title: The life cycle of SARS coronavirus in Vero E6 cells

text: The aim of the study was to establish the life cycle of severe acute respiratory syndrome‐associated coronavirus (SARS CoV) in host cells and determine the pathogenesis of SARS. Vero E6 cells (African green monkey kidney cells) were inoculated with SARS coronavirus for 3, 7, 24, 48, and 72 hr, respectively, and were observed under electron microscope. It was found that the SARS coronavirus entered the cells through membrane fusion instead of endocytosis, and then the nucleocapsids assembled in the RER and matured by budding into the smooth vesicles, which were derived from the Golgi apparatus. The smooth vesicles fused with the cell membrane, and the mature particles were released. A special phenomenon was that some virus‐like particles appeared in the nucleus. We propose a scheme of the life cycle of SARS coronavirus and discuss the mechanism of its replication in Vero E6 cells. J. Med. Virol. 73:332–337, 2004. © 2004 Wiley‐Liss, Inc.


title: COVID-19 and respiratory support devices

text: There are significant logistical challenges to providing respiratory support devices, beyond simple oxygen flow, when centres run out of supplies or do not have these devices at all, such as in low resource settings. At the peak of the COVID-19 crisis, it was extremely difficult to import medical equipment and supplies, because most countries prohibited the medical industry from selling outside of their own countries. As a consequence, engineering teams worldwide volunteered to develop emergency devices, and medical experts in mechanical ventilation helped to guide the design and evaluation of prototypes. Although regulations vary among countries, given the emergency situation, some Regulatory Agencies facilitated expedited procedures. However, laboratory and animal model testing are crucial to minimize the potential risk for patients when treated with a device that may worsen clinical outcome if poorly designed or misused.


title: Activation of Vγ9Vδ2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication

text: Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human Vγ9Vδ2 T lymphocytes play a critical role in the immune response against viruses, we analyzed their antiviral functions on Huh7 hepatoma cells carrying the subgenomic HCV replicon (Rep60 cells). In a transwell culture system, Rep60 cells were co-cultured with either PBMCs or highly purified γδ T cells stimulated by non-peptidic antigens. Vγ9Vδ2 T cell activation was associated with a dramatic reduction of HCV RNA levels. Neutralizing antibodies targeting IFN-γ revealed a critical role for this cytokine in the inhibition of HCV replication. Interestingly, drugs already in clinical use, such as Phosphostim and Zoledronate, known to activate γδ T cells, were shown to induce the inhibition of HCV replication mediated by Vγ9Vδ2 T cells of HCV patients. Our data suggest that the therapeutic activation of Vγ9Vδ2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a T(h)1-oriented immune response in HCV-infected patients.


title: Modifiable areal unit problem and environmental factors of COVID-19 outbreak

text: Abstract Several recent studies have explored the association between environmental factors, such as temperature, humidity, and air pollution, and the severity of the COVID-19 outbreak by analyzing the statistical association at the district level. However, we argue that the modifiable areal unit problem (MAUP) arises when aggregating disease and environmental data into districts, leading to bias in such studies. Therefore, in this study, we analyzed the association between environmental factors and the number of COVID-19 death cases under different aggregation strategies to illustrate the presence of MAUP. We used real-world COVID-19 outbreak data from the Hubei and Henan Provinces and studied their association with atmospheric NO2 levels. By fitting linear regression models with penalized splines on NO2, we found that the association between COVID-19 mortality and NO2 varies when data were aggregated (1) at the city level, (2) under two different aggregation strategies, and (3) at the provincial level, indicating the presence of MAUP. Therefore, this study reminds researchers of the presence of MAUP and the necessity to minimize this problem while exploring the environmental determinants of the COVID-19 outbreak.


title: Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections

text: Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine® reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.


Why ophthalmologists should mask: a perspective from Hong Kong


title: The “Three Italy” of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia

text: Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the number of cases soared dramatically, spreading across China and worldwide. Italy has had 12,462 confirmed cases according to the Italian National Institute of Health (ISS) as of March 11, and after the “lockdown” of the entire territory, by May 4, 209,254 cases of COVID-19 and 26,892 associated deaths have been reported. We performed a review to describe, in particular, the origin and the diffusion of COVID-19 in Italy, underlying how the geographical circulation has been heterogeneous and the importance of pathophysiology in the involvement of cardiovascular and neurological clinical manifestations.


title: COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning

text: To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID-19), but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8–10) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and linear B-cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID-19 vaccine development.


title: Venous thromboembolism in COVID‐19 patients

text: We read with interest the study published by Tang and coll.(1) in a recent issue of the Journal of Thrombosis and Haemostasis. In this retrospective analysis, conducted at the Tongji Hospital of Wuhan, China, it is reported that heparin treatment reduces mortality in subjects affected by severe COVID‐19 who have “sepsis‐induced coagulopathy”. The definition of severe COVID‐19 was the presence of at least one of following: respiratory rate ≥30 breaths /min; arterial oxygen saturation ≤93% at rest; PaO2/FiO2 ≤300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D‐dimer levels. Of note, patients that received heparin in this study were mostly treated with enoxaparin, at the thromboprophylactic dose of 40‐60 mg/day, for at least 7 days.


docid: tvqaubye

title: Acute disseminated encephalomyelitis progressing to multiple sclerosis: Are infectious triggers involved?

text: Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are demyelinating disorders affecting the central nervous system. An autoimmune aetiology has been proposed for both. ADEM principally affects adolescents following acute infection by a variety of pathogens and has also been reported to occur following vaccination. ADEM typically resolves following medical treatment, whereas MS follows a more relapsing and remitting course. The pathogenesis of MS remains unclear, but it is thought that a combination of infectious and non-infectious environmental factors and host genetics act synergistically to cause disease. A variety of viruses, including Epstein Barr virus, cytomegalovirus, herpes simplex virus and varicella zoster virus, have been implicated as possible infectious triggers. The similar clinical and pathological presentation of ADEM and MS presents a diagnostic challenge for distinguishing ADEM from a first episode of MS. Some cases of ADEM progress to MS for reasons that are not currently clear. This review examines the evidence for infectious agents as triggers for ADEM progressing to MS and suggests potential methods that may facilitate identification of infectious agents that may be responsible for the pathogenesis of ADEM to MS.


title: Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

text: Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.


title: The COVID-19 pandemic: consideration for brain infection

text: • The entry of SARS-CoV-2 to brain via olfactory nerves. • The entry of SARS-CoV-2 to brain via ACE-2. • The entry of SARS-CoV-2 via cytokine storms.


title: Managing Bladder Cancer Care during the COVID-19 Pandemic Using a Team-Based Approach

text: The recent novel coronavirus, named coronavirus disease 2019 (COVID-19), has developed into an international pandemic affecting millions of individuals with hundreds of thousands of deaths worldwide. The highly infectious nature and widespread prevalence of this disease create a new set of obstacles for the bladder cancer community in both delivering and receiving care. In this manuscript, we address the unique issues regarding treatment prioritization for the patient with bladder cancer and how we at City of Hope have adjusted our clinical practices using a team-based approach that utilizes shared decision making with all stakeholders (physicians, patients, caregivers) to optimize outcomes during this difficult time. In addition to taking standard precautions for minimizing COVID-19 risk of exposure for those entering a healthcare facility (screening all personnel upon entry and donning facemasks at all times), we suggest the following three measures: (1) delay post-treatment surveillance visits until there is a decrease in local COVID-19 cases, (2) continue curative intent treatments for localized bladder cancer with COVID-19 precautions (i.e., choosing gemcitabine/cisplatin (GC) over dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) neoadjuvant chemotherapy), and (3) increase the off-treatment period between cycles of palliative systemic therapy in metastatic urothelial carcinoma patients.


Importance of metabolic health in the era of COVID-19


title: Homologous RNA recombination allows efficient introduction of site-specific mutations into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs.

text: We describe a novel strategy to site-specifically mutagenize the genome of an RNA virus by exploiting homologous RNA recombination between synthetic defective interfering (DI) RNA and the viral RNA. The construction of a full-length cDNA clone, pMIDI, of a DI RNA of coronavirus MHV strain A59 was reported previously (R.G. Van der Most, P.J. Bredenbeek, and W.J.M. Spaan (1991). J. Virol. 65, 3219-3226). RNA transcribed from this construct, is replicated efficiently in MHV-infected cells. Marker mutations introduced in MIDI RNA were replaced by the wild-type residues during replication. More importantly, however, these genetic markers were introduced into viral genome: even in the absence of positive selection MHV recombinants could be isolated. This finding provides new prospects for the study of coronavirus replication using recombinant DNA techniques. As a first application, we describe the rescue of the temperature sensitive mutant MHV Albany-4 using DI-directed mutagenesis. Possibilities and limitations of this strategy are discussed.


title: Recombinant Vectors as Influenza Vaccines

text: The antiquated system used to manufacture the currently licensed inactivated influenza virus vaccines would not be adequate during an influenza virus pandemic. There is currently a search for vaccines that can be developed faster and provide superior, long-lasting immunity to influenza virus as well as other highly pathogenic viruses and bacteria. Recombinant vectors provide a safe and effective method to elicit a strong immune response to a foreign protein or epitope. This review explores the advantages and limitations of several different vectors that are currently being tested, and highlights some of the newer viruses being used as recombinant vectors.


title: Potential utilities of mask‐wearing and instant hand hygiene for fighting SARS‐CoV‐2

text: The surge of patients in the pandemic of COVID‐19 caused by the novel coronavirus SARS‐CoV‐2 may overwhelm the medical systems of many countries. Mask‐wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real‐time reverse transcription‐polymerase chain reaction. Previous studies on mask‐wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four‐layer kitchen paper and one‐layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask‐wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask‐wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID‐19. Collectively, a simple approach to slow the exponential spread of SARS‐CoV‐2 was proposed with the support of experiments, literature review, and control experiences.


title: Structure-Guided Design of Potent and Permeable Inhibitors of MERS Coronavirus 3CL Protease that Utilize a Piperidine Moiety as a Novel Design Element

text: There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.


N’oublions pas le moral des « troupes » ! La santé mentale des soignants et l’impact psychiatrique de la pandémie de covid-19


title: Coronavirus, Ageism, and Twitter: An Evaluation of Tweets about Older Adults and COVID‐19

text: OBJECTIVES: In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID‐19) a pandemic. High morbidity and mortality rates of COVID‐19 have been observed among older adults and widely reported in both mainstream and social media. The objective of this study was to analyze tweets related to COVID‐19 and older adults, and to identify ageist content. DESIGN: We obtained a representative sample of original tweets containing the keywords “elderly,” “older,” and/or “boomer” plus the hashtags “#COVID19” and/or “#coronavirus.” SETTING: Tweets posted between March 12 and March 21, 2020. MEASUREMENTS: We identified the type of user and number of followers for each account. Tweets were classified by three raters as (1) informative, (2) personal accounts, (3) personal opinions, (4) advice seeking, (5) jokes, and (6) miscellaneous. Potentially offensive content, as well as that downplaying the severity of COVID‐19 because it mostly affects older adults, was identified. RESULTS: A total of 18,128 tweets were obtained, of which a random sample of 351 was analyzed. Most accounts (91.7%) belonged to individuals. The most common types of tweets were personal opinions (31.9%), followed by informative tweets (29.6%), jokes/ridicule (14.3%), and personal accounts (13.4%). Overall, 72 tweets (21.9%) likely intended to ridicule or offend someone and 21.1% had content implying that the life of older adults was less valuable or downplayed the relevance of COVID‐19. CONCLUSION: Most tweets related to COVID‐19 and older adults contained personal opinions, personal accounts, and jokes. Almost one‐quarter of analyzed tweets had ageist or potentially offensive content toward older adults.


title: Rabies: a preventable but incurable disease

text: Abstract Rabies is a typical zoonotic disease which has been known for more than 4300 years. To date, no effective medical therapy has been established for overt rabies. The rabies post-exposure prophylaxis (PEP), which is a serial vaccination against rabies starting as soon as possible after the patient was bitten by a suspected rabid animal, is the only way to prevent death. In Japan, no rabies case has been reported for about 50 years. However, rabies is epizootic in many Asian countries, where more than 50% of the rabies deaths in the world occur. The Japanese travelers who visit these countries every year may not be aware of this fact since no rabies occurs in their own country. Therefore, the risk of being bitten by a rabid animal abroad and developing rabies after returning to Japan seems to be high. All medical staff should keep in mind that imported rabies cases can occur at any time. In addition, pre-exposure vaccination against rabies should be recommended to international travelers in order to ensure the preventative effect of PEP.


title: Substitutions of conserved amino acids in the receptor-binding domain of the spike glycoprotein affect utilization of murine CEACAM1a by the murine coronavirus MHV-A59

text: Abstract The host range of the murine coronavirus (MHV) is limited to susceptible mice and murine cell lines by interactions of the spike glycoprotein (S) with its receptor, mCEACAM1a. We identified five residues in S (S33, L79, T82, Y162 and K183) that are conserved in the receptor-binding domain of MHV strains, but not in related coronaviruses. We used targeted RNA recombination to generate isogenic viruses that differ from MHV-A59 by amino acid substitutions in S. Viruses with S33R and K183R substitutions had wild type growth, while L79A/T82A viruses formed small plaques. Viruses with S33G, L79M/T82M or K183G substitutions could only be recovered from cells that over-expressed a mutant mCEACAM1a. Viruses with Y162H or Y162Q substitutions were never recovered, while Y162A viruses formed minute plaques. However, viruses with Y162F substitutions had wild type growth, suggesting that Y162 may comprise part of a hydrophobic domain that contacts the MHV-binding site of mCEACAM1a.


title: Characterization of a Structural Intermediate of Flavivirus Membrane Fusion

text: Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E) mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion.


COVID-19 gastrointestinal symptoms mimicking surgical presentations


title: More targeted use of oseltamivir and in-hospital isolation facilities after implementation of a multifaceted strategy including a rapid molecular diagnostic panel for respiratory viruses in immunocompromised adult patients

text: Abstract Background Immunocompromised adults are more vulnerable to a complicated course of viral respiratory tract infections (RTI). Objectives Provide evidence on the effect of implementation of rapid molecular diagnostics for viruses on use of in-hospital isolation facilities, oseltamivir and antibiotic usage, and other clinical outcomes in immunocompromised patients. Study design A before-after study during two consecutive respiratory viral seasons, including immunocompromised adult patients presenting at a tertiary care emergency department with clinical suspicion of RTI. During the first season (2016/2017), respiratory viruses were detected using inhouse real-time PCR. The second season (2017/2018), we implemented a diagnostic flowchart including a rapid molecular test for 15 respiratory viruses (FilmArray®). We assessed the effect of this implementation on need for isolation, antivirals and empirical antibiotics. Results We included 192 immunocompromised adult patients during the first and 378 during the second season. Respiratory viral testing was performed in 135 patients (70%) during the first and 284 (75%) during the second season (p = 0.218) of which 213 (75%) using the rapid test. After implementation, use of in-hospital isolation facilities was reduced (adjusted odds ratio 0.35, 95%CI 0.19-0.64). Furthermore, adequate use of oseltamivir improved, with fewer prescriptions in influenza negative patients (0.15, 95%CI 0.08-0.28) and more in influenza positive patients (11.13, 95%CI 1.75–70.86). No effect was observed on empirical antibiotic use, hospital admissions, length of hospital stay or safety outcomes. Conclusions Implementation of rapid molecular testing for respiratory viruses in adult immunocompromised patients results in more adequate use of oseltamivir and in-hospital isolation facilities without compromising safety.


title: Severe acute respiratory syndrome (SARS): Knowledge, attitudes, practices and sources of information among physicians answering a SARS fever hotline service

text: Summary In June 2003, Taiwan introduced a severe acute respiratory syndrome (SARS) telephone hotline service to provide concerned callers with rapid access to information, advice and appropriate referral where necessary. This paper reports an evaluation of the knowledge, attitude, practices and sources of information relating to SARS among physicians who staffed the SARS fever hotline service. A retrospective survey was conducted using a self-administered postal questionnaire. Participants were physicians who staffed a SARS hotline during the SARS epidemic in Taipei, Taiwan from June 1 to 10, 2003. A response rate of 83% was obtained. All respondents knew the causative agent of SARS, and knowledge regarding SARS features and preventive practices was good. However, only 54% of respondents knew the incubation period of SARS. Hospital guidelines and news media were the major information sources. In responding to two case scenarios most physicians were likely to triage callers at high risk of SARS appropriately, but not callers at low risk. Less than half of all respondents answered both scenarios correctly. The results obtained suggest that knowledge of SARS was generally good although obtained from both medical and non-medical sources. Specific knowledge was however lacking in certain areas and this affected the ability to appropriately triage callers. Standardized education and assessment of prior knowledge of SARS could improve the ability of physicians to triage callers in future outbreaks.


title: Imaging & other potential predictors of deterioration in COVID-19

text: Abstract This case report describes a young patient with COVID-19 who is initially diagnosed with CT chest imaging. Upon admission to the hospital, his clinical condition deteriorates requiring ventilatory support. We explore the value of imaging and other potential predictors of deterioration.


The CPC Program of IAP and NCTB of IIT Madras


title: The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009–2013

text: Abstract Background Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions. Methods We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6months to 17years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment. Results Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: −25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B. Conclusions Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year.


title: Properties of a coronavirus isolated from a cow with epizootic diarrhea

text: Abstract A coronavirus (Kakegawa isolate) isolated from a cow with epizootic diarrhea was grown in BEK-1 cells and examined for biophysical and biochemical properties. The Kakegawa isolate was able to replicate in the presence or absence of 5-iodo-2′-deoxy-uridine, indicating that its viral nucleic acid was RNA. It was highly sensitive to ether and chloroform, and moderately sensitive to trypsin and heat. It was, however, readily stabilized by treatment with cation at 50°C for 1 h. Its infectivity was slightly reduced at pH 3.0. The virus passed through a membrane filter of 200 nm pore size, but not through one of 100 nm pore size. The buoyant density of the virus was determined in a sucrose density gradient. The peak of infectivity and hemagglutinin activity was found at a density of 1.182. Neutralization and hemagglutination inhibition tests showed a close serological relationship between the Kakegawa isolate and the American strain of calf diarrhea coronavirus.


title: Association of the COVID-19 pandemic with Internet Search Volumes: A Google TrendsTM Analysis

text: Abstract Objectives To assess the association of public interest in coronavirus infections with the actual number of infected cases for selected countries across the globe. Methods We performed a Google TrendsTM search for “Coronavirus” and compared Relative Search Volumes (RSV) indices to the number of reported COVID-19 cases by the European Center for Disease Control (ECDC) using time-lag correlation analysis. Results Worldwide public interest in Coronavirus reached its first peak end of January when numbers of newly infected patients started to increase exponentially in China. The worldwide Google TrendsTM index reached its peak on the 12th of March 2020 at a time when numbers of infected patients started to increase in Europe and COVID-19 was declared a pandemic. At this time the general interest in China but also the Republic of Korea has already been significantly decreased as compared to end of January. Correlations between RSV indices and number of new COVID-19 cases were observed across all investigated countries with highest correlations observed with a time lag of -11.5 days, i.e. highest interest in coronavirus observed 11.5 days before the peak of newly infected cases. This pattern was very consistent across European countries but also holds true for the US. In Brazil and Australia, highest correlations were observed with a time lag of -7 days. In Egypt the highest correlation is given with a time lag of 0, potentially indicating that in this country, numbers of newly infected patients will increase exponentially within the course of April. Conclusions Public interest indicated by RSV indices can help to monitor the progression of an outbreak such as the current COVID-19 pandemic. Public interest is on average highest 11.5 days before the peak of newly infected cases.


Monitoring the burden of respiratory syncytial virus in different age groups from 2011 to 2015 at National Influenza Centre in Slovenia


Hospital infection and COVID-19: Do not put all your eggs on the “swab” tests


title: Prevalence of canine coronavirus (CCoV) in dog in Japan: detection of CCoV RNA and retrospective serological analysis

text: We collected rectal swabs from dogs in Japan during 2011 to 2014, and canine coronavirus (CCoV) nucleocapsid gene was detected by RT-PCR. The relationship between CCoV infection and the manifestation of diarrhea symptoms was investigated, and a correlation was noted (df=1, χ(2)=8.90, P<0.005). The types of CCoV detected in samples from CCoV-infected dogs were CCoV-I in 88.9% and CCoV-II in 7.4%, respectively. We retrospectively investigated the seroprevalence of CCoV-I in dogs in Japan during 1998 to 2006. The sera were tested with a neutralizing antibody test. In the absence of CCoV-I laboratory strain, we used feline coronavirus (FCoV)-I that shares high sequence homology in the S protein with CCoV-I. 77.7% of the sera were positive for neutralizing anti-FCoV-I antibodies.


docid: gvaovkqn

title: Molecular and functional insights into a novel teleost malectin from big-belly seahorse Hippocampus abdominalis

text: Abstract Malectin is a carbohydrate-binding lectin protein found in the endoplasmic reticulum (ER). It selectivity binds to Glc2-N-glycan and is involved in a glycoprotein quality control mechanism. Even though malectin may play a role in immunity, its role in innate immunity is not fully known. In the present study, we identified and characterized the malectin gene from Hippocampus abdominalis (HaMLEC). We analyzed sequence features, spatial expression levels, temporal expression profiles upon immune responses, bacterial and carbohydrate binding abilities and anti-viral properties to investigate the potential role of HaMLEC in innate immunity. The molecular weight and isoelectric point (pI) were estimated to be 31.99 kDa and 5.17, respectively. The N-terminal signal peptide, malectin superfamily domain and C-terminal transmembrane region were identified from the amino acid sequence of HaMLEC. The close evolutionary relationship of HaMLEC with other teleosts was identified by phylogenetic analysis. According to quantitative PCR (qPCR) results, HaMLEC expression was observed in all the examined tissues and high expression was observed in the ovary and brain, compared to other tested tissues. Temporal expression of HaMLEC in liver and blood tissues were significant modulated upon exposure to immunogens Edwardasiella tarda, Streptococcus iniae, polyinosinic:polycytidylic and lipopolysaccharide. The presence of carbohydrate binding modules (CBMs) of bacterial glycosyl hydrolases were functionally confirmed by a bacterial binding assay. Anti-viral activity significantly reduced viral hemorrhagic septicemia virus (VHSV) replication in cells overexpressing HaMLEC. The observed results suggested that HaMLEC may have a significant role in innate immunity in Hippocampus abdominalis.


title: Practical Fluid Therapy and Treatment Modalities for Field Conditions for Horses and Foals with Gastrointestinal Problems

text: With advances in technology and owner education, field management in equine veterinary medicine continues to evolve. Equine gastrointestinal disease is one of the most common types of emergencies evaluated by equine practitioners, and many of these patients can be effectively managed in the field. Although the equine veterinarian must make numerous decisions, fluid therapy, pain management, and antimicrobial use are 3 of the major choices that must be addressed when initiating field treatment of equine gastrointestinal disease. This article addresses the practical use of these 3 treatment categories that are essential to field practice.


Lung Cancer with Diffuse Ground-glass Shadow in Two Lungs and Respiratory Failure


title: In-plate recapturing of a dual-tagged recombinant Fasciola antigen (FhLAP) by a monoclonal antibody (US9) prevents non-specific binding in ELISA

text: Recombinant proteins expressed in E. coli are frequently purified by immobilized metal affinity chromatography (IMAC). By means of this technique, tagged proteins containing a polyhistidine sequence can be obtained up to 95% pure in a single step, but some host proteins also bind with great affinity to metal ions and contaminate the sample. A way to overcome this problem is to include a second tag that is recognized by a preexistent monoclonal antibody (mAb) in the gene encoding the target protein, allowing further purification. With this strategy, the recombinant protein can be directly used as target in capture ELISA using plates sensitized with the corresponding mAb. As a proof of concept, in this study we engineered a Trichinella-derived tag (MTFSVPIS, recognized by mAb US9) into a His-tagged recombinant Fasciola antigen (rFhLAP) to make a new chimeric recombinant protein (rUS9-FhLAP), and tested its specificity in capture and indirect ELISAs with sera from sheep and cattle. FhLAP was selected since it was previously reported to be immunogenic in ruminants and is expressed in soluble form in E. coli, which anticipates a higher contamination by host proteins than proteins expressed in inclusion bodies. Our results showed that a large number of sera from non-infected ruminants (mainly cattle) reacted in indirect ELISA with rUS9-FhLAP after single-step purification by IMAC, but that this reactivity disappeared testing the same antigen in capture ELISA with mAb US9. These results demonstrate that the 6XHis and US9 tags can be combined when double purification of recombinant proteins is required.


Virion-Liposome Interactions Identify a Cholesterol-Independent Coronavirus Entry Stage


'Molecular biocontainment' proposed to ease flu research worry


title: Human Respiratory Viruses☆

text: Abstract Viruses are the leading causes of acute lower respiratory-tract infection in infancy. Respiratory syncytial virus (RSV) is the most common pathogen in severe disease, with hMPV, PIV-3, influenza viruses, and rhinoviruses accounting for the majority of the remainder of acute viral respiratory infections. Humans generally do not develop lifelong immunity to reinfection with these viruses; rather, specific immunity protects against severe and lower respiratory-tract disease.


title: Porcine sapelovirus enters PK-15 cells via caveolae-dependent endocytosis and requires Rab7 and Rab11

text: Abstract To comprehensively understand the endocytosis of Sapelovirus A (PSV) entry into PK-15 cells, we studied PSV infection in the context of cell perturbations through drug inhibition, siRNA silencing and overexpression of dominant negative (DN) mutants. We showed here that PSV infection of PK-15 cells was unaffected by pretreated with chlorpromazine, EIPA, knockdown of the clathrin heavy chain or overexpression of Eps15 DN mutant. Conversely, PSV infection was sensitive to NH4Cl, chloroquine, dynasore, nystatin, MβCD and wortmannin with reduced PSV VP1 expression levels and virus titer. Additionally, PSV invasion leaded to rapid actin rearrangement and disruption of the cellular actin network enhanced PSV infection. After internalization the virus was transported to late endosomes and/or cycling endosomes that requires the participation of Rab7 and Rab11. Our findings demonstrate that PSV uses caveolae-dependent endocytosis as the predominant entry portal into PK-15 cells which requires low pH, dynamin, Rab7 and Rab11.


CD8+ T-Cell Priming During a Central Nervous System Infection with Mouse Hepatitis Virus


title: Antimicrobial Air Filters Using Natural Euscaphis japonica Nanoparticles

text: Controlling bioaerosols has become more important with increasing participation in indoor activities. Treatments using natural-product nanomaterials are a promising technique because of their relatively low toxicity compared to inorganic nanomaterials such as silver nanoparticles or carbon nanotubes. In this study, antimicrobial filters were fabricated from natural Euscaphis japonica nanoparticles, which were produced by nebulizing E. japonica extract. The coated filters were assessed in terms of pressure drop, antimicrobial activity, filtration efficiency, major chemical components, and cytotoxicity. Pressure drop and antimicrobial activity increased as a function of nanoparticle deposition time (590, 855, and 1150 µg/cm2(filter) at 3-, 6-, and 9-min depositions, respectively). In filter tests, the antimicrobial efficacy was greater against Staphylococcus epidermidis than Micrococcus luteus; ~61, ~73, and ~82% of M. luteus cells were inactivated on filters that had been coated for 3, 6, and 9 min, respectively, while the corresponding values were ~78, ~88, and ~94% with S. epidermidis. Although statistically significant differences in filtration performance were not observed between samples as a function of deposition time, the average filtration efficacy was slightly higher for S. epidermidis aerosols (~97%) than for M. luteus aerosols (~95%). High-performance liquid chromatography (HPLC) and electrospray ionization-tandem mass spectrometry (ESI/MS) analyses confirmed that the major chemical compounds in the E. japonica extract were 1(ß)-O-galloyl pedunculagin, quercetin-3-O-glucuronide, and kaempferol-3-O-glucoside. In vitro cytotoxicity and disk diffusion tests showed that E. japonica nanoparticles were less toxic and exhibited stronger antimicrobial activity toward some bacterial strains than a reference soluble nickel compound, which is classified as a human carcinogen. This study provides valuable information for the development of a bioaerosol control system that is environmental friendly and suitable for use in indoor environments.


title: Development and laboratory evaluation of a compact swirling aerosol sampler (SAS) for collection of atmospheric bioaerosols

text: Abstract Inhalation of infectious bioaerosols has been linked to a variety of respiratory diseases. However, efficient sampling techniques to allow high temporal resolution sampling are limited to collect and study bioaerosols in the various occupational and ambient micro–environmental atmospheres. This study introduces a medium flow swirling bioaerosol sampler (SAS) approach that collects atmospheric bioaerosols at the flow rate of 167 Lpm (10 cubic meter per hour). The collection of bioaerosols is achieved through a combination of impaction and cyclonic centrifugal motion. Aerosol deposition efficiency tests were performed with monodispersive polystyrene latex (PSL) particles ranging from 0.1 to 10 μm. Results have shown that the sampler has cut–off size of 0.7 μm and 1.5 μm, with and without the assistance of added water vapor, respectively. The bioaerosol collection and viability tests were performed with comparison to the commercially–available BioSampler, and the results show that the collection efficiency of the SAS is 97% at the designed flow rate, while the higher flow of the new system yields more than 13 times of the collection rate compared to the BioSampler. The high collection efficiency and observed viability preservation of the SAS make it an attractive alternative for high time resolution bioaerosol sampling for atmospheric, occupational and indoor air quality monitoring.


title: Two cases of COVID‐19 presenting with a clinical picture resembling chilblains: first report from the Middle East

text: Clinical characteristics of COVID-19 disease were identified in a cohort study involving 1099 patients from China. COVID-19 most commonly present with fever, cough, fatigue, and congestion. Two out of 1099 patients were reported to have skin rash, but time of onset and clinical description of rash were missing (Reference B). Another study focused primarily on cutaneous manifestations associated with COVID-19 evaluated 88 patients from Italy. 18 out of the 88 patients developed cutaneous manifestations, but only 8 patients developed skin lesions at onset of disease.


title: Novel coronavirus-related acute respiratory distress syndrome in a patient with twin pregnancy: A case report

text: We present the case of a 39-year-old woman, G1P0, who had conceived twins via in-vitro fertilization, who presented at 27 weeks of gestation with nasal congestion and dry cough for 7 days. On presentation, her physical examination was benign, except for sinus tachycardia, and she was oxygenating adequately on room air. Laboratory studies were unremarkable, except a PCR test positive for SARS-COV2, and a CT scan of her chest showed bilateral multi-focal ground-glass opacities. A fetal non-stress test was reassuring. She was treated with intravenous fluids, ceftriaxone, azithromycin, and hydroxychloroquine. During her hospital stay, she developed progressively worsening respiratory failure, initially requiring non-invasive ventilation, and subsequently progressed to acute respiratory distress syndrome requiring mechanical ventilation. She then suffered from sudden hypoxemia and hemodynamic collapse, on maximal ventilatory support, prompting an emergency cesarean section at bedside. This led to rapid stabilization of hemodynamic parameters, and of her overall respiratory status. Both the twins were born prematurely, and one of them tested positive for SARS-COV2.


title: 2016 International meeting of the Global Virus Network

text: Abstract The Global Virus Network (GVN) was established in 2011 in order to strengthen research and responses to current viral causes of human disease and to prepare against new viral pandemic threats. There are now 38 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. GVN scientists meet annually to learn about each other's current research, address collaborative priorities and plan future programs. The 2016 meeting was held from October 23–25 in Hokkaido, Japan, in partnership with the Japanese Society for Virology, the National Institute of Infectious Diseases of Japan and the Research Center for Zoonosis Control of Hokkaido University. This report highlights the accomplishments of GVN researchers in many priority areas of medical virology, including the current Zika epidemic, infections by human papillomavirus, influenza, Ebola, Lassa, dengue, HIV, hepatitis C, and chikungunya viruses, and the development of improved diagnostics and new vaccines.


title: Emergency Department and Out-of-Hospital Emergency System (112—AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre

text: Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating “out-of-hospital” and “hospital” activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The “out-of-hospital” response was analysed in terms of calls, rescues and missions, whereas the “hospital” response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21–March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17–February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21–March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate “Emergency Department—Infective Disease” was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the “out-of-hospital” and “in-hospital” systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future.


title: Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach

text: BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases Institute


title: Hospital-acquired viral pathogens in the neonatal intensive care unit

text: Hospital-acquired infections caused by viruses are a cause of considerable morbidity and occasional mortality in critically ill neonates. The intensive care environment allows for efficient spread of viral pathogens, and secondary cases among both patients and healthcare workers are frequently observed. We review the common viral causes of hospital-acquired infections in neonates, including rotavirus, respiratory syncytial virus, and others, discuss epidemiology and clinical syndromes, and summarize recommendations for control in outbreak situations. Chemoprophylaxis, isolation procedures, and care of affected staff are also addressed.


title: Bayesian mixture analysis for metagenomic community profiling

text: Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.


Blood transfusion strategies and ECMO during the COVID-19 pandemic – Authors' reply


docid: nvnywwcn

title: Human Bocavirus DNA in Paranasal Sinus Mucosa


title: The Effects of Media Reports on Disease Spread and Important Public Health Measurements

text: Controlling the spread of influenza to reduce the effects of infection on a population is an important mandate of public health. Mass media reports on an epidemic or pandemic can provide important information to the public, and in turn, can induce positive healthy behaviour practices (i.e., handwashing, social distancing) in the individuals, that will reduce the probability of contracting the disease. Mass media fatigue, however, can dampen these effects. Mathematical models can be used to study the effects of mass media reports on epidemic/pandemic outcomes. In this study we employ a stochastic agent based model to provide a quantification of mass media reports on the variability in important public health measurements. We also include mass media report data compiled by the Global Public Health Intelligence Network, to study the effects of mass media reports in the 2009 H1N1 pandemic. We find that the report rate and the rate at which individuals relax their healthy behaviours (media fatigue) greatly affect the variability in important public health measurements. When the mass media reporting data is included in the model, two peaks of infection result.


title: The relation between serum vitamin D levels, viral infections and severity of attacks in children with recurrent wheezing

text: Abstract Introduction and Objectives Vitamin D deficiency is associated with increased susceptibility to infections and wheezing. We aimed to evaluate the relation between vitamin D levels, viral infections and severity of attacks in children with recurrent wheezing. Materials and methods A total of 52 patients who applied with wheezing, at the ages of 12–60 months with a history of three or more wheezing attacks in the last year and 54 healthy children were included. Sociodemographic data, risk factors for recurrent wheezing, and the severity of the wheezing attacks were recorded. 25(OH)D3, calcium, phosphor, alkaline phosphatase and parathormone levels of all children were measured. Nasopharyngeal samples of the patients for viruses were studied by multiplex polymerase chain reaction. Results For the patient group, being breastfed for six months or less, history of cesarean section, cigarette exposure, humid home environment, and family history of allergic disease were significantly higher compared with the control group. Serum vitamin D levels in the patient group were significantly lower compared to the control group. There was no significant relationship between vitamin D levels and hospitalization, oxygen or steroid therapy. Virus was detected in 38 patients (73%). Rhinovirus (63.2%) was the most frequently detected virus. Coinfection was found in 14 (36.8%) patients. There was no statistically significant difference between detection of virus and vitamin D levels. Conclusions Cigarette exposure, being breastfed six months or less, humid home environment, history of cesarean section, family history of allergic disease and vitamin D deficiency might be risk factors for recurrent wheezing.


title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations

text: Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.


title: Short communication: Characterization of the serologic response induced by vaccination of late-gestation cows with a Salmonella Dublin vaccine

text: Abstract Diarrhea due to Salmonella infection is an important cause of neonatal calf diarrhea. The acquisition of passive immunity in the calf by vaccinating the dam has shown some success in previous studies; however, no data exists on the use of currently licensed vaccines in the United States. Therefore, the purpose of this study was to determine whether vaccinating cows in late gestation with a commercially available Salmonella Dublin vaccine would stimulate Salmonella-specific antibodies in the colostrum of cows at calving and whether these antibodies would be transferred to the calf. Thirty Holstein cows were vaccinated 3wk before the end of lactation with a Salmonella enterica serovar Dublin vaccine, with a second dose given at dry-off. An additional 30 cows received only saline. Calves had a blood sample collected immediately after birth and were then fed fresh colostrum from their dam within 2 h of calving. A postcolostrum blood sample was collected 24 to 48 h later. Salmonella Dublin antibodies in colostrum as well as serum from the cows and calves were measured using an ELISA technique. Results of this study showed that vaccinated cattle had elevated Salmonella Dublin antibody titers at the time of calving (40.3±9.1) as compared with control cows (−9.4±1.1). Calves that received colostrum from vaccinated cattle also had a significant increase in Salmonella Dublin antibodies (88.5±8.9) as compared with calves born to unvaccinated cows (−3.2±1.2). This study demonstrated that the use of a commercially available Salmonella Dublin vaccine can stimulate antibodies that are passed on to the calf via colostral transfer. Further studies need to be done to determine whether these antibodies will offer protection against Salmonella challenge.


Treating the Mental Health Effects of COVID-19: The Need for At-Home Neurotherapeutics Is Now


Avian Infectious Bronchitis Virus Enters Cells Via the Endocytic Pathway


title: Changes in attitudes toward wildlife and wildlife meats in Hunan Province, central China, before and after the severe acute respiratory syndrome outbreak

text: Two surveys of opinions about wildlife conservation were carried out in Hunan Province, China, before and after the severe acute respiratory syndrome (SARS) epidemic. Hunan is the northern neighbor of Guangdong Province, where the first SARS case was reported. The custom of consuming wild meat was not common in Hunan 30 years ago. However, in recent years, consumption of wildlife such as snakes has spread to northern China. We handed out 1300 questionnaires between 22 February and 10 May 2002, before the SARS epidemic. Survey sites included the provincial capital, major cities, towns, and villages in Hunan. Another 1300 questionnaires were distributed between 10 March and 10 May 2004, after the SARS epidemic. The 2004 survey covered the same sites as the 2002 survey. Questionnaire recovery rates for the 2002 and 2004 surveys were 81.2% and 84.6%, respectively. The valid return rate was 73.0%. Frog, snake, hare, and pheasant were the wild meats most frequently eaten by local people. At the time of the first survey, more than 80% of interviewees claimed to have eaten frogs. That number had reduced to 60% by the time of the second survey. Monkey, Chinese pangolin, and bear paw were the wild meats least frequently eaten. Although palm civet was suspected to be the carrier of SARS, it was interesting to note that, after the SARS epidemic, the proportion of people surveyed who ate palm civets had declined only slightly. The results of the surveys indicate a low level of conservation consciousness; however, after the SARS and bird flu epidemics, there were obvious changes in the conservation consciousness of people in Hunan Province. We recommend some measures that could be taken to change the habits of people who consume wildlife.


title: Aplicación de los métodos moleculares al diagnóstico y el estudio epidemiológico de las infecciones respiratorias causadas por virus

text: Hasta la fecha se han identificado más de 200 virus pertenecientes a 6 familias taxonómicas diferentes asociados con la infección del tracto respiratorio humano. La utilización generalizada de métodos moleculares en los laboratorios de microbiología clínica no sólo ha aportado grandes ventajas al diagnóstico de estas infecciones, sino también está permitiendo profundizar en el conocimiento de la enfermedad y el comportamiento epidemiológico de los virus causantes. Esta tecnología incrementa de manera notable el rendimiento de detección de virus en las muestras respiratorias, debido a su elevada sensibilidad en comparación con las técnicas clásicas y a la posibilidad de identificar virus no cultivables o de crecimiento fastidioso en las líneas celulares habituales, lo que permite realizar el diagnóstico etiológico con mayor rapidez. Sin embargo, también comporta algunos inconvenientes, como son detectar virus que se encuentran colonizando la mucosa respiratoria de personas asintomáticas, o en secreciones de pacientes que ya se han recuperado de una infección pasada, a consecuencia de excreción prolongada de éstos. La secuenciación de los productos obtenidos en la reacción de amplificación genómica permite caracterizar de forma adicional los virus detectados mediante su genotipado, realizar estudios de epidemiología molecular e identificar resistencias a determinados antivirales, por citar sólo algunos ejemplos. To date, more than two hundred viruses, belonging to six different taxonomic families, have been associated with human respiratory tract infection. The widespread incorporation of molecular methods into clinical microbiology laboratories has not only led to notable advances in the etiological diagnosis of viral respiratory infections but has also increased insight into the pathology and epidemiological profiles of the causative viruses. Because of their high sensitivity, molecular techniques markedly increase the efficiency of viral detection in respiratory specimens, particularly those that fail to propagate successfully in common cell cultures, thus allowing more rapid etiologic diagnosis. However, there are also some disadvantages in the use of these new technologies such as detection of viruses that merely colonize the respiratory tract of healthy people, or those found in the nasopharyngeal secretions of patients who have recovered from respiratory infections, due to longterm viral shedding, when the viruses are unlikely to act as pathogens. Additionally, sequencing of the amplification products allows further characterization of detected viruses, including molecular epidemiology, genotyping, or detection of antiviral resistance, to cite only a few examples.


title: A Dual Mesh Finite Domain Method for the Analysis of Functionally Graded Beams

text: A method that employs a dual mesh, one for primary variables and another for dual variables, for the numerical analysis of functionally graded beams is presented. The formulation makes use of the traditional finite element interpolation of the primary variables (primal mesh) and the concept of the finite volume method to satisfy the integral form afforganizationof the governing differential equations on a dual mesh. The method is used to analyze bending of straight, through-thickness functionally graded beams using the Euler–Bernoulli and the Timoshenko beam theories, in which the axial and bending deformations are coupled. Both the displacement and mixed models using the new method are developed accounting for the coupling. Numerical results are presented to illustrate the methodology and a comparison of the generalized displacements and forces/stresses computed with those of the corresponding finite element models. The influence of the coupling stiffness on the deflections is also brought out.


COVID‐19 associated myositis with severe proximal and bulbar weakness


title: Resources to Discover and Use Short Linear Motifs in Viral Proteins

text: Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.


title: Examining Shopping Patterns, Use of Food-Related Resources, and Proposed Solutions to Improve Healthy Food Access Among Food Insecure and Food Secure Eastern North Carolina Residents

text: In the Southern United States (U.S.), food insecurity rates are higher in rural (20.8%) versus urban communities (15%). Food insecurity can exacerbate diet-related disease. Thus, the purpose of this study was to examine differences in the use of food-related community resources and potential solutions proposed among food insecure versus food secure residents. A community survey (n = 370) was conducted in rural eastern North Carolina, with questions pertaining to food security status and food-related resources. The IBM SPSS Statistics software and SAS software were used to examine differences in food-related resources, and qualitative data analysis was used to examine differences in solutions offered between food insecure and food secure participants. Of the 370 respondents, forty-eight-point-six percent were classified as food insecure. Food insecure participants were more likely to report shopping for groceries at a convenience/discount store, less likely to use their own vehicle for transportation, and less likely to purchase food from local producers. Food insecure participants were more likely to suggest solutions related to reducing the cost of healthy food, while food secure participants were more likely to suggest educational or convenience-related interventions.


docid: qeynvway

title: Simultaneous onset of COVID‐19 and autoimmune haemolytic anaemia

text: Autoimmune hemolytic anemia (AIHA) can rarely complicate infections. We wish to report a case of simultaneous presentation of COVID-19 disease and warm AIHA. A 46 year old female with a medical history of congenital thrombocytopenia not on therapy presented with dyspnea and cough to the Emergency Department. She was found to have pneumonia after a CT chest revealed a dense left upper lobe consolidation with minimal surrounding ground glass opacities and no evidence of pulmonary embolism. (Figure) She had normal vital signs and pulse oximetry on ambient air. She was initiated on azithromycin 500mg day one then 250 mg daily and discharged home.


title: Spike Gene Analysis of the DE072 Strain of Infectious Bronchitis Virus: Origin and Evolution

text: The entire S2 gene of the DE072 strain of infectious bronchitis virus (IBV) was sequenced. The nucleotide and amino acid sequence was most similar to the D1466 strain and was 84.8% and 89.9% identity, respectively. The nucleotide and amino acid sequence similarity among the DE072 strain and other IBV strains was less than 71.9% and 76.6%, respectively. Phylogenetic analysis, based on both nucleotide and amino acid sequence, showed that IBV isolates were divided into two distinct groups. The DE072 strain clustered only with the D1466 strain, and all of the other strains were distinct from those two viruses. Further the nucleotide sequence analysis of the entire spike glycoprotein gene of the DE072 strain demonstrated that most of the gene contained a D1466-like sequence, and five putative cross-over sites were identified. Based on cross-over site, phylogenetic trees were constructed for different regions of the spike gene, and a difference in topology between these trees was observed. Considering the difference in S2 gene sequence identity and tree topology, we assume that DE072 and D1466 viruses share a different origin from other isolates of IBV. Furthermore, entire spike gene analysis indicates that the DE072 strain has undergone recombination event as well as extensive antigenic variation.


docid: qjutakxs

title: A journey of zoonotic discovery David Quammen Spillover:

text: Unknown


Mental Health Stigma Related to novel coronavirus disease (COVID‐19) in elderly


title: Characterization of the Humoral Immune Response to Porcine Epidemic Diarrhea Virus Infection under Experimental and Field Conditions Using an AlphaLISA Platform

text: Coronavirus infections are a continuous threat raised time and again. With the recent emergence of novel virulent strains, these viruses can have a large impact on human and animal health. Porcine epidemic diarrhea (PED) is considered to be a reemerging pig disease caused by the enteropathogenic alphacoronavirus PED virus (PEDV). In the absence of effective vaccines, infection prevention and control through diagnostic testing and quarantine are critical. Early detection and differential diagnosis of PEDV infections increase the chance of successful control of the disease. Therefore, there is a continuous need for development of reduced assay-step protocols, no-wash, high-throughput immunoassays. This study described the characterization of the humoral immune response against PEDV under experimental and field conditions using a rapid, sensitive, luminescent proximity homogenous assay (AlphaLISA). PEDV IgG and IgA antibodies were developed toward the beginning of the second week of infection. PEDV IgG antibodies were detected for at least 16 weeks post-exposure. Remarkably, the serum IgA levels remained high and relatively stable throughout the study, lasting longer than the serum IgG response. Overall, AlphaLISA allows the detection and characterization of pathogen-specific antibodies with new speed, sensitivity, and simplicity of use. Particularly, the bridge assay constitutes a rapid diagnostic that substantially improves upon the “time to result” metric of currently available immunoassays.


title: First case of bacteremia caused by Janibacter hoylei

text: Janibacter hoylei has previously been isolated only from an air sample in the upper atmosphere and clinical significance of J. hoylei was not yet established. Herein, we report a case of bacteremia caused by J. hoylei. An 8‐week‐old previously healthy male infant presented to the emergency room with fever. Blood culture yielded growth of Gram‐positive bacilli and this microorganism could not be identified with conventional phenotypic methods. The isolate was identified by 16S rRNA gene sequencing, and the patient was successfully treated with vancomycin. To our knowledge, this is the first report of the recovery of J. hoylei in humans. This case shows that J. hoylei can be a potential pathogen in young children.


title: Detection of viral acute lower respiratory tract infection in hospitalized infants using real-time PCR

text: Abstract Introduction Acute lower respiratory tract infection in children causes significant morbidity in the developing countries. Documentation of virus infection using PCR and clinical characteristics of patients affected with viral pneumonia are reviewed in this study. Methods 51 children less than three years admitted to the Pediatric Hospital, Cairo University with viral pneumonia were included. All patients had undergone nasopharyngeal aspirate for PCR viral detection. Results A total of 51 cases were enrolled in the study, of which 7 cases were negative while 44 children were positive for viruses. The most common respiratory virus was Rhinovirus in 32 patients (72.2%), then parainfluenza virus (PIV) in 12 (27.3%), of which subtypes PIV1 were 2 (4.5%), PIV3 were 5 (11.4%) and PIV4 were 5 (11.4%) cases. The third common viruses were respiratory syncytial virus (RSV) in 9 (20.5%) cases of which 3 (6.8%) were RSVA and 6 (13.6%) were RSVB and adenovirus in 9 cases (20.5%). Boca virus was found in 8 (18.2%) patients, corona virus 2 (4.5%) patients, H1N1 2 (4.5%) patients, enterovirus 2 patients (4.5%) and human metapneumovirus in one case (2.3%). Influenza B and PIV2 were not detected. Coinfection was found in 28 (63.7%). Mortality occurred in 12 (23.5%). There was no significant relation between virus type or coinfection with disease severity. Conclusions RV was the most commonly detected virus in children under 3years admitted with acute lower respiratory tract infections. Coinfection was present in the majority of our patients; however it was not related significantly to parameters of disease severity.


Zika Virus Focuses the Gain-of-Function Debate


title: An empirical analysis of the Ebola outbreak in West Africa

text: The data for the Ebola outbreak that occurred in 2014–2016 in three countries of West Africa are analysed within a common framework. The analysis is made using the results of an agent based Susceptible-Infected-Removed (SIR) model on a Euclidean network, where nodes at a distance l are connected with probability P(l) ∝ l(−δ), δ determining the range of the interaction, in addition to nearest neighbors. The cumulative (total) density of infected population here has the form [Image: see text], where the parameters depend on δ and the infection probability q. This form is seen to fit well with the data. Using the best fitting parameters, the time at which the peak is reached is estimated and is shown to be consistent with the data. We also show that in the Euclidean model, one can choose δ and q values which reproduce the data for the three countries qualitatively. These choices are correlated with population density, control schemes and other factors. Comparing the real data and the results from the model one can also estimate the size of the actual population susceptible to the disease. Rescaling the real data a reasonably good quantitative agreement with the simulation results is obtained.


title: Topological data analysis to model the shape of immune responses during co-infections

text: Co-infections by multiple pathogens have important implications in many aspects of health, epidemiology and evolution. However, how to disentangle the non-linear dynamics of the immune response when two infections take place at the same time is largely unexplored. Using data sets of the immune response during influenza-pneumococcal co-infection in mice, we employ here topological data analysis to simplify and visualise high dimensional data sets. We identified persistent shapes of the simplicial complexes of the data in the three infection scenarios: single viral infection, single bacterial infection, and co-infection. The immune response was found to be distinct for each of the infection scenarios and we uncovered that the immune response during the co-infection has three phases and two transition points. During the first phase, its dynamics is inherited from its response to the primary (viral) infection. The immune response has an early shift (few hours post co-infection) and then modulates its response to react against the secondary (bacterial) infection. Between 18 and 26 h post co-infection the nature of the immune response changes again and does no longer resembles either of the single infection scenarios.


title: Emergency physicians cannot inflate or estimate endotracheal tube cuff pressure using standard techniques

text: Study objectives: Tracheal necrosis and stenosis may result from an overinflated endotracheal tube cuff. Safe, appropriate pressure in endotracheal tube cuffs is considered to be between 15 and 25 cm H2O, pressures below normal capillary perfusion pressure. We seek to determine the ability of emergency medicine residents and attending physicians in accredited emergency medicine residency training programs to inflate an endotracheal tube cuff to appropriate pressure using standard syringe technique and assess appropriateness of pressure of previously inflated endotracheal tube cuffs by palpating the pilot balloon. Methods: This institutional review board–approved descriptive survey of resident and attending physicians in accredited emergency medicine residency training programs in New York City used a previously tested, tracheal simulation model with a 7.5-mm endotracheal tube with a high-volume low-pressure cuff (Mallinkrodt, St. Louis, MO). Using their choice of a 5-mL or 10-mL plastic syringe with standard Luer Lock (Beckton-Dickson, Franklin Lakes, NJ), participants inflated the endotracheal tube cuff by standard method of injecting air as they deemed appropriate in conjunction with palpating the pilot balloon to estimate cuff pressure. Subsequently, the endotracheal tube cuff pressure was measured using a highly sensitive and accurate analog manometer (Boehringer Laboratories, Norristown, PA). Later, participants palpated the pilot balloon of 9 endotracheal tubes with cuffs previously inflated to known pressures ranging from 0 to 120 cm H2O and reported whether the pressure was low, appropriate, or high. Results: Twenty-five resident physicians and 42 attending physicians from 5 emergency medicine residency training programs were surveyed. Only 0.4% (n=3) of participants inflated the cuff to a safe pressure; all were attending physicians. The average cuff pressure generated by emergency medicine attending physicians was greater than 98 cm H2O (attending physicians >93 cm H2O, residents >106 cm H2O). The true mean could not be determined because 57% (n=38) inflated to pressures greater than the upper limit of manometer sensitivity (>120 cm H2O). Using palpation, participants were only 33% sensitive detecting inappropriately inflated endotracheal tube cuffs (attending physicians 22% sensitive, residents 53% sensitive), and they were only 26% sensitive in detecting overinflated endotracheal tube cuffs (attending physicians 22%, residents 33%). Average experience as an attending emergency physician was 9 years; average experience as a resident was 2.1 years. Conclusion: This group of emergency physicians had little ability to inflate an endotracheal tube cuff to safe pressure, little ability to accurately estimate pressure of a previously inflated cuff using standard technique, and minimal ability to detect overinflated endotracheal tube cuffs. Nearly all inflated the cuff to dangerously high pressures. Clinicians should consider using devices that permit safe and accurate inflation and measurement of endotracheal tube cuff pressure rather than relying on standard palpation technique, which is potentially unsafe and highly inaccurate.


title: De huisartsenpraktijk en COVID-19

text: Half maart brak de mitigatiefase aan in de strijd tegen COVID-19 en veranderde het werk in veel Nederlandse huisartsenpraktijken totaal, met grote regionale verschillen. H&W-fotograaf Margot Scheerder bracht begin april in beeld hoe diverse huisartsenpraktijken in Nederland hiermee omgaan.


title: Chapter 39 Microbial Forensics: Educating the Workforce and the Community

text: Publisher Summary Disciplines related to microbial forensics are evolving rapidly. This evolution includes technology, analytical capabilities, and, equally as important, education and training. The scientific bases, applications, interpretations, and lessons learned by those who have been intimately involved in the early years of microbial forensics need to be documented and transferred to the next generation of scientists and decision makers so that we can protect society from potential harm resulting from bioterrorism and biocrime. The burgeoning field of microbial forensics should be accompanied by a parallel development of educational infrastructure and resources targeted at the next generation of practitioners, as well as diverse elements for the policy, research, and law enforcement communities. A microbial forensics education program can be broad, providing information encompassing all aspects of the field from science to policy, or more focused depending on its purpose and target audience. Policy makers must have a general understanding of microbial forensics results and better appreciation of their implications in order to effect sound and defensible policy decisions. Finally, an important group that informs the public and government is the news media. They are frequently the primary interface between the scientist and the public, making their observations, insights, or inaccuracies of great importance and impact. Educational efforts will better prepare such individuals to be informed and responsible and must be varied in depth and scope to match the target audience of various entities involved in microbial forensics.


title: Avian flu (H5N1): its epidemiology, prevention, and implications for anesthesiology

text: Abstract Avian flu, influenza A subtype H5N1, is an emergent and virulent disease that poses a threat to the health and safety of the world community. Avian flu is 1 of more than 25 influenza A viruses that reside primarily in birds but also infect humans and other mammals. Avian flu is responsible for the current outbreak in Asia; H5N1 has now displayed probable human-to-human transmission; it could be a harbinger of a global epidemic. Anesthesiologists are exposed to a risk for infection when they are involved in airway instrumentation of infected patients. Given the evidence of emerging resistance to common antiviral agents used to treat H5N1 influenza virus and limited supply of H5N1 vaccine, prevention is our best protection. The following article will detail the virology and preventive public health practices for H5N1. This knowledge can also be used to define and prevent other yet unidentified infectious threats.


title: Telbivudine preserves T‐helper 1 cytokine production and downregulates programmed death ligand 1 in a mouse model of viral hepatitis

text: Summary. Telbivudine is an orally bioavailable L‐nucleoside with potent and specific anti‐hepatitis B virus activity. The higher rate of hepatitis B e antigen (HBeAg) seroconversion during telbivudine treatment than other potent anti‐HBV agents suggests a potential immunomodulatory effect. We sought to determine the effects of telbivudine on the immune system, particularly on cytokine production and T‐cell response, using an animal model with mouse hepatitis virus strain 3 (MHV‐3)‐induced hepatitis. The effects of telbivudine on virus replication and cytokine production were investigated in vitro using MHV‐3‐infected macrophages, and the effects on T‐cell response were investigated in vivo in an MHV‐3‐induced viral hepatitis model. Telbivudine had no effect on MHV‐3 replication in macrophages. However, the production of tumour necrosis factor‐α and interleukin‐12 was increased significantly in MHV‐3‐induced macrophages treated with telbivudine. In vivo survival was enhanced in telbivudine‐treated mice, with marked normalization in clinical conditions and histological lesions. Serum levels of interferon‐γ were elevated significantly after telbivudine treatment in MHV‐3‐infected C3H mice. In contrast, serum interleukin‐4 levels were decreased significantly. Furthermore, telbivudine treatment enhanced the ability of T cells to undergo proliferation and secrete cytokines but did not affect cytotoxicity of infected hepatocytes. Of note, we found that telbivudine treatment suppressed programmed death ligand 1 expression on T cells. The results demonstrate the immunomodulatory properties of telbivudine, independent of its antiviral activity, in a mouse model of MHV‐3‐induced hepatitis.


title: ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis

text: Viruses are responsible for the majority of infectious diseases, from the common cold to HIV/AIDS or hemorrhagic fevers, the latter with devastating effects on the human population. Accordingly, the development of efficient antiviral therapies is a major goal and a challenge for the scientific community, as we are still far from understanding the molecular mechanisms that operate after virus infection. Interferon-stimulated gene 15 (ISG15) plays an important antiviral role during viral infection. ISG15 catalyzes a ubiquitin-like post-translational modification termed ISGylation, involving the conjugation of ISG15 molecules to de novo synthesized viral or cellular proteins, which regulates their stability and function. Numerous biomedically relevant viruses are targets of ISG15, as well as proteins involved in antiviral immunity. Beyond their role as cellular powerhouses, mitochondria are multifunctional organelles that act as signaling hubs in antiviral responses. In this review, we give an overview of the biological consequences of ISGylation for virus infection and host defense. We also compare several published proteomic studies to identify and classify potential mitochondrial ISGylation targets. Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy.


docid: jumohbcf

title: Differential Inhibitory Activities and Stabilisation of DNA Aptamers against the SARS Coronavirus Helicase

text: The helicase from severe acute respiratory syndrome coronavirus (SARS‐CoV) possesses NTPase, duplex RNA/DNA‐unwinding and RNA‐capping activities that are essential for viral replication and proliferation. Here, we have isolated DNA aptamers against the SARS‐CoV helicase from a combinatorial DNA library. These aptamers show two distinct classes of secondary structure, G‐quadruplex and non‐G‐quadruplex, as shown by circular dichroism and gel electrophoresis. All of the aptamers that were selected stimulated ATPase activity of the SARS‐CoV helicase with low‐nanomolar apparent K (m) values. Intriguingly, only the non‐G‐quadruplex aptamers showed specific inhibition of helicase activities, whereas the G‐quadruplex aptamers did not inhibit helicase activities. The non‐G‐quadruplex aptamer with the strongest inhibitory potency was modified at the 3′‐end with biotin or inverted thymidine, and the modification increased its stability in serum, particularly for the inverted thymidine modification. Structural diversity in selection coupled to post‐selection stabilisation has provided new insights into the aptamers that were selected for a helicase target. These aptamers are being further developed to inhibit SARS‐CoV replication.


title: Fever in travellers returning from the tropics

text: Abstract The increase in international travel, the growing presence of arbovirus vectors in our country, and notifications of haemorrhagic fever such as the current outbreak of Ebola in D.R. Congo and the cases of Crimea-Congo haemorrhagic fever in our country have again cast the spotlight on tropical diseases. Isolating suspected cases of highly contagious and lethal diseases must be a priority (haemorrhagic fever, MERS-CoV). Assessing the patient, taking a careful medical history based on epidemiological aspects of the area of origin, activities they have carried out, their length of stay in the area and the onset of symptoms, will eventually help us, if not to make a definitive diagnosis, at least to exclude diseases that pose a threat to these patients. Malaria should be ruled out because of its frequency, without forgetting other common causes of fever familiar to emergency doctors.


title: The 2b protein as a minor structural component of PRRSV

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) ORF2 contains an internal ORF that codes for a small non-glycosylated protein known as 2b. Previous work had identified the presence of a 10kDa 2b protein in virus-infected cells and the induction of an anti-2b response in PRRSV-infected pigs, as well as a possible association of 2b with the virion (Wu et al., 2001, Virology 287:183–191). In this study, we utilized two experimental approaches, including the use of a 2b peptide-specific monoclonal antibody, to demonstrate that the PRRSV 2b protein is an integral component of the PRRSV virion. This study suggests that 2b in PRRSV is similar to the E protein in EAV and forms a minor structural component of the virion.


title: A key role for the carboxy-terminal tail of the murine coronavirus nucleocapsid protein in coordination of genome packaging

text: Abstract The prototype coronavirus mouse hepatitis virus (MHV) exhibits highly selective packaging of its genomic positive-stranded RNA into assembled virions, despite the presence in infected cells of a large excess of subgenomic viral mRNAs. One component of this selectivity is the MHV packaging signal (PS), an RNA structure found only in genomic RNA and not in subgenomic RNAs. It was previously shown that a major determinant of PS recognition is the second of the two RNA-binding domains of the viral nucleocapsid (N) protein. We have now found that PS recognition additionally depends upon a segment of the carboxy-terminal tail (domain N3) of the N protein. Since domain N3 is also the region of N protein that interacts with the membrane (M) protein, this finding suggests a mechanism by which selective genome packaging is accomplished, through the coupling of genome encapsidation to virion assembly.


Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage


title: Studying Human Pathogens in Animal Models: Fine Tuning the Humanized Mouse

text: Humanized mice are crucial tools for studying human pathogens in systemic situations. An animal model of human coronavirus infectious disease has been generated by gene transfer of the human receptor for virus-cell interaction (aminopeptidase N, APN, CD13) into mice. We showed that in vitro and in vivo infections across the species barrier differ in their requirements. Transgenic cells were susceptible to human coronavirus HCoV-229E infection demonstrating the requirement of hAPN for viral cell entry. Transgenic mice, however, could not be infected suggesting additional requirements for in vivo virus susceptibility. Crossing hAPN transgenic mice with interferon unresponsive Stat1(−/− )mice resulted in markedly enhanced virus replication in vitro but did not result in detectable virus replication in vivo. Adaptation of the human virus to murine cells led to successful infection of the humanized transgenic mice. Future genetic engineering approaches are suggested to provide animal models for the better understanding of human infectious diseases.


title: Guidelines for communicating about bats to prevent persecution in the time of COVID-19

text: While the current COVID-19 pandemic continues to wreak havoc on human health and national economies, conservationists are struggling to prevent misguided persecution of bats, which are misleadingly being blamed for spreading the disease. Although at a global level, such persecution is relatively uncommon, even a few misguided actions have the potential to cause irrevocable damage to already vulnerable species. Here, we draw on the latest findings from psychology, to explain why some conservation messaging may be reinforcing misleading negative associations. We provide guidelines to help ensure that conservation messaging is working to neutralize dangerous and unwarranted negative-associations between bats and disease-risk. We provide recommendations around three key areas of psychological science: (i) debunking misinformation; (ii) counteracting negative associations; and (iii) changing harmful social norms. We argue that only by carefully framing accurate, honest, and duly contextualized information, will we be able to best serve society and present an unbiased perspective of bats. We hope this guidance will help conservation practitioners and researchers to develop effective message framing strategies that minimize zoonotic health risks and support biodiversity and its associated ecosystem services.


title: Early Respiratory Viral Acquisition after Allogeneic Hematopoietic Cell Transplant (HCT)

text: Introduction Respiratory infections after HCT lead to significant morbidity, mortality, and health care costs due to pulmonary complications. In up to a third of patients following allogeneic HCT, infection can progress from an upper to a lower respiratory tract infection. Without vaccines or effective therapeutics for most viruses, very little can be done beyond supportive care. Objectives There is a need to identify risk factors for virus acquisition in HCT recipients in order to develop and implement better preventative interventions. Methods In a prospective study, 471 HCT patients enrolled between 2005 and 2010 underwent weekly PCR-based surveillance for RSV, metapneumovirus, parainfluenza virus 1-4, influenza A and B, rhinovirus, coronavirus, and adenovirus. Detailed weekly surveys were collected from subjects for up to 1 year post-transplant on symptoms and exposures to children under 10 years or sick contacts (within 3 feet for more than 1 hour total in the past week). We performed multivariable Cox regression analysis to identify risk factors associated with the time to first positive respiratory viral detection by PCR (asymptomatic and symptomatic) within the first 100 days HCT. Results In this cohort, 211 patients (45%) acquired a respiratory virus in the first 100 days after transplant. Of those infected, 88 (42%) were symptomatic with at least 2 respiratory symptoms. We found significantly higher risk of acquiring any respiratory viral infection for patients with underlying chronic leukemia compared with other hematologic malignancies [hazard ratio (HR) 1.79 (1.16 – 2.77)], exposure to children under or over 4 years [HR 1.84 (1.36 – 2.48)], exposure to contacts with cold symptoms [HR 1.47 (1.02 – 2.12)], exposure to systemic steroids [HR 1.49 (1.07 – 2.08)], and absolute monocyte counts < 100/µL [HR 1.81 (1.12 – 2.94)]. Age, age of child exposure, gender, smoking history, season, conditioning regimen, donor relationship, cell source, presence of acute GVHD, albumin level, total IgG level, lymphocyte counts, and neutrophil counts were not associated with risk for acquisition. We also analyzed the association of these same variables with the time to first positive respiratory viral detection with symptomatic respiratory disease. We found that exposure to children [HR 1.56 (1.03 – 2.35)] and exposure to steroids [HR 1.59 (1.01 – 2.52)] remained associated with acquisition of symptomatic respiratory viral infection. Conclusions These data support the contribution of both exposure and immunologic determinants to the risk of respiratory viral acquisition with and without development of symptoms. Although many infections were asymptomatic, patients receiving steroids and those in close proximity to children may benefit from closer monitoring and counseling in the early post-transplant period.


docid: zkymgsvl

title: Pets in Voluntary Household Quarantine