title: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China

text: Abstract Background A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. Methods We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. Results 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. Conclusions The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.


Another vision from the coronavirus health crisis in Spain: the perspective from 'Plena inclusión' Developmental Disabilities associative movement.


title: Geographical Information Systems and Health: Current State and Future Directions

text: This paper provides an introduction to Geographical Information Systems (GIS) and how they can be used. It reviews the current state of GIS use in health care before identifying the barriers to more pervasive use of GIS in health. Finally, it makes recommendations for the direction of health GIS research over the next decade and concludes with a call to action to health informatics researchers to stop ignoring a tool and methodology that has such immense potential for improving the health of our communities.


title: Molecular analysis of an outbreak of influenza in the United Kingdom

text: The first outbreak of influenza virus in Europe in 1995/1996 occurred in a school in the south of England. RT-PCR-restriction analysis was performed on the HA1 portion of influenza haemagglutinin gene amplified directly from clinical samples. These were taken at the onset of the outbreak and indicated co-circulation of two distinct genetic variants of influenza virus which were antigenically identical. Investigations of this nature demonstrate the genetic diversity of circulating variants of influenza and have the potential to provide information on molecular evolution of strains within closed populations.


title: Fecal‐Oral Transmission of COVID‐19: Could Hypochlorhydria Play a Role?

text: Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) which emerged in Wuhan, China in 2019 (1). Respiratory symptoms remain the most common clinical manifestations of COVID‐19. However, non‐respiratory symptoms are increasingly being recognized. Gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, diarrhea, and abdominal pain are noted in COVID‐19 patients either alone or in association with respiratory manifestations (2). Stool viral RNA can be detected by up to 50% in patients with diarrhea (3). This article is protected by copyright. All rights reserved.


title: Identification and characterization of potent small molecule inhibitor of hemorrhagic fever New World arenaviruses

text: Abstract Category A arenaviruses as defined by the National Institute of Allergy and Infectious Diseases (NIAID) are human pathogens that could be weaponized by bioterrorists. Many of these deadly viruses require biosafety level-4 (BSL-4) containment for all laboratory work, which limits traditional laboratory high-throughput screening (HTS) for identification of small molecule inhibitors. For those reasons, a related BSL-2 New World arenavirus, Tacaribe virus, 67–78% identical to Junín virus at the amino acid level, was used in a HTS campaign where approximately 400,000 small molecule compounds were screened in a Tacaribe virus-induced cytopathic effect (CPE) assay. Compounds identified in this screen showed antiviral activity and specificity against not only Tacaribe virus, but also the Category A New World arenaviruses (Junín, Machupo, and Guanarito). Drug resistant variants were isolated, suggesting that these compounds act through inhibition of a viral protein, the viral glycoprotein (GP2), and not through cellular toxicity mechanisms. A lead compound, ST-294, has been chosen for drug development. This potent and selective compound, with good bioavailability, demonstrated protective anti-viral efficacy in a Tacaribe mouse challenge model. This series of compounds represent a new class of inhibitors that may warrant further development for potential inclusion in a strategic stockpile.


title: Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy

text: BACKGROUND: Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. METHODS: We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. RESULTS: For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. CONCLUSION: The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.


title: Short hairpin RNA targeting NP mRNA inhibiting Newcastle disease virus production and other viral structural mRNA transcription

text: Newcastle disease virus (NDV), formally recognized as avian paramyxovirus 1 (APMV-1), is the etiological agent of Newcastle disease (ND), an affliction which can cause severe losses in the poultry industry. Better understanding of the molecular basis of viral structural genes involved with production should contribute significantly toward the development of improved prophylactic and therapeutic reagents to control the infection. Here we show that a short hairpin RNA (shRNA) eukaryotic expression vector targeting nucleocapsid (NP) gene of NDV can potently inhibit NDV production in both primary cells and embryonated chicken eggs. Moreover, shRNA specific for NP abolished the accumulation of not only the corresponding mRNA but also P, HN, F, M gene mRNA. The findings reveal that newly synthesized NP mRNA is essential for NDV transcription and replication, and provide a basis for the development of shRNAs as a prophylaxis and therapy for NDV infection in poultry.


title: Chapter Thirteen Intracellular Antiviral Immunity

text: Abstract Innate immunity is traditionally thought of as the first line of defense against pathogens that enter the body. It is typically characterized as a rather weak defense mechanism, designed to restrict pathogen replication until the adaptive immune response generates a tailored response and eliminates the infectious agent. However, intensive research in recent years has resulted in better understanding of innate immunity as well as the discovery of many effector proteins, revealing its numerous powerful mechanisms to defend the host. Furthermore, this research has demonstrated that it is simplistic to strictly separate adaptive and innate immune functions since these two systems often work synergistically rather than sequentially. Here, we provide a broad overview of innate pattern recognition receptors in antiviral defense, with a focus on the TRIM family, and discuss their signaling pathways and mechanisms of action with special emphasis on the intracellular antibody receptor TRIM21.


title: Gambling during the COVID-19 crisis - A cause for concern?

text: The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.


title: An Update on Feline Chronic Gingivostomatitis

text: Feline chronic gingivostomatitis is a frustrating disease to manage owing to its elusive etiopathogenesis and its subsequently suboptimal treatment options. Nevertheless, efforts to shed light on the disease over the past few decades have advanced the knowledge on its potential etiopathogenesis and the success rates of available treatment options. Further research is ongoing, with promising attempts to better understand and treat this, likely, multifactorial disease.


title: Popular economic narratives advancing the longest U.S. expansion 2009–2019

text: Abstract The U.S. economic expansion since 2009 is the longest on record since 1854, according to the National Bureau of Economic Research Business Cycle Dating Committee. This paper seeks to understand this phenomenon better by looking at the time paths of popular narratives over this interval, of stories that people have been telling that offer clues into their economic behavior. Six constellations of narratives are studied, identified by keywords “Great Depression,” “secular stagnation,” “sustainability,” “housing bubble,” “strong economy,” and “save more.”


title: CAMBIOS A PARTIR DE LA COVID-19. UNA PERSPECTIVA DESDE LA PEDIATRÍA INTERNA HOSPITALARIA

text: Resumen La dimensión de la pandemia por SARS-CoV2 ha afectado a la organización asistencial de la Pediatría Hospitalaria de nuestro país. Los nuevos retos generados por la COVID-19 exigen una serie de medidas proactivas basadas en los conocimientos científicos existentes y las normas de buena práctica, que permitan la preparación y la mayor operatividad de los servicios pediátricos hospitalarios. La Pediatría Interna Hospitalaria, como responsable de la atención integral del niño hospitalizado, tiene un papel principal en el nuevo modelo de hospital surgido de esta epidemia. En la presente revisión se analiza la repercusión pediátrica que ha tenido la epidemia por SARS-CoV2 y la preparación ante futuros rebrotes, en posible coexistencia con otras infecciones virales. Se revisa también la implicación de las unidades pediátricas en la asistencia de adultos y la atención de pacientes crónicos complejos y se ofrecen recomendaciones sobre aspectos de seguridad, consideraciones éticas y docencia de los futuros pediatras durante la crisis. La Sociedad Española de Pediatría Hospitalaria (SEPHO) pretende con este documento ofrecer a los pediatras internistas hospitalarios una serie de reflexiones y recursos de utilidad en un escenario con muchas incertidumbres. Abstract SARS-CoV2 pandemic dimension has affected the Hospital Pediatrics Medicine assistance in our country. New challenges generated by COVID-19 require a series of proactive measures, based on existing scientific knowledge and standards of good practice, that allow the Pediatric Hospital services readiness and operability. Hospital Internal Pediatrics, as responsible of integral care of the hospitalized child, plays a leading role in the new hospital model emerging from this crisis. This review analyzes the impact of the current SARS-CoV2 epidemic on pediatric care, and perspective of new COVID-19 outbreaks in coexistence with other viral infections. Changes secondary to pandemic involved in Hospital Pediatric units must be analyzed, and how to prepare for future epidemics, also the involvement of pediatric units in adult care and the possible opportunities for improvement. Assistance of patients with chronic complex conditions in epidemic circumstances, safety aspects, opportunities for teaching and ethical considerations are reviewed. The Spanish Society of Hospital Pediatrics Medicine offers with this article a series of resources for Internal Pediatric Medicine practitioners responsible to face next challenges in pediatric hospitalization units.


title: Globally Mobile Populations and the Spread of Emerging Pathogens

text: During the past decade, the global public health community has been challenged by the emergence and rapid worldwide spread of novel influenza strains, severe acute respiratory syndrome, chikungunya virus, drug-resistant tuberculosis, and other conditions and pathogens. Modern transportation and increased tourism, business travel, and immigration contributed to dissemination of these high-impact pathogens. The effectiveness of interventions such as airport screening, travel restrictions, and other community mitigation measures remains uncertain. However, human migration has occurred for centuries and will continue, despite the threats posed by microbes.


title: Simple framework for real-time forecast in a data-limited situation: the Zika virus (ZIKV) outbreaks in Brazil from 2015 to 2016 as an example

text: BACKGROUND: In 2015–2016, Zika virus (ZIKV) caused serious epidemics in Brazil. The key epidemiological parameters and spatial heterogeneity of ZIKV epidemics in different states in Brazil remain unclear. Early prediction of the final epidemic (or outbreak) size for ZIKV outbreaks is crucial for public health decision-making and mitigation planning. We investigated the spatial heterogeneity in the epidemiological features of ZIKV across eight different Brazilian states by using simple non-linear growth models. RESULTS: We fitted three different models to the weekly reported ZIKV cases in eight different states and obtained an R(2) larger than 0.995. The estimated average values of basic reproduction numbers from different states varied from 2.07 to 3.41, with a mean of 2.77. The estimated turning points of the epidemics also varied across different states. The estimation of turning points nevertheless is stable and real-time. The forecast of the final epidemic size (attack rate) is reasonably accurate, shortly after the turning point. The knowledge of the epidemic turning point is crucial for accurate real-time projection of the outbreak. CONCLUSIONS: Our simple models fitted the epidemic reasonably well and thus revealed the spatial heterogeneity in the epidemiological features across Brazilian states. The knowledge of the epidemic turning point is crucial for real-time projection of the outbreak size. Our real-time estimation framework is able to yield a reliable prediction of the final epidemic size. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-019-3602-9) contains supplementary material, which is available to authorized users.


title: Rapid detection of respiratory picornaviruses in nasopharyngeal aspirates by immunofluorescence assay

text: Abstract Background Respiratory picornaviruses (enteroviruses and rhinoviruses) are commonly cited as causes of self-limited upper respiratory tract infection. However, it has recently been suggested that they may cause more severe respiratory disease. Immunofluorescence (IF) assays are rapid and inexpensive and are often used for the detection of respiratory viruses. Objectives We sought to develop an IF procedure, using commercially available reagents, for the detection of respiratory picornaviruses directly from nasopharyngeal aspirates (NPA). Study design From 1st November 2006 until 31st October 2007 all NPA from patients with respiratory infection were stained with the Light Diagnostic Pan-Enterovirus Reagent – “Blend” by IF (IF-ENVPAN). Those specimens which tested positive with this stain were further tested (subject to the availability of frozen specimen) with the xTAG respiratory viral panel, a multiplex PCR directed against respiratory picornaviruses, adenovirus (ADV), respiratory sincytial virus (RSV), influenza viruses A and B (IFA and IFB), parainfluenza virus (PIV) 1–4, human metapneumovirus (HMPV) and coronaviruses. Results 241/1122 NPA tested positive by IF-ENVPAN. 143 NPA were available for testing by xTAG respiratory viral panel. The multiplex PCR detected respiratory picornaviruses in 139 NPA, in 126 as the sole viral pathogen. Conclusions Our results indicate the potential of IF-ENVPAN for the laboratory detection of respiratory picornaviruses in clinical specimens. As far as we are aware, this is the first publication of such a method.


title: Coronavirus humains (HCoV)

text: Résumé Les coronavirus forment un grand groupe de virus infectant les mammifères et les oiseaux ; cinq d’entre eux infectent l’homme : HCoV 229E et OC43, connus depuis les années 1960, SARS-CoV identifié en mars 2003 lors de l’épidémie de syndrome de détresse respiratoire aigu sévère, NL63 et HKU1, identifiés respectivement en 2004 et 2005. Ce sont des virus enveloppés dont le génome est une molécule d’ARN de polarité positive de très grande taille. Leur mode évolutif fait intervenir plusieurs paramètres : la génération de nombreux mutants lors de la réplication, responsable d’une distribution en quasi-espèces de la population virale, la capacité à établir des infections persistantes, la possibilité de délétions importantes, la grande flexibilité du génome due à un fort taux de recombinaisons homologues et hétérologues, la capacité à franchir les barrières d’espèces et à s’adapter au nouvel environnement. Les coronavirus (hors SARS-CoV) sont ubiquitaires et circulent sous forme épidémique. Les différents HCoV co-circulent avec une distribution entre les types qui est variable selon les années et les régions géographiques. Ce sont essentiellement des virus responsables d’infections respiratoires hautes et basses. Le SARS-CoV est, lui, un virus émergent responsable de l’épidémie de pneumopathies atypiques entre novembre 2002 et juillet 2003. Sa circulation a été interrompue grâce à la mise en place de mesures sanitaires drastiques. L’implication des HCoV dans des pathologies digestives et neurologiques reste à préciser. La détection des coronavirus est difficile, et fait appel surtout à des techniques moléculaires. Il n’existe actuellement aucun traitement spécifique des infections à HCoV. Abstract Coronaviruses are a large group of viruses and infect a lot of species of mammals and birds. Five coronaviruses currently infect humans: HCoVs 229E and OC43, identified in the 1960s, SARS-CoV identified in March 2003 during the SARS epidemic, and the HCoVs NL63 and HKU1, identified in 2004 and 2005 respectively. The genome of the coronaviruses is a linear, non-segmented, positive-sense single-stranded RNA molecule of approximately 30kb. The evolution of these viruses occurs through some features: the generation of multiple mutants during the replication resulting on a quasispecies structure of the viral population, the demonstrated ability of coronaviruses to establish persistent infections, the flexibility of the genome due to a high frequency of homologue or heterologue recombinations, the ability to jump barrier species and to adapt to the new environment. Two epidemiologic pictures of HCoV infections have to be distinguished: as suggested by recent studies, HCoVs except SARS-CoV, are distributed worldwide and cocirculate during seasonal outbreaks. The distribution of the different HCoV species varies according to the geographic area and season. In contrast, the SARS-CoV is responsible of the first emerging infectious disease of this millennium, infecting more than 8000 people between November 2002 and July 2003. Its circulation has been stopped by drastic public health policy. Human coronaviruses may be also involved in enteric and neurologic diseases. The detection of these viruses is difficult and mainly based on molecular assays (RT-PCR). There is no established specific therapy to date.


title: Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response

text: Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS.


title: At the height of the storm: Healthcare staff’s health conditions and job satisfaction and their associated predictors during the epidemic peak of COVID-19

text: Abstract This study reports the physical health, mental health, anxiety, depression, distress, and job satisfaction of healthcare staff in Iran when the country faced its highest number of total active COVID-19 cases. In a sample of 304 healthcare staff (doctors, nurses, radiologists, technicians, etc.), we found a sizable portion reached the cutoff levels of disorders in anxiety (28.0%), depression (30.6%), and distress (20.1%). Age, gender, education, access to PPE (personal protective equipment), healthcare institutions (public vs. private), and individual status of COVID-19 infection each predicted some but not all the outcome variables of SF-12, PHQ-4, K6, and job satisfaction. The healthcare workers varied greatly in their access to PPE and in their status of COVID-19 infection: negative (69.7%), unsure (28.0%), and positive (2.3%). The predictors were also different from those identified in previous studies of healthcare staff during the COVID-19 crisis in China. This study helps to identify the healthcare staff in need to enable more targeted help as healthcare staff in many countries are facing peaks in their COVID-19 cases.


Investment Income of US Nonprofit Hospitals in 2017


Crises and opportunities in terms of energy and AI technologies during the COVID-19 pandemic


title: Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition

text: Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.


COVID-19 pandemic and the stethoscope: don't forget to sanitize


title: Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

text: Coronavirus host and cell specificities are determined by specific interactions between the viral spike (S) protein and host cell receptor(s). Avian coronavirus infectious bronchitis (IBV) has been adapted to embryonated chicken eggs, primary chicken kidney (CK) cells, monkey kidney cell line Vero, and other human and animal cells. Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. Expression of S protein derived from Vero- and CK-adapted strains showed efficient induction of membrane fusion. However, expression of S protein cloned from the third passage of IBV in chicken embryo (EP3) did not show apparent syncytia formation. By construction of chimeric S constructs and site-directed mutagenesis, a point mutation (L857-F) at amino acid position 857 in the heptad repeat 1 region of S protein was shown to be responsible for its acquisition of the cell–cell fusion activity. Furthermore, a G405-D point mutation in the S1 domain, which was acquired during further propagation of Vero-adapted IBV in Vero cells, could enhance the cell–cell fusion activity of the protein. Re-introduction of L857 back to the S gene of Vero-adapted IBV allowed recovery of variants that contain the introduced L857. However, compensatory mutations in S1 and some distant regions of S2 were required for restoration of the cell–cell fusion activity of S protein carrying L857 and for the infectivity of the recovered variants in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins.


title: First Complete Genome Sequence of Currently Circulating Infectious Bronchitis Virus Strain DMV/1639 of the GI-17 Lineage

text: Avian infectious bronchitis virus is the causative agent of a highly contagious disease that results in severe economic losses to the poultry industry worldwide. Here, we report the first coding-complete genome sequence of strain DMV/1639 of the GI-17 lineage, isolated from broiler chickens in Georgia in 2019.


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title: The spread of the COVID‐19 coronavirus: Health agencies worldwide prepare for the seemingly inevitability of the COVID‐19 coronavirus becoming endemic

text: While it is too late to confine the COVID‐19 coronovirus outbreak to China, a wealth of data spurs epidemiological and vaccine research. [Image: see text]


title: When The Wrong People Are Immune

text: After a disaster such as the COVID-19 pandemic, there will be an irresistible desire to blame others. Despite documented failures in the federal government’s response to the pandemic, injured individuals will not be able to hold it accountable due to the broad application of governmental immunity. Congress and state governments have provided targeted immunity to various device manufacturers and emergency volunteers. However, the one group with huge targets on their backs are individual physicians, who are often making impossible choices that are reasonable at the time, but might not appear reasonable to a jury after the fact, and with the bias of hindsight. Recognizing that the potential for liability might cause undue psychological stress on health care providers, this essay argues for statutory immunity that protects them from rationing and other health care decisions that are made in good faith, and that are in compliance with documented state, institutional, or professional pandemic-response guidelines.


title: The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

text: The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.


title: Macroeconomic factors and frequency domain causality between Gold and Silver returns in India

text: Abstract This paper examines the relationship between gold and silver returns in India, using monthly data for the period May 1991 to June 2018. To this end, we employ the recently developed frequency domain rolling-window analysis (which is able to show that transitory high frequency shocks are not equal to permanent low frequency shocks over time), as well as the conditional, partial conditional, difference conditional approaches, in addition to the Toda Yamamoto and frequency domain Granger Causalities methods. Further, the relationship is examined in conditional and unconditional frameworks. To condition the relationship, three macroeconomic variables, namely interest rate, BSE stock index and inflation rate are used as the control variables. The results uncover some interesting predictability patterns that vary along the spectrum. Specifically, by applying the rolling-window analysis, we find mixed results of the causality between the gold and silver markets based on the frequencies of different lengths. Our results provide policy inputs, assist investors and hedgers who wish to invest in these markets by constructing strategies and diversify their portfolios based on different frequencies.


Letter of concern re: “Comparison of seven commercial RT-PCR Diagnostic kits for COVID-19” van Kasteren et al, Clinical Journal of Virology: https://doi.org/10.1016/j.jcv.2020.104412


title: Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes

text: BACKGROUND: T-cell epitopes that promiscuously bind to multiple alleles of a human leukocyte antigen (HLA) supertype are prime targets for development of vaccines and immunotherapies because they are relevant to a large proportion of the human population. The presence of clusters of promiscuous T-cell epitopes, immunological hotspots, has been observed in several antigens. These clusters may be exploited to facilitate the development of epitope-based vaccines by selecting a small number of hotspots that can elicit all of the required T-cell activation functions. Given the large size of pathogen proteomes, including of variant strains, computational tools are necessary for automated screening and selection of immunological hotspots. RESULTS: Hotspot Hunter is a web-based computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes through analysis of antigenic diversity. It allows screening and selection of hotspots specific to four common HLA supertypes, namely HLA class I A2, A3, B7 and class II DR. The system uses Artificial Neural Network and Support Vector Machine methods as predictive engines. Soft computing principles were employed to integrate the prediction results produced by both methods for robust prediction performance. Experimental validation of the predictions showed that Hotspot Hunter can successfully identify majority of the real hotspots. Users can predict hotspots from a single protein sequence, or from a set of aligned protein sequences representing pathogen proteome. The latter feature provides a global view of the localizations of the hotspots in the proteome set, enabling analysis of antigenic diversity and shift of hotspots across protein variants. The system also allows the integration of prediction results of the four supertypes for identification of hotspots common across multiple supertypes. The target selection feature of the system shortlists candidate peptide hotspots for the formulation of an epitope-based vaccine that could be effective against multiple variants of the pathogen and applicable to a large proportion of the human population. CONCLUSION: Hotspot Hunter is publicly accessible at . It is a new generation computational tool aiding in epitope-based vaccine design.


title: Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers

text: The filoviruses Marburg virus and Ebola virus (EBOV) quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs). A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, “druggable” countermeasures for filoviruses and other microbial pathogens.


title: The fiscal value of human lives lost from coronavirus disease (COVID-19) in China

text: OBJECTIVE: According to the WHO coronavirus disease (COVID-19) situation report 35, as of 24th February 2020, there was a total of 77,262 confirmed COVID-19 cases in China. That included 2595 deaths. The specific objective of this study was to estimate the fiscal value of human lives lost due to COVID-19 in China as of 24th February 2020. RESULTS: The deaths from COVID-19 had a discounted (at 3%) total fiscal value of Int$ 924,346,795 in China. Out of which, 63.2% was borne by people aged 25–49 years, 27.8% by people aged 50–64 years, and 9.0% by people aged 65 years and above. The average fiscal value per death was Int$ 356,203. Re-estimation of the economic model alternately with 5% and 10 discount rates led to a reduction in the expected total fiscal value by 21.3% and 50.4%, respectively. Furthermore, the re-estimation of the economic model using the world’s highest average life expectancy of 87.1 years (which is that of Japanese females), instead of the national life expectancy of 76.4 years, increased the total fiscal value by Int$ 229,456,430 (24.8%).


title: Behavioural intentions in response to an influenza pandemic

text: BACKGROUND: Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. METHODS: A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. RESULTS: Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. CONCLUSIONS: Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react.


title: A pilot study of minimum operational flow for loose-fitting powered air-purifying respirators used in healthcare cleaning services

text: The objective of this pilot study was to determine the minimum operational flow for loose-fitting powered air-purifying respirators (PAPR) used in healthcare cleaning services. An innovative respiratory flow recording device was worn by nine healthcare workers to obtain the minute volume (MV, L/min), mean inhalation flow (MIF, L/min), and peak inhalation flow (PIF, L/min) while performing “isolation unit work” (cleaning and disinfecting) of a patient room within 30 min. The MV and PIF were compared with the theoretical values obtained from an empirical formula. The correlations of MV, MIF, and PIF with subjects’ age, weight, height, body surface area (A(Du)), and body mass index (BMI) were analyzed. The average MV, MIF, and PIF were 33, 74, and 107 L/min, with maximal airflow rates of 41, 97, and 145 L/min, respectively, which are all below the current 170 L/min minimum operational flow for NIOSH certified loose-fitting PAPRs.


title: Rapid syndromic molecular testing in pneumonia: The current landscape and future potential

text: Summary Community acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) are all associated with significant mortality and cause huge expense to health care services around the world. Early, appropriate antimicrobial therapy is crucial for effective treatment. Syndromic diagnostic testing using novel, rapid multiplexed molecular platforms represents a new opportunity for rapidly targeted antimicrobial therapy to improve patient outcomes and facilitate antibiotic stewardship. In this article we review the currently available testing platforms and discuss the potential benefits and pitfalls of rapid testing in pneumonia.


Neurosurgical Service Coverage During the Coronavirus 2019 (COVID-19) Pandemic: The “Battle Plan” at the University of South of Florida Affiliate Hospitals


title: Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells

text: The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold resembling a right hand with a flexible, positively charged β-hairpin and a hydrophobic palm. This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.


Fatty acid composition of human milk lipids in Chilean women


title: Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review

text: BACKGROUND: Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications. METHODS: A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs? RESULTS: We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems. CONCLUSIONS: We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.


title: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis

text: Abstract Introduction We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. Methods We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. Results We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41–57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091–0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4–12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35–1.8). Conclusion In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.


title: Solution Characterization of the Extracellular Region of CD147 and Its Interaction with Its Enzyme Ligand Cyclophilin A

text: The CD147 receptor plays an integral role in numerous diseases by stimulating the expression of several protein families and serving as the receptor for extracellular cyclophilins; however, neither CD147 nor its interactions with its cyclophilin ligands have been well characterized in solution. CD147 is a unique protein in that it can function both at the cell membrane and after being released from cells where it continues to retain activity. Thus, the CD147 receptor functions through at least two mechanisms that include both cyclophilin-independent and cyclophilin-dependent modes of action. In regard to CD147 cyclophilin-independent activity, CD147 homophilic interactions are thought to underlie its activity. In regard to CD147 cyclophilin-dependent activity, cyclophilin/CD147 interactions may represent a novel means of signaling since cyclophilins are also peptidyl–prolyl isomerases. However, direct evidence of catalysis has not been shown within the cyclophilin/CD147 complex. In this report, we have characterized the solution behavior of the two most prevalent CD147 extracellular isoforms through biochemical methods that include gel-filtration and native gel analysis as well as directly through multiple NMR methods. All methods indicate that the extracellular immunoglobulin-like domains are monomeric in solution and, thus, suggest that CD147 homophilic interactions in vivo are mediated through other partners. Additionally, using multiple NMR techniques, we have identified and characterized the cyclophilin target site on CD147 and have shown for the first time that CD147 is also a substrate of its primary cyclophilin enzyme ligand, cyclophilin A.


title: The Structure and Topology of α-Helical Coiled Coils

text: α-Helical coiled coils constitute one of the most diverse folds yet described. They range in length over two orders of magnitude; they form rods, segmented ropes, barrels, funnels, sheets, spirals, and rings, which encompass anywhere from two to more than 20 helices in parallel or antiparallel orientation; they assume different helix crossing angles, degrees of supercoiling, and packing geometries. This structural diversity supports a wide range of biological functions, allowing them to form mechanically rigid structures, provide levers for molecular motors, project domains across large distances, mediate oligomerization, transduce conformational changes and facilitate the transport of other molecules. Unlike almost any other protein fold known to us, their structure can be computed from parametric equations, making them an ideal model system for rational protein design. Here we outline the principles by which coiled coils are structured, review the determinants of their folding and stability, and present an overview of their diverse architectures.


title: Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia

text: Summary Objectives To report the experience with Middle East respiratory syndrome coronavirus (MERS-CoV) infection at a single center in Saudi Arabia. Methods Cases of laboratory-confirmed MERS-CoV occurring from October 1, 2012 to May 31, 2014 were reviewed retrospectively. Information sources included medical files, infection control outbreak investigations, and the preventive medicine database of MERS-CoV-infected patients. Data were collected on clinical and epidemiological aspects and outcomes. Results Seventy consecutive patients were included. Patients were mostly of older age (median 62 years), male (46, 65.7%), and had healthcare acquisition of infection (39, 55.7%). Fever (43, 61.4%), dyspnea (42, 60%), and cough (38, 54.3%) were the most common symptoms. The majority developed pneumonia (63, 90%) and required intensive care (49, 70%). Infection commonly occurred in clusters. Independent risk factors for severe infection requiring intensive care included concomitant infections (odds ratio (OR) 14.13, 95% confidence interval (CI) 1.58–126.09; p =0.018) and low albumin (OR 6.31, 95% CI 1.24–31.90; p =0.026). Mortality was high (42, 60%), and age ≥65 years was associated with increased mortality (OR 4.39, 95% CI 2.13–9.05; p <0.001). Conclusions MERS-CoV can cause severe infection requiring intensive care and has a high mortality. Concomitant infections and low albumin were found to be predictors of severe infection, while age ≥65 years was the only predictor of increased mortality.


title: The response of hotel performance to international tourism development and crisis events

text: Abstract This study uses panel regression tests to examine the response of hotel performance to international tourism development and crisis events in Taiwan. Hotel performance measures are revenue (revenue per available room and occupancy rate), profitability (return on assets and return on equity) and stock performance. The crises were the earthquake on September 21, 1999 (the 9/21 earthquake), the terrorist attacks of September 11, 2001 in the US (the 9/11 terrorist attacks) and the outbreak of Severe Acute Respiratory Syndrome on April 22, 2003 (the SARS outbreak). This study makes four major contributions. First, test results confirm that international tourism development (ITD), proxied by the growth of total inbound tourist arrivals, has a more direct influence on hotel sales and profitability than it does on hotel stock performance. Second, this study identifies that the absence of a strong tie between ITD and hotel stock returns that was found in previous studies is due to the time-varying discount rate caused by investors’ changing expectations for the prospect of future cash flows from holding hotel stocks. Third, this study finds new evidence that while the poor performance of hotel stocks caused by the 9/21 earthquake and the 9/11 terrorist attacks was attributed to the loss of hotel sales revenue, the adverse effect of the SARS outbreak on hotel stock returns is attributed not only to decreased hotel sales revenue but also to the increased discount rate. Lastly, this study is the first to investigate whether the response of hotel stock returns to ITD depends on the state of economy and concludes that the response of hotel stock performance to ITD in business cycle contraction is statistically different from that in business cycle expansion. Further, although the influence of ITD on hotel stock performance is still irrelevant during expansion periods, ITD can significantly enhance hotel stock returns during contraction periods.


title: Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study

text: Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0–54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m(2) (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m(2) and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.


title: A quick evaluation method of nosocomial infection risk for cancer hospitals during the COVID-19 pandemic

text: Nosocomial infections caused by COVID-19 will result in the immediate closure of the infected medical facility due to the highly contagious nature of COVID-19, further worsening medical shortages. We performed a Delphi consulting study to develop a risk model based on the experience of recently resumed activities in many cancer hospitals in China. Similar method had been used in a Chinese cancer hospital and effectively reduced the nosocomial Infection. We believe that the model can quickly identify COVID-19 cluster risks for medical facilities. The evaluation model could also be integrated into the hospital’s emergency response system in a timely manner.


title: COVID-19 medical papers have fewer women first authors than expected

text: The COVID-19 pandemic has resulted in school closures and distancing requirements that have disrupted both work and family life for many. Concerns exist that these disruptions caused by the pandemic may not have influenced men and women researchers equally. Many medical journals have published papers on the pandemic, which were generated by researchers facing the challenges of these disruptions. Here we report the results of an analysis that compared the gender distribution of authors on 1893 medical papers related to the pandemic with that on papers published in the same journals in 2019, for papers with first authors and last authors from the United States. Using mixed-effects regression models, we estimated that the proportion of COVID-19 papers with a woman first author was 19% lower than that for papers published in the same journals in 2019, while our comparisons for last authors and overall proportion of women authors per paper were inconclusive. A closer examination suggested that women’s representation as first authors of COVID-19 research was particularly low for papers published in March and April 2020. Our findings are consistent with the idea that the research productivity of women, especially early-career women, has been affected more than the research productivity of men.


Outbreaks of enterovirus D68 in Malaysia: genetic relatedness to the recent US outbreak strains


title: Chapter 14 Future Directions for Biosecurity

text: Abstract This chapter discusses the likely future of bioweapons development and the research that is needed to counter them. Methods for creating customized pathogens that can evade an immune system or work around a conventional antibiotic are discussed. In addition, emerging trends in synthetic biology are discussed. Biological warfare and bioterrorism are multifaceted problems requiring multifaceted solutions. Fortunately, the same advances in genomic biotechnologies that can be used to create bioweapons can also be used to set up countermeasures against them. We currently have in place sophisticated and well-developed biosecurity and biodefense programs. These programs are essential to countering the asymmetric warfare threat, but they are costly and perishable. Future directions in biosecurity and biodefense may very well be determined by the “next event.” However, the most likely events are those that naturally and accidentally threaten human and animal health through the emergence of novel pathogens and the reemergence of others in light of new environmental or societal factors.


title: Effect of Wall Texture on Perceptual Spaciousness of Indoor Space

text: As the main place of people’s daily activities, indoor space (its size, shape, colors, material and textures, and so on) has important physical, emotional and health-based implications on people’s behavior and quality of life. Material texture is an integral part of architectural environment perception and quality evaluation, but the effect of material texture on perceptual spaciousness lacks the support of experimental data. This research examined the effects between different wall textures on the observer’s perception of spaciousness in indoor space, the influence of wall texture changes in different room sizes, and how the associational meaning of texture affects the degree of influence of wall texture on the spaciousness of indoor space. By using VR technology and the magnitude estimation (ME) analysis method, the authors found that the effect of wall texture on perceptual spaciousness varies depending on the wall material, and the textural effect is affected by room size. The perception of spaciousness is influenced by the observer’s associational meaning of material texture, and the influence of associational meaning of material texture varies contingent on the room size. In relatively small rooms, the objective aspect (such as hardness, surface reflectivity, texture direction and texture depth) of the wall texture has a significant impact on perceived space. In contrast, the effects of subjective aspects (such as affinity and ecology) become more pronounced in relatively larger rooms. This research makes up for the lack of material texture research in perceptual spaciousness, and provides a new way for the designer to choose materials for the design of a spatial scale.


Prevention of COVID-19 in patients with IBD – Authors' reply


title: A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin

text: BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. CASE PRESENTATION: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. CONCLUSION: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.


title: Does early EBV infection protect against IgE sensitization?

text: Background There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood. Objective To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization. Methods A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Results There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV. Conclusion Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.


Reforming the World Health Assembly


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title: Emerging and Re-Emerging Infectious Diseases: Influenza as a Prototype of the Host-Pathogen Balancing Act

text: To respond to emerging and re-emerging infections, it is necessary to understand the interactions between microbial pathogens and their hosts and the impact of environmental and social factors on these interactions. The importance of understanding host-pathogen interactions is underscored by the emergence of virulent H5N1 avian influenza viruses and their transmission to humans, and the potential pandemic threat they pose.


title: Mathematical prediction of the time evolution of the COVID-19 pandemic in Italy by a Gauss error function and Monte Carlo simulations

text: In this paper are presented mathematical predictions on the evolution in time of the number of positive cases in Italy of the COVID-19 pandemic based on official data and on the use of a function of the type of a Gauss error function, with four parameters, as a cumulative distribution function. We have analyzed the available data for China and Italy. The evolution in time of the number of cumulative diagnosed positive cases of COVID-19 in China very well approximates a distribution of the type of the error function, that is, the integral of a normal, Gaussian distribution. We have then used such a function to study the potential evolution in time of the number of positive cases in Italy by performing a number of fits of the official data so far available. We then found a statistical prediction for the day in which the peak of the number of daily positive cases in Italy occurs, corresponding to the flex of the fit, that is, to the change in sign of its second derivative (i.e., the change from acceleration to deceleration), as well as of the day in which a substantial attenuation of such number of daily cases is reached. We have also analyzed the predictions of the cumulative number of fatalities in both China and Italy, obtaining consistent results. We have then performed 150 Monte Carlo simulations to have a more robust prediction of the day of the above-mentioned peak and of the day of the substantial decrease in the number of daily positive cases and fatalities. Although official data have been used, those predictions are obtained with a heuristic approach since they are based on a statistical approach and do not take into account either a number of relevant issues (such as number of daily nasopharyngeal swabs, medical, social distancing, virological and epidemiological) or models of contamination diffusion.


title: The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy

text: Cancer immunotherapy has made remarkable clinical advances in recent years. Antibodies targeting the immune checkpoint receptors PD-1 and CTLA-4 and adoptive cell therapy (ACT) based on ex vivo expanded peripheral CTLs, tumor infiltrating lymphocytes (TILs), gene-engineered TCR- and chimeric antigen receptor (CAR)-T cells have all shown durable clinical efficacies in multiple types of cancers. However, these immunotherapeutic approaches only benefit a small fraction of cancer patients as various immune resistance mechanisms and limitations make their effective use a challenge in the majority of cancer patients. For example, adaptive resistance to therapeutic PD-1 blockade is associated with an upregulation of some additional immune checkpoint receptors. The efficacy of transferred tumor-specific T cells under the current clinical ACT protocol is often limited by their inefficient engraftment, poor persistence, and weak capability to attack tumor cells. Recent studies demonstrate that the complement receptor C3aR and C5aR function as a new class of immune checkpoint receptors. Complement signaling through C3aR and C5aR expressed on effector T lymphocytes prevent the production of the cytokine interleukin-10 (IL-10). Removing C3aR/C5aR-mediated transcriptional suppression of IL-10 expression results in endogenous IL-10 production by antitumor effector T cells, which drives T cell expansion and enhances T cell-mediated antitumor immunity. Importantly, preclinical, and clinical data suggest that a signaling axis consisting of complement/C3aR/C5aR/IL-10 critically regulates T cell mediated antitumor immunity and manipulation of the pathway ex vivo and in vivo is an effective strategy for cancer immunotherapy. Furthermore, a combination of treatment strategies targeting the complement/C3aR/C5aR/IL-10 pathway with other treatment modalities may improve cancer therapeutic efficacy.


title: Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data

text: BACKGROUND: The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. METHODS: We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. RESULTS: For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. CONCLUSIONS: For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.


title: Good ACE, bad ACE do battle in lung injury, SARS

text: Two studies show how the enzyme ACE2 protects against lung injury caused by SARS and other agents. ACE2 seems to counteract the effects of ACE, which are more damaging (pages 875–879).


title: A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat

text: BACKGROUND: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. METHODS: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. RESULTS: Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. CONCLUSIONS: AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. TRIAL REGISTRATION: ISRCTN: ISRCTN00003567


title: Efficacy of toltrazuril as a metaphylactic and therapeutic treatment of coccidiosis in first–year grazing calves

text: A multicentric, placebo–controlled, randomised, blinded and blocked field study was conducted to evaluate the efficacy and safety of toltrazuril (Baycox(®), Bayer AG, Leverkusen, Germany) in the treatment of coccidiosis in first–year grazing calves naturally infected with Eimeria spp. Three–hundred and thirty–one calves were enrolled in the study and allocated to one of two treatments at a ratio of 1:1. One hundred and sixty–seven animals were treated once orally with 15 mg/kg toltrazuril, and 164 animals served as placebo–treated controls. Two treatment regimes were compared, a metaphylactic (treatment on the day, or 1 day after, turn out) and a therapeutic treatment (4 or 7 days after turn out). During an observation period of 14 days after treatment the animals were clinically examined for diarrhoea and faecal samples were regularly assessed for Eimeria oocysts. Other possible causes of diarrhoea were excluded on the basis of microbiological and virological examination. Animals were predominantly infected with Eimeria alabamensis. Number of days with diarrhoea in animals treated with toltrazuril was significantly lower compared to the placebo–treated group (therapeutic treatment: P=0.0024; metaphylactic treatment: P<0.0001). Furthermore, the number of animals with diarrhoea during the observation period for a minimum of at least 3 days, the number of animals positive for Eimeria oocysts, and the number of animals with both diarrhoea for a period of at least 3 days and positive for Eimeria oocysts, were signiflicantly lower (P<0.01), in the toltrazuril– compared to the placebo–treated animals. Body weight in the toltrazuril–treated animals significantly exceeded that of the placebo–treated animals at the end of the observation period. Mean difference in body weight was higher in the metaphylactic (+7.3 kg) compared to the therapeutic treatment group (+3.4 kg). No adverse reactions were observed. The results indicate that toltrazuril is highly efficacious and safe in the metaphylactic and therapeutic treatment of coccidiosis caused by E. alabamensis in first–year grazing calves.


SARS-CoV-2 pandemic in India: what might we expect?


title: Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate

text: Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K(6)HPTi(2)W(10)O(40)). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.


title: Retention of p63 in an ER-Golgi intermediate compartment depends on the presence of all three of its domains and on its ability to form oligomers

text: The type II membrane protein p63 is a resident protein of a membrane network interposed between rough ER and Golgi apparatus. To study the retention of p63, mutant forms were expressed in COS cells and the intracellular distribution determined by immunofluorescence microscopy. Investigation of chimeric constructs between p63 and the plasma membrane protein dipeptidylpeptidase IV showed that protein sequences from all three domains of the p63 protein are required to achieve complete intracellular retention. Mutational analysis of the 106-amino acid cytoplasmic tail of p63 revealed that the NH2-terminal 23 amino acids are necessary for retention. When p63 was solubilized with Triton X-100 and subjected to centrifugation at 100,000 g, it formed large, insoluble oligomers, particularly at neutral pH and below. A comparison of the behavior of wildtype and mutant p63 proteins in this assay revealed a perfect correlation between the formation of large oligomers and correct intracellular retention. These results suggest that self- association may be a major mechanism by which p63 is retained between the rough ER and the Golgi apparatus.


title: Fluorescent probes for proteolysis: Tools for drug discovery

text: Cells contain numerous proteases, which are found at many different locations. These proteases recognize an even larger number of different substrates and are involved in almost every process in the cell. Aberrations in proteolysis are linked to a plethora of diseases, such as cancer, inflammation, arteriosclerosis, neurodegeneration and infection. Because of their well-defined chemistry and key role in pathologies, proteases have been important targets for drug development. Recent progress in the development of fluorescent probes has opened up the possibility of visualizing protease activities in the natural environment of the cell. We will describe various strategies to follow protease activities in cells and organisms.


title: Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study

text: BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula. METHODS: In this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses. FINDINGS: Between Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean R(e) of 1·16. INTERPRETATION: Despite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility. FUNDING: German Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership.


Molecular Insights into Classic Examples of Evolution


Legal Immunity for Physicians During the Covid-19 Pandemic: Needs to Address Legal and Ethical Challenges


title: Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13

text: SARS coronavirus encodes non-structural protein 13 (nsP13), a nucleic acid helicase/NTPase belonging to superfamily 1 helicase, which efficiently unwinds both partial-duplex RNA and DNA. In this study, unwinding of DNA substrates that had different duplex lengths and 5′-overhangs was examined under single-turnover reaction conditions in the presence of excess enzyme. The amount of DNA unwound decreased significantly as the length of the duplex increased, indicating a poor in vitro processivity. However, the quantity of duplex DNA unwound increased as the length of the single-stranded 5′-tail increased for the 50-bp duplex. This enhanced processivity was also observed for duplex DNA that had a longer single-stranded gap in between. These results demonstrate that nsP13 requires the presence of a long 5′-overhang to unwind longer DNA duplexes. In addition, enhanced DNA unwinding was observed for gapped DNA substrates that had a 5′-overhang, indicating that the translocated nsP13 molecules pile up and the preceding helicase facilitate DNA unwinding. Together with the propensity of oligomer formation of nsP13 molecules, we propose that the cooperative translocation by the functionally interacting oligomers of the helicase molecules loaded onto the 5′-overhang account for the observed enhanced processivity of DNA unwinding.


title: Living with COVID-19-triggered pseudoscience and conspiracies

text: OBJECTIVE: This piece of work proposes a way for the wise management of pseudoscience and conspiracy theories. METHODS: This work encompassed a review of relevant literature and synthesized the critical thoughts on the proper management of pseudoscience and conspiracy theories. RESULT: The coronavirus disease 2019 (COVID-19) overwhelmingly challenges the competency of the digital generation. Consequently, public had been left stranded, helpless and anxious, especially during the peak season of the pandemic. However, this crisis creates a conducive environment for pseudoscience and conspiracy theories to proliferate. Pseudoscience and conspiracy theories negatively impacted the effort made to contain COVID-19. CONCLUSION: This piece of work, however, argues that although pseudoscience and conspiracy theories are real threats to conventional science, effort needs to be made to develop a sort of database to archive and curate them for downstream use.


title: Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette I. Inhalation toxicology and histopathology

text: Abstract Sprague-Dawley rats were exposed 6 hr per day for 14 consecutive days to aged and diluted sidestream smoke (ADSS), used as a surrogate for Environmental Tobacco Smoke (ETS), at concentrations of 0.1 (typical), 1 (extreme), or 10 (exaggerated) mg of particulates per cubic meter. Animals were exposed nose-only, inside whole-body chambers, to ADSS from the 1R4F reference cigarette. End-points included histopathology, CO-oximetry, plasma nicotine and cotinine, clinical pathology, and organ and body weights. The only pathological response observed was slight to mild epithelial hyperplasia and inflammation in the most rostral part of the nasal cavity, in the high-exposure group only. No effects were noted at medium or low exposures. The minimal changes noted were reversible, using a subgroup of animals kept without further treatment for an additional 14 days. Overall, the end-points used in the study demonstrated that there was no detectable biological activity of ADSS at typical or even 10-fold ETS concentrations and that the activity was only minimal at very exaggerated concentrations (particle concentrations 100 times higher than typical real-world concentrations).


title: Clinical features and chest CT findings of three cases of 2019 novel coronavirus (COVID-2019) pneumonia

text: BACKGROUND: Since December 2019, a new type of acute respiratory disease caused by the 2019 novel coronavirus (COVID-2019) appeared to Wuhan, China. Currently, positive of virus nucleic acid in respiratory or blood samples is the gold standard for the diagnosis of the disease, but the nucleic acid test may be false negative. Chest CT examination plays an important role in diagnosis of COVID-2019 pneumonia. CASE PRESENTATION: The clinical manifestations, laboratory examination, and chest CT characteristics of 3 patients with COVID-2019 pneumonia were reported. The mainly clinical manifestation of the 3 patients was fever. white blood cell, neutrophil cell and lymphocyte cell count can be normal, only C-Reactive Protein slightly elevated. Real-time fluorescence polymerase chain reaction of throat swab detection can be negative. Chest CT showed multifocal ground-glass opacities (GGO) in the peripheral of bilateral lungs. GGOs with consolidation, air bronchogram, vascular enlargement and halo sign were be found. CONCLUSIONS: In the early stages of COVID-2019 pneumonia, the laboratory parameters may be normal, the nucleic acid test may be false negative. Chest CT examination may be helpful for diagnosis of COVID-2019 pneumonia.


title: Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts

text: Abstract We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon–silicon bonds, but NN16 possesses some oxygen–silicon bonds that are unstable in water. The nucleic acid used in the experiments was targeted against GAG-1 gene from the human immunodeficiency virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane dendrimers decreased the fluidity of the hydrophilic part of the membrane but increased the fluidity of the hydrophobic interior. They induced hemolysis, but did not change the morphology of the cells. Increasing concentrations of dendrimers induced erythrocyte aggregation. Binding of short interfering ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of cationic groups and diminished their cytotoxicity. siRNA–dendrimer complexes changed neither the fluidity of biological membranes nor caused cell hemolysis. Addition of dendriplexes to red blood cell suspension induced echinocyte formation.


title: Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways

text: Acute respiratory distress syndrome (ARDS) caused by severe sepsis remains a major challenge in intensive care medicine. ACE2 has been shown to protect against lung injury. However, the mechanisms of its protective effects on ARDS are largely unknown. Here, we report that ACE2 prevents LPS-induced ARDS by inhibiting MAPKs and NF-κB signaling pathway. Lentiviral packaged Ace2 cDNA or Ace2 shRNA was intratracheally administrated into the lungs of male SD rats. Two weeks after gene transfer, animals received LPS (7.5 mg/Kg) injection alone or in combination with Mas receptor antagonist A779 (10 μg/Kg) or ACE2 inhibitor MLN-4760 (1 mg/Kg) pretreatment. LPS-induced lung injury and inflammatory response were significantly prevented by ACE2 overexpression and deteriorated by Ace2 shRNA. A779 or MLN-4760 pretreatment abolished the protective effects of ACE2. Moreover, overexpression of ACE2 significantly reduced the Ang II/Ang-(1-7) ratio in BALF and up-regulated Mas mRNA expression in lung, which was reversed by A779. Importantly, the blockade of ACE2 on LPS-induced phosphorylation of ERK1/2, p38 and p50/p65 was also abolished by A779. Whereas, only the ERK1/2 inhibitor significantly attenuated lung injury in ACE2 overexpressing rats pretreated with A779. Our observation suggests that AEC2 attenuates LPS-induced ARDS via the Ang-(1-7)/Mas pathway by inhibiting ERK/NF-κB activation.


title: Do we have enough evidence how seasonal influenza is transmitted and can be prevented in hospitals to implement a comprehensive policy?

text: PURPOSE: To identify if there is enough evidence at low risk-of-bias to prevent influenza transmission by vaccinating health-care workers (HCWs), patients and visitors; screening for laboratory-proven influenza all entering hospitals; screening asymptomatic individuals; identifying influenza supershedders; hand-washing and mask-wearing by HCWs, patients and visitors; and cleaning hospital rooms and equipment. PRINCIPAL RESULTS: Vaccination reduces influenza episodes of vaccinated (4.81/100 HCW) compared to unvaccinated (7.54/100) HCWs/influenza season. A Cochrane review found for inactivated vaccines the Number Needed to Vaccinate (NNV) = 71 (95%CI 64%, 80%) for adults 18–60 (same age as HCWs) to prevent laboratory-proven influenza. There are no RCTs of screening HCWs, patients, visitors and influenza supershedders to prevent transmission. None of four RCTs of HCWs mask-wearing (two directly observed, two not) showed an effect because they were underpowered either due to small size or low circulation of influenza. Hospital rooms and equipment can effectively be cleaned of influenza by many chemicals and hydrogen peroxide vapor machines but the cleaning cycle needs shortening to increase the likelihood of adoption. MAJOR CONCLUSIONS: HCW vaccination is a partial solution with current vaccination levels. There are no RCTs of screening HCWs, patients and visitors demonstrating preventing influenza transmission. Only one study costed furloughing HCWs with influenza and no RCTs have identified benefits of isolating influenza supershedders. RCTs of directly- and electronically continuously-observed mask-wearing and hand-hygiene and RCTs of incentives for meticulous hygiene are required. RCTs of engineering solutions (external venting, frequent room air changes) are needed. A wide range of chemicals effectively cleans hospital rooms and equipment from influenza. Hydrogen peroxide vapor is effective against influenza and a wide range of bacterial pathogens with patient room changes, and clean areas cleaners do not clean but its cleaning cycle needs shortening to increase the likelihood of adoption of cleaning rooms vacated by influenza patients.


title: Dynamical response of multi-patch, flux-based models to the input of infected people: Epidemic response to initiated events

text: Abstract The time course of an epidemic can be modeled using the differential equations that describe the spread of disease and by dividing people into “patches” of different sizes with the migration of people between these patches. We used these multi-patch, flux-based models to determine how the time course of infected and susceptible populations depends on the disease parameters, the geometry of the migrations between the patches, and the addition of infected people into a patch. We found that there are significantly longer lived transients and additional “ancillary” epidemics when the reproductive rate R is closer to 1, as would be typical of SARS (Severe Acute Respiratory Syndrome) and bird flu, than when R is closer to 10, as would be typical of measles. In addition we show, both analytical and numerical, how the time delay between the injection of infected people into a patch and the corresponding initial epidemic that it produces depends on R.


Impacto de la pandemia COVID-19 en los tratamientos inmunomoduladores/inmunosupresores en dermatología: actitudes de los pacientes y los dermatólogos en Argentina


title: A deep dive into testing and management of COVID-19 for Australian high performance and professional sport

text: Abstract The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.


title: No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs

text: We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n = 3) was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.


title: The Genome Organization of the Nidovirales: Similarities and Differences between Arteri-, Toro-, and Coronaviruses

text: Abstract Viruses in the families Arteriviridae and Coronaviridae have enveloped virions which contain nonsegmented, positive-stranded RNA, but the constituent genera differ markedly in genetic complexity and virion structure. Nevertheless, there are striking resemblances among the viruses in the organization and expression of their genomes, and sequence conservation among the polymerase polyproteins strongly suggests that they have a common ancestry. On this basis, the International Committee on Taxonomy of Viruses recently established a new order, Nidovirales, to contain the two families. Here, the common traits and distinguishing features of the Nidovirales are reviewed.


COVID‐19 era: A chance to learn something new about monitoring psoriatic patients in biological therapy


title: Effect of Trade Openness on Food Security in the EU: A Dynamic Panel Analysis

text: The problem of food insecurity is growing across the world, including economically developed countries. In Europe, the question is not just about the total supply of foods, but it includes even the accessibility of prices and their nutritional and qualitative adequacy. In this context many countries recognize the importance of trade policies to ensure adequate levels of food security. The aim of this work was to analyze the impact of trade openness on the level of food security in European countries, using a dynamic panel analysis with the generalized method of moments (GMM) approach. We selected two different indicators of food security (average protein supply, average dietary energy supply adequacy) capable of offering information both on the quantity and on the nutritional quality of the food supply. In order to improve the robustness of the empirical results, we developed three different regressions, with three trade openness indicators (trade openness, tariff, globalization) for each food security indicator. The results showed that commercial opening has, on average, a statistically significant net positive impact on the food security of European countries. Additional results indicate that also economic development, together with the importance of the agricultural sector, can improve food security levels.


A newly designed real-time RT-PCR for SAFV detects SAFV-2 and SAFV-3 in the respiratory tracts of ill children during 2011