by premature stop codons and frameshift mutations, which manifests in diminished expression of COOH-terminally truncated CFTR at the cell surface. Although the biosynthetic processing and plasma membrane targeting of truncated CFTRs are preserved, the turnover of the complex-glycosylated mutant is sixfold faster than its wild-type (wt) counterpart. Destabilization of the truncated CFTR coincides with its enhanced susceptibility to proteasome-dependent degradation from post-Golgi compartments globally, and the plasma membrane specifically, determined by pulse–chase analysis in conjunction with cell surface biotinylation. Proteolytic cleavage of the full-length complex-glycosylated wt and degradation intermediates derived from both T70 and wt CFTR requires endolysosomal proteases. The enhanced protease sensitivity in vitro and the decreased thermostability of the complex-glycosylated T70 CFTR in vivo suggest that structural destabilization may account for the increased proteasome susceptibility and the short residence time at the cell surface. These in turn are responsible, at least in part, for the phenotypic manifestation of CF. We propose that the proteasome-ubiquitin pathway may be involved in the peripheral quality control of other, partially unfolded membrane proteins as well.


title: Association of classroom ventilation with reduced illness absence: a prospective study in California elementary schools

text: Limited evidence associates inadequate classroom ventilation rates (VRs) with increased illness absence (IA). We investigated relationships between VRs and IA in California elementary schools over two school years in 162 3rd–5th‐grade classrooms in 28 schools in three school districts: South Coast (SC), Bay Area (BA), and Central Valley (CV). We estimated relationships between daily IA and VR (estimated from two year daily real‐time carbon dioxide in each classroom) in zero‐inflated negative binomial models. We also compared IA benefits and energy costs of increased VRs. All school districts had median VRs below the 7.1 l/s‐person California standard. For each additional 1 l/s‐person of VR, IA was reduced significantly (p<0.05) in models for combined districts (−1.6%) and for SC (−1.2%), and nonsignificantly for districts providing less data: BA (−1.5%) and CV (−1.0%). Assuming associations were causal and generalizable, increasing classroom VRs from the California average (4 l/s‐person) to the State standard would decrease IA by 3.4%, increase attendance‐linked funding to schools by $33 million annually, and increase costs by only $4 million. Further increasing VRs would provide additional benefits. These findings, while requiring confirmation, suggest that increasing classroom VRs above the State standard would substantially decrease illness absence and produce economic benefits.


title: Exudative epidermitis and porcine circovirus-2 infection in a Swedish SPF-herd

text: Abstract An outbreak of exudative epidermitis (EE) among piglets in a Swedish SPF-herd initiated a survey for indications as to the cause of disease. The herd was established by caesarean section and has been closed to all new animal material, with the exception of semen for artificial insemination (AI). The study comprised serum samples from the SPF-herd over a 10-year period (n=109) and a close monitoring of animals in the herd during the period after the EE outbreak. Serum samples from conventional boars at the AI-station servicing the herd were also included (n=9). All serum samples were tested for antibodies to porcine circovirus-2 (PCV-2). In addition, 3-week-old piglets from three litters (n=24) farrowed close after the initial EE outbreak were closely monitored for clinical signs of skin disease, sampled for Staphylococcus hyicus, tested for antibodies to porcine parvovirus and in sequentially collected serum samples tested for interferon-α (IFN-α) and interleukin-6. The PVC-2 serology showed that animals in the herd were sero-negative at least until 2 months prior to the EE outbreak. During the period close after the EE outbreak the animals showed varying levels of antibodies to PCV-2 but all the tested animals had sero-converted 4 months later. The AI boars were also sero-positive to PCV-2 at the time of the EE outbreak. Animals in the SPF-herd remained sero-positive to PCV-2 during the following 7 years. In the monitored litters, one piglet had clinical EE and 15 piglets displayed defined erythemas on the abdomen. Fourteen of the piglets also had IFN-α in serum on one or more occasions during the study, indicating viral activity among the animals. S. hyicus was isolated from all of the piglets from the earliest sampling point (3 days of age) and onwards, irrespective of clinical signs. PCV-2 was isolated from lymphnode tissue collected from one of the EE affected pigs. Further, increases in the number of stillborn piglets, small litters (<6 piglets) and repeat breeders could be correlated to the time of PCV-2 sero-conversion. Coincidence of active viral infection and sero-conversion to PCV-2 points to the virus as the cause of the EE outbreak and reproductive disturbances.


title: Infections associated with adventure travel: A systematic review

text: Abstract Aim To review infections associated with adventure travel. Methods The PubMed, Embase and Scopus databases were searched combining the words infection with the following keywords: rafting, whitewater, surfing, (surfer* or windsurf*), (caves or caving or spelunking), (triathlon or trekking) or (hiking or adventure race), bicycling, backpacking, (mountain climb* or bouldering), horseback riding, orienteering, trekking, and skiing. Results Adventure travel is becoming much more common among travelers and it is associated with a subset of infectious diseases including: leptospirosis, schistosomiasis, viral hemorrhagic fevers, rickettsial diseases and endemic mycosis. Caving and whitewater rafting places individuals at particular risk of leptospirosis, schistosomiasis and endemic mycosis, while adventure races also place individuals at high risk of a variety of infections including campylobacter, norovirus and leptospirosis. Conclusion Travel practitioners need to be aware of the risks associated with adventure travel and should educate individuals about the risks associated with various activities. Doxycycline prophylaxis should be considered for travelers who are susceptible to leptospirosis due to participation in high-risk sports such as whitewater rafting, caving or adventure races.


docid: qjdbvwih

title: Roy Anderson

text: Forced by scandal to leave Oxford University, infectious disease expert Roy Anderson seemed destined to be persona non grata in the scientific community. Three years later, however, Anderson is back in the thick of things, investigating HIV/AIDS, foot-and-mouth disease and, lately, severe acute respiratory syndrome.


title: Phosphorylated abacavir analogue (ABC‐1) has ameliorative action against Newcastle disease virus induced pathogenesis in chicken

text: Newcastle disease virus (NDV) causes huge economic loss to the poultry industry due to high mortality and morbidity. The present study aimed to assess the protective role of novel phosphorylated analogue ABC‐1 in vivo in NDV‐infected chickens through the inhibition of fusion protein. Both NDV‐induced oxidative damage and protective role of novel phosphorylated ABC‐1 were evaluated in vital organs such as the liver and lung of chickens. Enzyme linked immunosorbent assay (ELISA) results showed that protein oxidation and nitration levels were significantly raised in NDV‐infected tissues compared to healthy controls, whereas these levels were reduced significantly (P < 0.05) in birds treated with phosphorylated compounds compared to the NDV‐infected group alone. Additional investigation with double immunofluorescence showed that the large amount of immuno colocalization and Western blot analysis also confirmed this observation through its band pattern in NDV‐infected birds compared to healthy birds, whereas these alterations were reduced in treatment with novel phosphorylated ABC‐1. The expression of fusion glycoprotein was studied by immuno colocalization, PCR, and flow cytometry, and results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC‐1 protects chickens from NDV‐induced pathogenesis, protein oxidation/nitration, and exerts potent antiviral activity.


title: Natural bovine lentiviral type 1 infection in Holstein dairy cattle. I. Clinical, serological, and pathological observations

text: Abstract Clinical, serological, and pathological abnormalities observed in Holstein cows naturally infected with bovine lentivirus 1 bovine immunodeficiency virus (BIV) and other infections were progressive and most commonly associated with weight loss, lymphoid system deficiency, and behavioral changes. Clinical evidence of meningoencephalitis was dullness, stupor, and occasional head or nose pressing postures. The polymerase chain reactions associated the BIV provirus with the lesions in the central nervous system and lymphoid tissues. Multiple concurrent infections developed in retrovirally infected cows undergoing normal stresses associated with parturition and lactation. A major functional correlate of the lymphoreticular alterations was the development of multiple secondary infections which failed to resolve after appropriate antibacterial therapy. The chronic disease syndrome in dairy cows associated with BIV may be useful as a model system for investigation of the pathogenesis of the nervous system lesions and lymphoid organ changes that occur in humans with lentiviral infection.


title: A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos

text: BACKGROUND: The insulated isothermal PCR (iiPCR) technology enables consistent PCR amplification and detection in a simple heating device. A pan-dengue virus (DENV) RT-iiPCR, targeting the 5’ untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. Working on the same technologies, a compact automated sample-in-answer-out system (POCKIT Central Nucleic Acid Analyser) has been available commercially for iiPCR, minimizing human error risks and allowing easy molecular bio-detection near points of need. Here, we evaluated the analytical and clinical performance of the pan-DENV RT-iiPCR on the fully automated system by comparison to those on the semi-automated system. METHODOLOGY/PRINCIPAL FINDINGS: Testing sera containing serial diluted DENV-1, -2, -3, or -4 cell culture stock, the pan-DENV RT-iiPCR system had similar 100% detection endpoints on the two systems; i.e. at 1, 10, 1 and 10 PFU/ml, respectively, on the fully automated system, and at 10, 1, 10 and 10 PFU/ml, respectively, on the semi-automated system. Furthermore, both fully automated and semi-automated PCR system can detect all four DENV serotypes in mosquitos. Clinical performance of the reagent on the two systems was evaluated by testing 60 human serum samples. Both systems detected the same 40 samples (ten DENV-1, -2, -3, and -4 positive each) and did not detect the other 20; 100% agreement (κ = 1) was found between the two systems. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease.


docid: wywhmeow

title: Clinical Characteristics of Coronavirus Disease 2019 in China Guan W, Ni Z, Hu Y, et al. N Engl J Med. 2020 Feb 28 [Online ahead of print] DOI: 10.1056/NEJMoa2002032.

text: The novel coronavirus (SARS-CoV-2, causing COVID-19) was originally isolated in Wuhan, China. This virus spread quickly throughout many countries in Asia and now Europe, Australia, North America, leading the World Health Organization to declare COVID-19 a pandemic. Given the rapid spread of cases, the authors sought to provide analysis of patients with COVID-19, their clinical characteristics, and severity of disease. This was a retrospective review of Chinese medical records for laboratory-confirmed COVID-19 reported to the National Health Commission between December 11, 2019 to January 29, 2020. Electronic medical records were used to record various clinical data including exposure risk, signs and symptoms, laboratory findings, and radiologic findings. Several researchers performed chart abstraction and disagreements were made by a third reviewer. If radiologic findings were included, these were reviewed by respiratory medicine attending physicians who interpreted the findings. Incubation periods of less than 1 day were excluded. Fever was defined as an axillary temperature of 37.5 degrees Celsius or higher. Patients were categorized into severe or nonsevere based on the American Thoracic Society guidelines for community acquired pneumonia. The primary composite endpoint was admission to the intensive care unit (ICU), use of mechanical ventilation, or death. Secondary outcomes included death rates from symptom onset until each component of the composite end-point. There were 7736 patients admitted at 552 sites during the study period and data were obtained on 1099 patients (14.2%). The majority were nonsevere disease (926, 84.3%). The median age was 47 years (IQR 35-58), 41.9% were female, and most were nonsmokers (85.4%). Any comorbidity was recorded in 23.7% of patients, with hypertension being the most common (15.0%). The majority of patients (72.3%) had recent contact with a Wuhan resident, although 25.9% had no reported exposure. The median incubation period was 4.0 days (IQR 2.0-7.0). Regarding symptoms, only 43.8% of patients had fever on presentation but 88.7% developed fever during hospitalization. Besides fever, the most common symptoms overall were cough (67.8%), fatigue (38.1%), sputum production (33.7%), and shortness of breath (18.7%). Chest radiograph findings were available for 274 patients, with the majority being abnormal (59.1%). Findings included bilateral patchy shadowing (36.5%), local patchy shadowing (28.1%), ground-glass opacity (20.1%), and interstitial abnormality (4.4%). Chest CT results were available on 975 patients. The majority (86.2%) were abnormal and consisted of ground-glass opacity (56.4%), bilateral patchy shadowing (51.8%), local patchy shadowing (41.9%), and interstitial abnormalities (14.7%). Laboratory testing was available on most, depending on the test, and showed a median white blood cell count of 4700/mm3 (IQR 3500-6000), elevated C-reactive protein (>10mg/L in 60.7%), and normal procalcitonin (<0.5ng/mL in 94.5%). Other notable laboratory abnormalities included elevated D-dimer (> 0.5mg/L in 46.4%) and elevated LDH (>250U/L in 41%). The most common complications were pneumonia (91.1%) followed by acute respiratory distress syndrome (3.4%) and most common treatments were intravenous antibiotics (58.0%), oxygen therapy (41.3%), and oseltamivir (35.8%). Systemic glucocorticoids and immune globulin were less common therapies, and mechanical ventilation was needed in only 6.1%. At the conclusion of the study, 15 (1.4%) of patients had died and 55 (5.0%) had been discharged fro the hospital. The majority of the remaining patients were still hospitalized. Regarding the composite endpoint, there were 67 patients (6.1%) with ICU admission, mechanical ventilation, or death, leading to a cumulative risk of 3.6%. This percentage increased if you were designated as severe disease; in this case 24.9% had the composite outcome, leading to a cumulative risk of 20.6%. The authors concluded that presenting symptoms and workup can be variable, with many patients being afebrile and having normal radiologic studies. Several limitations were noted including missing data for many on incubation periods. Additionally the majority of the patients were still hospitalized at the end of the study and therefore outcomes could not be provided for those patients. Comment: While this study provides helpful clinical information to assist emergency physicians in identifying potential COVID-19 patients, we must understand the limitations. Most significantly, this was only a very small portion of the overall sample size of confirmed COVID-19 patients. Additionally, be cautious in directly applying these results to patients in the United States as populations may differ.


title: Academics engaging through the media—Insights from creating a monthly column on crisis management

text: Universities increasingly expect academics to engage with external stakeholders. This includes providing media commentary. In this article I describe my experience writing a monthly column on Crisis Management in the New Zealand Herald, the most widely read newspaper in New Zealand with an average daily readership of over 460,000 people (New Zealand Herald, 2019). The article also describes the benefits of writing a newspaper column including educating the public about issues relating to Crisis Management such as managing Covid-19, creating a platform for enhancing collaboration between academics and Public Relations firms, and enhancing the reputation of both the academic and university. This article will benefit academics in the field of Public Relations who are interested in writing a newspaper column to engage through the media.


How to Manage a Public Health Crisis and Bioterrorism in Korea


Effects of the COVID-19 pandemic on mental well-being amongst individuals in society- A letter to the editor on “The Socio-Economic Implications of the Coronavirus and COVID-19 Pandemic: A Review”