title: Experiences and challenges in the health protection of medical teams in the Chinese Ebola treatment center, Liberia: a qualitative study

text: BACKGROUND: Health care workers are at the frontline in the fight against infectious disease, and as a result are at a high risk of infection. During the 2014–2015 Ebola outbreak in West Africa, many health care workers contracted Ebola, some fatally. However, no members of the Chinese Anti-Ebola medical team, deployed to provide vital medical care in Liberia were infected. This study aims to understand how this zero infection rate was achieved. METHODS: Data was collected through 15 in-depth interviews with participants from the People’s Liberation Army of China medical team which operated the Chinese Ebola Treatment Center from October 2014 to January 2015 in Liberia. Data were analysed using systematic framework analysis. RESULTS: This study found numerous bio-psycho-socio-behavioural risk factors that directly or indirectly threatened the health of the medical team working in the Chinese Ebola Treatment Center. These factors included social and emotional stress caused by: (1) the disruption of family and social networks; (2) adapting to a different culture; (3) and anxiety over social and political unrest in Liberia. Exposure to Ebola from patients and local co-workers, and the incorrect use of personal protective equipment due to fatigue was another major risk factor. Other risk factors identified were: (1) shortage of supplies; (2) lack of trained health personnel; (3) exposure to contaminated food and water; (4) and long working hours. Comprehensive efforts were taken throughout the mission to mitigate these factors. Every measure was taken to prevent the medical team’s exposure to the Ebola virus, and to provide the medical team with safe, comfortable working and living environments. There were many challenges in maintaining the health safety of the team, such as the limited capability of the emergency command system (the standardized approach to the command, control, and coordination of an emergency response), and the lack of comprehensive international protocols for dealing with emerging infectious disease pandemics. CONCLUSIONS: The comprehensive and multidisciplinary measures employed to protect the health of the medical team proved successful even in Liberia’s resource-limited setting. The global health community can learn valuable lessons from this experience which could improve the safety of health care workers in future emergencies. These lessons include: establishing capable command systems; implementing effective coordination mechanisms; providing adequate equipment; providing training for medical teams; investing in the development of global health professionals; and improving research on ways to protect health care workers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0468-6) contains supplementary material, which is available to authorized users.


title: Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells

text: The receptor-binding domain (RBD) of SARS coronavirus (SARS-CoV) spike (S) protein contains multiple conformation-dependent epitopes that induce neutralizing antibody responses. Here we used CHO-K1 cells to establish a cell line for stable expression of a 193-mer (residues 318–510) RBD (RBD193-CHO) and determined its antigenicity and immunogenicity. We found that RBD193-CHO reacted strongly with a panel of six monoclonal antibodies recognizing various conformational and linear epitopes in RBD, suggesting that this recombinant protein maintains intact conformation and good antigenicity. Immunization of mice with RBD193-CHO resulted in induction of high titers of RBD-specific neutralizing antibodies and potent IL-4-expressing T cell responses. RBD193-CHO induced immunity that protected a majority of the vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD produced in an established stable cell line maintains strong immunogenicity with high potential for use as an effective and economic subunit SARS vaccine.


title: Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles

text: All viruses that carry a positive-sense RNA genome (+RNA), such as picornaviruses, hepatitis C virus, dengue virus, and SARS- and MERS-coronavirus, confiscate intracellular membranes of the host cell to generate new compartments (i.e., replication organelles) for amplification of their genome. Replication organelles (ROs) are membranous structures that not only harbor viral proteins but also contain a specific array of hijacked host factors that create a unique lipid microenvironment optimal for genome replication. While some lipids may be locally synthesized de novo, other lipids are shuttled towards ROs. In picornavirus-infected cells, lipids are exchanged at membrane contact sites between ROs and other organelles. In this paper, we review recent advances in our understanding of how picornaviruses exploit host membrane contact site machinery to generate ROs, a mechanism that is used by some other +RNA viruses as well.


title: In vitro human fecal microbial metabolism of Forsythoside A and biological activities of its metabolites

text: Abstract The present study aimed to investigate the metabolism of Forsythoside A (FTA) by human fecal bacteria to clarify the relationship between its intestinal metabolism and its pharmacological activities. FTA was incubated with human fecal microflora in vitro to investigate its metabolic process, and highly sensitive and specific ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF/MS) was performed using MetaboLynx™ software for metabolite analysis. Caffeic acid (CA) and hydroxytyrosol (HT) were obtained by hydrolysis of FTA, and CA was further hydrogenated to form 3,4-dihydroxybenzenepropionic acid (DCA). The anticomplementary, antimicrobial and antiendotoxin activities of FTA and its metabolites by human fecal microflora were evaluated in vitro with a hemolysis assay, the agar disc-diffusion method, the MIC value and the gel clot LAL assay, respectively. The metabolites showed higher biological activity than FTA, especially HT and DCA. Orally administered FTA may be metabolized to HT and DCA, and the pharmacological effects of FTA may be dependent on intestinal bacterial metabolism.


title: A novel IDEA: The impact of serial interval on a modified-Incidence Decay and Exponential Adjustment (m-IDEA) model for projections of daily COVID-19 cases

text: The SARS-CoV-2 virus causes the disease COVID-19, and has caused high morbidity and mortality worldwide. Empirical models are useful tools to predict future trends of disease progression such as COVID-19 over the near-term. A modified Incidence Decay and Exponential Adjustment (m-IDEA) model was developed to predict the progression of infectious disease outbreaks. The modification allows for the production of precise daily estimates, which are critical during a pandemic of this scale for planning purposes. The m-IDEA model was employed using a range of serial intervals given the lack of knowledge on the true serial interval of COVID-19. Both deterministic and stochastic approaches were applied. Model fitting was accomplished through minimizing the sum-of-square differences between predicted and observed daily incidence case counts, and performance was retrospectively assessed. The performance of the m-IDEA for projection cases in the near-term was improved using shorter serial intervals (1–4 days) at early stages of the pandemic, and longer serial intervals at mid-to late-stages (5–9 days) thus far. This, coupled with epidemiological reports, suggests that the serial interval of COVID-19 might increase as the pandemic progresses, which is rather intuitive: Increasing serial intervals can be attributed to gradual increases in public health interventions such as facility closures, public caution and social distancing, thus increasing the time between transmission events. In most cases, the stochastic approach captured the majority of future reported incidence data, because it accounts for the uncertainty around the serial interval of COVID-19. As such, it is the preferred approach for using the m-IDEA during dynamic situation such as in the midst of a major pandemic.


title: Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature

text: We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.


title: Update on T cells in the virally infected brain: friends and foes

text: The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated. RECENT FINDINGS: The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific. SUMMARY: T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.


title: Saving Human Lives: What Complexity Science and Information Systems can Contribute

text: We discuss models and data of crowd disasters, crime, terrorism, war and disease spreading to show that conventional recipes, such as deterrence strategies, are often not effective and sufficient to contain them. Many common approaches do not provide a good picture of the actual system behavior, because they neglect feedback loops, instabilities and cascade effects. The complex and often counter-intuitive behavior of social systems and their macro-level collective dynamics can be better understood by means of complexity science. We highlight that a suitable system design and management can help to stop undesirable cascade effects and to enable favorable kinds of self-organization in the system. In such a way, complexity science can help to save human lives.


title: Doing Things Differently: What It Would Take to Ensure Continued Access to Contraception During COVID-19

text: COVID-19 may fundamentally change women’s contraceptive use, meaning that the future we have been planning and procuring for, may not match these changes. In these unprecedented times, we must rethink how we link product and program in the short-term to ensure women’s changing needs are met.


title: Antiviral activity of recombinant porcine surfactant protein A against porcine reproductive and respiratory syndrome virus in vitro

text: Porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses in the swine industry worldwide. However, there is not an ideal vaccine to provide complete protection against PRRSV. Thus, the need for new antiviral strategies to control PRRSV still remains. Surfactant protein A (SP-A) belongs to the family of C-type lectins, which can exert antiviral activities. In this present study, we assessed the antiviral properties of recombinant porcine SP-A (RpSP-A) on PRRSV infection in Marc 145 cells and revealed its antiviral mechanism using a plaque assay, real-time qPCR, western blotting analysis and an attachment and penetration assay. Our results showed that RpSP-A could inhibit the infectivity of PRRSV in Marc 145 cells and could reduce the total RNA and protein level. The attachment assay indicated that RpSP-A in the presence of Ca(2+) could largely inhibit Marc 145 cell attachment; however, in the penetration assay, it was relatively inactive. Furthermore, our study suggested that virus progeny released from infected Marc145 cells were blocked by RpSP-A from infecting other cells. We conclude that RpSP-A has antiviral activity against PRRSV, most probably by blocking viral attachment and the cell-to-cell transmission pathway, and therefore, RpSP-A holds promise as a novel antiviral agent against PRRSV.


title: Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19)

text: [Figure: see text] The Coronavirus Disease 2019 (COVID-19) has been declared as a global pandemic, but specific medicines and vaccines are still being developed. In China, interventional therapies with traditional Chinese medicine for COVID-19 have achieved significant clinical efficacies, but the underlying pharmacological mechanisms are still unclear. This article reviewed the etiology of COVID-19 and clinical efficacy. Both network pharmacological study and literature search were used to demonstrate the possible action mechanisms of Chinese medicines in treating COVID-19. We found that Chinese medicines played the role of antivirus, anti-inflammation and immunoregulation, and target organs protection in the management of COVID-19 by multiple components acting on multiple targets at multiple pathways. AEC2 and 3CL protein could be the direct targets for inhibiting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Quercetin, kaempferol, luteolin, isorhamnetin, baicalein, naringenin, and wogonin could be the main active ingredients of Chinese medicines for the management of COVID-19 by targeting on AEC2 and 3CL protein and inhibiting inflammatory mediators, regulating immunity, and eliminating free radicals through COX-2, CASP3, IL-6, MAPK1, MAPK14, MAPK8, and REAL in the signaling pathways of IL-17, arachidonic acid, HIF-1, NF-κB, Ras, and TNF. This study may provide meaningful and useful information on further research to investigate the action mechanisms of Chinese medicines against SARS-CoV-2 and also provide a basis for sharing the “China scheme" for COVID-19 treatment.


title: Lactate dehydrogenase, an independent risk factor of severe COVID-19 patients: a retrospective and observational study

text: Background: The World Health Organization has declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the risk factors of illness severity. Results: The median age was 63 years, and 44.9% were severe cases. Severe patients had higher APACHE II (8.5 vs. 4.0) and SOFA (2 vs. 1) scores on admission. Among all univariable parameters, lymphocytes, CRP, and LDH were significantly independent risk factors of COVID-19 severity. LDH was positively related both with APACHE II and SOFA scores, as well as P/F ratio and CT scores. LDH (AUC = 0.878) also had a maximum specificity (96.9%), with the cutoff value of 344.5. In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocytes and its subsets. Conclusions: This study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. Methods: We extracted data regarding 107 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society guidelines for community acquired pneumonia.


docid: bqivjudl

title: SARS-COV-2 Presenting as New Onset Atrial Fibrillation: A Case Report

text: Current literature has documented numerous different presentations of SARS-COV-2 (COVID-19). Common symptoms include fever, cough and shortness of breath, however, lack of these symptoms does not exclude COVID-19. Given the incomplete understanding of the virus at this time, healthcare professionals must continue to remain informed of the vast number of clinical presentations of the virus to ensure early supportive treatment, ideally leading to improved outcomes.


title: Seasonal variation of respiratory pathogen colonization in asymptomatic health care professionals: A single-center, cross-sectional, 2-season observational study

text: BACKGROUND: The purpose of this study was to determine the seasonal variance of potentially pathogenic bacterial and viral organisms in nasopharyngeal specimens obtained from asymptomatic health care professionals (HCPs) during the 2014 winter and summer months. METHODS: Nasopharyngeal specimens from 100 HCPs were collected from Huntsville Hospital (Huntsville, AL) during the winter and from 100 HCPs during the summer. All subjects were tested for 22 viruses and 19 bacteria using Target Enriched Multiplex Polymerase Chain Reaction. Both seasonal cohorts were composed of students, nurses, physicians, and residents. RESULTS: Of the 100 HCPs tested during the winter, 34 subjects were colonized with at least 1 bacterium, and 11 tested positive for at least 1 virus. Methicillin-resistant Staphylococcus aureus (MRSA), Moraxella catarrhalis, and coronavirus were the most frequently detected potentially infectious agents. Of the 100 HCPs tested during the summer, 37 tested positive for at least 1 bacterium, and 4 tested positive for a viral agent. The most prevalent bacteria were MRSA and Klebsiella pneumonia. CONCLUSION: Nasopharyngeal carriage among asymptomatic HCPs was common, but the frequency and presence of potential pathogens varied with each season. Understanding the colonization and infection potential of upper respiratory organisms is important, particularly for viruses. Although asymptomatic HCPs certainly harbor a number of different potentially infectious agents, future studies are needed to determine whether colonized pathogens are transmitted or initiate infection in at-risk patient populations.


title: Nitazoxanide/Azithromycin combination for COVID-19: A suggested new protocol for COVID-19 early management

text: Abstract Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical cases.


title: Enabling new mindsets and transformative skills for negotiating and activating climate action: Lessons from UNFCCC conferences of the parties

text: Technological and policy solutions for transitioning to a fossil-free society exist, many countries could afford the transition, and rational arguments for rapid climate action abound. Yet effective action is still lacking. Dominant policy approaches have failed to generate action at anywhere near the rate, scale or depth needed to avoid potentially catastrophic futures. This is despite 30 years of climate negotiations under the United Nations Framework Convention on Climate Change (UNFCCC), and wide-ranging actions at national, transnational and sub-national levels. Practitioners and scholars are, thus, increasingly arguing that also the root causes of the problem must be addressed – the mindset (or paradigm) out of which the climate emergency has arisen. Against this background, we investigate decision-makers’ views of the need for a different mindset and inner qualities that can support negotiating and activating climate action, along with factors that could enable such a mindset shift. Data were collected during participatory workshops run at the 25th UNFCCC Conference of the Parties (COP25) in 2019, and comprise surveys, as well as social media communication and semi-structured interviews with COP attendees. Our results underline vast agreement among participants regarding the need for a mindset shift that can support new ways of communication and collaboration, based on more relational modes of knowing, being and acting. They also suggest the emergence of such a mindset shift across sectors and contexts, but not yet at the collective and systems levels. Finally, they highlight the importance of transformative skills and the need for experimental, safe spaces. The latter are seen as a visible manifestation and enabler that can support agency for change through shared self-reflection, experience and practice. We present a transformative skills framework, and conclude with further research needs and policy recommendations.


title: Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions

text: Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms.


title: Development and evaluation of real-time PCR assays for the detection of the newly identified KI and WU polyomaviruses

text: Abstract Background Recently, novel human polyomaviruses, KI (KIV) and WU (WUV) were described. Their role in human disease has not yet been determined. Objectives The aim of this study was to develop sensitive and specific assays for the detection of KIV and WUV. Study Two KIV (KI-A and KI-B) and three WUV (WU-A, WU-B and WU-C) real-time polymerase chain reaction (rtPCR) assays were developed and evaluated. Clinical sensitivities and specificities were determined by testing 200 respiratory specimens and the results compared to those for previously described conventional PCR assays. Limits of detection were determined, and the analytical specificities of the assays were investigated. Results No cross-reactivity was observed between the rtPCR methods and unrelated organisms. All five rtPCR assays could reliably detect 10 copies of genomic DNA equivalents per reaction, which was more sensitive than conventional methods. Compared to the conventional PCR assays, the sensitivity of the KI-A, KI-B, WU-A, WU-B and WU-C assays was 100%, 86.7% 95.5%, 100% and 100%, respectively. Specificity was 94.6%, 97.3%, 96.6%, 97.7% and 97.2%, respectively. Conclusions The KI-A, WU-B and WU-C assays provide the most sensitive detection of KIV and WUV in clinical specimens and may be used for further research into these viruses.


title: Long‐term surveillance of bat coronaviruses in Korea: Diversity and distribution pattern

text: Bats harbour diverse coronaviruses (CoVs), some of which are associated with zoonotic infections, as well as inter‐species transmission. In this study, a total of 512 bat faecal samples from the bat habitats at different geographical locations in South Korea were investigated between 2016 and 2019. Seventy‐eight samples were positive for coronaviruses (15.2%), comprising 68 alphacoronaviruses (13.3%) and 10 betacoronaviruses (2.0%). The positive rates tended to increase during the awakening (April) period. Notably, betacoronaviruses were only found in the site where Rhinolophus ferrumequinum was the major species of bats, and were related to SARS‐ and MERS‐related CoVs identified in China and South Korea, respectively. No betacoronaviruses were closely related to SARS‐CoV‐2 in this study. Alphacoronaviruses were detected in the sites where Hypsugo alaschanicus, Miniopterus fuliginosus, Miniopterus schreibersii, Rhinolophus ferrumequinum, Myotis bombinus, Myotis macrodactylus and Myotis petax were found to be the major bat species. Furthermore, alphacoronaviruses had higher genetic diversity than betacoronaviruses and had a wider distribution in Korea. Considering that different bat species are co‐roosting in crowded conditions in the same habitat, the diverse coronaviruses in Korean bats are likely to undergo cross‐species transmission events due to the richness in host species. Therefore, continuous monitoring should be performed, especially at the awakening time of the hibernating bats in the habitats where diverse bat species co‐roost, to better understand the evolution of coronaviruses in bats.


title: Development and evaluation of a real-time RT-PCR and a field-deployable RT-insulated isothermal PCR for the detection of Seneca Valley virus

text: BACKGROUND: Seneca Valley virus (SVV) has emerged in multiple countries in recent years. SVV infection can cause vesicular lesions clinically indistinguishable from those caused by other vesicular disease viruses, such as foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), vesicular stomatitis virus (VSV), and vesicular exanthema of swine virus (VESV). Sensitive and specific RT-PCR assays for the SVV detection is necessary for differential diagnosis. Real-time RT-PCR (rRT-PCR) has been used for the detection of many RNA viruses. The insulated isothermal PCR (iiPCR) on a portable POCKIT™ device is user friendly for on-site pathogen detection. In the present study, SVV rRT-PCR and RT-iiPCR were developed and validated. RESULTS: Neither the SVV rRT-PCR nor the RT-iiPCR cross-reacted with any of the vesicular disease viruses (20 FMDV, two SVDV, six VSV, and two VESV strains), classical swine fever virus (four strains), and 15 other common swine viruses. Analytical sensitivities of the SVV rRT-PCR and RT-iiPCR were determined using serial dilutions of in vitro transcribed RNA as well as viral RNA extracted from a historical SVV isolate and a contemporary SVV isolate. Diagnostic performances were further evaluated using 125 swine samples by two approaches. First, nucleic acids were extracted from the 125 samples using the MagMAX™ kit and then tested by both RT-PCR methods. One sample was negative by the rRT-PCR but positive by the RT-iiPCR, resulting in a 99.20% agreement (124/125; 95% CI: 96.59–100%, κ = 0.98). Second, the 125 samples were tested by the taco™ mini extraction/RT-iiPCR and by the MagMAX™ extraction/rRT-PCR system in parallel. Two samples were positive by the MagMAX™/rRT-PCR system but negative by the taco™ mini/RT-iiPCR system, resulting in a 98.40% agreement (123/125; 95% CI: 95.39–100%, κ = 0.97). The two samples with discrepant results had relatively high C(T) values. CONCLUSIONS: The SVV rRT-PCR and RT-iiPCR developed in this study are very sensitive and specific and have comparable diagnostic performances for SVV RNA detection. The SVV rRT-PCR can be adopted for SVV detection in laboratories. The SVV RT-iiPCR in a simple field-deployable system could serve as a tool to help diagnose vesicular diseases in swine at points of need.


title: The alpha-1 subunit of the Na(+),K(+)-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells

text: Human respiratory syncytial virus (RSV) is the leading viral cause of acute pediatric lower respiratory tract infections worldwide, with no available vaccine or effective antiviral drug. To gain insight into virus-host interactions, we performed a genome-wide siRNA screen. The expression of over 20,000 cellular genes was individually knocked down in human airway epithelial A549 cells, followed by infection with RSV expressing green fluorescent protein (GFP). Knockdown of expression of the cellular ATP1A1 protein, which is the major subunit of the Na(+),K(+)-ATPase of the plasma membrane, had one of the strongest inhibitory effects on GFP expression and viral titer. Inhibition was not observed for vesicular stomatitis virus, indicating that it was RSV-specific rather than a general effect. ATP1A1 formed clusters in the plasma membrane very early following RSV infection, which was independent of replication but dependent on the attachment glycoprotein G. RSV also triggered activation of ATP1A1, resulting in signaling by c-Src-kinase activity that transactivated epidermal growth factor receptor (EGFR) by Tyr845 phosphorylation. ATP1A1 signaling and activation of both c-Src and EGFR were found to be required for efficient RSV uptake. Signaling events downstream of EGFR culminated in the formation of macropinosomes. There was extensive uptake of RSV virions into macropinosomes at the beginning of infection, suggesting that this is a major route of RSV uptake, with fusion presumably occurring in the macropinosomes rather than at the plasma membrane. Important findings were validated in primary human small airway epithelial cells (HSAEC). In A549 cells and HSAEC, RSV uptake could be inhibited by the cardiotonic steroid ouabain and the digitoxigenin derivative PST2238 (rostafuroxin) that bind specifically to the ATP1A1 extracellular domain and block RSV-triggered EGFR Tyr845 phosphorylation. In conclusion, we identified ATP1A1 as a host protein essential for macropinocytic entry of RSV into respiratory epithelial cells, and identified PST2238 as a potential anti-RSV drug.


title: Habitat disturbance results in chronic stress and impaired health status in forest-dwelling paleotropical bats

text: Anthropogenic habitat disturbance is a major threat to biodiversity worldwide. Yet, before population declines are detectable, individuals may suffer from chronic stress and impaired immunity in disturbed habitats, making them more susceptible to pathogens and adverse weather conditions. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the body mass and immunity of bats. We measured and compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios) and the number of circulating immune cells between several bat species with different roost types living in recovering areas, actively logged forests, and fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress levels were higher in individuals from fragmented habitats compared with conspecifics from actively logged areas. Foliage-roosting species showed a reduced body mass and decrease in total white blood cell counts in actively logged areas and fragmented forests compared with conspecifics living in recovering habitats. Our study highlights that habitat disturbance may have species-specific effects on chronic stress and immunity in bats that are potentially related to the roost type. We identified foliage-roosting species as particularly sensitive to forest habitat deterioration. These species may face a heightened extinction risk in the near future if anthropogenic habitat alterations continue.


title: A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population

text: Infections and mental disorders are two of the major global disease burdens. While correlations between mental disorders and infections have been reported, the possible genetic links between them have not been assessed in large-scale studies. Moreover, the genetic basis of susceptibility to infection is largely unknown, as large-scale genome-wide association studies of susceptibility to infection have been lacking. We utilized a large Danish population-based sample (N = 65,534) linked to nationwide population-based registers to investigate the genetic architecture of susceptibility to infection (heritability estimation, polygenic risk analysis, and a genome-wide association study (GWAS)) and examined its association with mental disorders (comorbidity analysis and genetic correlation). We found strong links between having at least one psychiatric diagnosis and the occurrence of infection (P = 2.16 × 10(−208), OR = 1.72). The SNP heritability of susceptibility to infection ranged from ~2 to ~7% in samples of differing psychiatric diagnosis statuses (suggesting the environment as a major contributor to susceptibility), and polygenic risk scores moderately but significantly explained infection status in an independent sample. We observed a genetic correlation of 0.496 (P = 2.17 × 10(−17)) between a diagnosis of infection and a psychiatric diagnosis. While our GWAS did not identify genome-wide significant associations, we found 90 suggestive (P ≤ 10(−5)) associations for susceptibility to infection. Our findings suggest a genetic component in susceptibility to infection and indicate that the occurrence of infections in individuals with mental illness may be in part genetically driven.


title: Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

text: Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.


Usefulness of telerehabilitation for stroke patients during the COVID-19 pandemic


title: Evaluation of the influenza sentinel surveillance system in the Democratic Republic of Congo, 2012–2015

text: BACKGROUND: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012–2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60–79% moderate performance; ≥80% good performance. RESULTS: During 2012–2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December–May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. CONCLUSIONS: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.


title: Detection of respiratory pathogens by real-time PCR in children with clinical suspicion of pertussis

text: The use of a multiplex respiratory real-time PCR in patients clinically suspected of pertussis increases the number of pathogens detected.


title: Preparedness Lessons from Modern Disasters and Wars

text: Disasters come in all shapes and forms, and in varying magnitudes and intensities. Nevertheless, they offer many of the same lessons for critical care practitioners and responders. Among these, the most important is that well thought out risk assessment and focused planning are vital. Such assessment and planning require proper training for providers to recognize and treat injury from disaster, while maintaining safety for themselves and others. This article discusses risk assessment and planning in the context of disasters. The article also elaborates on the progress toward the creation of portable, credible, sustainable, and sophisticated critical care outside the walls of an intensive care unit. Finally, the article summarizes yields from military-civilian collaboration in disaster planning and response.


title: Can COVID-Era Export Restrictions Be Deterred?

text: The COVID-19 pandemic has led some 75 countries to restrict their exports of hundreds of essential products, ranging from antibiotics and face masks to medical ventilators. Since banning exports decreases global supply and leads to price surges on world markets, the cost of these measures may ultimately be counted in human lives.


title: Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Éminences Grises”?

text: This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together.


title: Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected

text: Abstract Nitric oxide is an important molecule playing a key role in a broad range of biological process such as neurotransmission, vasodilatation and immune responses. While the anti-microbiological properties of nitric oxide-derived reactive nitrogen intermediates (RNI) such as peroxynitrite, are known, the mechanism of these effects are as yet poorly studied. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) belongs to the family Coronaviridae, was first identified during 2002-2003. Mortality in SARS patients ranges from between 6 to 55%. We have previously shown that nitric oxide inhibits the replication cycle of SARS-CoV in vitro by an unknown mechanism. In this study, we have further investigated the mechanism of the inhibition process of nitric oxide against SARS-CoV. We found that peroxynitrite, an intermediate product of nitric oxide in solution formed by the reaction of NO with superoxide, has no effect on the replication cycle of SARS-CoV, suggesting that the inhibition is either directly effected by NO or a derivative other than peroxynitrite. Most interestingly, we found that NO inhibits the replication of SARS-CoV by two distinct mechanisms. Firstly, NO or its derivatives cause a reduction in the palmitoylation of nascently expressed spike (S) protein which affects the fusion between the S protein and its cognate receptor, angiotensin converting enzyme 2. Secondly, NO or its derivatives cause a reduction in viral RNA production in the early steps of viral replication, and this could possibly be due to an effect on one or both of the cysteine proteases encoded in Orf1a of SARS-CoV.


title: Compressed fluids and phytochemical profiling tools to obtain and characterize antiviral and anti-inflammatory compounds from natural sources

text: Many natural compounds, found mainly in plants, are associated with the treatment of various diseases. The search for natural therapeutic agents includes compounds with antiviral and anti-inflammatory activities. Among the many steps involved in bioprospection, extraction is the first and most critical step for obtaining bioactive compounds. One of the main advantages of using compressed fluids extraction is the high quality of the final product obtained due to the use of green solvents, while the selectivity towards target compounds can be tuned by adjusting the process parameters, especially pressure, temperature and solvent characteristics. In this review, a discussion is provided on the power of compressed fluids, such as supercritical fluid extraction (SFE), pressurized liquid extraction (PLE) and subcritical water extraction (SWE) to obtain antiviral and anti-inflammatory compounds from natural sources. In addition, an adequate knowledge about the identity and quantity of the compounds present in the extract is essential to correlate biological activity with chemical composition. Phytochemical profiling tools used for identification and quantification of these bioactive natural compound are also discussed. It can be anticipated that after the current SARS-COV-2 pandemic, the search of new natural compounds with antiviral and anti-inflammatory activity will be a hot research topic, so, this review provides an overview on the technologies currently used that could help this research.


title: A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa

text: Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.


title: Experiences and needs of caregivers of persons with dementia in India during the COVID-19 pandemic – A Qualitative Study

text: OBJECTIVES: To describe the experiences and needs of caregivers of persons with dementia during the COVID-19 pandemic and lockdown in a city in India. DESIGN: Qualitative study using a telephonic semi-structured interview SETTING: A specialist geriatric outpatient mental health service based in a non-governmental organization in Chennai, India. PARTICIPANTS: A purposive sampling of family members of persons with dementia registered in the database and seen within the previous 6 months. RESULTS: Thirty-one caregivers participated. Thematic analysis of the data showed two sets of issues that the caregivers of persons with dementia faced in their experiences during the pandemic. The first set was unique to the caregivers that directly related to their caregiving role, while the second set did not relate directly to their caregiving role. These two sets also appeared to have a two-way interaction influencing each other. These issues generated needs, some of which required immediate support while others required longer-term support. The caregivers suggested several methods, such as use of video-consultations, telephone-based support and clinic-based in-person visits to meet their needs. They also wanted more services post-pandemic. CONCLUSIONS: Caregivers of persons with dementia had multiple needs during the pandemic. Supporting them during these times require a pragmatic multi-layered approach. Systemic changes, policies and frameworks, increased awareness, use of technology, and better access to health are necessary.


title: Human parainfluenza virus circulation, United States, 2011–2019

text: Abstract Background Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1–3 have been described, less is known about national patterns of HPIV-4 circulation. Objectives To describe patterns of HPIVs circulation in the United States (US). Study design We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011–2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015–2019 to analyze differences in patient demographics. Results During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged ≤ 2 years (36 %) with fluctuations in the distribution of age by type. Conclusions HPIVs were detected year-round during 2011–2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged ≤ 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.


Chilblain‐like lesions during the COVID‐19 pandemic: early or late sign?


title: Identification of a novel nidovirus associated with a neurological disease of the Australian brushtail possum (Trichosurus vulpecula)

text: Abstract A novel, fatal neurological disease of the Australian brushtail possum (Trichosurus vulpecula) was first identified in 1995 in a research facility and subsequently in free-living possums in New Zealand and termed wobbly possum disease (WPD). The results of previous transmission studies suggested that the aetiological agent of WPD is most likely a virus. However, the identity of the presumed viral agent had not been elucidated. In the current report, we describe identification of a novel virus from tissues of WPD-affected possums using a combination of next generation sequencing and traditional molecular methods. The proportion of possums positive for the novel virus by PCR was significantly higher (p <0.0001) among animals with WPD than clinically healthy possums, strongly suggesting an aetiological involvement of the virus in WPD. Analysis of the partial genomic sequence of the putative WPD virus indicated that it is a novel nidovirus, most closely related to the current members of the family Arteriviridae.


title: Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – possible lessons from a systematic review of SARS-CoV therapy

text: Abstract The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been detected in a number of countries in the Middle East and Europe with an apparently high mortality rate. It is phylogenetically related to the SARS coronavirus and has also been associated with severe respiratory illness as well as nosocomial transmission in healthcare settings. Current international recommendations do not support any specific therapies; however, there are a number of agents, which were used during the SARS epidemic of 2003. It is possible that these might be active against the related MERS coronavirus. We have reviewed the literature on the safety and efficacy of therapies used in patients with SARS with a view to their potential use in patients with MERS-CoV infections.


docid: xmrjnrwi

title: Comparative efficacy of metoclopramide, ondansetron and maropitant in preventing parvoviral enteritis‐induced emesis in dogs

text: The aim of the study was to evaluate the efficiencies of selected anti‐emetic drugs (metoclopramide, ondansetron and maropitant) in preventing vomiting in the treatment of canine parvoviral enteritis. We designed a randomized, prospective clinical study. PVE quick ELISA test‐positive dogs between 4 and 12 months of age were included in the study. Each of metoclopramide, ondansetron, maropitant and control group had 8 dogs. Metoclopramide and ondansetron were administered as 0.5 mg/kg doses three times a day via intravenous route, and maropitant was administered as 1 mg/kg doses once a day subcutaneously. The number and severity of daily vomitings were recorded. All dogs were treated and monitored for five days; treatments were continued until all animals healed. Metoclopramide, ondansetron and maropitant decreased the severity of vomiting from the first day and the vomiting numbers from the third day in PVE treatment. Obtained results showed that maropitant can be used successfully such as metoclopramide and ondansetron, which are frequently used for PVE treatment. At the same time, it was discovered that metoclopramide, ondansetron and maropitant were equally effective in reducing the frequency and severity of vomiting.


title: Study of viral pathogenesis in humanized mice

text: Many of the viral pathogens that cause infectious disease in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. The improvement of humanized mouse models over the past 30 years has greatly facilitated researchers’ abilities to study host responses to viral infections in a cost effective and ethical manner. From HIV to hepatotropic viruses to Middle East respiratory syndrome coronavirus, humanized mice have led to the identification of factors crucial to the viral life cycle, an outlet for testing candidate therapies, and improved analysis of human immune responses to infection. In tackling both the new and old viruses as they emerge, humanized mice will continue to be an indispensable tool.


title: Contact Investigation for Imported Case of Middle East Respiratory Syndrome, Germany

text: On March 19, 2013, a patient from United Arab Emirates who had severe respiratory infection was transferred to a hospital in Germany, 11 days after symptom onset. Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. A contact investigation was initiated to identify possible person-to-person transmission and assess infection control measures. Of 83 identified contacts, 81 were available for follow-up. Ten contacts experienced mild symptoms, but test results for respiratory and serum samples were negative for MERS-CoV. Serologic testing was done for 53 (75%) of 71 nonsymptomatic contacts; all results were negative. Among contacts, the use of FFP2/FFP3 face masks during aerosol exposure was more frequent after MERS-CoV infection was suspected than before. Infection control measures may have prevented nosocomial transmission of the virus.


title: COVID-19 will stimulate a new coronavirus research breakthrough: a 20-year bibliometric analysis.

text: Background COVID-19 is currently rampant in China, causing unpredictable harm to humans. This study aimed to quantitatively and qualitatively investigate the research trends on coronaviruses using bibliometric analysis to identify new prevention strategies. Methods All relevant publications on coronaviruses were extracted from 2000-2020 from the Web of Science database. An online analysis platform of literature metrology, bibliographic item co-occurrence matrix builder (BICOMB) and CiteSpace software were used to analyse the publication trends. VOSviewer was used to analyse the keywords and research hotspots and compare COVID-19 information with SARS and MERS information. Results We found a total of 9,760 publications related to coronaviruses published from 2000 to 2020. The Journal of Virology has been the most popular journal in this field over the past 20 years. The United States maintained a top position worldwide and has provided a pivotal influence, followed by China. Among all the institutions, the University of Hong Kong was regarded as a leader for research collaboration. Moreover, Professors Yuen KY and Peiris JSM made great achievements in coronavirus research. We analysed the keywords and identified 5 coronavirus research hotspot clusters. Conclusions We considered the publication information regarding different countries, institutions, authors, journals, etc. by summarizing the literature on coronaviruses over the past 20 years. We analysed the studies on COVID-19 and the SARS and MERS coronaviruses. Notably, COVID-19 must become the research hotspot of coronavirus research, and clinical research on COVID-19 may be the key to defeating this epidemic.


title: Substantial differences in preparedness for emergency infection control measures among major hospitals in Japan: lessons from SARS

text: Abstract Emergency infection control measures are essential in hospitals. Although Japan was spared from the 2003 epidemic of severe acute respiratory syndrome (SARS), hospitals were placed on high alert. The actual preparedness level of hospitals can be determined by examining individual perceptions among the hospital healthcare workers (HCWs). The objective of this study was to assess the level of preparedness of emergency infection control measures in Japan and to quantify the differences in preparedness across institutions and disciplines. From July to September 2003, a questionnaire survey concerning the perceptions of risks and countermeasures and knowledge about SARS was distributed at seven tertiary hospitals. Disciplines were categorized as emergency room (ER)/intensive care unit (ICU), surgical, medical, and “others”. Of the 9978 questionnaires administered, 6929 valid responses were received and analyzed. After adjusting for age, sex, and job category, specific institutional measures (I-scores) were found to be more indicative of the level of preparedness across institutions and disciplines than were measures of overall effectiveness (E-scores) or knowledge of preventive measures (K-scores). In particular, the difference in I-scores was much more substantial across institutions than across disciplines. Across disciplines, surgical ranked lower than ER/ICU or medical. In conclusion, substantial differences in emergency infection control measures, as perceived by HCWs, exists among hospitals in Japan, with the differences across institutions exceeding those across disciplines. To achieve a higher level of preparedness for infectious diseases, institutions should designate and implement effective emergency infection control measures.


title: SARS-CoV-2 (COVID 19) Infection in Hypertensive Patients and in Patients With Cardiac Disease

text: COVID 19, caused by the SARS-CoV-2 virus, a newly discovered coronavirus, has caused the global pandemic of early 2020. The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. Patients with pre-existing hypertension and cardiovascular comorbidities were reported to be at an increased risk of serious infections caused by SARS-CoV-2. Considering that those are among the most common chronic medical conditions in the Western world, the potential impact of it is huge. The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. The reports on the association between hypertension and COVID 19 morbidity and mortality are less clear, and the International Society of Hypertension even claims that there is none. The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.


title: An Approach to Quantify Endomembrane Dynamics in Pollen Utilizing Bioactive Chemicals

text: ABSTRACT Tip growth of pollen tubes and root hairs occurs via rapid polar growth. These rapidly elongating cells require tip-focused endomembrane trafficking for the deposition and recycling of proteins, membranes, and cell wall materials. Most of the image-based data published to date are subjective and non-quantified. Quantitative and comparative descriptors of these highly dynamic processes have been a major challenge, but are highly desirable for genetic and chemical genomics approaches to dissect this biological network. To address this problem, we screened for small molecules that perturbed the localization of a marker for the Golgi Ras-like monomeric G-protein RAB2:GFP expressed in transgenic tobacco pollen. Semi-automated high-throughput imaging and image analysis resulted in the identification of novel compounds that altered pollen tube development and endomembrane trafficking. Six compounds that caused mislocalization and varying degrees of altered movement of RAB2:GFP-labeled endomembrane bodies were used to generate a training set of image data from which to quantify vesicle dynamics. The area, velocity, straightness, and intensity of each body were quantified using semi-automated image analysis tools revealing quantitative differences in the phenotype caused by each compound. A score was then given to each compound enabling quantitative comparisons between compounds. Our results demonstrate that image analysis can be used to quantitatively evaluate dynamic subcellular endomembrane phenotypes induced by bioactive chemicals, mutations, or other perturbing agents as part of a strategy to quantitatively dissect the endomembrane network.


title: Age-dependent immune responses and immune protection after avian coronavirus vaccination

text: Abstract Infectious bronchitis virus (IBV) is an endemic disease of chickens and a major contributor to economic losses for the poultry industry despite vaccination. Recent observations indicated that chicks may have an immature immune system immediately after hatching when vaccinated for IBV. Therefore we hypothesized that early IBV vaccination will generate an immature, poorly protective IBV-specific immune response contributing to immune escape and persistence of IBV. To test this hypothesis the IBV-specific immune response and immune protection were measured in chicks vaccinated at different ages. This demonstrated a delayed production of IgG and IgA plasma antibodies in the 1, 7 and 14-day-old vaccination groups and also lower IgA antibody levels were observed in plasma of the 1-day-old group. Similar observations were made for antibodies in tears. In addition, IgG antibodies from the 1-day-old group had lower avidity indices than day 28 vaccinated birds. The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. The lack of vaccine-mediated protection was most pronounced in the 1-day-old vaccination group and to a lesser extent the 7-day-old group, while the 14-day-old and older chickens were protected. These data strongly support IBV vaccination after day 7 post hatch.


docid: shmephya

title: Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

text: BACKGROUND: Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. METHODS: To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. RESULTS: Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation. CONCLUSION: In outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts.


title: Efficacy of a Test-Retest Strategy in Residents and Health Care Personnel of a Nursing Home facing a COVID-19 Outbreak

text: Abstract Objective To assess the American Testing Guidance for Nursing Homes (NHs) - updated May 19, 2020 - with a new COVID-19 case. Design Case investigation. Setting and Subjects: All 79 residents and 34 Health Care Personnel (HCP) of a NH. Methods 7 days after identification of a COVID-19 resident, all residents and HCP underwent rRT-PCR testing for SARS-CoV-2 with nasopharyngeal swabs. This was repeated weekly in all previously negative subjects until the testing identified no new cases and in all positive subjects until the testing was negative. COVID-19 infection prevention and control (IPC) measures were implemented in all residents and HCP with positive testing or with COVID-19 symptoms. Standard IPC was also implemented in all HCP. Six weeks after initial testing, all residents underwent testing for ELISA-based IgG antibodies directed against the SARS-CoV-2. Symptoms were serially recorded in residents and HCP. Results 36 residents had a positive RT-PCR at baseline and two at day 7. Six HCP had a positive RT-PCR at baseline and two at day 7. No new COVID-19 cases were diagnosed later. Among the SARS-CoV-2-positive cases, six residents (16%) and three HCP (37%) were asymptomatic during the 14 days before testing. Twenty-five residents (92.3%) and all 8 HCP (100%) with a positive RT-PCR developed IgG antibodies against SARS-CoV-2. Among the residents and HCP always having tested negative, 2 (5%) and 5 (11.5%) developed IgG antibodies against SARS-CoV-2. These 2 residents had typical COVID-19 symptoms before and after testing and 2/5 HCP were asymptomatic before and after testing. Conclusions and Implications This study shows the validity of the updated American Testing Guidance for Nursing Homes (NHs). It suggests implementing COVID-19 IPC in both residents and HCP with positive testing or COVID-19 symptoms and warns that asymptomatic HCP with repeated negative RT-PCR testing can develop antibodies against SARS-CoV-2.


title: Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults

text: BACKGROUND: Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. OBJECTIVES: To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. STUDY DESIGN: Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. RESULTS: Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). CONCLUSIONS: Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.


title: [Pyr(1)]Apelin-13((1–12)) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr(1)]Apelin-13

text: Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr(1)]apelin-13((1–12)) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated. Methods and Results: [Pyr(1)]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr(1)]apelin-13((1–12)) identified by mass spectrometry. Endogenous [Pyr(1)]apelin-13((1–12)) was detected by immunostaining in human heart and lung localized to the endothelium. Expression was undetectable in lung from patients with pulmonary arterial hypertension. In human heart [Pyr(1)]apelin-13((1–12)) (pK(i) = 8.04 ± 0.06) and apelin-13(F13A) (pK(i) = 8.07 ± 0.24) competed with [(125)I]apelin-13 binding with nanomolar affinity, 4-fold lower than for [Pyr(1)]apelin-13 (pK(i) = 8.83 ± 0.06) whereas apelin-17 exhibited highest affinity (pK(i) = 9.63 ± 0.17). The rank order of potency of peptides to inhibit forskolin-stimulated cAMP was apelin-17 (pD(2) = 10.31 ± 0.28) > [Pyr(1)]apelin-13 (pD(2) = 9.67 ± 0.04) ≥ apelin-13(F13A) (pD(2) = 9.54 ± 0.05) > [Pyr(1)]apelin-13((1–12)) (pD(2) = 9.30 ± 0.06). The truncated peptide apelin-13(R10M) retained nanomolar potency (pD(2) = 8.70 ± 0.04) but shorter fragments exhibited low micromolar potency. In a β-arrestin recruitment assay the rank order of potency was apelin-17 (pD(2) = 10.26 ± 0.09) >> [Pyr(1)]apelin-13 (pD(2) = 8.43 ± 0.08) > apelin-13(R10M) (pD(2) = 8.26 ± 0.17) > apelin-13(F13A) (pD(2) = 7.98 ± 0.04) ≥ [Pyr(1)]apelin-13((1–12)) (pD(2) = 7.84 ± 0.06) >> shorter fragments (pD(2) < 6). [Pyr(1)]apelin-13((1–12)) and apelin-13(F13A) contracted human saphenous vein with similar sub-nanomolar potencies and [Pyr(1)]apelin-13((1–12)) was a potent inotrope in paced mouse right ventricle and human atria. [Pyr(1)]apelin-13((1–12)) elicited a dose-dependent decrease in blood pressure in anesthetized rat and dose-dependent increase in forearm blood flow in human volunteers. Conclusions: We provide evidence that ACE2 cleaves [Pyr(1)]apelin-13 to [Pyr(1)]apelin-13((1–12)) and this cleavage product is expressed in human cardiovascular tissues. We have demonstrated biological activity of [Pyr(1)]apelin-13((1–12)) at the human and rodent apelin receptor in vitro and in vivo. Our data show that reported enhanced ACE2 activity in cardiovascular disease should not significantly compromise the beneficial effects of apelin based therapies for example in PAH.


title: Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate Host or Long-Time Animal Reservoir?

text: While dromedary camels are the immediate animal source of MERS coronavirus (MERS-CoV) infection, the evolutionary origin of MERS-CoV remains obscure. We analyzed 219 camel and human MERS-CoV genome sequences available in GenBank. Phylogenetic analysis showed that 5 and 214 strains belong to clade A and B, respectively, with clade A further divided into lineage A1 (3 human strains) and lineage A2 (2 camel strains), and clade B divided into B1 to B6 (each containing both human and camel strains). Recombination analysis showed potential recombination events in five strains from dromedaries in Saudi Arabia, with recombination between lineage B5 and B3 in four strains, and between lineage B3 and B4 in one strain. The spike protein showed the highest number of amino acid substitutions, especially between A2 and other lineages, and contained positively selected codons. Notably, codon 1020 was positively selected among B and B5 strains, and can distinguish between clade A (Q1020) and B (R1020/H1020) strains, suggesting that this residue may play a role in the evolution of S protein during divergence of different lineages. The time of the most recent common ancestor of all MERS-CoV was dated to approximately 2010. The implications on the role of camels in the evolution of MERS-CoV are discussed.


title: Changes in sleep pattern, sense of time and digital media use during COVID‐19 lockdown in Italy

text: Italy is one of the major COVID‐19 hotspots. To reduce the spread of the infections and the pressure on Italian healthcare systems, since March 10, 2020, Italy has been under a total lockdown, forcing people into home confinement. Here we present data from 1,310 people living in the Italian territory (M (age) = 23.91 ± 3.60 years, 880 females, 501 workers, 809 university students), who completed an online survey from March 24 to March 28, 2020. In the survey, we asked participants to think about their use of digital media before going to bed, their sleep pattern and their subjective experience of time in the previous week (March 17–23, which was the second week of the lockdown) and up to the first week of February (February 3–10, before any restriction in any Italian area). During the lockdown, people increased the usage of digital media near bedtime, but this change did not affect sleep habits. Nevertheless, during home confinement, sleep timing markedly changed, with people going to bed and waking up later, and spending more time in bed, but, paradoxically, also reporting a lower sleep quality. The increase in sleep difficulties was stronger for people with a higher level of depression, anxiety and stress symptomatology, and associated with the feeling of elongation of time. Considering that the lockdown is likely to continue for weeks, research data are urgently needed to support decision making, to build public awareness and to provide timely and supportive psychosocial interventions.


title: Antibiotiques en pratique courante pédiatrique indications et contre-indications

text: Les infections sont nombreuses chez l'enfant en raison de sa sensibilité naturelle aux virus et aux bactéries. Elles représentent en conséquence un des motifs de consultation les plus fréquents en pédiatrie et motivent souvent la prescription d'antibiotiques.


title: Autophagy-Independent Functions of the Autophagy Machinery

text: Macroautophagy (herein referred to as autophagy) is an evolutionary ancient mechanism that culminates with the lysosomal degradation of superfluous or potentially dangerous cytosolic entities. Over the past 2 decades, the molecular mechanisms underlying several variants of autophagy have been characterized in detail. Accumulating evidence suggests that most, if not all, components of the molecular machinery for autophagy also mediate autophagy-independent functions. Here, we discuss emerging data on the non-autophagic functions of autophagy-relevant proteins.


title: Sozialmedizin in Zeiten der Corona-Pandemie

text: Die gesundheitlichen Auswirkungen und Folgen der Coronavirus-Pandemie (Covid-19) sind derzeit nicht vorhersagbar. Als Dauer der Pandemie wurde von Seiten des RKI ein Zeitraum von bis zu 2 Jahren geschätzt. Aktuelle Lagebeurteilungen, Prognosen und Bewertungen getroffener Maßnahmen müssen ständig überprüft und angepasst werden und sollten auch nützlich sein.


docid: zzykyblm

title: Human Coronavirus 229E can Use CD209L (L-Sign) to Enter Cells


title: Molecular Interactions in the Assembly of Coronaviruses

text: Publisher Summary This chapter describes the interactions between the different structural components of the viruses and discusses their relevance for the process of virion formation. Two key factors determine the efficiency of the assembly process: intracellular transport and molecular interactions. Many viruses have evolved elaborate strategies to ensure the swift and accurate delivery of the virion components to the cellular compartment(s) where they must meet and form (sub) structures. Assembly of viruses starts in the nucleus by the encapsidation of viral DNA, using cytoplasmically synthesized capsid proteins; nucleocapsids then migrate to the cytosol, by budding at the inner nuclear membrane followed by deenvelopment, to pick up the tegument proteins.


title: Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

text: A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.


title: A nested PCR approach for unambiguous typing of pestiviruses infecting cattle

text: Abstract An atypical pestivirus (‘Hobi’-like pestivirus, putative bovine viral diarrhoea 3, BVDV-3) was identified firstly in contaminated foetal calf serum batches and isolated subsequently from an outbreak of respiratory disease in a cattle herd in Italy. The isolation of the novel pestivirus from animals affected clinically posed concerns about the validity of BVDV eradication programs, considering that ‘Hobi’-like pestivirus (BVDV-3) is undetected or mistyped by the molecular diagnostic tools currently employed. In this paper, the development of a nested PCR (nPCR) assay for unambiguous typing of all bovine pestiviruses is reported. The assay consisted of a first-round amplification using an oligonucleotide pair which binds to conserved sequences located in the 5′ untranslated region and capsid gene, followed by a heminested PCR using virus-specific forward primers. The assay performances were evaluated analytically, showing good sensitivity and specificity. By analysis of 100 BVDV-positive samples typed using a nPCR assay discriminating ruminant pestiviruses, five samples recognised previously as BVDV-2 were not typed when submitted to the new assay (n =2) or reacted as ‘Hobi’-like pestivirus BVDV-3 (n =3). Sequence analysis of the first-round amplification products showed that the untyped strains were border disease viruses, whereas the other three strains were true ‘Hobi’-like viruses. The development of a molecular assay able to identify simultaneously all bovine pestiviruses known currently will help warrant biosafety of live vaccines and other biological products and assess the molecular epidemiology of ‘Hobi’-like pestivirus, thus leading to the improvement of the eradication programs through unambiguous typing of pestiviruses infecting cattle.


docid: xsvklawt

title: Virological study of two commercial pig herds with respiratory disease *

text: A longitudinal virological and serological study was carried out in two pig herds with respiratory disease. From 598 nasal and rectal swab samples, 299 viruses were isolated which belonged to six groups, viz, adeno-, corona-, entero-, herpes-, parvo- and reovirus. Infection with porcine cytomegalovirus and enterovirus, serotype V13, was universal in both herds. In herd A, as neonatal antibody to PCMV and reovirus type 3 declined, the majority of pigs became infected with these viruses at five to eight weeks and 11 weeks respectively. The majority of pigs showed seroconversion to these viruses. Enteroviruses were excreted continuously from eight weeks and one adenovirus was isolated at 11 weeks. In herd B, a similar pattern of PCMV excretion and antibody development was found in one group of pigs but infection in the other group occurred much earlier and all pigs in this group had a poor antibody response following infection. The coronavirus of vomiting-and-wasting disease (VWD) was isolated from some three-week-old pigs which had moderate, rising antibody titres. Adenoviruses, including type 4, and enteroviruses were also recovered from pigs at an earlier age than those in herd A and in addition a parvovirus was isolated. Porcine cytomegalovirus, porcine adenovirus type 4 and the coronavirus (VWD) were considered to be the only viruses which may have been directly associated with the respiratory disease. Of the other viruses isolated only an enterovirus, serotype F34, had a tenuous link with respiratory disease.


title: In vitro antimicrobial activities of animal-used quinoxaline 1,4-di-N-oxides against mycobacteria, mycoplasma and fungi

text: BACKGROUND: The quinoxaline 1,4-di-N-oxides (QdNOs) were known as potent antibacterial agents. For the purpose of evaluating the bioactivity of existing animal-used QdNOs drugs against representative pathogenic microorganism, the representative drugs of quinoxalines including cyadox, mequindox, quinocetone and their metabolites were submitted to the in vitro evaluation for antituberculosis, antimycoplasma, antifungal and antiviral activities. RESULTS: In antituberculosis assays, the prototype compounds were active (MIC = 4 ~ 8 μg/mL) against Mycobacterium tuberculosis H37Rv and M. bovis. Combined antimicrobial susceptibility test indicated that cyadox, mequindox and quinocetone combined with rifampicin had additive effect against M. tuberculosis complex with Fractional Inhibitory Concentration Index (FIC) of 0.75. Results of antifungal assays showed that quinocetone was active against Microsporum canis with MIC of 8 μg/mL. Antimycoplasma screening showed a generally good activity of quinocetone against Mycoplasma gallisepticum and Mycoplasma hyopneumoniae, with MIC between 8 and 16 μg/mL. As shown from the combined antimicrobial susceptibility test, cyadox, mequindox and quinocetone combined with tetracycline had additive effect against Mycoplasma gallisepticum with FIC of 0.75. These compounds were also submitted to antiviral assay against infectious bursal disease virus, porcine reproductive and respiratory syndrome virus, porcine parvovirus and classical swine fever virus. The results obtained showed that these QdNOs and their metabolites have no inhibitory activity against these viruses in vitro. CONCLUSIONS: QdNOs exhibit antimicrobial activities against mycobacteria, mycoplasma and fungi. This study gives new insight in further application of QdNOs and offers a way to promote the healthcare of animal husbandry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0812-7) contains supplementary material, which is available to authorized users.


title: Dispersal of Respiratory Droplets With Open vs Closed Oxygen Delivery Masks Implications for the Transmission of Severe Acute Respiratory Syndrome

text: Nosocomial transmission of droplet-borne respiratory infections such as severe acute respiratory syndrome (SARS) may be influenced by the choice of oxygen face mask. A subject inhaled saline mist and exhaled through three oxygen masks to illustrate the pattern of dispersal of pulmonary gas. In two commonly used masks, exhaled gas formed a plume emanating from the side vents, while a third mask with a valved manifold, which was modified by adding a respiratory filter, retained the droplets. Maintaining respiratory isolation during the administration of oxygen may reduce the risk of the nosocomial transmission of respiratory infections such as SARS.


docid: coesfldm

title: Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome

text: BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) can be inhibited by means of RNA silencing or interference (RNAi) using synthetic short interfering RNAs (siRNAs) or gene constructs encoding short hairpin RNAs (shRNAs) or long hairpin RNAs (lhRNAs). The use of siRNA and shRNA as antiviral therapeutic is limited because of the emergence of viral escape mutants. This problem is theoretically prevented by intracellular expression of lhRNAs generating multiple siRNAs that target the virus simultaneously, thus reducing the chance of viral escape. However, gene constructs encoding lhRNA molecules face problems with delivery to the right cells in an infected individual. In order to solve this problem, we constructed an HIV-1 variant with a 300 bp long hairpin structure in the 3' part of the genome corresponding to the Nef gene (HIV-lhNef). RESULTS: Intriguingly, HIV-lhNef potently inhibited wild-type HIV-1 production in trans. However, HIV-lhNef demonstrated a severe production and replication defect, which we were able to solve by selecting spontaneous virus variants with truncated hairpin structures. Although these escape variants lost the ability to trans-inhibit HIV-1, they effectively outgrew the wild-type virus in competition experiments in SupT1 cells. CONCLUSION: Expression of the lhNef hairpin within the HIV-1 genome results in potent trans-inhibition of wild-type HIV-1. Although the mechanism of trans-inhibition is currently unknown, it remains of interest to study the molecular details because the observed effect is extremely potent. This may have implications for the development of virus strains to be used as live-attenuated virus vaccines.


title: Protection of Shrimp against White Spot Syndrome Virus (WSSV) with β-1,3-d-glucan-encapsulated vp28-siRNA Particles

text: White spot syndrome virus (WSSV) is a major shrimp viral pathogen responsible for large economic losses to shrimp aquaculture all over the world. The RNAi mediated by siRNA contributes a new strategy to control this viral disease. However, the efficient approach to deliver the siRNA into shrimp remains to be addressed. In this investigation, an antiviral vp28-siRNA was encapsulated in β-1,3-d-glucan, and then the β-1,3-d-glucan-encapsulated vp28-siRNA particles (GeRPs) were delivered into Marsupenaeus japonicus shrimp. The results showed that the vp28-siRNA in GeRPs could be released in hemocytes of shrimp. It was found that the GeRPs containing the vp28-siRNA inhibited the replication of WSSV in vivo, which presented a better antiviral activity than the non-encapsulated vp28-siRNA. Further evidence indicated that the mortality of WSSV-infected shrimp was significantly delayed by the GeRPs containing vp28-siRNA. Therefore, our study presented that the glucan-encapsulated siRNA might represent a novel potential therapeutic or preventive approach to control the shrimp disease.


title: Viral Infections and Their Relationship with Catastrophic Antiphospholipid Syndrome: A Possible Pathogenic Mechanism of Severe COVID‐19 Thrombotic Complications

text: The disease caused by SARS‐CoV‐2 (COVID‐19) has different presentations and outcomes. Severe COVID‐19 is commonly complicated by markedly elevated D‐dimer, thrombocytopenia and coagulation abnormalities that are considered to be regulated by various pro‐inflammatory cytokines and similar to pneumonia induced by other pathogens(1), and are correlated with mortality. Recently, a small case series described aPL antibodies in patients with COVID‐19 (2). About 1% of APS patients develop a severe life‐threatening clinical condition characterized by multiple thrombosis involving mainly small vessels, which has been described as catastrophic APS (CAPS). Patients with CAPS have in common: 1) clinical evidence of multiple organ involvement developing over a very short period of time; 2) histopathological findings of multiple small vessel occlusions, and 3) laboratory confirmation of the presence of aPL, usually in high titres.


title: Is the presence of lung injury in COVID-19 an independent risk factor for secondary lung cancer?

text: The morbidity and mortality of lung cancer are increasing. The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells. Meanwhile, 2019-nCoV-2 can activate PI3K/Akt and ERK signaling pathways, which can play the double roles as both anti-inflammatory and carcinogenic factors. Moreover, hypoxemia may be developed, resulting in the up-regulation of HIF-1 α expression, which can be involved in the occurrence, angiogenesis, invasion and metastasis of lung cancer. Additionally, the immune system in 2019-nCoV-2 infected cases can be suppressed to cause tumor immune evasion. Therefore, we speculate that COVID-19 may be a risk factor of secondary lung cancer.


docid: ylmdrjus

title: In Coronavirus Times


title: Human Bocavirus Infection among Children, Jordan

text: Human bocavirus was detected in 57 (18.3%) of 312 children with acute respiratory infection (ARI) who required hospitalization in Jordan. It was also detected in 30 (21.7%) of 138 children with severe ARI, in 27 (15.5%) of 174 with mild or moderate disease, and in 41 (72%) of 57 with other pathogens.


docid: javffmku

title: When Nature turns cook: An epidemiological feast: Report of the John Snow Society Pumphandle Lecture 2009, delivered by Dr David Heymann


Virtual Visits for Care of Patients with Heart Failure in the Era of COVID-19: A Statement from the Heart Failure Society of America


title: DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials

text: Summary Background Because the general population is largely naive to H5N1 influenza, antibodies generated to H5 allow analysis of novel influenza vaccines independent of background immunity from previous infection. We assessed the safety and immunogenicity of DNA encoding H5 as a priming vaccine to improve antibody responses to inactivated influenza vaccination. Methods In VRC 306 and VRC 310, two sequentially enrolled phase 1, open-label, randomised clinical trials, healthy adults (age 18–60 years) were randomly assigned to receive intramuscular H5 DNA (4 mg) at day 0 or twice, at day 0 and week 4, followed by H5N1 monovalent inactivated vaccine (MIV; 90 μg) at 4 or 24 weeks, and compared with a two-dose regimen of H5N1 MIV with either a 4 or 24 week interval. Antibody responses were assessed by haemagglutination inhibition (HAI), ELISA, neutralisation (ID80), and immunoassays for stem-directed antibodies. T cell responses were assessed by intracellular cytokine staining. After enrolment, investigators and individuals were not masked to group assignment. VRC 306 and VRC 310 are registered with ClinicalTrials.gov, numbers NCT00776711 and NCT01086657, respectively. Findings In VRC 306, 60 individuals were randomly assigned to the four groups (15 in each) and 59 received the vaccinations. In VRC 310, of the 21 individuals enrolled, 20 received the vaccinations (nine received a two-dose regimen of H5N1 MIV and 11 received H5 DNA at day 0 followed by H5N1 MIV at week 24). H5 DNA priming was safe and enhanced H5-specific antibody titres following an H5N1 MIV boost, especially when the interval between DNA prime and MIV boost was extended to 24 weeks. In the two studies, DNA priming with a 24-week MIV boost interval induced protective HAI titres in 21 (81%) of 26 of individuals, with an increase in geometric mean titre (GMT) of more than four times that of individuals given the MIV-MIV regimen at 4 or 24 weeks (GMT 103–206 vs GMT 27–33). Additionally, neutralising antibodies directed to the conserved stem region of H5 were induced by this prime-boost regimen in several individuals. No vaccine-related serious adverse events were recorded. Interpretation DNA priming 24 weeks in advance of influenza vaccine boosting increased the magnitude of protective antibody responses (HAI) and in some cases induced haemagglutinin-stem-specific neutralising antibodies. A DNA-MIV vaccine regimen could enhance the efficacy of H5 or other influenza vaccines and shows that anti-stem antibodies can be elicited by vaccination in man. Funding National Institutes of Health.


title: Facial pressure ulcers in COVID-19 patients undergoing prone positioning: How to prevent an underestimated epidemic?

text: Abstract Prone positioning is an adjuvant therapy used to treat COVID-19 pneumonia complicated by acute respiratory distress syndrome. However, prolonged pressure on facial skin at the level of the bony structures may be responsible for facial pressure ulcers. In the context of severe COVID-19 pneumonia, we hypothesized that hypoxemia, microvascular injury and thrombosis can increase the risk of pressure ulcers. We described two cases in order to emphasize the risk of facial pressure ulcers as a result of prone positioning, so as to discuss their physiopathology and highlight the importance of appropriate preventive measures.


Ebola—challenge and revival of theoretical epidemiology: Why Extrapolations from early phases of epidemics are problematic