title: Sensitivity of L132 Cells to Some “New” Respiratory Viruses

text: THERE are several reports of the isolation from cases of human upper respiratory infections of viruses with a structure known previously only in the viruses causing avian infectious bronchitis(1) and mouse hepatitis(2). The first isolate, named B814, was propagated in organ cultures of human embryo respiratory epithelium(3), and most of the other isolates have been made in organ culture(4). Some viruses of humans, of the type 229E, multiply in tissue cultures of human embryo kidney fibroblasts where they cause a slight cytopathic effect, and in human embryo lung fibroblasts where they cause a definite progressive cytopathic effect(5). Those viruses only cultivated in organ culture were detected either by electron, microscopy, or by inoculation into human volunteers, or by stopping the ciliary activity of the organ culture epithelium. It has been proposed that the group of virsues with this morphology should be called “coronaviruses”(6).


title: Rethinking hospital general ward ventilation design using computational fluid dynamics

text: Summary Indoor ventilation with good air quality control minimises the spread of airborne respiratory and other infections in hospitals. This article considers the role of ventilation in preventing and controlling infection in hospital general wards and identifies a simple and cost-effective ventilation design capable of reducing the chances of cross-infection. Computational fluid dynamic (CFD) analysis is used to simulate and compare the removal of microbes using a number of different ventilation systems. Instead of the conventional corridor air return arrangement used in most general wards, air return is rearranged so that ventilation is controlled from inside the ward cubicle. In addition to boosting the air ventilation rate, the CFD results reveal that ventilation performance and the removal of microbes can be significantly improved. These improvements are capable of matching the standards maintained in a properly constructed isolation room, though at much lower cost. It is recommended that the newly identified ventilation parameters be widely adopted in the design of new hospital general wards to minimise cross-infection. The proposed ventilation system can also be retrofitted in existing hospital general wards with far less disruption and cost than a full-scale refurbishment.


title: Anti-oxidant and Anti-Inflammatory Cyclic Diarylheptanoids from Alnus japonica Stem Bark

text: A new cyclic diarylheptanoid namely alnuheptanoid B (3), along with four known cyclic diarylheptanoids: myricanone (1), (+)-S-myricanol (2), myricanone 5-O- -D-glucopyranoside (4), and (+)-S-myricanol 5-O- -D-glucopyranoside (5) were isolated from the EtOAc fraction of Alnus japonica Steud (family: Betulaceae) stem bark. Their structures were established by different spectroscopic analyses, as well as optical rotation measurement. Compounds 1, 2, 4, and 5 are isolated for the first time from A. japonica. The antioxidant and anti-inflammatory activities of compounds (1-5) were assessed using DPPH assay and carrageenin induced rat paw edema model, respectively. They displayed significant antioxidant activity in relation to propyl gallate (standard antioxidant) at concentration 50 µM. Compound 2 demonstrated anti-inflammatory effect at a dose 10 mg/kg compared with indomethacin (positive control).


title: 10 recommendations for African governments to ensure food security for poor and vulnerable populations during COVID-19

text: In addressing COVID-19, African governments should not forget the livelihoods as well as the food and nutrition security of their citizens. With over 70% of the workforce in the informal sector without any social protection and health insurance, the pandemic could have a devastating impact on income and livelihoods as well as food and nutrition security for workers up and down the food chain. There are ten steps African governments can take to ensure that their response to the disease takes food and nutrition security into account: 1. Protect food supply chains and consider them essential services; 2. Consider fiscal and monetary incentives; 3. Prioritize healthy diets; 4. Use food reserves wisely; 5. Keep food markets open while ensuring safety; 6. Use mobile cash transfers for social protection; 7. Protect farmers and food workers; 8. Prioritize gender equality; 9. Instill a sense of solidarity; and 10. Avoid export bans.


title: COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

text: BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV–host interactome was carried out in order to provide a theoretic host–pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein–protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.


title: An 'elaborated' pseudoknot is required for high frequency frameshifting during translation of HCV 229E polymerase mRNA.

text: The RNA polymerase gene (gene 1) of the human coronavirus 229E is approximately 20 kb in length and is located at the 5' end of the positive-strand genomic RNA. The coding sequence of gene 1 is divided into two large open reading frames, ORF1a and ORF1b, that overlap by 43 nucleotides. In the region of the ORF1a/ORF1b overlap, the genomic RNA displays two elements that are known to mediate (-1) ribosomal frameshifting. These are the slippery sequence, UUUAAAC, and a 3' pseudoknot structure. By introducing site-specific mutations into synthetic mRNAs, we have analysed the predicted structure of the HCV 229E pseudoknot and shown that besides the well-known stem structures, S1 and S2, a third stem structure, S3, is required for a high frequency of frameshifting. The requirement for an S3 stem is independent of the length of loop 2.


title: Acute respiratory infection and influenza‐like illness viral etiologies in Brazilian adults

text: Influenza‐like illness (ILI) definitions have been used worldwide for influenza surveillance. These different case definitions can vary with regard to sensitivity and predictive values for laboratory confirmed influenza. The literature has indicated the inclusion of other viruses may be the cause of these variable results. The objective of the study was to evaluate ILI national sentinel criteria and viral etiologies in adults diagnosed with acute respiratory infection (ARI) and/or ILI from 2001 to 2003 in Sao Paulo, Brazil. Clinical and laboratory evaluations were observed from 420 adults and collected on a daily basis from outpatient care units at University Hospital. The ILI definition included: fever plus at least one respiratory symptom (cough and/or sore throat) and one constitutional symptom (headache, malaise, myalgia, sweat or chills, or fatigue). DFA and RT‐PCR for influenza, parainfluenza, respiratory syncytial virus, adenovirus, enterovirus, coronavirus, rhinovirus, and metapneumovirus were performed on nasal washes and 61.8% resulted positive. The respiratory viruses detected most often were influenza and rhinovirus. ILI was reported for 240/420 patients (57.1%), with influenza and rhinovirus etiologies accounting for 30.9% and 19.6%, respectively. Rhinovirus peak activity was concurrent with the influenza season. These findings highlight the implications of other viruses in ILI etiology and suggest that during the influenza season, this clinical overlap must be considered in the diagnosis and clinical management of patients. J. Med. Virol. 80:1824–1827, 2008. © 2008 Wiley‐Liss, Inc.


title: Evaluation of antirotavirus activity of flavonoids

text: Abstract Flavonoids are dietary components and the most ubiquitous phenolic compounds found in nature, showing a range of pharmacological activities including antiviral action. This study describes the antiviral screening of 60 different flavones and flavonols against human rotavirus (Wa-1 strain) as well as their cytotoxicity in MA104 cells. Cytotoxicity was investigated by cell morphology assessment and antirotavirus activity by cytopathic effect inhibition. Results were expressed as CC50 and IC50, respectively, in order to calculate the selectivity index (SI=CC50/IC50) of each compound. Structure–activity relationships (SAR) were proposed based on antirotavirus activity.


title: The effect of human mobility and control measures on the COVID-19 epidemic in China

text: The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.


title: CovidSens: a vision on reliable social sensing for COVID-19

text: With the spiraling pandemic of the Coronavirus Disease 2019 (COVID-19), it has becoming inherently important to disseminate accurate and timely information about the disease. Due to the ubiquity of Internet connectivity and smart devices, social sensing is emerging as a dynamic AI-driven sensing paradigm to extract real-time observations from online users. In this paper, we propose CovidSens, a vision of social sensing-based risk alert systems to spontaneously obtain and analyze social data to infer the state of the COVID-19 propagation. CovidSens can actively help to keep the general public informed about the COVID-19 spread and identify risk-prone areas by inferring future propagation patterns. The CovidSens concept is motivated by three observations: (1) people have been actively sharing their state of health and experience of the COVID-19 via online social media, (2) official warning channels and news agencies are relatively slower than people reporting their observations and experiences about COVID-19 on social media, and (3) online users are frequently equipped with substantially capable mobile devices that are able to perform non-trivial on-device computation for data processing and analytics. We envision an unprecedented opportunity to leverage the posts generated by the ordinary people to build a real-time sensing and analytic system for gathering and circulating vital information of the COVID-19 propagation. Specifically, the vision of CovidSens attempts to answer the questions: How to distill reliable information about the COVID-19 with the coexistence of prevailing rumors and misinformation in the social media? How to inform the general public about the latest state of the spread timely and effectively, and alert them to remain prepared? How to leverage the computational power on the edge devices (e.g., smartphones, IoT devices, UAVs) to construct fully integrated edge-based social sensing platforms for rapid detection of the COVID-19 spread? In this vision paper, we discuss the roles of CovidSens and identify the potential challenges in developing reliable social sensing-based risk alert systems. We envision that approaches originating from multiple disciplines (e.g., AI, estimation theory, machine learning, constrained optimization) can be effective in addressing the challenges. Finally, we outline a few research directions for future work in CovidSens.


title: Knowledge and attitudes of medical staff in Chinese psychiatric hospitals regarding COVID-19

text: Abstract On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus COVID-19 a pandemic. There are patients in psychiatric hospitals in China who have been infected with COVID-19, however, the knowledge and attitudes of psychiatric hospital staff towards infectious diseases and their willingness to work during the COVID-19 outbreak has not yet been investigated. This study was performed to assess the knowledge and attitudes of medical staff in two Chinese mental health centers during the COVID-19 outbreak. We included 141 psychiatrists and 170 psychiatric nurses in the study. We found that during the COVID-19 epidemic, 89.51% of the medical staff of the psychiatric hospitals studied had extensive knowledge of COVID-19, and 64.63% of them received the relevant training in hospitals. Furthermore, about 77.17% of participants expressed a willingness to care for psychiatric patients suffering from COVID-19 virus infection. Independent predictors of willingness to care for patients included advanced training and experience of caring for patients with COVID-19. In conclusion, this study suggests that increased attention should be paid to the knowledge and attitudes of medical staff at psychiatric hospitals during the COVID-19 outbreak.


title: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2

text: The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.


title: Proteomic alteration of Marc-145 cells and PAMs after infection by porcine reproductive and respiratory syndrome virus

text: Abstract Viral infections usually result in alterations in the host cell proteome, which determine the fate of infected cells and the progress of pathogenesis. To uncover cellular protein responses in porcine reproductive and respiratory syndrome virus (PRRSV), infected pulmonary alveolar macrophages (PAMs) and Marc-145 cells were subjected to proteomic analysis involving two-dimensional electrophoresis (2-DE) followed by MALDI-TOF-MS/MS identification. Altered expression of 44 protein spots in infected cells was identified in 2D gels, of which the 29 characterised by MALDI-TOF-MS/MS included 17 up-regulated and 12 down-regulated proteins. Some of these proteins were further confirmed at the mRNA level using real-time RT-PCR. Moreover, Western blot analysis confirmed the up-regulation of HSP27, vimentin and the down-regulation of galectin-1. Our study is the first attempt to analyze the cellular protein profile of PRRSV-infected Marc-145 cells using proteomics to provide valuable information about the effects of PRRSV-induced alterations on Marc-145 cell function. Further study of the affected proteins may facilitate our understanding of the mechanisms of PRRSV infection and pathogenesis.


title: WSE, a new sequence distance measure based on word frequencies

text: Abstract In this article, we present a new distance metric, the Weighted Sequence Entropy (WSE), based on the short word composition of biological sequences. As a revision of the classical relative entropy (RE), our metric (1) works equivalently with RE in the case of small k, (2) avoids the degeneracy when some word types are absent in one sequence but not in the other. Experiments on 25 viruses including SARS-CoVs show that our method and RE give exactly the same phylogenetic tree when word length k ⩽ 3 . When k > 3 , our method still works and gets convergent phylogenetic topology but the RE gives degenerate results.


Incidence and patterns of COVID-19 among inflammatory bowel disease patients from the Nancy and Milan cohorts


title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets

text: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.


title: A novel DNA vaccine containing multiple TB-specific epitopes casted in a natural structure (ECANS) confers protective immunity against pulmonary mycobacterial challenge

text: Abstract Epitope-based DNA vaccines designed to induce T cell responses specific for Mycobacterium tuberculosis (M. tb) are being developed as a means of addressing vaccine potency. In this study, we predicted 4 T cell epitopes from ESAT-6, Ag85A/B and CFP-10 antigens and constructed an ECANS (epitopes casted in a natural structure) DNA vaccine by inserting the epitope DNA segments separately into the gene backbone of M. tb-derived HSP65 (heat shock protein 65) carrier. The immunogenicity and protective efficacy of pECANS DNA vaccine were assessed in BALB/c mice after intramuscular immunization with 4 doses of 50μg ECANS DNA and followed by mycobaterial challenge 4 weeks after the last immunization. Compared to plasmid encoding HSP65, pECANS DNA immunization elicited remarkably higher levels of IFN-γ production by both CD4+ and CD8+ T cells, which were coupled with higher frequencies of antigen-specific T cells and higher CTL activity. Significantly enhanced levels of Th1 cytokines (IFN-γ and IL-12) and increased serum IgG2a/IgG1 ratio were also noted, indicating a predominant Th1 immune response achieved by pECANS DNA immunization. In the consequence, a better protection against Mycobacterium bovis BCG challenge was achieved which was evidenced by reduced bacterial loads in lungs and spleens and profound attenuation of lung inflammation and injury. Our results suggested that multi-T cell-epitope based ECANS gene vaccine induced T cell response to multiple T cell epitopes and led to enhanced protection against mycobacterial challenge. This strategy might be a useful platform to design multi-T cell epitope-based vaccine against M. tb infection.


title: 11 Governance of Biodiversity and Health

text: Abstract: The 1968 UNESCO Biosphere Conference (in partnership with the FAO, WHO and the UN) was the first intergovernmental conference to consider both human and health ecology from a scientific point of view. Thus, it has a leading role in addressing health issues related to ecological diversity on a global scale. It insists on the need for integrated, planned, multidisciplinary policy action for the use and conservation of natural resources within the framework of international cooperation.


title: Zielgerichtete Therapie beim metastasierten Mammakarzinom – welche molekularen Tests sind notwendig?

text: In recent years, targeted therapy for breast cancer has received increasingly more attention. In addition to hormone receptors and human epidermal growth factor 2 (HER2), the immunohistochemical detection of programmed cell death ligand 1 (PD-L1) in advanced triple-negative breast cancer and the detection of mutations in the breast cancer 1 (BRCA1) or BRCA2 gene in the patient’s germline and mutations in the phosphatidylinositol 3 kinase (PI3K) pathway are currently relevant when making decisions regarding targeted therapy.


title: Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals

text: Abstract Viral infection induces translocation of the nucleolar protein GLTSCR2 from the nucleus to the cytoplasm, resulting in attenuation of the type I interferon IFN-β. Addressing the role of GLTSCR2 in viral replication, we detect that knocking down GLTSCR2 by shRNAs results in significant suppression of viral replication in mammalian and chicken cells. Injection of chicken embryo with the GLTSCR2-specific shRNA-1370 simultaneously or 24 h prior to infection with Newcastle disease virus (NDV) substantially reduces viral replication in chicken embryo fibroblasts. Injection of shRNA-1370 into chicken embryo also reduces the replication of avian influenza virus (AIV). In contrast, GLTSCR2-derived protein G4-T, forming α-helical dimers, increases replication of seven various DNA and RNA viruses in cells. Our studies reveal that alteration of the function of cellular GLTSCR2 plays a role in supporting viral replication. GLTSCR2 should be seriously considered as a therapeutic target for developing broad spectrum antiviral agents to effectively control viral infection.


title: Bariatric Surgical Practice During the Initial Phase of COVID-19 Outbreak

text: There is no data on patients with severe obesity who developed coronavirus disease 2019 (COVID-19) after bariatric surgery. Four gastric bypass operations, performed in a 2-week period between Feb 24 and March 4, 2020, in Tehran, Iran, were complicated with COVID-19. The mean age and body mass index were 46 ± 12 years and 49 ± 3 kg/m(2). Patients developed their symptoms (fever, cough, dyspnea, and fatigue) 1, 2, 4, and 14 days after surgery. One patient had unnoticed anosmia 2 days before surgery. Three patients were readmitted in hospital. All 4 patients were treated with hydroxychloroquine. In two patients who required admission in intensive care unit, other off-label therapies including antiretroviral and immunosuppressive agents were also administered. All patients survived. In conclusion, COVID-19 can complicate the postoperative course of patients after bariatric surgery. Correct diagnosis and management in the postoperative setting would be challenging. Timing of infection after surgery in our series would raise the possibility of hospital transmission of COVID-19: from asymptomatic patients at the time of bariatric surgery to the healthcare workers versus acquiring the COVID-19 infection by non-infected patients in the perioperative period.


title: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts

text: BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2·5 more than 70% of contacts had to be traced, and for an R(0) of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1·5. For R(0) values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.


title: Preventing problematic internet use during the COVID-19 pandemic: Consensus guidance

text: As a response to the COVID-19 pandemic, many governments have introduced steps such as spatial distancing and “staying at home” to curb its spread and impact. The fear resulting from the disease, the ‘lockdown’ situation, high levels of uncertainty regarding the future, and financial insecurity raise the level of stress, anxiety, and depression experienced by people all around the world. Psychoactive substances and other reinforcing behaviors (e.g., gambling, video gaming, watching pornography) are often used to reduce stress and anxiety and/or to alleviate depressed mood. The tendency to use such substances and engage in such behaviors in an excessive manner as putative coping strategies in crises like the COVID-19 pandemic is considerable. Moreover, the importance of information and communications technology (ICT) is even higher in the present crisis than usual. ICT has been crucial in keeping parts of the economy going, allowing large groups of people to work and study from home, enhancing social connectedness, providing greatly needed entertainment, etc. Although for the vast majority ICT use is adaptive and should not be pathologized, a subgroup of vulnerable individuals are at risk of developing problematic usage patterns. The present consensus guidance discusses these risks and makes some practical recommendations that may help diminish them.


title: Measuring the part worth of the mode of transport in a trip package: An extended Bradley–Terry model for paired-comparison conjoint data

text: Abstract This study measures the travelers' perceived change in utility by accepting one of the modes of transport air, rail, or bus as one component of a packaged city trip. The part-worth values for the trip product elements are expected to depend on a number of traveler characteristics. The predictors hypothesized are city travel experience, general modal preference, socio-economic status, and car ownership. In the survey, the combinations of trip attributes differed between the two subgroups of leisure and business travelers. The leisure travelers rated three levels of mode, length of stay, and price, but only one level of the hotel category. The business travelers were shown four mode alternatives and only two levels for each of the other trip product elements. The conjoint measurements were elaborated by fitting an Extended Bradley–Terry Model. Demonstrating the application of the EBTM is the main purpose of the paper. The EBTM offers several advantages over the more popular versions of conjoint analysis. It correctly treats ties and allows for simultaneous estimation of the trip package (‘object’) parameters, object covariates (trip attributes), subject covariates (traveler characteristics) and their interactions. For both the business and the leisure travelers, the mode of transport dominated the assessment of a city trip package. For leisure tourists, e.g., switching from train 2nd class to an economy flight boosted the trip package more than twice as much as replacing train for bus. A variation of the package price was much more important for the leisure than for the business travelers. The socio-economic status proved to be an important factor and was particularly influential among the business travelers. In the leisure tourists' sub-sample age was not only important for valuing the mode of transport, but had a preferential impact for all trip components. Finally, the limitations of this demonstration study that discourage extrapolation to city travelers in general are emphasized.


title: Delayed Kinetics of Poliovirus RNA Synthesis in a Human Cell Line with Reduced Levels of hnRNP C Proteins

text: The hnRNP C heterotetramer [(C1(3))C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to relocalize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis.


title: Development of a rapid and sensitive europium (III) chelate microparticle-based lateral flow test strip for the detection and epidemiological surveillance of porcine epidemic diarrhea virus

text: Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus, is the predominant cause of severe enteropathogenic diarrhea in swine. A simple, rapid, specific, and sensitive method is critical for monitoring PEDV on pig farms. In this study, a simple and rapid lateral flow immunoassay detection system that integrates europium (Eu) (III) chelate microparticles was developed to identify PEDV in fecal swabs. This newly developed diagnostic sandwich immunoassay utilizes lateral flow test strips (LFTSs). The fluorescence peak heights of the test line (HT) and the control line (HC) were measured using a fluorescence strip reader, and the HT/HC ratio was used for quantitation. The limit of detection of PEDV with this LFTS was ??ten times the median tissue culture infectious dose (TCID(50)) per mL??. Fecal swab samples were used to determine the cutoff value. Field samples, various PEDV strains and other viruses were used to determine the sensitivity and specificity of the Eu (III) chelate microparticle-based LFTSs, which were 97.8% and 100%, respectively, with a cutoff value of 0.05, as compared with reverse transcription polymerase chain reaction (RT-PCR). In samples from piglets experimentally infected with PEDV, the results were in high agreement with those obtained by RT-PCR. Epidemiological surveillance of PEDV using the LFTSs ??in areas threatened by African swine fever virus?? suggested that the PEDV positive rate on pig farms had significantly decreased, mainly due to the implementation of strict biosecurity measures. The results indicate that the Eu (III) chelate microparticle-based LFTS system is a rapid, sensitive, and reliable method for the identification of PEDV, indicating its suitability for epidemiological surveillance of PEDV infection.


Testosterone, a key hormone in the context of COVID-19 pandemic


title: A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera

text: BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.


title: Some fractal thoughts about the COVID-19 infection outbreak

text: Abstract Some ideas are presented about a geometric motivation of the apparent capacity of generalized logistic equations to describe the outbreak of quite many epidemics, possibly including that of the COVID-19 infection. This interpretation pivots on the complex, possibly fractal, structure of the locus describing the “contagion event set”, and on what can be learnt from the models of trophic webs with “herd behaviour”. Under the hypothesis that the total number of cases, as a function of time, is fitted by a solution of the Generalized Richards Model, it is argued that the exponents appearing in that differential equation, usually determined empirically, represent the geometric signature of the non-space filling, network-like locus on which contagious contacts take place.


title: A Strategy for Searching Antigenic Regions in the SARS-CoV Spike Protein

text: In the face of the worldwide threat of severe acute respiratory syndrome (SARS) to human life, some of the most urgent challenges are to develop fast and accurate analytical methods for early diagnosis of this disease as well as to create a safe anti-viral vaccine for prevention. To these ends, we investigated the antigenicity of the spike protein (S protein), a major structural protein in the SARS-coronavirus (SARS-CoV). Based upon the theoretical analysis for hydrophobicity of the S protein, 18 peptides were synthesized. Using Enzyme-Linked Immunosorbent Assay (ELISA), these peptides were screened in the sera from SARS patients. According to these results, two fragments of the S gene were amplified by PCR and cloned into pET-32a. Both S fragments were expressed in the BL-21 strain and further purified with an affinity chromatography. These recombinant S fragments were confirmed to have positive cross-reactions with SARS sera, either by Western blot or by ELISA. Our results demonstrated that the potential epitope regions were located at Codons 469–882 in the S protein, and one epitope site was located at Codons 599–620. Identification of antigenic regions in the SARS-CoV S protein may be important for the functional studies of this virus or the development of clinical diagnosis.


title: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection after allogeneic stem cell transplantation

text: This is the first report of a case of COVID‐19 after allogeneic stem cell transplantation. Our case suggests that COVID‐19 may exist without characteristic CT images, especially in immunocompromised hosts, such as patients after transplantation.


title: Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells

text: Infection by porcine reproductive and respiratory syndrome virus (PRRSV) results in a weak induction of the innate immune response. There are many genes that collectively comprise this response and the extent to which each gene responds to PRRSV infection is unclear and warrants further investigation. To this end, we have utilized real-time PCR using SYBR Green I dye-based detection to quantify transcript abundance of the type I interferons (IFN-α and -β) and IFN-β transcriptional enhanceasome genes. In MARC-145 cells, both IFN-α and -β transcript abundance were unaffected by PRRSV infection. However, stimulation of MARC-145 cells by exogenous double-stranded RNA, resulted in significant increases in transcript abundance of both IFN-α and -β as well as IFN-β enhanceasome components, indicating that a type I IFN response could be induced in these cells. The double-stranded RNA induction of type I IFN transcription was significantly inhibited by dual-exposure with PRRSV. These results suggest that PRRSV infection directly interferes with type I IFN transcriptional activation early in its pathway, at the level of IFN-β gene transcription.


title: Endangered wild salmon infected by newly discovered viruses

text: The collapse of iconic, keystone populations of sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon in the Northeast Pacific is of great concern. It is thought that infectious disease may contribute to declines, but little is known about viruses endemic to Pacific salmon. Metatranscriptomic sequencing and surveillance of dead and moribund cultured Chinook salmon revealed a novel arenavirus, reovirus and nidovirus. Sequencing revealed two different arenavirus variants which each infect wild Chinook and sockeye salmon. In situ hybridisation localised arenavirus mostly to blood cells. Population surveys of >6000 wild juvenile Chinook and sockeye salmon showed divergent distributions of viruses, implying different epidemiological processes. The discovery in dead and dying farmed salmon of previously unrecognised viruses that are also widely distributed in wild salmon, emphasizes the potential role that viral disease may play in the population dynamics of wild fish stocks, and the threat that these viruses may pose to aquaculture.


Telemedicine and eConsults for hospitalized patients during COVID-19


title: Detection of antibodies against SARS-CoV in serum from SARS-infected donors with ELISA and Western blot

text: Abstract Recombinant fragments of S proteins from the Severe Acute Respiratory Syndrome (SARS) coronavirus (SARA-CoV) were generated and used in a Western blot (WB) assay that was compared to a commercial SARS ELISA method. In 85% of confirmed SARS cases (n = 20), the S2 recombinant fragment based WB was positive and this was comparable to the commercial ELISA using heat killed SARS-CoV. WB using the other four recombinant fragments in confirmed SARS cases generated lower rates of detection (S1—75%, S1-N—25%, S1-C—55%). Evaluation of sera from healthy controls (n = 60) resulted in two weakly positive ELISA results with the remainder being negative while the S2 protein WB demonstrated three positive results from the 20 controls with a history of SARS contact and no positive results in 40 noncontact controls. A discrepancy between the ELISA and S2 WB arose when evaluating per-2003 sera from individuals (n = 10) with SARS-like symptoms (ELISA—100% positive, S2 WB—30% positive). These data suggest that the S2 WB assay may be particularly useful in ELISA-negative SARS cases and in some ELISA-positive non-SARS cases.


title: Caring for patients with pain during the COVID‐19 pandemic: consensus recommendations from an international expert panel

text: Chronic pain causes significant suffering, limitation of daily activities and reduced quality of life. Infection from COVID‐19 is responsible for an ongoing pandemic that causes severe acute respiratory syndrome, leading to systemic complications and death. Led by the World Health Organization, healthcare systems across the world are engaged in limiting the spread of infection. As a result, all elective surgical procedures, outpatient procedures and patient visits, including pain management services, have been postponed or cancelled. This has affected the care of chronic pain patients. Most are elderly with multiple comorbidities, which puts them at risk of COVID‐19 infection. Important considerations that need to be recognised during this pandemic for chronic pain patients include: ensuring continuity of care and pain medications, especially opioids; use of telemedicine; maintaining biopsychosocial management; use of anti‐inflammatory drugs; use of steroids; and prioritising necessary procedural visits. There are no guidelines to inform physicians and healthcare providers engaged in caring for patients with pain during this period of crisis. We assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to guide practice. As the COVID‐19 situation continues to evolve rapidly, these recommendations are based on the best available evidence and expert opinion at this present time and may need adapting to local workplace policies.


title: Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data

text: Abstract Introduction Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. Patients and methods: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. Results During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). Conclusion MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.


title: COVID-19 and lung cancer: risks, mechanisms and treatment interactions

text: Cases of the 2019 novel coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to rise worldwide. To date, there is no effective treatment. Clinical management is largely symptomatic, with organ support in intensive care for critically ill patients. The first phase I trial to test the efficacy of a vaccine has recently begun, but in the meantime there is an urgent need to decrease the morbidity and mortality of severe cases. It is known that patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments. Therefore, these patients might be at increased risk of pulmonary complications from COVID-19. The SARS-CoV-2 could in some case induce excessive and aberrant non-effective host immune responses that are associated with potentially fatal severe lung injury and patients can develop acute respiratory distress syndrome (ARDS). Cytokine release syndrome and viral ARDS result from uncontrolled severe acute inflammation. Acute lung injury results from inflammatory monocyte and macrophage activation in the pulmonary luminal epithelium which lead to a release of proinflammatory cytokines including interleukin (IL)-6, IL-1 and tumor necrosis factor-α. These cytokines play a crucial role in immune-related pneumonitis, and could represent a promising target when the infiltration is T cell predominant or there are indirect signs of high IL-6-related inflammation, such as elevated C-reactive protein. A monoclonal anti-IL-6 receptor antibody, tocilizumab has been administered in a number of cases in China and Italy. Positive clinical and radiological outcomes have been reported. These early findings have led to an ongoing randomized controlled clinical trial in China and Italy. While data from those trials are eagerly awaited, patients’ management will continue to rely for the vast majority on local guidelines. Among many other aspects, this crisis has proven that different specialists must join forces to deliver the best possible care to patients.


title: Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing system and had mechanisms to inhibit this action in MARC-145 cells

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important disease in swine-producing area, and interferon beta (IFN-β) is the first responder against the animal virus infection. However, whether PRRSV could induce the production of IFN-β is controversial. In this paper, we first time found that PRRSV could phosphorylate IFN-regulatory factor 3 (IRF-3) and weakly activate the IFN-β promoter in MARC-145 cells in early infection, but the activations of IRF-3 and IFN-β promoter were rapidly inhibited in the following infection. Furthermore, which components or products of the invading PRRSV cause PRRSV to inhibit IFN-β promoter activity attracted our attentions. The obtained results showed that PRRSV nsp1 could inhibit Poly(I:C)-induced IFN-β promoter activity in MARC-145 cells by down-regulating the protein level of IRF-3 and inhibiting the phosphorylation of IRF-3. In conclusion, our results suggested that PRRSV could be sensed by professional IFN-β-producing system and had mechanisms to inhibit this action in MARC-145 cells.


title: Major medical causes by breed and life stage for dogs presented at veterinary clinics in the Republic of Korea: a survey of electronic medical records

text: BACKGROUND: Age and breed are considered the greatest risk factors for disease prevalence and mortality in companion dogs. Understanding the prevalence of diseases, in relation to age and breed, would support appropriate guidance for future health care strategies and provide useful information for the early diagnosis of diseases. The purpose of this study was to investigate the major medical causes for dogs visiting primary-care veterinary clinics in the Republic of Korea, stratified by age and breed. METHODS: A total of 15,531 medical records of canine patients were analyzed from 11 veterinary clinics who shared data from January 1, 2016 to December 31, 2016. An electronic medical record (EMR) system was used for data collection, which included the animal identification number, age, breed, gender, neuter status, clinical information, and diagnosis. EMR data were classified using the International Classification of Disease system from the World Health Organization; presenting signs or diagnoses were identified according to breed and life stage. RESULTS: Within the age groups, preventive medicine (16.7% confidence intervals (CI) [15.9–17.5]) was the most common cause for clinic visits for the <1 year and 1–3 year groups. Additionally, neutering surgery (6.6% CI [6.0–7.1]) and patella luxation (1.4% CI [1.8–2.7]) were frequently performed in these age groups. In the 4–6 year group, otitis externa (8.8% CI [7.8–10.0]) and dermatitis or eczema (8.5% CI [7.5–9.6]) were common medical problems. In older dogs (>10 year), the prevalences of heart disease, kidney disease, Cushing’s disease, and mammary tumors were higher than in the other age groups. Small and toy breed dogs comprised 67.7% of all dogs in this analysis. For all breeds, otitis externa, dermatitis or eczema, vomiting, and diarrhea were common medical problems. DISCUSSION: This study identified the most common medical disorders and differences in prevalences of diseases, according to age and breeds. The information from EMRs for dogs visiting primary-care veterinary clinics can provide background knowledge that is required to enable a better understanding of disease patterns and occurrence by age and breeds. The information from this study could enable the creation of strategies for preventing diseases and enable the identification of health problems for more effective disease management in companion dogs.


title: Synthetic Compounds with 2-Amino-1,3,4-Thiadiazole Moiety Against Viral Infections

text: Viral infections have resulted in millions of victims in human history. Although great efforts have been made to find effective medication, there are still no drugs that truly cure viral infections. There are currently approximately 90 drugs approved for the treatment of human viral infections. As resistance toward available antiviral drugs has become a global threat to health, there is an intrinsic need to identify new scaffolds that are useful in discovering innovative, less toxic and highly active antiviral agents. 1,3,4-Thiadiazole derivatives have been extensively studied due to their pharmacological profile, physicochemical and pharmacokinetic properties. This review provides an overview of the various synthetic compounds containing the 2-amino-1,3,4-thiadiazole moiety that has been evaluated for antiviral activity against several viral strains and could be considered possible prototypes for the development of new antiviral drugs.


title: Clostridial abomasitis in calves: Case report and review of the literature

text: Abstract Infections by Clostridium perfringens type A are perhaps the most common causes of clostridial hemorrhagic enteritis in neonatal ruminants. Affected calves exhibit tympany, hemorrhagic abomasitis, and abomasal ulceration. Gram-positive bacilli are often found on affected mucosa and in submucosa. Aspects of etiology beyond the infecting organism are little understood, but probably include dietary issues, perhaps relating to overfeeding, feeding of barely thawed or contaminated colostrum, or conditions which effect decreased gut motility. Fatal hemorrhagic enteritis in a cloned gaur calf is illustrative of the syndrome. The calf developed pasty yellow and bloody diarrhea, and the abdomen became distended and painful. In spite of intensive therapy, the calf died ∼48h after birth. At necropsy, the distended abomasum contained clotted milk and bloody fluid, and the abomasal and omasal walls were thickened and hemorrhagic. The proximal duodenum was hemorrhagic and emphysematous, and microscopic examination revealed Gram-positive rods in association with acute, necrotizing, hemorrhagic mucosal inflammation. Isolates of C. perfringens from this calf were PCR positive for cpb2, the gene encoding beta2 toxin. This finding is of unknown significance; only 14.3% (8/56) of isolates from other calves with the syndrome have been cpb2 positive, and only 50% of cpb2 positive bovine isolates express CPB2. The most prominent needs to further our understanding of this problem are consistent experimental reproduction of the disease, elucidation of virulence attributes, and development and application of prevention and control strategies.


Allergiesymptome oder Covid-19?


title: Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells

text: Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. Alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. In this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being used to study the innate immune response to coronavirus infection. We have shown that rat coronavirus infection of rat alveolar type I epithelial cells in vitro induces expression of CXC chemokines, which may recruit and activate neutrophils. Although neutrophils are recruited early in infection in several coronavirus models including rat coronavirus. However, their role in viral clearance and/or immune-mediated tissue damage is not understood. Primary cultures of differentiated alveolar epithelial cells will be useful for identifying the interactions between coronaviruses and alveolar epithelial cells that influence the innate immune responses to infection in the lung. Understanding the molecular details of these interactions will be critical for the design of effective strategies to prevent and treat coronavirus infections in the lung.


title: Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020

text: We analyzed 2 clusters of 12 patients in Vietnam with severe acute respiratory syndrome coronavirus 2 infection during January–February 2020. Analysis indicated virus transmission from a traveler from China. One asymptomatic patient demonstrated virus shedding, indicating potential virus transmission in the absence of clinical signs and symptoms.


title: Vaccine use and disease prevalence in dogs and cats

text: Abstract A yearly revaccination of adult pets against distemper, the adenoviral and parvoviral diseases is scientifically unwarranted, professionally obsolete and ethically questionable; other vaccinal antigens, however, may need yearly or even more frequent injections. Base immunisation is redefined: it is complete only after the multivalent booster in the second year of life. A yearly revaccination interview, not necessarily an injection, should become the new standard. This interview is a professional service that must be taught, expertly performed and invoiced. Adult animals should be “vaccinated to measure”, taking age, breed, lifestyle, the epidemiologic situation, etc. into account. Post-vaccination serology should become a guide in revaccination decisions. For a solid herd immunity, more animals of the population must be vaccinated. The profession should issue regular updates of the ‘code of vaccination practice’. To counteract vaccination antagonism, a concerted action of academia, the veterinary profession and industry is required.


title: The impact of reclassification of C3 predominant glomerulopathies on diagnostic accuracy, outcome and prognosis in patients with C3 glomerulonephritis

text: BACKGROUND: C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features. This study was conducted to assess the effect of reclassification of C3 glomerulopathies on renal outcomes, mortality, and response to therapy. METHODS: We undertook a retrospective analysis of 857 renal biopsies collected at The Canberra Hospital. Samples with predominant C3 staining were reviewed by a renal histopathologist. Of 31 biopsies with predominant C3 staining, 10 fulfilled histological criteria for C3 glomerulonephritis, while the remaining 21 cases were used as C3 Controls. RESULTS: Aside from a higher incidence of C3 glomerulonephritis in Torres Strait islanders (40% vs 5% C3 Controls, p = 0.04), presentation demographics were similar between the two groups. Median creatinine at diagnosis was higher in patients with C3 glomerulonephritis (253 umol/L IQR 103–333 vs 127 umol/L C3 Controls, IQR 105–182, p = 0.01). Prior to reclassification, a majority of C3 glomerulonephritis cases were diagnosed as membranoproliferative glomerulonephritis (60% vs 5% (C3 Controls) p < 0.01). Electron microscopy demonstrated all C3 glomerulonephritis patients had C3 deposition (100% vs 38% p = 0.02), these deposits were amorphous in nature (50% vs 5% respectively p = 0.007). C3 glomerulonephritis patients had shorter median follow-up (405 days IQR 203–1197 vs 1822 days respectively, IQR 1243–3948, p = 0.02). Mortality was higher in C3 glomerulonephritis patients (30% vs 14% in C3 Controls (log rank p = 0.02)). CONCLUSION: We have devised a diagnostic and treatment algorithm based on the results of literature review and our current study. Further prospective assessment is required to review diagnostic and treatment outcomes for this disease in Australian centres.


Emergency medicine: the finest hour in our time


title: Virtual bedside teaching rounds with patients with COVID‐19

text: The Coronavirus disease (COVID-19) pandemic presents a significant challenge to medical education. Recent guidelines suggest that medical students not be involved in direct patient care activities unless there is a critical health care workforce need locally (Whelan et al.). These guidelines exist for several reasons, including limitations in personal protective equipment (PPE).


title: Importance of viral and bacterial infections in chronic obstructive pulmonary disease exacerbations

text: Abstract Background Few studies have evaluated the contribution of both viruses and bacteria in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Objectives This study estimated the burden of both types of pathogens among adults seeking care for an AECOPD during two consecutive winter seasons. Study design Patients 50 years or older who consulted within 10 days of AECOPD onset were eligible. Clinical data were collected on a standardized questionnaire, and nasopharyngeal aspirates (NPA), paired sera, and non-induced sputum were collected. Polymerase chain reaction (PRC) assays were used to identify viral, atypical and bacterial pathogens in NPA specimen. Results Overall, 108 patients with AECOPD were included, 88% of patients were admitted and 2 patients (2%) received intensive care. A third of patients (31%) had evidence of a viral infection, 9% with influenza A, 7% RSV and 7% with PIV-3. One patient was positive for Mycoplasma pneumoniae. Bacterial pathogens were identified in 49% of patients with available sputum, most frequently Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae. Among virus-infected patients, 14 (58%) also had bacteria in their sputum, but co-infected patients did not present with different symptoms than patients with single infections. Conclusions These results suggest that influenza and RSV are frequent contributors of AECOPD, and that coinfection with bacteria does not appear to be more severe among virus-infected patients. Clinicians should be aware that AECOPD may be frequently triggered by viruses, and may consider antivirals and proper infection control measures in appropriate epidemiological setting.


Six Feet Apart: Lessons Learned from COVID-19 and Social Distancing


title: « Soigner avec plaisir » dans la démence : une utopie ? L’expérience d’une équipe de gérontopsychiatrie entre 1987 et 1999

text: Résumé L’auteure revient sur les enseignements de l’expérience d’un projet de soin à visée psychothérapique dans la démence, dénommé par les soignants « soigner avec plaisir », conçu et mené de 1987 à 1999 par l’équipe pluridisciplinaire d’une unité de gérontopsychiatrie. Sont présentées les conditions qui ont présidé à sa réalisation puis à son devenir et ses effets dans le soin, pour le patient, et pour les soignants. Summary A psychotherapeutic project named by the care team “Enjoying dementia care” (soigner avec plaisir) was designed and conducted by a pluri-disciplinary psychogeriatric team. We present here the setting of the project, its outcomes and its effects on care for patients and caregivers.


title: Apparent and occult infections of medical staff in a COVID-19 designated hospital

text: Since the outbreak of novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19), numerous medical staff are fighting on the frontline. However, the possibility of occult infection in medical staff is ignored in many recent studies. Herein, we collected data in a COVID-19 designated hospital from January 22, 2020 to March 10, 2020. A total of 33 medical staff had at least one nucleic acid test of throat swab, immunoglobulin G (IgG) or IgM serum antibody test, and chest computed tomography (CT), were enrolled. Finally, we identified 25 cases (75.8%) were isolated for hospitalized treatment after positive virus detection. In addition, 4 cases who were all negative for nucleic acid test detection with no clinical symptoms, and none of their chest CT were abnormal. However, the results of serum IgG or IgM antibody test in these 4 cases were positive, suggesting the presence of occult infection. In conclusion, data from our single center indicated that SARS-CoV-2 had a high medical infection rate (29/33 = 87.9%) and might have a potential risk of occult infection.


title: Viral Diseases of New World Camelids

text: The increased popularity and population of New World camelids in the United States requires the development of a broader base of knowledge of the health and disease parameters for these animals by the veterinary livestock practitioner. Although our knowledge regarding infectious diseases of camelids has increased greatly over the past decade, the practice of camelid medicine is a relatively new field in North America, so it is important to seek out seasoned colleagues and diagnostic laboratories that are involved in camelid health treatment and diagnosis.


Economic Implications of the COVID-19 Pandemic on the Plastic Surgery Community


title: Behavioural finance perspectives on Malaysian stock market efficiency

text: Abstract This paper provides historical, theoretical, and empirical syntheses in understanding the rationality of investors, stock prices, and stock market efficiency behaviour in the theoretical lenses of behavioural finance paradigm. The inquiry is guided by multidisciplinary behavioural-related theories. The analyses employed a long span of Bursa Malaysia stock market data from 1977 to 2014 along the different phases of economic development and market states. The tests confirmed the presence of asymmetric dynamic behaviour of prices predictability as well as risk and return relationships across different market states, risk states and quantiles data segments. The efficiency tests show trends of an adaptive pattern of weak market efficiency across various economic phases and market states. Collectively, these evidences lend support to bounded-adaptive rational of investors' behaviour, dynamic stock price behaviour, and accordingly forming bounded-adaptive market efficiency.


title: Production of virus-like particles for vaccines

text: Abstract Virus-like particles (VLPs) are nanostructures that resemble the structures of viruses. They are composed of one or more structural proteins that can be arranged in several layers and can also contain a lipid outer envelope. VLPs trigger a high humoral and cellular immune response due to their repetitive structures. A key factor regarding VLP safety is the lack of viral genomic material, which enhances safety during both manufacture and administration. Contemporary VLP production may take advantage of several systems, including bacterial, yeast, insect and mammalian cells. The choice of production platform depends on several factors, including cost and the need for post-translational modifications (PTMs), which can be essential in generating an optimal immune response. Some VLP-based vaccines designed to prevent several infectious diseases are already approved and on the market, with many others at the clinical trial or research stage. Interest in this technology has recently increased due to its advantages over classical vaccines. This paper reviews the state-of-the-art of VLP production systems and the newest generation of VLP-based vaccines now available.


title: Variable Oligomerization Modes in Coronavirus Non-structural Protein 9

text: Abstract Non-structural protein 9 (Nsp9) of coronaviruses is believed to bind single-stranded RNA in the viral replication complex. The crystal structure of Nsp9 of human coronavirus (HCoV) 229E reveals a novel disulfide-linked homodimer, which is very different from the previously reported Nsp9 dimer of SARS coronavirus. In contrast, the structure of the Cys69Ala mutant of HCoV-229E Nsp9 shows the same dimer organization as the SARS-CoV protein. In the crystal, the wild-type HCoV-229E protein forms a trimer of dimers, whereas the mutant and SARS-CoV Nsp9 are organized in rod-like polymers. Chemical cross-linking suggests similar modes of aggregation in solution. In zone-interference gel electrophoresis assays and surface plasmon resonance experiments, the HCoV-229E wild-type protein is found to bind oligonucleotides with relatively high affinity, whereas binding by the Cys69Ala and Cys69Ser mutants is observed only for the longest oligonucleotides. The corresponding mutations in SARS-CoV Nsp9 do not hamper nucleic acid binding. From the crystal structures, a model for single-stranded RNA binding by Nsp9 is deduced. We propose that both forms of the Nsp9 dimer are biologically relevant; the occurrence of the disulfide-bonded form may be correlated with oxidative stress induced in the host cell by the viral infection.


title: Coronavirus nucleocapsid protein is an RNA chaperone

text: Abstract RNA chaperones are nonspecific nucleic acid binding proteins with long disordered regions that help RNA molecules to adopt its functional conformation. Coronavirus nucleoproteins (N) are nonspecific RNA-binding proteins with long disordered regions. Therefore, we investigated whether transmissible gastroenteritis coronavirus (TGEV) N protein was an RNA chaperone. Purified N protein enhanced hammerhead ribozyme self-cleavage and nucleic acids annealing, which are properties that define RNA chaperones. In contrast, another RNA-binding protein, PTB, did not show these activities. N protein chaperone activity was blocked by specific monoclonal antibodies. Therefore, it was concluded that TGEV N protein is an RNA chaperone. In addition, we have shown that purified severe acute respiratory syndrome (SARS)-CoV N protein also has RNA chaperone activity. In silico predictions of disordered domains showed a similar pattern for all coronavirus N proteins evaluated. Altogether, these data led us to suggest that all coronavirus N proteins might be RNA chaperones.


title: Circle the Wagons: Circular RNAs Control Innate Immunity

text: Circular RNAs are generated at low levels from many protein-coding genes. Liu et al. now reveal that many of these transcripts bind and inhibit the double-stranded RNA (dsRNA)-dependent kinase PKR. Upon viral infection, circular RNAs are globally degraded to release PKR, which becomes activated to aid in the immune response.


title: Nosocomial infantile gastroenteritis associated with minirotavirus and calicivirus

text: A prospective study was carried out to determine the epidemiology and etiology of acute gastroenteritis on the general infant ward of The Montreal Children's Hospital in the late fall of 1976. Diarrhea occurred in 41 of 165 infants (25%), with probable nosocomial acquisition in 26 patients. Two infants each had two episodes of diarrhea, and one had three. A putative pathogen was found in 31 of 45 case episodes (69%). Virus-like particles were present in 28 of 45 patients, and in 24 of 74 asymptomatic room contacts. Particles belonging to six morphologic classes were identified: adenovirus, rotavirus, minirotavirus, calicivirus, picorna-parvovirus, and coronavirus. More than one agent was identified in 12 infants with diarrhea and in five asymptomatic room contacts. No wardwide etiologic pattern was evident, but minirotavirus or calicivirus or both were associated with diarrhea in 20 patients, accompanied by vomiting in 15 of these infants. Moreover, spread of individual agents was almost entirely limited to minirotavirus and calicivirus, with diarrhea in six of ten, and four of seven, virus positive room contacts, respectively. These viruses were also identified in stools from 12 infants without diarrhea, seven of whom had repeated vomiting. Data support the etiologic role of minirotavirus and calicivirus in diarrhea or vomiting or both in hospitalized infants.


title: Tudor-SN interacts with and co-localizes with G3BP in stress granules under stress conditions

text: SGs are mRNA containing cytoplasmic structures that are assembled in response to stress. Tudor-SN protein is a ubiquitously expressed protein. Here, Tudor-SN protein was found to physiologically interact with G3BP, which is the marker and effector of SG. The kinetics of the assembly of SGs in the living cells demonstrated that Tudor-SN co-localizes with G3BP and is recruited to the same SGs in response to different stress stimuli. Knockdown of endogenous Tudor-SN did not inhibit the formation of SGs, but retarded the aggregation of small SGs into large SGs. Thus Tudor-SN may not be an initiator as essential as G3BP for the formation of SGs, but affects the aggregation of SGs. These findings identify Tudor-SN as a novel component of SGs. STRUCTURED SUMMARY: MINT-7968768, MINT-7968779: Tudor-SN (uniprotkb:Q7KZF4) physically interacts (MI:0915) with G3BP (uniprotkb:Q13283) by anti bait coimmunoprecipitation (MI:0006) MINT-7968800: Tudor-SN (uniprotkb:Q7KZF4) and TIA-1 (uniprotkb:P31483) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7968789: Tudor-SN (uniprotkb:Q7KZF4) and G3BP (uniprotkb:Q13283) colocalize (MI:0403) by fluorescence microscopy (MI:0416)


title: H1N1 pneumonia: our experience in 50 patients with a severe clinical course of novel swine-origin influenza A (H1N1) virus (S-OIV)

text: PURPOSE: The authors reviewed chest radiographs (CXR) and thin-section computed tomography (CT) findings of pulmonary complications in a selected population of 50 consecutive patients with severe novel swine-origin influenza A (H1N1) virus (S-OIV) pneumonia who were seen at the Subintensive Respiratory Unit (UTSIR) and at the Intensive Care Unit (ICU) at Monaldi Hospital, Naples, Italy. MATERIALS AND METHODS: CXR and CT findings of 50 patients who fulfilled the World Health Organisation (WHO) criteria for S-OIV infection were reviewed by four radiologists. The final study group of 50 patients was divided into two subgroups on the basis of clinical course: group 1 consisted of 42 patients requiring noninvasive mechanical ventilation and admitted to the UTSIR; group 2 consisted of eight patients who required ICU admission and extracorporeal membrane oxygenation or advanced mechanical ventilation from October 2009 to December 2009. All patients underwent CXR and thinsection multidetector CT (MDCT) scan; the initial and follow-up radiographs and CT scans were evaluated for the presentation and follow-up pattern (consolidation, groundglass opacities, nodules, reticulation), distribution and extent of abnormality. RESULTS: All patients had radiological signs of pulmonary involvement. Ground-glass opacity and consolidation, which was mainly peripheral, was the most frequent finding. In three patients, we report for the first time in viral pneumonia the reversed halo sign. Lesion extent was related to aggressiveness of the illness. More often, both lungs were involved (82%). Thoracic comorbidity was present in 18% of patients; 22% of patients was obese, and in this group, the clinical course was more aggressive than in the others with the same lesion extent at imaging. Furthermore, superinfection led to worsening of the clinical conditions. CONCLUSIONS: The most common CXR and CT findings in patients with S-OIV infection were unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On MDCT, ground-glass opacities and areas of consolidation had a predominant peribronchovascular and subpleural distribution, resembling organising pneumonia; they progressed to bilateral extensive airspace disease in severely ill patients.


title: A trans-spliced leader sequence on actin mRNA in C. elegans

text: Abstract While determining the 5′ ends of C. elegans actin mRNAs, we have discovered a 22 nucleotide spliced leader sequence. The leader sequence is found on mRNA from three of the four nematode actin genes. The leader also appears to be present on some, but not all, nonactin mRNAs. The actin mRNA leader sequence is identical to the first 22 nucleotides of a novel 100 nucleotide RNA transcribed adjacent, and in the opposite orientation, to the 5S ribosomal gene. The evidence suggests that the actin mRNA leader sequence is acquired from this novel nucleotide transcript by an intermolecular trans-splicing mechanism.


title: Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

text: Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime–boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime–boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime–boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime–boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime–boost regimens did not. Thus, heterologous prime–boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime–boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.


title: Serious and lethal respiratory tract infections of viral etiology in children

text: Abstract Viruses may lead to serious and lethal pulmonary infections in immunocompetent and immunocompromised children. Series of children with acute respiratory distress syndrome and series of children requiring extracorporeal membrane oxygenation, as well as reported series of nosocomial viral illness, offer an insight into the extent of serious viral disease documented in the medical literature. Series of children with specific viral respiratory illness also will be reviewed, as will the means of diagnosis in these groups of patients. Copyright © 2000 by W.B. Saunders Company


title: A “One-Health” approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy

text: Abstract The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. IZSAM, is currently testing more than 600 samples per day and WGS from positive samples. Sequence analysis of these samples suggested that outbreaks in Abruzzo region may be related to outbreaks of northern Italy and northern Europe, these latter as for the presence of mutations in the N protein. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.


title: Bat consumption in Thailand

text: BACKGROUND: Human consumption of bats poses an increasing public health threat globally. Communities in which bat guano is mined from caves have extensive exposure to bat excreta, often harvest bats for consumption, and are at risk for bat-borne diseases. METHODS: This rapid ethnographic study was conducted in four provinces of Thailand (Ratchaburi, Sakaeo, Nakorn Sawan, and Phitsanulok), where bat guano was mined and sold during the period April–August 2014. The aim of this study was to understand behaviors and risk perceptions associated with bat conservation, exposure to bats and their excreta, and bat consumption. Sixty-seven respondents playing various roles in bat guano mining, packaging, sale, and use as fertilizer participated in the study. Data were collected through interviews and/or focus group discussions. RESULTS: In spite of a bat conservation program dating back to the 1980s, the benefits of conserving bats and the risks associated with bat consumption were not clear and infrequently articulated by study respondents. DISCUSSION: Since bat consumption continues, albeit covertly, the risk of bat-borne diseases remains high. There is an opportunity to reduce the risk of bat-borne diseases in guano-mining communities by strengthening bat conservation efforts and raising awareness of the health risks of bat consumption. Further research is suggested to test behavior change strategies for reducing bat consumption.


title: Co-circulation of diverse paramyxoviruses in an urban African fruit bat population

text: Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat–human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.


title: CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy?

text: Abstract Purpose Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described. Methods A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS). Results There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases. Conclusion Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease.


Latest outbreak news from ProMED-mail Novel coronavirus – Middle East


title: Emerging view of the human virome

text: The human virome is the collection of all viruses that are found in or on humans, including both eukaryotic and prokaryotic viruses. Eukaryotic viruses clearly have important effects on human health, ranging from mild, self-limited acute or chronic infections to those with serious or fatal consequences. Prokaryotic viruses can also influence human health by affecting bacterial community structure and function. Therefore, definition of the virome is an important step toward understanding how microbes affect human health and disease. We review progress in virome analysis, which has been driven by advances in high-throughput, deep sequencing technology. Highlights from these studies include the association of viruses with clinical phenotypes and description of novel viruses that may be important pathogens. Together these studies indicate that analysis of the human virome is critical as we aim to understand how microbial communities influence human health and disease. Descriptions of the human virome will stimulate future work to understand how the virome affects long-term human health, immunity, and response to coinfections. Analysis of the virome ultimately may affect the treatment of patients with a variety of clinical syndromes.


title: Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2—a molecular dynamic study

text: Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA (ssRNA) virus, responsible for severe acute respiratory disease (COVID-19). A large number of natural compounds are under trial for screening compounds, possessing potential inhibitory effect against the viral infection. Keeping in view the importance of marine compounds in antiviral activity, we investigated the potency of some marine natural products to target SARS-CoV-2 main protease (M(pro)) (PDB ID 6MO3). The crystallographic structure of M(pro) in an apo form was retrieved from Protein Data Bank and marine compounds from PubChem. These structures were prepared for docking and the complex with good docking score was subjected to molecular dynamic (MD) simulations for a period of 100 ns. To measure the stability, flexibility, and average distance between the target and compounds, root mean square deviations (RMSD), root mean square fluctuation (RMSF), and the distance matrix were calculated. Among five marine compounds, C-1 (PubChem CID 11170714) exhibited good activity, interacting with the active site and surrounding residues, forming many hydrogen and hydrophobic interactions. The C-1 also attained a stable dynamic behavior, and the average distance between compound and target remains constant. In conclusion, marine natural compounds may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19. [Figure: see text]


title: On the importance of population-based serological surveys of SARS-CoV-2 without overlooking their inherent uncertainties

text: Abstract The SARS-CoV-2 epidemic has caused an unprecedented public health situation and more than ever it is important to be well informed on methods to monitor and analyse the progression of the epidemic. This brief note aims to explain the scope in conducting large-scale serological surveys of SARS-CoV-2 to define the landscape of population immunity, without overlooking the inherent uncertainty steaming from sampling design and diagnostic validity. The note completes with a succinct appendix of simple statistical methods for estimating prevalence from random population samples using imperfect diagnostic tests.


title: „Wir vermuten einen Schutzfaktor!“: COVID-19 trifft HIV-Patienten meist nur leicht

text: Nur relativ wenige HIV-Patienten haben sich bisher — entgegen vieler Befürchtungen — mit SARS-CoV-2 infiziert. Schwere Erkrankungen scheinen in dieser Gruppe eher selten zu sein. Experten wie der Münchner Schwerpunktarzt Dr. Hans Jäger vermuten einen noch unbekannten Schutzfaktor.


title: Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication

text: Many RNA viruses remodel intracellular membranes to generate specialized sites for RNA replication. How membranes are remodeled and what properties make them conducive for replication are unknown. Here we show how RNA viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. Specific viral proteins modulate effector recruitment by Arf1 GTPase and its guanine nucleotide exchange factor GBF1, promoting preferential recruitment of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) to membranes over coat proteins, yielding uncoated phosphatidylinositol-4-phosphate (PI4P) lipid-enriched organelles. The PI4P-rich lipid microenvironment is essential for both enteroviral and flaviviral RNA replication; PI4KIIIβ inhibition interferes with this process; and enteroviral RNA polymerases specifically bind PI4P. These findings reveal how RNA viruses can selectively exploit specific elements of the host to form specialized organelles where cellular phosphoinositide lipids are key to regulating viral RNA replication. PAPERFLICK:


title: Clinical Approach to Acute Cough

text: Acute cough is among the most common symptoms for which patients seek medical attention. It accounts for millions of days lost from school and work and billions of dollars spent on medical care. Acute cough is defined as cough present for 3 weeks or less. It most often is caused by a viral infection of the upper respiratory tract (“common cold”) or lower respiratory tract (i.e., “acute bronchitis”). The most effective treatment for cough due to the common cold is a combination first-generation antihistamine plus decongestant. Antibiotics are not indicated for most cases of acute cough. Occasionally, acute cough can be a symptom of a life-threatening condition.


title: Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin

text: Abstract Highly pathogenic human coronaviruses associated with a severe respiratory syndrome, including Middle East respiratory syndrome coronavirus (MERS-CoV), have recently emerged. The MERS-CoV epidemic started in 2012 and is still ongoing, with a mortality rate of approximately 35%. No vaccine is available against MERS-CoV and therapeutic options for MERS-CoV infections are limited to palliative and supportive care. A search for specific antiviral treatments is urgently needed. Coronaviruses are enveloped viruses, with the spike proteins present on their surface responsible for virus entry into the target cell. Lectins are attractive anti-coronavirus candidates because of the highly glycosylated nature of the spike protein. We tested the antiviral effect of griffithsin (GRFT), a lectin isolated from the red marine alga Griffithsia sp. against MERS-CoV infection. Our results demonstrate that while displaying no significant cytotoxicity, griffithsin is a potent inhibitor of MERS-CoV infection. Griffithsin also inhibits entry into host cells of particles pseudotyped with the MERS-CoV spike protein, suggesting that griffithsin inhibits spike protein function during entry. Spike proteins have a dual function during entry, they mediate binding to the host cell surface and also the fusion of the viral envelope with host cell membrane. Time course experiments show that griffithsin inhibits MERS-CoV infection at the binding step. In conclusion, we identify griffithsin as a potent inhibitor of MERS-CoV infection at the entry step.


title: Nucleocapsid protein-dependent assembly of the RNA packaging signal of Middle East respiratory syndrome coronavirus

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) consists of a positive-sense, single-stranded RNA genome and four structural proteins: the spike, envelope, membrane, and nucleocapsid protein. The assembly of the viral genome into virus particles involves viral structural proteins and is believed to be mediated through recognition of specific sequences and RNA structures of the viral genome. METHODS AND RESULTS: A culture system for the production of MERS coronavirus-like particles (MERS VLPs) was determined and established by electron microscopy and the detection of coexpressed viral structural proteins. Using the VLP system, a 258-nucleotide RNA fragment, which spans nucleotides 19,712 to 19,969 of the MERS-CoV genome (designated PS258(19712–19969)(ME)), was identified to function as a packaging signal. Assembly of the RNA packaging signal into MERS VLPs is dependent on the viral nucleocapsid protein. In addition, a 45-nucleotide stable stem-loop substructure of the PS258(19712–19969)(ME) interacted with both the N-terminal domain and the C-terminal domain of the viral nucleocapsid protein. Furthermore, a functional SARS-CoV RNA packaging signal failed to assemble into the MERS VLPs, which indicated virus-specific assembly of the RNA genome. CONCLUSIONS: A MERS-oV RNA packaging signal was identified by the detection of GFP expression following an incubation of MERS VLPs carrying the heterologous mRNA GFP-PS258(19712–19969)(ME) with virus permissive Huh7 cells. The MERS VLP system could help us in understanding virus infection and morphogenesis.


title: Efficacy of hydrogel patches in preventing facial skin damage caused by mask compression in fighting against coronavirus disease‐2019: a short‐term, self‐controlled study

text: During the recent ongoing coronavirus disease‐2019 (COVID‐19) outbreak, healthcare workers around the world are fighting at the front lines of this epidemic, as well as the dermatologists. Our previous research revealed that long‐term wearing of N95 masks could lead to various facial skin lesions, which might affect their routine work and mental health. More importantly, severe skin lesions (e.g. ulcers) might put them in danger of being infected. Generally, hydrogels have been used to treat patients with pressure ulcers.


title: The bacterial lysate Lantigen B reduces the number of acute episodes in patients with recurrent infections of the respiratory tract: The results of a double blind, placebo controlled, multicenter clinical trial

text: Abstract Studies in the 1970s and 1980s reported that bacterial lysates (BL) had a prophylactic effect on recurrent respiratory tract infections (RRTI). However, controlled clinical study procedures have evolved substantially since then. We performed a trial using updated methods to evaluate the efficacy of Lantigen B®, a chemical BL. This double blind, placebo controlled, multi-center clinical trial had the primary objective of assessing the capacity of Lantigen B to significantly reduce the total number of infectious episodes in patients with RRTI. Secondary aims were the RRTI duration, the frequency and the severity of the acute episodes, the use of drugs and the number of missed workdays. In the subgroup of allergic patients with RRTI, the number of allergic episodes (AE) and the use of anti-allergic drugs were also evaluated. One hundred and sixty patients, 79 allocated to the treated group (TG) and 81 to the placebo group (PG), were enrolled; 30 were lost during the study and 120 (79 females and 38 males) were evaluated. The PG had 1.43 episodes in the 8-months of follow-up while the TG had 0.86 episodes (p =0.036). A similar result was observed in the allergic patients (1.80 and 0.86 episodes for the PG and the TG, respectively, p =0.047). The use of antibiotics was reduced (mean 1.24 and 2.83 days of treatment for the TG and the PG). Logistic regression analysis indicated that the estimated risk of needing antibiotics and NSAIDs was reduced by 52.1 and 30.6%, respectively. With regard to the number of AE, no significant difference was observed between the two groups, but bronchodilators, antihistamines and local corticosteroids were reduced by 25.7%, 56.2% and 41.6%, respectively, in the TG. Lantigen B significantly reduced the number of infectious episodes in patients with RRTI. This finding suggests a first line use of this drug for the prophylaxis of infectious episodes in these patients.