Hyperferritinemia in critically ill COVID-19 patients – Is ferritin the product of inflammation or a pathogenic mediator?


title: Health benefits of orally administered anti-IL-10 antibody in in milk-fed dairy calves.

text: The primary objective of this randomized controlled trial was to determine if anti-IL-10 egg yolk antibodies fed upon arrival to a calf ranch would lower the prevalence of C. parvum shedding in naturally challenged preweaned dairy calves. Secondary objectives included measuring the effect of anti-IL-10 antibodies on calf health, performance, and shedding of less common diarrheal pathogens. A total of 133 calves, enrolled at 24 – 72 h of age, received a daily dose of 0.96 gm of egg yolk powder with anti-IL-10 antibodies (MAB, n = 71) or without anti-IL-10 antibodies (MEP, n = 62) split between 2 feedings for the first 11 d on feed at a calf ranch. Daily health evaluations were completed for 15 days after arrival and on d 56. Digital weights were collected at enrollment and d 56 and hipometer weights at enrollment, d 7 and 56. Packed cell volume and serum total protein concentration were measured at enrollment, d 7 and 14. Fecal pH was measured at enrollment, d 5 and 14, and fecal pathogen (C. parvum, coronavirus, rotavirus, and Salmonella spp) shedding was assessed at d 5 and 14. Continuous outcomes were compared between groups using a student’s t-test or Wilcoxon rank sum test. Fecal pathogen shedding at d 14, respiratory disease at d 56, and antibiotic usage were compared using relative risk and chi square test. Fecal pH (median, IQR) on d 14 was 6.65 (6.39 – 6.99) and 6.52 (5.97 – 6.81) for MAB and MEP, respectively. On d 56, the risk of respiratory disease was lower for MAB compared to MEP (RR: 0.40; CI: 0.16 – 0.99). The risk for antibiotic treatment was lower for MAB compared to MEP treated calves (RR = 0.38; CI: 0.17 – 0.88). The risk of shedding rotavirus was higher in MAB (RR = 1.38; CI: 1.10 – 1.81) calves. After multivariable analyses, hipometer weights (LSM ± SE) were 1.7 ± 0.8 kg greater on d 56 in MAB compared to MEP; however ADG was 0.04 ± 0.02 kg/d lower in MAB calves. Total health score, diarrhea days, average respiratory score, packed cell volume, and serum total protein were not affected by feeding anti-IL-10 egg antibodies. In summary, feeding anti-IL-10 antibodies was associated with increased fecal pH, reduced risk of respiratory disease later in the preweaning period, and decreased antibiotic usage despite higher rotavirus infection. These findings might be associated with improved mucosal immunity, enhanced host defenses, or reduced susceptibility and warrant further investigation.


title: High mortality in COVID‐19 patients with mild respiratory disease

text: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS‐CoV‐2, presenting with mild symptoms, and requiring hospitalization in a non‐intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non‐invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 10(3)/mm(3)) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in‐hospital mortality. CONCLUSIONS: In‐hospital mortality of patients with COVID‐19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID‐19.


title: Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors

text: Foreign nucleic acids, the essential signature molecules of invading pathogens that act as danger signals for host cells, are detected by endosomal nucleic acid-sensing toll-like receptors (TLRs) 3, 7, 8, 9, and 13. These TLRs have evolved to recognize ‘non-self’ nucleic acids within endosomal compartments and rapidly initiate innate immune responses to ensure host protection through induction of type I interferons, inflammatory cytokines, chemokines, and co-stimulatory molecules and maturation of immune cells. In this review, we highlight our understanding of the recognition of pathogen-associated nucleic acids and activation of corresponding signaling pathways through endosomal nucleic acid-sensing TLRs 3, 7, 8, 9, and 13 for an enormous diversity of pathogens, with particular emphasis on their compartmentalization, intracellular trafficking, proteolytic cleavage, autophagy, and regulatory programs.


title: The association between D‐dimers in COVID‐19 patients and mortality remains beset of uncertainties

text: We appreciated the response to our letter from Dr. Zhang and colleagues who actively support D‐dimer level at admission as an effective and easy‐to‐perform laboratory predictor in patients with coronavirus disease 2019 (COVID‐19) (1). We congratulate them for the work and thank them for the arguments they have provided. However, we still have many doubts, which observation of the cases we have managed in our university hospital do not dispel.


Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection


title: Chapter Six TMV Particles: The Journey From Fundamental Studies to Bionanotechnology Applications

text: Abstract Ever since its initial characterization in the 19th century, tobacco mosaic virus (TMV) has played a prominent role in the development of modern virology and molecular biology. In particular, research on the three-dimensional structure of the virus particles and the mechanism by which these assemble from their constituent protein and RNA components has made TMV a paradigm for our current view of the morphogenesis of self-assembling structures, including viral particles. More recently, this knowledge has been applied to the development of novel reagents and structures for applications in biomedicine and bionanotechnology. In this article, we review how fundamental science has led to TMV being at the vanguard of these new technologies.


docid: irjhmxsg

title: O'nyong nyong Virus Molecular Determinants of Unique Vector Specificity Reside in Non-Structural Protein 3

text: O'nyong nyong virus (ONNV) and Chikungunya virus (CHIKV) are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3), was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3) replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.


title: Antiparallel Four-Stranded Coiled Coil Specified by a 3-3-1 Hydrophobic Heptad Repeat

text: Summary Coiled-coil sequences in proteins commonly share a seven-amino acid repeat with nonpolar side chains at the first (a) and fourth (d) positions. We investigate here the role of a 3-3-1 hydrophobic repeat containing nonpolar amino acids at the a, d, and g positions in determining the structures of coiled coils using mutants of the GCN4 leucine zipper dimerization domain. When three charged residues at the g positions in the parental sequence are replaced by nonpolar alanine or valine side chains, stable four-helix structures result. The X-ray crystal structures of the tetramers reveal antiparallel, four-stranded coiled coils in which the a, d, and g side chains interlock in a combination of knobs-into-knobs and knobs-into-holes packing. Interfacial interactions in a coiled coil can therefore be prescribed by hydrophobic-polar patterns beyond the canonical 3-4 heptad repeat. The results suggest that the conserved, charged residues at the g positions in the GCN4 leucine zipper can impart a negative design element to disfavor thermodynamically more stable, antiparallel tetramers.


title: Phylogeny matters: revisiting ‘a comparison of bats and rodents as reservoirs of zoonotic viruses’

text: Diseases emerging from wildlife have been the source of many major human outbreaks. Predicting key sources of these outbreaks requires an understanding of the factors that explain pathogen diversity in reservoir species. Comparative methods are powerful tools for understanding variation in pathogen diversity and rely on correcting for phylogenetic relatedness among reservoir species. We reanalysed a previously published dataset, examining the relative effects of species' traits on patterns of viral diversity in bats and rodents. We expanded on prior work by using more highly resolved phylogenies for bats and rodents and incorporating a phylogenetically controlled principal components analysis. For rodents, sympatry and torpor use were important predictors of viral richness and, as previously reported, phylogeny had minimal impact in models. For bats, in contrast to prior work, we find that phylogeny does have an effect in models. Patterns of viral diversity in bats were related to geographical distribution (i.e. latitude and range size) and life history (i.e. lifespan, body size and birthing frequency). However, the effects of these predictors were marginal relative to citation count, emphasizing that the ability to accurately assess reservoir status largely depends on sampling effort and highlighting the need for additional data in future comparative studies.


title: Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19)

text: PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-020-01464-x) contains supplementary material, which is available to authorized users.


title: Use of albumin quotient and IgG index to differentiate blood‐ vs brain‐derived proteins in the cerebrospinal fluid of cats with feline infectious peritonitis

text: Background: Inflammation of the central nervous system (CNS) is a frequent condition in cats but etiology often remains unsolved. Routine cerebrospinal fluid (CSF) analysis can be extended through the calculation of the albumin quotient (Q (alb)), a marker of the integrity of the blood–brain barrier (BBB), and IgG index, an estimate of intrathecal IgG synthesis. Objectives: The purpose of this study was to validate nephelometric methods for CSF protein analysis, and to use the Q (alb) and IgG index to discriminate blood‐ and brain‐derived immunoglobulin fractions in cats with feline infectious peritonitis (FIP). Methods: Cats presented to our clinic between 2001 and 2005 were included in the study based on clinical and laboratory data and histopathologic findings at necropsy. Cats were grouped as having nonneurologic disease (controls; n=37), brain tumors (n=8), FIP involving the CNS (n=12), and extraneural FIP (n=12). CSF‐total protein (TP) was measured and albumin and IgG concentrations were measured in paired CSF/serum samples; Q (alb) and IgG index were calculated. Intraassay and interassay precision of the nephelometric assays were determined using pooled samples. Results: Coefficients of variation for the nephelometric assays ranged from 2.7% to 7.2%. In control cats, CSF‐TP concentration ranged from 0.06 to 0.36 g/L, Q (alb) ranged from 0.6 to 5.7 × 10(−3), and IgG index ranged from 0.3 to 0.6. Q (alb) and IgG index were significantly higher in cats with brain tumors and cats with CNS‐FIP compared with other groups. Compared with control cats, pleocytosis was evident in 8 of 12 (67%) cats and CSF‐TP was increased in 3 of 12 (25%) cats with CNS‐FIP. Conclusion: Nephelometry is a reliable method for measurement of CSF protein, albumin, and IgG in cats. The Q (alb) and IgG index did not identify a CSF protein pattern specific for BBB dysfunction or intrathecal IgG synthesis in cats with CNS‐FIP.


title: Infection control and anesthesia: Lessons learned from the Toronto SARS outbreak

text: PURPOSE: To describe the outbreak of severe acute respiratory syndrome (SARS) in Toronto, its impact on anesthesia practice and the infection control guidelines adopted to manage patients in the operating room (OR) and to provide emergency intubation outside the OR. CLINICAL FEATURES: The SARS outbreak in Toronto was the result of a single index patient. The causative virus, SARS-CoV, is moderately contagious, and is spread by droplets and contact. The virus gains access to host through the mucosa of the respiratory tract and the eyes. It can affect both healthy and compromised patients. The use of several precautionary measures such as goggles, gloves, gowns and facemasks and the application of various infection control strategies designed to minimize the spread of the virus are discussed. CONCLUSION: In containing the spread of SARS, vigilance and strict infection control are important. This results in the rediscovery of standards of infection control measures in daily anesthesia practice.


docid: gycxlzwy

title: Resident physician exposure to novel coronavirus (2019-nCoV, SARS-CoV-2) within New York City during exponential phase of COVID-19 pandemic: Report of the New York City Residency Program Directors COVID-19 Research Group

text: Background From March 2-April 12, 2020, New York City (NYC) experienced exponential growth of the COVID-19 pandemic due to novel coronavirus (SARS-CoV-2). Little is known regarding how physicians have been affected. We aimed to characterize COVID-19 impact on NYC resident physicians. Methods IRB-exempt and expedited cross-sectional analysis through survey to NYC residency program directors (PDs) April 3-12, 2020, encompassing events from March 2-April 12, 2020. Findings From an estimated 340 residency programs around NYC, recruitment yielded 91 responses, representing 24 specialties and 2,306 residents. 45.1% of programs reported at least one resident with confirmed COVID-19: 101 resident physicians were confirmed COVID-19-positive, with additional 163 residents presumed positive for COVID-19 based on symptoms but awaiting or unable to obtain testing. 56.5% of programs had a resident waiting for, or unable to obtain, COVID-19 testing. Two COVID-19-positive residents were hospitalized, with one in intensive care. Among specialties with >100 residents represented, negative binomial regression indicated that infection risk differed by specialty (p=0.039). Although most programs (80%) reported quarantining a resident, with 16.8% of residents experiencing quarantine, 14.9% of COVID-19-positive residents were not quarantined. 90 programs, encompassing 99.2% of the resident physicians, reported reuse or extended mask use, and 43 programs, encompassing 60.4% of residents, felt that personal protective equipment (PPE) was suboptimal. 65 programs (74.7%) have redeployed residents elsewhere to support COVID-19 efforts. Interpretation Many resident physicians around NYC have been affected by COVID-19 through direct infection, quarantine, or redeployment. Lack of access to testing and concern regarding suboptimal PPE are common among residency programs. Infection risk may differ by specialty. Funding AHA, MPB, RWSC, CGM, LRDG, and JDH are supported by NEI Core Grant P30EY019007, and unrestricted grant from RPB. ACP and JS are supported by Parker Family Chair. SXX is supported by University of Pennsylvania.


docid: ncufofro

title: Viral and Cellular mRNA Translation in Coronavirus-Infected Cells

text: Coronaviruses have large positive-strand RNA genomes that are 5′ capped and 3′ polyadenylated. The 5′-terminal two-thirds of the genome contain two open reading frames (ORFs), 1a and 1b, that together make up the viral replicase gene and encode two large polyproteins that are processed by viral proteases into 15–16 nonstructural proteins, most of them being involved in viral RNA synthesis. ORFs located in the 3′-terminal one-third of the genome encode structural and accessory proteins and are expressed from a set of 5′ leader-containing subgenomic mRNAs that are synthesized by a process called discontinuous transcription. Coronavirus protein synthesis not only involves cap-dependent translation mechanisms but also employs regulatory mechanisms, such as ribosomal frameshifting. Coronavirus replication is known to affect cellular translation, involving activation of stress-induced signaling pathways, and employing viral proteins that affect cellular mRNA translation and RNA stability. This chapter describes our current understanding of the mechanisms involved in coronavirus mRNA translation and changes in host mRNA translation observed in coronavirus-infected cells.


title: Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives on Assessment and Management

text: Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.


title: El impacto del covid-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de italia: análisis multicéntrico

text: Resumen Introducción Y Objetivos: Nuestro objetivo fue evaluar el impacto de la enfermedad del coronavirus de 2019 (COVID-19)* en los ingresos en los servicios de urgencias (SU)**, las hospitalizaciones y el manejo clínico de los pacientes con urolitiasis. Pacientes Y Métodos: Realizamos un análisis retrospectivo multicéntrico de las admisiones en los servicios de urgencias de tres departamentos de urología de gran volumen (uno directamente implicado en el tratamiento de los pacientes de COVID-19 y dos no implicados) en Roma (Italia) entre marzo y abril de 2020 y en el mismo período de 2019. Se realizó un análisis estadístico del número de admisiones por urolitiasis, la tasa de complicaciones, hospitalización y el tipo de tratamiento recibido. Resultados: 304 pacientes fueron incluidos en el análisis. Se observó una reducción significativa en el número global de pacientes ingresados en urgencias por urolitiasis entre 2019 y 2020 (48,8%). Además, con respecto a la elección del tratamiento de los pacientes hospitalizados, se informó un aumento estadísticamente significativo de los procedimientos de extracción de cálculos en comparación con el drenaje urinario en 2020 (p: 0,015). Conclusiones: Durante la pandemia de COVID-19 en Roma ha habido una reducción significativa de los ingresos en urgencias por urolitiasis. Los pacientes ingresados en el SU tuvieron más complicaciones, necesitaron hospitalización con mas frecuencia y en cuanto al manejo clínico, se prefirió la extracción temprana de los cálculos en vez del drenaje urinario. Todos los urólogos deben ser conscientes de que en los próximos meses podrían enfrentarse a un mayor número de admisiones por urolitiasis y al manejo de casos más complicados. Abstract Introduction And Objectives: We aimed to evaluate how the corona virus disease of 2019 (COVID-19)* outbreak influenced emergency department (ED)** admissions for urolithiasis, hospitalizations and clinical management of the hospitalized Patients. Patients And Methods: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. Results: 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8 %) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p: 0.015). Conclusions: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases.


title: Case Report: Human Bocavirus Associated Pneumonia as Cause of Acute Injury, Cologne, Germany

text: Although the human bocavirus (HBoV) is known since a decade, limited information about its pathogenesis is available due to the lack of an animal model. Thus, clinical cases and studies are the major source of novel information about the course of infection and the related pathophysiology. In this context, a clinical case of an adult patient suffering from severe HBoV-pneumonia is described that was associated with loss of consciousness followed by acute rib fracture and subsequent neurological disorder. Following initial global respiratory dysfunction the clinical respiratory symptoms recovered but the neurological symptoms maintained after weaning and intensive care in the stroke unit. During the initial phase, an acute active HBoV infection was confirmed by positive polymerase chain reactions from bronchoalveolar lavage fluid and serum. The case further demonstrates that HBoV can cause severe pneumonia, induce secondary disease also in adults, and may be associated with neurological symptoms as previously assumed.


title: Immunochromatographic assay for simple and rapid detection of Satsuma dwarf virus and related viruses using monoclonal antibodies

text: A simple and rapid immunochromatographic assay (ICA) to detect Satsuma dwarf virus (SDV) was developed using colloidal gold conjugates of anti-SDV monoclonal antibodies. Of six homogenization buffers tested, 0.1 M citrate buffer (pH 7.0) gave the best results for the ICA. In the ICA, addition of 0.1% thioglycolic acid in the homogenization buffers that have been widely used in enzyme-linked immunosorbent assays (ELISA) was deleterious to the reaction because of undesirable coagulation of the colloidal gold. ICA using the anti-SDV monoclonal antibodies was 8 times and 16 times more sensitive than double antibody sandwich-ELISA and ICA using the anti-SDV polyclonal antibody, respectively. The analysis is complete in only 15 min. Furthermore, ICA using the anti-SDV monoclonal antibodies could also detect SDV-related viruses.


Thinking beyond the box: preparing for the end of COVID-19 outbreak in a vascular surgery department


title: Viruses associated with acute respiratory infection in a community‐based cohort of healthy New Zealand children

text: Acute respiratory infections (ARIs) are a major cause of morbidity among children. Respiratory viruses are commonly detected in both symptomatic and asymptomatic periods. The rates of infection and community epidemiology of respiratory viruses in healthy children needs further definition to assist interpretation of molecular diagnostic assays in this population. Children otherwise healthy aged 1 to 8 years were prospectively enrolled in the study during two consecutive winters, when ARIs peak in New Zealand. Parents completed a daily symptom diary for 8 weeks, during which time they collected a nasal swab from the child for each clinical ARI episode. A further nasal swab was collected by research staff during a clinic visit at the conclusion of the study. All samples were tested for 15 respiratory viruses commonly causing ARI using molecular multiplex polymerase chain reaction assays. There were 575 ARIs identified from 301 children completing the study, at a rate of 1.04 per child‐month. Swabs collected during an ARI were positive for a respiratory virus in 76.8% (307 of 400), compared with 37.3% (79 of 212) of swabs collected during asymptomatic periods. The most common viruses detected were human rhinovirus, coronavirus, parainfluenza viruses, influenzavirus, respiratory syncytial virus, and human metapneumovirus. All of these were significantly more likely to be detected during ARIs than asymptomatic periods. Parent‐administered surveillance is a useful mechanism for understanding infectious disease in healthy children in the community. Interpretation of molecular diagnostic assays for viruses must be informed by understanding of local rates of asymptomatic infection by such viruses.


title: Interplay between Janus Kinase/Signal Transducer and Activator of Transcription Signaling Activated by Type I Interferons and Viral Antagonism

text: Interferons (IFNs), which were discovered a half century ago, are a group of secreted proteins that play key roles in innate immunity against viral infection. The major signaling pathway activated by IFNs is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which leads to the expression of IFN-stimulated genes (ISGs), including many antiviral effectors. Viruses have evolved various strategies with which to antagonize the JAK/STAT pathway to influence viral virulence and pathogenesis. In recent years, notable progress has been made to better understand the JAK/STAT pathway activated by IFNs and antagonized by viruses. In this review, recent progress in research of the JAK/STAT pathway activated by type I IFNs, non-canonical STAT activation, viral antagonism of the JAK/STAT pathway, removing of the JAK/STAT antagonist from viral genome for attenuation, and the potential pathogenesis roles of tyrosine phosphorylation-independent non-canonical STATs activation during virus infection are discussed in detail. We expect that this review will provide new insight into the understanding the complexity of the interplay between JAK/STAT signaling and viral antagonism.


title: Cytoplasmic sensing of viral nucleic acids

text: Viruses are the most abundant pathogens on earth. A fine-tuned framework of intervening pathways is in place in mammalian cells to orchestrate the cellular defence against these pathogens. Key for this system is sensor proteins that recognise specific features associated with nucleic acids of incoming viruses. Here we review the current knowledge on cytoplasmic sensors for viral nucleic acids. These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. Their ability to respond to a given nucleic acid is based on both the differential specificity of the individual proteins and the downstream signalling or adaptor proteins. The cooperation of these multiple proteins and pathways plays a key role in inducing successful immunity against virus infections.


Is it Crohn’s disease?


Prisons are “in no way equipped” to deal with COVID-19


docid: uoflvqmq

title: Akte AIDS 2020: „Gesund bleiben mit HIV“: Editorial

text: Unser Motto versammelt Fachbeiträge zu Komorbiditäten und zur Vorsorge bei HIV-Infizierten. Das Großthema COVID-19-Pandemie konnte bei der Planung dieser „Akte AIDS“ zwar noch niemand absehen, doch spüren wir der Frage, ob HIV hier einen Risikofaktor darstellt, in aktuellen Beiträgen nach.


title: In vivo morphogenesis of a new porcine enteric coronavirus, CV 777

text: The morphogenesis of a new porcine enteric coronavirus, CV777, in intestinal epithelial cells of experimentally infected newborn piglets is described. The virus shows a morphogenetic pattern characteristic for members of the Coronaviridae family. It is formed by budding through membranes of the endoplasmic reticulum. Some specific aspects of this morphogenesis are discussed.


title: Relationship between Chest CT manifestations and immune response in COVID-19 patients

text: Abstract Objectives To study the and correlations of lymphocytes and cytokines between changes of lung lesion volumes in patients with COVID-19, and to predict their correlation. Methods 93 patients with COVID-19 were divided into mild and severe groups. The data of lymphocyte subgroups and cytokines were collected, the imaging characteristics were measured and correlation analysis was performed to analyze the differences. Results 60 mild and 33 severe patients were included, Lymphocyte subsets decreased in both groups. The percentages of reduction of absolute lymphocytes value in mild and severe groups were 32% and 64% respectively. The lung CT lesion volume of all patients was 241.45 ± 282.92 cm3, among which the mild group was 151.29 ± 226.04 cm3 and the severe group was 405.38 ± 304.90 cm3, respectively. In critically ill patients, the decrease of absolute value of CD4 + T cells and increase of IL-6 level are significantly correlated with the volume of lung lesions. Conclusions The absolute values of CD3+, CD4+, and CD8 + T cells are lower in patients with COVID-19, the levels of IL-6 and IL-10 are increased. The severity of lung lesions predicts poor clinical outcomes and may be a predictor of the transition from mild to severe.


title: Collaborative Research Approaches to the Role of Wildlife in Zoonotic Disease Emergence

text: Emerging infectious diseases are a key threat to public health and the majority are caused by zoonotic pathogens. Here we discuss new collaborative approaches to understanding the process of zoonotic disease emergence that link veterinary medicine, public health, and ecological approaches: conservation medicine and one health. We demonstrate how studies on the underlying drivers of disease emergence (bushmeat hunting, wildlife trade, and deforestation) can provide ways to model, predict, and ultimately prevent zoonotic disease emergence and spread.


The challenges of avian influenza virus: mechanism, epidemiology and control


title: Molecular characterization of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China

text: BACKGROUND: Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5–50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. RESULTS: Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5′ non-coding region (GCUUUU) and 3′ non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, μA, μNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. CONCLUSIONS: The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1877-x) contains supplementary material, which is available to authorized users.


Pulmonary function and exercise capacity in survivors of Severe Acute Respiratory Syndrome


title: Chapter 11 Molecular Testing for Respiratory Viruses

text: Abstract Respiratory tract infections are actually a spectrum of diseases associated with infection of both the upper and lower respiratory tract and include the common cold, otitis media, influenza-like illness, croup, bronchiolitis, and pneumonia. Viruses are the most common cause of respiratory tract infection and the viruses associated are more diverse than the respiratory diseases they cause with influenza viruses, respiratory syncytial virus, human metapneumovirus, parainfluenza viruses, adenovirus, rhinoviruses, enteroviruses, and human coronavirus having a major role. It is often difficult to clinically differentiate viral and bacterial etiologies for some respiratory diseases. Nucleic acid amplification assays provide a rapid and extremely sensitive means to detect respiratory viruses. Understanding the biology and pathogenesis of the associated viruses is key to understanding diagnostic testing limitations.


Declines in Acute Cardiovascular Emergencies during the COVID-19 Pandemic


title: Clinical characteristics of four cancer patients with SARS-CoV-2 infection in Wuhan, China

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. CASE PRESENTATION: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3(+) T cells, B cells, and natural killer cells after infection of the virus. CONCLUSIONS: The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.


title: Structural, Biochemical, and in Vivo Characterization of the First Virally Encoded Cyclophilin from the Mimivirus

text: Although multiple viruses utilize host cell cyclophilins, including severe acute respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their role in infection is poorly understood. To help elucidate these roles, we have characterized the first virally encoded cyclophilin (mimicyp) derived from the largest virus discovered to date (the Mimivirus) that is also a causative agent of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also forms trimers unlike any previously characterized homologue. Strikingly, immunofluorescence assays reveal that mimicyp localizes to the surface of the mature virion, as recently proposed for several viruses that recruit host cell cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl isomerase activity in contrast to human cyclophilins. Thus, this study suggests that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a subset of viruses.


COVID-19 and Evolutionary Medicine


title: Origins of major human infectious diseases

text: Many of the major human infectious diseases, including some now confined to humans and absent from animals, are ‘new’ ones that arose only after the origins of agriculture. Where did they come from? Why are they overwhelmingly of Old World origins? Here we show that answers to these questions are different for tropical and temperate diseases; for instance, in the relative importance of domestic animals and wild primates as sources. We identify five intermediate stages through which a pathogen exclusively infecting animals may become transformed into a pathogen exclusively infecting humans. We propose an initiative to resolve disputed origins of major diseases, and a global early warning system to monitor pathogens infecting individuals exposed to wild animals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature05775) contains supplementary material, which is available to authorized users.


title: Framework for the design and operation of high-level isolation units: consensus of the European Network of Infectious Diseases

text: Summary Patients with highly infectious diseases require safe, secure, high-quality medical care with high-level infection control, which may be most effectively delivered by specially trained staff in the setting of a high-level isolation unit (HLIU). The European Network of Infectious Diseases is a European Commission co-funded network of experts in the management of highly infectious diseases from national (or regional) centres designated for the care of this patient population. Participants took a consensus-based approach to develop a framework for the design and operation of HLIUs in Europe, covering clinical care provision, diagnostic services, transport, health and safety, and essential design and construction features, to support planning by health authorities for the safe and effective management of highly infectious diseases and preparedness for infectious disease emergencies in Europe.


title: The Blood Supply Management amid the COVID-19 Outbreak

text: Abstract Due to the government’s early intervention such as mass lock-down and curtailment strategies towards mass gatherings, amid the COVID-19 outbreak, the organization of the voluntary blood donation camps have been suspended. It’s most significant impact on the blood community has been a dramatic reduction in the number of blood donors. Therefore, our blood stock has almost dried up and put our inventory in a state of jeopardy. Additionally, all the elective surgeries and non-urgent clinical interventions have also been deferred during this time. This has led to a drop in the blood collection, demand as well as the issue at our blood center. With this background, we intended to assess the effect of this lock-down on our blood supply management particularly in two phases [phase-I prior to outbreak] and phase-II [during the outbreak]. Transitioning back to normal conditions would most likely depend on the extent and the time duration of this pandemic and associated behavioural change, which is anticipated to remain in effect well beyond the original estimates.


docid: pccawunf

title: Acute Lung Injury Results from Innate Sensing of Viruses by an ER Stress Pathway

text: Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting are poorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stress during infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resulting from recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections.


title: COVID-19 pandemic and burden of non-communicable diseases: An ecological study on data of 185 countries: COVID-19 and non-communicable diseases

text: BACKGROUND: The interaction between coronavirus disease 2019 (COVID-19) and non-communicable diseases may increase the global burden of disease. We assessed the association of COVID-19 with ageing and non-communicable diseases. METHODS: We extracted data regarding non-communicable disease, particularly cardiovascular disease, deaths, disability-adjusted life years (DALYs), and healthy life expectancy (HALE) from the Global Burden of Disease Study (GBD) 2017. We obtained data of confirmed COVID-19 cases, deaths, and tests from the Our World in Data database as of May 28, 2020. Potential confounders of pandemic outcomes analyzed include institutional lockdown delay, hemispheric geographical location, and number of tourists. We compared all countries according to GBD classification and World Bank income level. We assessed the correlation between independent variables associated with COVID-19 caseload and mortality using Spearman's rank correlation and adjusted mixed model analysis. FINDINGS: High-income had the highest, and the Southeast Asia, East Asia, and Oceania region had the least cases per million population (3050.60 vs. 63.86). Sub-saharan region has reported the lowest number of COVID-19 mortality (1.9). Median delay to lockdown initiation varied from one day following the first case in Latin America and Caribbean region, to 34 days in Southeast Asia, East Asia, and Oceania. Globally, non-communicable disease DALYs were correlated with COVID-19 cases (r=0.32, p<0.001) and deaths (r=0.37, p<0.001). HALE correlated with COVID-19 cases (r=0.63, p<0.001) and deaths (r=0.61, p<0.001). HALE was independently associated with COVID-19 case rate and the number of tourists was associated with COVID-19 mortality in the adjusted model. INTERPRETATION: Preventive measures against COVID-19 should protect the public from the dual burden of communicable and non-communicable diseases, particularly in the elderly. In addition to active COVID-19 surveillance, policymakers should utilize this evidence as a guide for prevention and coordination of health services. This model is timely, as many countries have begun to reduce social isolation.


title: Clinical implications of nicotine as an antimicrobial agent and immune modulator

text: Nicotine is perhaps the most important and potent, pharmacologically active substance in tobacco products. This commentary examines the possible effects that nicotine has on microbial viability and also on the host's immune system as it responds to the indigenous microflora (the microbiome) due to nicotine-induced changes to the indigenous microbial environment and any associated antigenic stimulation / immunization that may occur. To our knowledge, the analysis of such profound microbiologic changes attributable to a tobacco-related product, such as nicotine, has not been fully explored in the context of its consequences on the viability of the microbiome/microbiota and on some of the host’s basic physiologic processes, such as the immune response, and its possible association on the induction and persistence of certain immunologically related diseases. Future studies should be aimed at uncovering the molecular mechanisms involved in such interactions, especially in the context of manipulating them for therapeutic purposes.


docid: kphmcurd

title: Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese Medicine for respiratory tract infection?

text: INTRODUCTION: Shuanghuanglian (SHL) oral liquid is a well-known traditional Chinese medicine preparation administered for respiratory tract infections in China. However, the underlying pharmacological mechanisms remain unclear. The present study aims to determine the potential pharmacological mechanisms of SHL oral liquid based on network pharmacology. METHODS: Network pharmacology-based strategy including collection and analysis of putative compounds and target genes, network construction, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology(GO) enrichment, identification of key compounds and target genes, and molecule docking was performed in this study. RESULTS: A total of 82 bioactive compounds and 226 putative target genes of SHL oral liquid were collected. Of note, 28 hub target genes including 4 major hub target genes: estrogen receptor 1 (ESR1), nuclear receptor coactivator 2 (NCOA2), nuclear receptor coactivator 1 (NCOA1), androgen receptor (AR) and 5 key compounds (quercetin, luteolin, baicalein, kaempferol and wogonin) were identified based on network analysis. The hub target genes mainly enriched in pathways including PI3K-Akt signaling pathway, human cytomegalovirus infection, and human papillomavirus infection, which could be the underlying pharmacological mechanisms of SHL oral liquid for treating diseases. Moreover, the key compounds had great molecule docking binding affinity with the major hub target genes. CONCLUSION: Using network pharmacology analysis, SHL oral liquid was found to contain anti-virus, anti-inflammatory, and “multi-compounds and multi-targets” with therapeutic actions. These findings may provide a valuable direction for further clinical application and research.


title: Genetic and environmental interaction in allergy and asthma

text: Abstract Asthma is an inflammatory disorder of the airways involving coordinate up-regulation of TH2-type cytokines encoded in a cluster on chromosome 5q31-33 on T cells and inflammatory cells. There is also a requirement for local airway susceptibility factors that, together with TH2 polarization, results in hyperresponsiveness, variable airflow obstruction, and, over time, remodeling of the airway wall. Asthma has strong genetic and environmental components that interact both in the induction and subsequent expression of the disease phenotypes. Multiple genes are involved and probably interact. Whole genome screens are beginning to identify gene-rich regions of special relevance to asthma and atopy, although a novel disease-related gene has yet to be discovered from these. By contrast, there are a plethora of candidate genes whose function in relation to disease pathophysiologic mechanisms and response to treatment are known. Two examples are polymorphisms involving IL-4 receptors and the enzymes controlling cysteinyl leukotriene production. Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both TH2 polarization and airway wall remodeling. (J Allergy Clin Immunol 1999;104:1139-46.)


title: Medical students and COVID-19: the need for pandemic preparedness

text: The COVID-19 pandemic has prompted unprecedented global disruption. For medical schools, this has manifested as examination and curricular restructuring as well as significant changes to clinical attachments. With the available evidence suggesting that medical students’ mental health status is already poorer than that of the general population, with academic stress being a chief predictor, such changes are likely to have a significant effect on these students. In addition, there is an assumption that these students are an available resource in terms of volunteerism during a crisis. This conjecture should be questioned; however, as those engaging in such work without sufficient preparation are susceptible to moral trauma and adverse health outcomes. This, in conjunction with the likelihood of future pandemics, highlights the need for ‘pandemic preparedness’ to be embedded in the medical curriculum.


title: Sustainability of High-Level Isolation Capabilities among US Ebola Treatment Centers

text: To identify barriers to maintaining and applying capabilities of US high-level isolation units (HLIUs) used during the Ebola virus disease outbreak, during 2016 we surveyed HLIUs. HLIUs identified sustainability challenges and reported the highly infectious diseases they would treat. HLIUs expended substantial resources in development but must strategize models of sustainability to maintain readiness.


title: Emerging health care-associated infections in the geriatric population.

text: The increasing number of persons >65 years of age form a special population at risk for nosocomial and other health care-associated infections. The vulnerability of this age group is related to impaired host defenses such as diminished cell-mediated immunity. Lifestyle considerations, e.g., travel and living arrangements, and residence in nursing homes, can further complicate the clinical picture. The magnitude and diversity of health care-associated infections in the aging population are generating new arenas for prevention and control efforts.


title: Clinical evaluation of a panel of multiplex quantitative real-time reverse transcription polymerase chain reaction assays for the detection of 16 respiratory viruses associated with community-acquired pneumonia

text: We developed a panel of multiplex quantitative real-time reverse transcription polymerase chain reaction (mqRT-PCR) assay consisting of seven internally controlled qRT-PCR assays to detect 16 different respiratory viruses. We compared the new mqRT-PCR with a previously reported two-tube mRT-PCR assay using 363 clinical sputum specimens. The mqRT-PCR assay performed comparably with the two-tube assay for most viruses, offering the advantages of quantitative analysis, easier performance, lower susceptibility to contamination, and shorter turnaround time in laboratories equipped with conventional real-time PCR instrumentation, and it could therefore be a valuable tool for routine surveillance of respiratory virus infections in China.


title: Infectious pancreatic necrosis virus proteins VP2, VP3, VP4 and VP5 antagonize IFNa1 promoter activation while VP1 induces IFNa1

text: Abstract Infectious pancreatic necrosis virus (IPNV) is one of the major viral pathogens causing disease in farmed Atlantic salmon worldwide. In the present work we show that several of the IPN proteins have powerful antagonistic properties against type I IFN induction in Atlantic salmon. Each of the five IPNV genes cloned into an expression vector were tested for the ability to influence activation of the Atlantic salmon IFNa1 promoter by the interferon promoter inducing protein one (IPS-1) or interferon regulatory factors (IRF). This showed that preVP2, VP3 and VP5 inhibited activation of both promoters, while VP4 only antagonized activation of the IFNa1 promoter. The viral protease VP4 was the most potent inhibitor of IFN induction, apparently targeting the IRF1 and IRF3 branch of the signaling cascade. VP4 antagonism is independent of its protease activity since the catalytically dead mutant VP4K674A inhibited activation of the IFNa1 promoter to a similar extent as wild type VP4. In contrast to the other IPNV proteins, the RNA-dependent RNA polymerase VP1 activated the IFNa1 promoter. The ability to activate the IFN response was disrupted in the mutant VP1S163A, which has lost the ability to produce dsRNA. VP1 also exhibited synergistic effects with IRF1 and IRF3 in inducing an IFNa1-dependent antiviral state in cells. Taken together these results suggest that IPNV has developed multiple IFN antagonistic properties to prevent IFN-induction by VP1 and its dsRNA genome.


title: Severe human infection with a novel avian-origin influenza A(H7N4) virus

text: Abstract Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient’s backyard, neighborhood, local live poultry markets (LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry (chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.


title: A prospective study comparing standard laryngoscopy to the trachview videoscope system for orotracheal intubation by emergency medicine residents and medical students

text: Study objectives: Flexible fiberoptic bronchoscopy is a skill that can be difficult for emergency physicians to use in the setting of an emergency intubation. The TrachView Videoscope (TV) consists of a narrow high-resolution fiberoptic cable whose tip is positioned at the distal end of the endotracheal tube. The image is displayed on a small portable bedside monitor. In this way, the TV does not alter the standard method of intubation but adds a second, possibly improved, view of the vocal cords. The TV has never been formally studied. We determine the ease of use and improvement in the percentage of glottic opening (POGO) score using the TV by individuals with various levels of intubation experience. Methods: The study was conducted in 2 phases on a mannequin model during an airway laboratory for emergency medicine residents and medical students in a university setting. Phase 1 consisted of a nonrandomized group sequential study design in which, after a 10-minute demonstration of the TV, emergency medicine residents assessed the POGO score using direct laryngoscopy (DL) and compared it with their observed POGO score using the TV. Part 2 consisted of a crossover study with first- and second-year medical students with no intubation experience. The students were randomized into 2 groups that differed by the method of intubation instruction given first: DL or TV. The students were given a 10-minute demonstration of each technique and had 2 attempts to return the demonstration. The POGO score noted by the student was recorded for each technique. The groups were then crossed and the process was repeated. Additional information collected from study subjects included ease of use of the TV and improvement in intubation using the TV. Results: In phase 1, the residents consisted of 4 postgraduate year (PGY)-1, 10 PGY-2, and 11 PGY-3 residents, and 3 participants whose level was not recorded, for a total of 28. Overall, the median POGO score for DL was 50%, and the median POGO score for TV was 100% (P<.001). The median difference in POGO scores (TV and DL) was as follows: 50% for PGY-1 residents, 50% for PGY-2 residents, and 25% for PGY-3 residents. As for ease of use, 85.7% (24) reported that the TV was “easy” to use, 10.7% (3) were undecided, and 3.6% (1) reported that the TV was “difficult” to use, whereas 82.1% (23) reported that the TV improved their intubation attempt, 14.3% (4) reported no difference, and 3.6% (1) reported that the TV made the intubation attempt more difficult. In phase 2, there were 37 participants. Overall, the median TV and DL POGO scores were 75% and 25%, respectively (P=.004). The median difference in POGO scores (TV and DL) for the 2 groups was as follows: 75% for group 1 and 50% for group 2. Of all the participants, 67.6% (25) ranked the TV as “easy” to use, 21.6% (8) were undecided, and 10.8% (4) ranked the TV as “difficult” to use, whereas 56.8% percent (21) reported that the TV improved their intubation attempts, 27% (10) reported no difference, and 10.8% (4) reported that the TV made the intubation attempts more difficult. Conclusion: The Trachview Videoscope is easy to use and improves the POGO score and subjective evaluation of performance for intubation by individuals with various experience levels.


title: Achievements and challenges of sialic acid research

text: Sialic acids are one of the most important molecules of life, since they occupy the terminal position on macromolecules and cell membranes and are involved in many biological and pathological phenomena. The structures of sialic acids, comprising a family of over 40 neuraminic acid derivatives, have been elucidated. However, many aspects of the regulation of their metabolism at the enzyme and gene levels, as well as of their functions remain mysterious. Sialic acids play a dual role, not only are they indispensable for the protection to and adaptation of life, but are also utilised by life-threatening infectious microorganisms. In this article the present state of knowledge in sialobiology, with an emphasis on my personal experience in this research area, is outlined including a discussion of necessary future work in this fascinating field of cell biology.


Adverse effects of nasopharyngeal swabs: Three-dimensional printed versus commercial swabs


title: A rare case of CMV pneumonia in HIV-infection

text: Cytomegalovirus (CMV) pneumonia is a rare opportunistic infection in the setting of HIV (Human Immunodeficiency Virus)-infection. Establishing accurate diagnosis of CMV pneumonia in HIV-infection can be challenging. Co-infections by multiple opportunistic pathogens are common and a high degree of clinical vigilance to evaluate for multiple infections, including CMV pneumonia, should be maintained. As there can be a degree of overlap in clinical and radiological features amongst different opportunistic infections affecting the lungs, definitive microbiological and cytohistologic evidences are needed. Reliance on microbiological evidence of CMV in respiratory specimens alone for the diagnosis of CMV pneumonia will lead to an over-diagnosis of the condition and unnecessary treatment. In our case report, we describe a 53-year-old man with recently diagnosed HIV-infection who presented with non-resolving pneumonia. A diagnosis of CMV pneumonia was reached through consistent clinical, radiological, microbiological and cytologic investigations. The patient made a full clinical recovery after being started on anti-CMV treatment.


title: A metagenomic comparison of endemic viruses from broiler chickens with runting-stunting syndrome and from normal birds

text: Runting-stunting syndrome (RSS) in broiler chickens is an enteric disease that causes significant economic losses to poultry producers worldwide due to elevated feed conversion ratios, decreased body weight during growth, and excessive culling. Of specific interest are the viral agents associated with RSS which have been difficult to fully characterize to date. Past research into the aetiology of RSS has implicated a wide variety of RNA and DNA viruses however, to date, no individual virus has been identified as the main agent of RSS and the current opinion is that it may be caused by a community of viruses, collectively known as the virome. This paper attempts to characterize the viral pathogens associated with 2–3-week-old RSS-affected and unaffected broiler chickens using next-generation sequencing and comparative metagenomics. Analysis of the viromes identified a total of 20 DNA and RNA viral families, along with 2 unidentified categories, comprised of 31 distinct viral genera and 7 unclassified genera. The most abundant viral families identified in this study were the Astroviridae, Caliciviridae, Picornaviridae, Parvoviridae, Coronaviridae, Siphoviridae, and Myoviridae. This study has identified historically significant viruses associated with the disease such as chicken astrovirus, avian nephritis virus, chicken parvovirus, and chicken calicivirus along with relatively novel viruses such as chicken megrivirus and sicinivirus 1 and will help expand the knowledge related to enteric disease in broiler chickens, provide insights into the viral constituents of a healthy avian gut, and identify a variety of enteric viruses and viral communities appropriate for further study.


docid: gzhnhtnl

title: Prevalence and control of bovine cryptosporidiosis in German dairy herds

text: Abstract In a 5-year survey regarding its prevalence and importance in five German state veterinary laboratories Cryptosporidium was diagnosed annually in 19–36% of faecal samples either submitted to the laboratories or taken post mortem. In approximately half of the cases no other enteropathogens were detected. However, only 73% of 30 laboratories participating in a questionnaire survey routinely tested for this parasite, and the majority of researchers considered cryptosporidiosis to be of minor importance. In a placebo-controlled field study 152 suckling calves were treated daily against cryptosporidiosis either with sulfadimidine or with halofuginone (Halocur®, Intervet) over 1 week. Treatment by oral drench started at the onset of diarrhoea in the herd. Oocyst excretion, faecal consistency and health status were recorded five times for a 3-week period. Oocyst excretion peaked 7–14 days in the placebo group after the onset of diarrhoea, and during that period prevalence and intensity of excretion were significantly lower in the halofuginone-treated group compared to the sulfadimidine and the placebo control groups. The health status (diarrhoea, dehydration) declined in all groups but was significantly (P<0.05–0.001) better in the halofuginone group in the first 2 weeks. Halofuginone effectively (P<0.05–0.001) reduced oocyst excretion and improved the health status of the treated animals, while sulfadimidine had no effect against Cryptosporidium.


title: From superspreaders to disease hotspots: linking transmission across hosts and space

text: Since the identification and imprisonment of “Typhoid Mary,” a woman who infected at least 47 people with typhoid in the early 1900s, epidemiologists have recognized that ‘superspreading’ hosts play a key role in disease epidemics. Such variability in transmission also exists among species within a community (amplification hosts) and among habitat patches across a landscape (disease ‘hotspots’), underscoring the need for an integrative framework for studying transmission heterogeneity. Here, we synthesize literature on human, plant, and animal diseases to evaluate the relative contributions of host, pathogen, and environmental factors in driving transmission heterogeneity across hosts and space. We show that host and spatial heterogeneity are closely linked and that quantitatively assessing the contribution of infectious individuals, species, or environmental patches to overall transmission can aid management strategies. We conclude by posing hypotheses regarding how pathogen natural history influences transmission heterogeneity and highlight emerging frontiers in the study of transmission heterogeneity.


title: Comparison of 3′-End Encoding Regions of Turkey Coronavirus Isolates from Indiana, North Carolina, and Minnesota with Chicken Infectious Bronchitis Coronavirus Strains

text: OBJECTIVE: To analyze the 3′-end structural protein-encoding region of turkey coronavirus (TCoV) isolates associated with outbreaks of acute enteritis in Indiana, North Carolina, or Minnesota. METHODS: Four isolates of TCoV were sequenced over the entire 3′-end structural protein-encoding region and compared phylogenetically along with the corresponding sequences of infectious bronchitis virus (IBV) strains. RESULTS: The sequence similarity between TCoV and IBV was lower than that among TCoV isolates or that among IBV strains. The variation of sequences between TCoV and IBV was mainly contributed by the S protein gene. The sequence similarity of S gene between TCoV and IBV was lower than that among TCoV isolates or that among IBV strains. The phylogenetic tree based on the S protein region was similar to that based on the entire 3′-end structural protein-encoding region with TCoV isolates and IBV strains grouped in two separate clusters. The phylogenetic tree based on other genes had a very different topology with TCoV isolates randomly forming groups with different IBV strains. CONCLUSIONS: These results suggested that TCoV probably shared the same origin with that of IBV and acquired sequences of S gene for turkey intestine tropism during the process of evolution in a separate environment.


title: Bacterial resistance: A sensitive issue Complexity of the challenge and containment strategy in Europe

text: Abstract The development of antimicrobial agents has been a key achievement of modern medicine. However, their overuse has led to an increasing incidence of infections due to antibiotic-resistant microorganisms. Quantitative figures on the current economic and health impact of antimicrobial resistance are scant, but it is clearly a growing challenge that requires timely action. That action should be at the educational, ethical, economic and political level. An important first step would be to increase public awareness and willingness to take the necessary measures to curb resistance. Hence, studies are needed that would provide solid, quantitative data on the societal impact of antibiotic resistance. This review discusses the complexity of resistance, identifies its main drivers and proposes measures to contain it on a European scale.


title: Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis

text: Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.


title: Engineering RNA for Targeted siRNA Delivery and Medical Application

text: RNA engineering for nanotechnology and medical applications is an exciting emerging research field. RNA has intrinsically defined features on the nanometer scale and is a particularly interesting candidate for such applications due to its amazing diversity, flexibility and versatility in structure and function. Specifically, the current use of siRNA to silence target genes involved in disease has generated much excitement in the scientific community. The intrinsic ability to sequence-specifically down-regulate gene expression in a temporally- and spatially-controlled fashion has led to heightened interest and rapid development of siRNA-based therapeutics. Though methods for gene silencing with high efficacy and specificity have been achieved in vitro, the effective delivery of nucleic acids to specific cells in vivo has been a hurdle for RNA therapeutics. This review covers different RNA-based approaches for diagnosis, prevention and treatment of human disease, with a focus on the latest developments of nonviral carriers of siRNA for delivery in vivo. The applications and challenges of siRNA therapy, as well as potential solutions to these problems, the approaches for using phi29 pRNA-based vectors as polyvalent vehicles for specific delivery of siRNA, ribozymes, drugs or other therapeutic agents to specific cells for therapy will also be addressed.


title: ICU and ventilator mortality among critically ill adults with COVID-19

text: We report preliminary data from a cohort of adults admitted to COVID-designated intensive care units from March 6 through April 17, 2020 across an academic healthcare system. Among 217 critically ill patients, mortality for those who required mechanical ventilation was 29.7% (49/165), with 8.5% (14/165) of patients still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 25.8% (56/217), and 40.1% (87/217) patients have survived to hospital discharge. Despite multiple reports of mortality rates exceeding 50% among critically ill adults with COVID-19, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.


title: Scorpion Venom: Detriments and Benefits

text: Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.


title: The Biologic Principles of Poliovirus Eradication

text: The biologic principles for the global eradication of poliomyelitis are as follows: Poliovirus causes acute, nonpersistent infections, virus is transmitted by infectious humans or their waste, survival of virus in the environment is finite, humans are the only reservoir, and immunization with polio vaccine interrupts virus transmission. These principles appear to be sound. The potential for prolonged virus excretion by immunocompromised patients requires further definition, although there is no epidemiologic evidence of a threat to eradication. Survival of poliovirus in the environment is highly variable, but viral inactivation is usually complete within months. Higher primates may be infected with poliovirus, but they are unlikely reservoirs in nature. The only poliovirus reservoir remaining after eradication will be laboratory stocks. Serious attention must be given to reducing this potential source of infection. Polio eradication through immunization is evidenced by the documented absence of poliomyelitis in an increasing number of countries and the progressive disappearance of poliovirus genotypes.


title: Intracerebral vaccination suppresses the spread of rabies virus in the mouse brain

text: Abstract To investigate the efficacy of intracerebral (IC) immunization in preventing viral spread in the brain, we immunized mice with inactivated rabies virus via the subcutaneous (SC) or IC route, followed by administration of a lethal dose of rabies virus (challenge virus standard strain), directly into the brains of immunized mice. Progressive paralytic neurological signs were observed in control and 75% of SC immunized mice, whereas only 20% of IC immunized mice exhibited symptoms. Neutralizing antibody titers in blood plasma were significantly elevated in SC and IC immunized mice, with the highest levels seen in IC immunized mice. Analysis of whole brain lysates revealed a strong induction of immunoglobulin in the brains of IC immunized mice that had virus neutralizing activity. Histopathological examination of brain tissue revealed mild encephalitis and disseminated viral antigen in control and SC immunized mice, but rare in IC immunized mice. These results suggest that IC immunization induces a preventive humoral immune response against intracerebrally inoculated rabies virus. Induction of neutralizing antibody in cerebrospinal fluid represents a putative therapeutic measure for the treatment of rabid animals and humans.


title: Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19

text: Crystallography in its broadest sense has a crucial role to play in addressing the current COVID-19 pandemic. An outpouring of structural information on key viral proteins has resulted and importantly these data have immediately been shared with researchers round the world to speed the discovery of effective therapeutic agents.


title: Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

text: The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.


title: Application of telemedicine during the coronavirus disease epidemics: A rapid review and meta-analysis

text: Background: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. Methods: We searched MEDLINE, Web of Science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. Results: A total of 2,041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. Conclusions: Telemedicine services should focus on the issues that the public is most concerned about, such as the symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.


title: Complementation and recombination between Alfalfa Mosaic Virus RNA3 mutants in tobacco plants

text: Abstract Deletions were made in an infectious cDNA clone of alfalfa mosaic virus (AIMV) RNA3 and the replication of RNA transcripts of these cDNAs was studied in tobacco plants transformed with AIMV replicase genes (P12 plants). Previously, we found that deletions in the P3 gene did not affect accumulation of RNA3 in P12 protoplasts whereas deletions in the coat protein (CP) gene reduced accumulation 100-fold (A. C. van der Kuyl, L. Neeleman, and J. F. Bol, 1991, Virology 183, 687–694). In P12 plants deletions in the P3 gene reduced accumulation by about 200-fold and accumulation of CP deletion mutants was not detectable. When P12 plants were inoculated with a mixture of P3- and CP-deletion mutants, both mutants replicated efficiently and various amounts of full-length RNA3 molecules were formed by recombination. The observation that some P3 and CP mutants did not recombine at a detectable level after several passages in P12 plants demonstrated that mutations in the AIMV P3 and CP genes can be complemented in trans.


title: Satellite-detected tropospheric nitrogen dioxide and spread of SARS-CoV-2 infection in Northern Italy

text: Abstract Following the outbreak of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) last December 2019 in China, Italy was the first European country to be severely affected, with the first local case diagnosed on 20 February 2020. The virus spread quickly, particularly in the North of Italy, with three regions (Lombardy, Veneto and Emilia-Romagna) being the most severely affected. These three regions accounted for >80% of SARS-CoV-2 positive cases when the tight lockdown was established (March 8). These regions include one of Europe's areas of heaviest air pollution, the Po valley. Air pollution has been recently proposed as a possible risk factor of SARS-CoV-2 infection, due to its adverse effect on immunity and to the possibility that polluted air may even carry the virus. We investigated the association between air pollution and subsequent spread of the SARS-CoV-2 infection within these regions. We collected NO2 tropospheric levels using satellite data available on the European Space Agency before the lockdown. Using a multivariable restricted cubic spline regression model, we compared NO2 levels with SARS-CoV-2 infection prevalence rate at different time points after the lockdown, namely March 8, 22 and April 5, in the 28 provinces of Lombardy, Veneto and Emilia Romagna. We found little association of NO2 levels with SARS-CoV-2 prevalence up to about 130 μmol/m2, while a positive association was evident at higher levels at each time point. Notwithstanding the limitations of the use of aggregated data, these findings lend some support to the hypothesis that high levels of air pollution may favor the spread of the SARS-CoV-2 infection.


title: Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists

text: The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.


title: Strong Association between Respiratory Viral Infection Early after Hematopoietic Stem Cell Transplantation and the Development of Life-Threatening Acute and Chronic Alloimmune Lung Syndromes

text: Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with ideopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS (P <.0001). This was true for all viruses tested. In multivariate analysis, allo-LS was the only predictor for higher mortality (P = .04). Paradoxically, prolonged administration of immunosuppressive agents because of acute graft-versus-host disease had a protective effect on the development of allo-LS (P = .004). We hypothesize that early infection of the respiratory tract with a common cold virus makes the lungs a target for alloimmunity.


title: Chapter 6 Virus population dynamics examined with experimental model systems

text: Abstract Experimental evolution permits exploring the effect of controlled environmental variables in virus evolution. Several designs in cell culture and in vivo have established basic concepts that can assist in the interpretation of evolutionary events in the field. Important information has come from cytolytic and persistent infections in cell culture that have unveiled the power of virus-cell coevolution in virus and cell diversification. Equally informative are comparisons of the response of viral populations when subjected to different passage régimens. In particular, plaque-to-plaque transfers in cell culture have revealed unusual genotypes and phenotypes that populate minority layers of viral quasispecies. Some of these viruses display properties that contradict features established in virology textbooks. Several hypotheses and principles of population genetics have found experimental confirmation in experimental designs with viruses. The possibilities of using experimental evolution to understand virus behavior are still largely unexploited.


title: Identification of Influential users on Twitter: A Novel Weighted Correlated Influence Measure for Covid-19

text: In the era of advanced mobile technology, freedom of expression over social media has become prevalent among online users. This generates a huge amount of communication that eventually forms a ground for extensive research and analysis. The social network analysis allows identifying the influential people in society over microblogging platforms. Twitter, being an evolving social media platform, has become increasingly vital for online dialogues, trends, and content virality. Applications of discovering influential users over Twitter are manifold. It includes viral marketing, brand analysis, news dissemination, health awareness spreading, propagating political movement, and opinion leaders for empowering governance. In our research, we have proposed a sustainable approach, namely Weighted Correlated Influence (WCI), which incorporates the relative impact of timeline-based and trend-specific features of online users. Our methodology considers merging the profile activity and underlying network topology to designate online users with an influence score, which represents the combined effect. To quantify the performance of our proposed method, the Twitter trend #CoronavirusPandemic is used. Also, the results are validated for another social media trend. The experimental outcomes depict enhanced performance of proposed WCI over existing methods that are based on precision, recall, and F1-measure for validation.


A special edition of the Journal of Visceral Surgery on Covid-19: what problems, dangers and solutions have been identified?


title: Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy?()

text: BACKGROUND AND OBJETIVE: On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy. PATIENTS AND METHODS: Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy. RESULTS: There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid. CONCLUSIONS: It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.


title: CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES‐I statement): an extension of the STROBE statement

text: BACKGROUND: Population‐based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting. OBJECTIVE: The objective of the CONSISE ROSES ‐I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results. METHODS: The ROSES‐I statement was developed as an expert consensus of the CONSISE epidemiology and laboratory working groups. The recommendations are presented in the familiar format of a reporting guideline. Because seroepidemiologic studies are a specific type of observational epidemiology study, the ROSES‐I statement is built upon the STROBE guidelines. As such, the ROSES‐I statement should be seen as an extension of the STROBE guidelines. RESULTS: The ROSES ‐I statement presents 42 items that can be used as a checklist of the information that should be included in the results of published seroepidemiologic studies, and which can also serve as a guide to the items that need to be considered during study design and implementation. CONCLUSIONS: We hope that the ROSES‐I statement will contribute to improving the quality of reporting of seroepidemiologic studies.


Abstract 42. Metabolic alterations of HSV-1-infected neurons: studies using the PC12 cell as a model system


title: Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design

text: In December 2019, the first cases of a novel coronavirus infection causing COVID-19 were diagnosed in Wuhan, China. Viral Papain-Like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library containing natural and a wide variety of nonproteinogenic amino acids and performed comprehensive activity profiling of SARS-CoV-2-PLpro. On the scaffold of best hits from positional scanning we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro variants versus other proteases. We determined crystal structures of two of these inhibitors (VIR250 and VIR251) in complex with SARS-CoV-2-PLpro which reveals their inhibitory mechanisms and provides a structural basis for the observed substrate specificity profiles. Lastly, we demonstrate that SARS-CoV-2-PLpro harbors deISGylating activities similar to SARS-CoV-1-PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Altogether this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repositioning.


docid: epgmbkoj

title: Korean Society for Laboratory Medicine Practice Guidelines for the Molecular Diagnosis of Middle East Respiratory Syndrome During an Outbreak in Korea in 2015

text: For two months between May and July 2015, a nationwide outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) occurred in Korea. On June 3, 2015, the Korean Society for Laboratory Medicine (KSLM) launched a MERS-CoV Laboratory Response Task Force (LR-TF) to facilitate clinical laboratories to set up the diagnosis of MERS-CoV infection. Based on the WHO interim recommendations, the Centers for Disease Control and Prevention of United States guidelines for MERS-CoV laboratory testing, and other available resources, the KSLM MERS-CoV LR-TF provided the first version of the laboratory practice guidelines for the molecular diagnosis of MERS-CoV to the clinical laboratories on June 12, 2015. The guidelines described here are an updated version that includes case definition, indications for testing, specimen type and protocols for specimen collection, specimen packing and transport, specimen handling and nucleic acid extraction, molecular detection of MERS-CoV, interpretation of results and reporting, and laboratory safety. The KSLM guidelines mainly focus on the molecular diagnosis of MERS-CoV, reflecting the unique situation in Korea and the state of knowledge at the time of publication.


title: Online Databases and Non-coding RNAs in Cardiovascular Diseases

text: Cardiovascular disease is characterized by its highest morbidity and mortality. One of the main pathological basis of this disease is the dysregulation of gene expression. Non-coding RNA (ncRNA) is a kind of functional RNA, which is transcript from DNA but not translated into proteins. More and more studies have established the important roles of ncRNAs, including transcription, RNA maturation, translation, protein degradation, and their involvement in the pathogenesis of diseases such as cancer and cardiovascular diseases. This chapter will focus on the biological functions of ncRNAs and their advances in cardiovascular disease. With the development of sequencing and computer technology, more and more databases can be easily obtained on the internet. In another part of this chapter, we will summarize some commonly used non-coding RNA databases, which can be easily and quickly used for relevant research.


title: Altitude impact on the chemical profile and biological activities of Satureja thymbra L. essential oil

text: BACKGROUND: Several agricultural or environmental factors affect plants’ chemical and pharmacological properties. METHODS: In this study, the essential oil of Libyan Satureja thymbra was isolated from plants collected during two successive years at two different altitudes; Wasita (WEO) and Safsaf (SEO), 156 and 661 m above sea level, respectively. RESULTS: GC/MS allowed the identification of 21 and 23 compounds, respectively. Thymol prevailed in WEO (26.69%), while carvacrol prevailed in SEO (14.30%). Antimicrobial activity was tested by agar-well diffusion method, and MIC/MLC values were determined by broth dilution method. Values of MIC/MLC were 0.125/0.25 μg/ml for SEO against S. aureus, P. mirabilis and K. pneumonia and for WEO against B. subtilus. It was observed that plants growing at lower altitude in Wasita locality had better antifungal activity, while those growing at higher altitude at Safsaf locality had better antibacterial activity. Both essential oils had a better anthelmintic activity than the standard piperazine citrate against a tested earthworm. However, SEO oil had a significantly higher anthelmintic activity than WEO. Cytotoxicity of the oils tested using SRB assay on human breast cancer (MCF-7) and colon cancer cell lines (HCT-116) showed better activity for SEO, especially against HCT-116 with IC(50) 2.45 ± 0.21 μg/ml. CONCLUSIONS: Thus, altitude is an important factor that should be considered as it affected the yield, composition and biology of the plant extracts.