title: Family-Centered Care During the COVID-19 Era

text: Abstract Family support is more, not less, important during crisis. However, during the COVID-19 pandemic, maintaining public safety necessitates restricting the physical presence of families for hospitalized patients. In response, health systems must rapidly adapt family-centric procedures and tools to circumvent restrictions on physical presence. Strategies for maintaining family integrity must acknowledge clinicians’ limited time and attention to devote to learning new skills. Internet-based solutions can facilitate the routine, predictable, and structured communication which is central to family-centered care. But the reliance on technology may compromise patient privacy and exacerbate racial, socioeconomic, and geographic disparities for populations that lack access to reliable internet access, devices or technological literacy. We provide a toolbox of strategies for supporting family-centered inpatient care during physical distancing responsive to the current clinical climate. Innovations in the implementation of family involvement during hospitalizations may lead to long-term progress in the delivery of family-centered care.


title: Pathogen profiles and molecular epidemiology of respiratory viruses in Japanese inpatients with community-acquired pneumonia

text: Abstract Background The etiological profile of viruses among adult patients with community-acquired pneumonia (CAP) has not been characterized yet. The aim of this study was twofold: first, investigate the pathogen profiles and the molecular epidemiology of respiratory viruses among Japanese CAP patients; and second, explore the clinical significance of viral infections. Methods A cross-sectional observational study was conducted at Kyorin University Hospital. To identify respiratory pathogens, hospitalized CAP patients were enrolled, and reverse transcriptase–polymerase chain reaction technology was applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. CAP patients were divided into four etiological groups (virus alone, bacteria alone, co-detection of virus and bacteria, and not detected) and the clinical findings were compared. Results Seventy-six patients were enrolled. Bacteria alone were detected in 39.5% (n=30) of CAP patients. Virus alone or co-detection were found in 10.5% (n=8) and 11.8% (n=9) of cases, respectively. Streptococcus pneumoniae and human metapneumovirus were the most frequently detected bacterium and virus, respectively. Phylogenetic analyses of human metapneumovirus, human rhinovirus, and human respiratory syncytial virus showed that different subgroups and genotypes might be associated with CAP. Respiratory failure was more common when a virus was detected (both virus alone and co-detection groups; n=17, 100%, p<0.05) than when a bacteria alone was detected (n=17, 56.7%). Conclusion Prevalence of respiratory virus infection in CAP inpatients was 22.3%. The detected viruses display high genetic divergence and correlate with increased respiratory failure.


title: Detection of Novel duck reovirus (NDRV) using visual reverse transcription loop-mediated isothermal amplification (RT-LAMP)

text: Here we present a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting the gene encoding the σB major outer-capsid protein of novel duck reovirus (NDRV). A set of primers, composed of two outer primers, two inner primers and two loop primers, was designed based on the gene of interest. The LAMP reaction was conducted in a traditional laboratory water bath at 65 °C for 50 min. We compared the performance of calcein/Mn(2+) and SYBR Green I dyes, as well as electrophoresis on agarose gel stained with GoldView nucleic acid dye to detect the RT-LAMP-amplified products and all assays could be employed to discriminate between positive and negative specimens in visible or UV light. Our data showed that there is no cross-reaction with other viruses and the RT-LAMP technique displayed high sensitivity for detecting NDRV with a minimal detection limit of 200 fg RNA input. This assay was more sensitive than conventional PCR in detecting NDRV both in natural and experimental infection. In conclusion, the RT-LAMP technique was remarkably sensitive, specific, rapid, simple and profitable for the identification of NDRV.


Community-wide Outbreak of Infection with a 229E-like Coronavirus in Tecumseh, Michigan


title: Artificial Intelligence in Public Health and Epidemiology

text: Objectives: To introduce and summarize current research in the field of Public Health and Epidemiology Informatics. Methods: The 2017 literature concerning public health and epidemiology informatics was searched in PubMed and Web of Science, and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to provide the editorial team with an enlightened vision to select the best papers. Results: Among the 843 references retrieved from PubMed and Web of Science, two were finally selected as best papers. The first one analyzes the relationship between the disease, social/mass media, and public emotions to understand public overreaction (leading to a noticeable reduction of social and economic activities) in the context of a nation-wide outbreak of Middle East Respiratory Syndrome (MERS) in Korea in 2015. The second paper concerns a new methodology to de-identify patient notes in electronic health records based on artificial neural networks that outperformed existing methods. Conclusions: Surveillance is still a productive topic in public health informatics but other very important topics in Public Health are appearing. For example, the use of artificial intelligence approaches is increasing.


title: Self-Replicating RNA Viruses for RNA Therapeutics

text: Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.


title: Fly repellency using deltamethrin may reduce intramammary infections of dairy cows under intensive management

text: Abstract The aim of this study was to assess the possible effect of the fly repellent deltamethrin on the full microbiological profile of the intramammary infections as well as on the somatic cell count in one Greek dairy cattle farm under intensive management, during peak fly season. Fifty five multiparous cows, stabled in the same farm, were randomly divided in three groups; cows of Group A were dressed on their back with deltamethrin, cows of Group B remained untreated within the same pen and cows of Group C remained untreated in a separate pen. Clinical records of the herd showed a history of clinical and subclinical mastitis (especially during spring and early summer) and fly infestation. Deltamethrin reduced fly population, landing on the cows of Group A, facilitating a significant decrease of S. aureus, coagulase negative staplylococci, E. coli intramammary infections and somatic cell count, throughout the study period. Consequently, there is a relationship between fly abundance and transmission of bacteria resulting in intramammary infections and mastitis in dairy cows. The use of the pyrethroid deltamethrin reduced fly abundance and therefore, the possibility of transmitting pathogenic bacteria in the mammary gland.


title: Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network

text: Host cells possess the metabolic assets required for viral infection. Recent studies indicate that control of the host’s metabolic resources is a core host-pathogen interaction. Viruses have evolved mechanisms to usurp the host’s metabolic resources, funneling them towards the production of virion components as well as the organization of specialized compartments for replication, maturation, and dissemination. Consequently, hosts have developed a variety of metabolic countermeasures to sense and resist these viral changes. The complex interplay between virus and host over metabolic control has only just begun to be deconvoluted. However, it is clear that virally induced metabolic reprogramming can substantially impact infectious outcomes, highlighting the promise of targeting these processes for antiviral therapeutic development.


title: Prise en charge nutritionnelle des patients de réanimation ayant une infection COVID-19

text: Résumé Les patients ayant eu des formes sévères de Covid-19 ont posé des problèmes nutritionnels en réanimation. L’immobilisation prolongée en réanimation, associée à une réaction inflammatoire systémique exacerbée, ont été à l’origine d’une faiblesse et d’une fatigue musculaire. Pour pallier ce problème, l’instauration d’une nutrition entérale précoce est recommandée, pour atteindre progressivement la cible énergétique de 25kcal/kg/jour et protéique de 1,3g/kg/jour en 4 jours environ. La survenue d’un syndrome de renutrition inappropriée doit être surveillée. En cas d’intolérance digestive réfractaire à un traitement prokinétique, une nutrition parentérale complémentaire ou totale est indiquée, en favorisant les émulsions lipidiques mixtes (contenant de l’huile de poisson) de nouvelle génération et en surveillant régulièrement la triglycéridémie. La prise en charge nutritionnelle des patients doit se faire en limitant les procédures à risque de contamination pour le personnel soignant. Summary Patients with severe cases of Covid-19 are at high nutritional risk during their ICU stay. Prolonged immobilization associated with an exacerbated systemic inflammatory response is a major provider of ICU-acquired muscle weakness. Early enteral nutrition is recommended to gradually reach the energy target of 25kcal/kg/day and protein target of 1.3g/kg/day around D4. The occurrence of a Refeeding syndrome should be closely monitored. In case of feeding intolerance refractory to a prokinetic treatment, complementary or total parenteral nutrition is advised, favouring new generation mixed lipid emulsions (containing fish oil) and regular monitoring of triglyceridemia. Nutrition care of critically ill patients should be carried out with limited procedures that may pose a risk of contamination for the healthcare staff.


title: Generating Vesicular Stomatitis Virus Pseudotype Bearing the Severe Acute Respiratory Syndrome Coronavirus Spike Envelope Glycoprotein for Rapid and Safe Neutralization Test or Cell‐Entry Assay

text: abstract: We generated a recombinant vesicular stomatitis virus (VSV) pseudotype (VSV Δ G*SG) by replacing the envelope G gene with the GFP gene and complementing with spike glycoprotein (S) of SARS‐CoV in trans. The neutralization and infection blocking tests showed that the VSV Δ G*SG and SARS‐CoV reacted similarly to SARS‐CoV specific antiserum, suggesting the VSVΔ G*SG can be a safe replacement of the live SARS‐CoV for neutralization test and cell‐entry assay.


title: Genotyping coronaviruses associated with feline infectious peritonitis

text: Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP.


title: D-RNA Molecules Associated with Subisolates of the VT Strain of Citrus Tristeza Virus which Induce Different Seedling-Yellows Reactions

text: Citrus tristeza virus (CTV) strains were previously catalogued as seedling-yellows (SY) and non-SY (nSY) types, according to their yellowing and stunting effects on indicator seedlings. Among subisolates of the VT strain, which were selected from chronically infected Alemow plants, there was a correlation between the presence of 2.4-, 2.7- and 4.5-kb D-RNAs, and SY and nSY reactions, respectively. Similarly, plants infected with Mor-T subisolates, which cause SY, contained D-RNAs of 2.6 to 2.8 kb, while nSY subisolates from recovered sour orange tissue contained a major D-RNA of 5.1 kb. Plants harboring the 2.7-kb D-RNA were protected against challenge inoculation with a subisolate harboring the 4.5-kb D-RNA. This study suggests that the nSY reaction results either from the absence of SY gene(s) in the genomes of certain CTV strains or through the suppression of the effects of SY gene(s) by D-RNAs with 5′ parts larger than 4000 nt.


title: Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities — Wyoming, 2020

text: In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.


title: Identification of Sugar Residues Involved in the Binding of TGEV to Porcine Brush Border Membranes

text: Coronaviruses most often infect the respiratory or intestinal tract. Transmissible gastroenteritis virus (TGEV), a group 1 coronavirus, infects the porcine small intestine. Piglets up to the age of 3 weeks die from diarrhea caused by the viral gastroenteritis unless they are protected by antibodies. In addition to the cellular receptor, porcine aminopeptidase N, the TGEV spike protein binds to sialic acid residues. We have shown that the sialic acid binding activity mediates the binding of TGEV to a mucin-like glycoprotein present in porcine brush border membranes. This was shown by performing a virus overlay binding assay with proteins obtained from brush border membranes by lectin precipitation. Because of the reactivity with specific lectins we assume that the recognized glycoprotein has the characteristics of a mucin.


title: How the Double Spherules of Infectious Bronchitis Virus Impact Our Understanding of RNA Virus Replicative Organelles

text: Powered by advances in electron tomography, recent studies have extended our understanding of how viruses construct “replication factories” inside infected cells. Their function, however, remains an area of speculation with important implications for human health. It is clear from these studies that whatever their purpose, organelle structure is dynamic (M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, Cell. Microbiol. 12:844-861, 2010) and intricate (K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, et al., PLOS Biol. 6:e226, 2008). But by concentrating on medically important viruses, these studies have failed to take advantage of the genetic variation inherent in a family of viruses that is as diverse as the archaea, bacteria, and eukaryotes combined (C. Lauber, J. J. Goeman, M. del Carmen Parquet, P. T. Nga, E. J. Snijder, et al., PLOS Pathog. 9:e1003500, 2013). In this climate, Maier et al. (H. J. Maier, P. C. Hawes, E. M. Cottam, J. Mantell, P. Verkade, et al., mBio 4:e00801-13, 2013) explored the replicative structures formed by an avian coronavirus that appears to have diverged at an early point in coronavirus evolution and shed light on controversial aspects of viral biology.


title: COVID‐19 and Cutaneous manifestations

text: We found that the article on “Cutaneous manifestations in COVID‐19: a first perspective” is very interesting [1]. Recalcati noted that 20.4 % of the patients have cutaneous problem and mentioned that this is the first report on this clinical aspect of COVID‐19.


title: Modelling the pandemic: attuning models to their contexts

text: The evidence produced in mathematical models plays a key role in shaping policy decisions in pandemics. A key question is therefore how well pandemic models relate to their implementation contexts. Drawing on the cases of Ebola and influenza, we map how sociological and anthropological research contributes in the modelling of pandemics to consider lessons for COVID-19. We show how models detach from their implementation contexts through their connections with global narratives of pandemic response, and how sociological and anthropological research can help to locate models differently. This potentiates multiple models of pandemic response attuned to their emerging situations in an iterative and adaptive science. We propose a more open approach to the modelling of pandemics which envisages the model as an intervention of deliberation in situations of evolving uncertainty. This challenges the ‘business-as-usual’ of evidence-based approaches in global health by accentuating all science, within and beyond pandemics, as ‘emergent’ and ‘adaptive’.


title: Taxonomy, Classification and Nomenclature of Viruses

text: Virus taxonomy is a man-made field of science aiming at helping the classification of viral entities and at using the same nomenclature for the description of these entities in their biological and physical properties. Taxonomy at the interface of conceptual and physical matters is by essence very controversial, but it is important for many purposes from virus diagnostics to virus evolution. Virus taxonomy, which officially began in 1966 under the activity of 43 virologists who created the International Committee on Taxonomy of Viruses (ICTV), has made tremendous progress in the last 40years to classify today about 6000 virus entities into more than 2000 species, themselves classified into 287 genera, 73 families, and 3 orders, as attested by the Eighth Report of the ICTV. Virus nomenclature has also progressed in parallel to virus taxonomy, and although virologists still debate about the best way to write virus species names, undoubtedly virus taxonomy and nomenclature are now in a very advanced state. However, major challenges are ahead for virologists with the exponential increase in virus genome sequencing which will be beyond 1million sequences by 2010 and the virologists have to face that challenge with organization and creativity, in order to offer to the virological community the best and most useful virus taxonomy and nomenclature.


title: Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection

text: Niemann-Pick disease type C (NPC) is associated with mutations in NPC1 and NPC2, whose gene products are key players in the endosomal/lysosomal egress of low-density lipoprotein-derived cholesterol. NPC1 is also the intracellular receptor for Ebola virus (EBOV). Here, we present a 4.4 Å structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of EBOV, both determined by single-particle electron cryomicroscopy. NPC1 contains 13 transmembrane segments (TMs) and three distinct lumenal domains A (also designated NTD), C, and I. TMs 2–13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3–7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling. A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection.


title: Emerging infectious diseases associated with bat viruses

text: Bats play important roles as pollen disseminators and pest predators. However, recent interest has focused on their role as natural reservoirs of pathogens associated with emerging infectious diseases. Prior to the outbreak of severe acute respiratory syndrome (SARS), about 60 bat virus species had been reported. The number of identified bat viruses has dramatically increased since the initial SARS outbreak, and most are putative novel virus species or genotypes. Serious infectious diseases caused by previously identified bat viruses continue to emerge throughout in Asia, Australia, Africa and America. Intriguingly, bats infected by these different viruses seldom display clinical symptoms of illness. The pathogenesis and potential threat of bat-borne viruses to public health remains largely unknown. This review provides a brief overview of bat viruses associated with emerging human infectious diseases.


title: COVID-19 panic, solidarity and equity—the Malta exemplary experience

text: AIM: The coronavirus (SARS-CoV-2) pandemic is a global crisis, with more than 2 million of the world’s population infected. Public health authorities across the world are working endlessly to contain the situation. The small nation of Malta has been applauded by the World Health Organization (WHO) Regional Director for Europe for the instituted escalated public health measures that have kept (up till the time of writing) the COVID-19 spread contained with low transmission rate. The aim of this overview is to give a comprehensive summary of the COVID-19 situation, measures, legislations and initiatives for containment, management and safeguarding the Maltese nation that were taken. SUBJECT AND METHOD: A literature search was conducted using the Google search engine and Maltese online newspapers. RESULTS: To date (22nd April 2020), the COVID-19 situation in Malta is a total confirmed cases of 444, of which 276 are active cases, 165 have recovered and there were three deaths. Various measures were taken early on, from travel bans to prohibition of more than three-person gatherings, backed up with penalties. Both public and private sectors are working together to ensure containment and provision of services to the population. Solidarity has spread across the country. CONCLUSION: A number of timely measures have been taken. However, it is down to the nation to continue to follow the restrictions and regulations instituted by the Superintendent of Public Health in conjunction with the health division and the government to overcome this pandemic together.


title: Intestinal pathogens, diarrhoea and acute phase proteins in naturally infected dairy calves

text: Abstract In this study, the association between Eimeria spp. related signs and innate immune response in dairy calves was examined. Calves (n =100) aged 15–60 days were clinically examined and faecal samples, blood samples and deep nasopharyngeal swabs obtained. The samples were analysed for intestinal pathogens, acute phase proteins and WBC count, and respiratory tract pathogens, respectively. Diarrhoea was diagnosed in 32.6% (23.3–43.0%, 95% CI) of calves. An association between the pathogenic Eimeria spp. and diarrhoea was detected by multiple correspondence analysis. Eimeria related signs (diarrhoea, presence of pathogenic species and total oocyst count) were combined resulting a four level variable. Calves with weak signs of eimeriosis had decreased haptoglobin concentrations (p =0.02) and increased fibrinogen concentrations (p =0.048) compared to no signs. Increased haptoglobin and fibrinogen concentrations were associated with respiratory tract infection and umbilical infection. Serum amyloid A and WBC counts showed no association with signs of eimeriosis or clinical diagnoses.


title: Insights into the Structural Basis of Antibody Affinity Maturation from Next-Generation Sequencing

text: Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism’s own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation. Crystal structures of antibodies from these lineages bound to their target antigens have revealed, at the atomic level, how antibodies evolve to penetrate the glycan shield of envelope glycoproteins, and how viruses in turn evolve to escape neutralization. Collectively, structural studies of affinity maturation have shown that increased antibody affinity can arise from any one or any combination of multiple diverse mechanisms, including improved shape complementarity at the interface with antigen, increased buried surface area upon complex formation, additional interfacial polar or hydrophobic interactions, and preorganization or rigidification of the antigen-binding site.


title: Broad-spectrum neutralization of avian influenza viruses by sialylated human milk oligosaccharides: in vivo assessment of 3′-sialyllactose against H9N2 in chickens

text: Two sialylated human milk oligosaccharides (SHMOs) 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) were accessed for their possible antiviral activity against six different subtypes of thirteen avian influenza (AI) viruses in vitro. 3′-SL exhibited promising antiviral activity against almost all subtypes of tested AI viruses in hemagglutination inhibition assay, whereas 6′-SL showed activity against few selected H1N1, H1N2, and H3N2 subtype strains. 3′-SL has minimum inhibitory concentration values of 15.62 mM or less in more than half of the viruses examined. 3′-SL also showed effective inactivation of H9N2 Korea isolate (A/Chicken/Korea/MS96/1996) at 12.5 mM concentration in Madin Darby Canine Kidney (MDCK) cell line. Thus, 3′-SL was further studied for in vivo study against H9N2 virus in pathogen free chicken experiment models. In vivo study exhibited improved clinical symptoms on H9N2 infected chickens when treated with 3′-SL. Moreover, treating chickens with 3′-SL resulted in complete elimination of H9N2 viruses within 24 h of virus infection (0.8 HAU of H9N2). Indirect ELISA assay confirmed complete wash-out of H9N2 viruses from the colon after neutralization by 3′-SL without entering the blood stream. These in vivo results open up possible applications of 3′-SL for the prevention of AI virus infections in birds by a simple cleansing mechanism.


title: G-Quadruplex DNA and RNA

text: G-quadruplexes (G4s) have become one of the most exciting nucleic acid secondary structures. A noncanonical, four-stranded structure formed in guanine-rich DNA and RNA sequences, G-quadruplexes can readily form under physiologically relevant conditions and are globularly folded structures. DNA is widely recognized as a double-helical structure essential in genetic information storage. However, only ~3% of the human genome is expressed in protein; RNA and DNA may form noncanonical secondary structures that are functionally important. G-quadruplexes are one such example which have gained considerable attention for their formation and regulatory roles in biologically significant regions, such as human telomeres, oncogene-promoter regions, replication initiation sites, and 5′- and 3′-untranslated region (UTR) of mRNA. They are shown to be a regulatory motif in a number of critical cellular processes including gene transcription, translation, replication, and genomic stability. G-quadruplexes are also found in nonhuman genomes, particularly those of human pathogens. Therefore, G-quadruplexes have emerged as a new class of molecular targets for drug development. In addition, there is considerable interest in the use of G-quadruplexes for biomaterials, biosensors, and biocatalysts. The First International Meeting on Quadruplex DNA was held in 2007, and the G-quadruplex field has been growing dramatically over the last decade. The methods used to study G-quadruplexes have been essential to the rapid progress in our understanding of this exciting nucleic acid secondary structure.


title: COVID‐19: Leaving lockdown—Of Schrodinger, cats, testing and masks

text: The COVID-19 pandemic progresses across the globe at pace, bringing lockdown of countries and continents. Over the Easter weekend as well as speculation that lockdown in the UK would need to be extended for a significant period, media attention became focussed on why the UK death rates from COVID-19 are significantly greater than in Germany (1). In a BBC television interview on Easter Sunday (2), Sir Jeremy Farrar who is a senior advisor to both UK and German governments commented that it is likely to be the significantly larger number of tests for SARS-Cov- 2 (the viral cause for COVID-19) undertaken in Germany when compared to the UK. He suggested that through early identification and isolation of cases that Germany, unlike the UK, had been able to contain COVID-19 and hence reduce transmission rates and need for hospitalisation.


title: Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?

text: The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.


title: COVID-19 outbreak control, example of ministry of health of Turkey

text: Our first COVID-19 case in Turkey was a 44-year-old male who referred to the hospital on March 9, 2020. The first related death occurred on March 17, 2020. Preparedness for the pandemic has been ongoing before the first case was detected. The National Pandemic Plan was published in 2006. The Pandemic Influenza National Preparedness Plan was available after being updated in light of experiences gained during the 2009 Influenza A pandemic. Accordingly, Pandemic Coordination Boards and Operation Centers have been established on the national and provincial levels. This was an adaptable plan to the Novel Coronavirus Disease (COVID-19). We formed teams to work on a 24/7 basis and established a Scientific Committee at the Public Health Emergency Operation Center within the General Directorate of Public Health. “COVID-19 Risk Assessment”, “COVID-19 Guideline” and “Case Report Form”, regulations of personal protective equipment along with need-based guidelines, treatment algorithms, brochures and related documents have been released. For the case-based follow-up, Public Health Management System (HSYS) is being used. PCR and rapid diagnostic kits are being used to analyze the samples at the central Microbiology Reference Laboratory and the authorized laboratories in several provinces. Various preventive measures were implemented including flight restrictions to certain countries, gradually expanded to suspending all flights and prohibiting the entry of foreign nationals, 14-day isolation and symptom monitoring for those that came from countries under risk. Persons with chronic diseases have been granted an administrative leave, on campus education at schools and activities of public rest and entertainment areas were temporarily suspended. The measures have been implemented for penitentiary institutions, dormitories, nursing homes, public transport and intercity buses, and also weekend curfews are implemented. In accordance with the pandemic plan, actions have been carried out with a multi-sectoral approach, and preventive measures have been implemented to cover the society as a whole.


title: Endothelial dysfunction in Coronavirus disease 2019 (COVID-19): gender and age influences

text: Several risk factors are associated with a worse outcome for COVID-19 patients; the most recognized are demographic characteristics such as older age and male gender, and pre-existing cardiovascular conditions. About the latter, hypertension and coronary heart disease are among the most common comorbidities recorded in infected patients, together with type 2 diabetes mellitus (T2DM). Data from Istituto Superiore di Sanità (ISS, Italy) show that more than 68.3% of patients had hypertension, 28.2% ischemic heart disease, 22.5% atrial fibrillation, while 30.1% T2DM. Several authors suggested that cardiovascular diseases and diabetes mellitus are linked to endothelial dysfunction, and all of them are strictly related to aging. Considering the impact of the gender on the COVID-19 epidemic, even if confirmed cases from each nation are changing every day, epidemiological data clearly evidence that in men the infection causes worse outcomes compared to women. In Italy, up to 21 May, in the age range of 60-89 years, male deaths were 63.9% of total cases. The reason behind this difference between genders appears not clear; however, the diversity in sex-hormones and styles of life are believed to play a role in the patient's susceptibility to severe SARS-CoV-2 outcomes. It is known that the activation of endothelial estrogen receptors increases NO and decreases ROS, protecting the vascular system from angiotensin II-mediated vasoconstriction, inflammation, and ROS production. During the pandemic, joining forces is vital; thus, as people help doctors by limiting their displacements out of their houses avoiding hence the spread of the infection, doctors help patients to overcome severe SARS-CoV-2 infections by using multiple pharmacological approaches. In this context, the preservation of endothelial function and the mitigation of vascular inflammation are prominent targets, essential to reduce severe outcomes also in male older patients.


title: Cluster-based dual evolution for multivariate time series: Analyzing COVID-19

text: This paper proposes a cluster-based method to analyze the evolution of multivariate time series and applies this to the COVID-19 pandemic. On each day, we partition countries into clusters according to both their cases and death counts. The total number of clusters and individual countries’ cluster memberships are algorithmically determined. We study the change in both quantities over time, demonstrating a close similarity in the evolution of cases and deaths. The changing number of clusters of the case counts precedes that of the death counts by 32 days. On the other hand, there is an optimal offset of 16 days with respect to the greatest consistency between cluster groupings, determined by a new method of comparing affinity matrices. With this offset in mind, we identify anomalous countries in the progression from COVID-19 cases to deaths. This analysis can aid in highlighting the most and least significant public policies in minimizing a country’s COVID-19 mortality rate.


title: COVID‐19 dentistry‐related aspects: a literature overview

text: A new coronavirus (Sars‐CoV‐2) was detected in China at the end of 2019 and has since caused a worldwide pandemic. This virus is responsible for an acute respiratory syndrome (COVID‐19), distinguished by a potentially lethal interstitial bilateral pneumonia. Because Sars‐CoV‐2 is highly infective through airborne contamination, the high infection risk in the dental environment is a serious problem for both professional practitioners and patients. This literature overview provides a description of the clinical aspects of COVID‐19 and its transmission, while supplying valuable information regarding protection and prevention measures.


title: Ghosts A travel barrier to tourism recovery

text: Abstract This study aims to assess whether or not beliefs in ghosts really deter tourists from traveling to disaster-hit destinations. To many it may appear that cultural differences do play a role in travel decision making between Asian and Western tourists. However, it is vital to provide empirical evidence of the impact of cultural differences in beliefs through a case study of the tsunami-hit destinations. Thus, this study aims to examine tourist barriers associated with tsunami-hit destinations, and also to assess cultural differences regarding such beliefs between Asians tourists from China and Thailand and Western tourists from Britain, Germany, and the United States and also across demographic profile.


title: Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system

text: Facing the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), high-volume respiratory testing is demanded in laboratories worldwide. We evaluated the performance of a molecular assay for the detection of SARS-CoV-2 on a high-throughput platform, the cobas 6800, using the ‘open channel’ for integration of a laboratory-developed assay. We observed good analytical performance in clinical specimens. The fully automated workflow enables high-throughput testing with minimal hands-on time, while offering fast and reliable results.


Psychological impact of lockdown (confinement) on young children and how to mitigate its effects: Rapid review of the evidence()


title: 6′-β-Fluoro-Homoaristeromycin and 6′-Fluoro-Homoneplanocin A Are Potent Inhibitors of Chikungunya Virus Replication through Their Direct Effect on Viral Nonstructural Protein 1

text: Alphaviruses are arthropod-borne, positive-stranded RNA viruses capable of causing severe disease with high morbidity. Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness which can progress into chronic arthralgia. The current lack of vaccines and specific treatment for CHIKV infection underscores the need to develop new therapeutic interventions. To discover new antiviral agents, we performed a compound screen in cell culture-based infection models and identified two carbocyclic adenosine analogues, 6′-β-fluoro-homoaristeromycin (FHA) and 6′-fluoro-homoneplanocin A (FHNA), that displayed potent activity against CHIKV and Semliki Forest virus (SFV) with 50% effective concentrations in the nanomolar range at nontoxic concentrations. The compounds, designed as inhibitors of the host enzyme S-adenosylhomocysteine (SAH) hydrolase, impeded postentry steps in CHIKV and SFV replication. Selection of FHNA-resistant mutants and reverse genetics studies demonstrated that the combination of mutations G230R and K299E in CHIKV nonstructural protein 1 (nsP1) conferred resistance to the compounds. Enzymatic assays with purified wild-type (wt) SFV nsP1 suggested that an oxidized (3′-keto) form, rather than FHNA itself, directly inhibited the MTase activity, while a mutant protein with the K231R and K299E substitutions was insensitive to the compound. Both wt nsP1 and the resistant mutant were equally sensitive to the inhibitory effect of SAH. Our combined data suggest that FHA and FHNA inhibit CHIKV and SFV replication by directly targeting the MTase activity of nsP1, rather than through an indirect effect on host SAH hydrolase. The high potency and selectivity of these novel alphavirus mRNA capping inhibitors warrant further preclinical investigation of these compounds.


Creating Opportunities to Advance Stem Cell Science: 2019–2020 Year in Review


COVID-19 Through the Lens of Gerontology


title: Universal Do-Not-Resuscitate Orders, Social Worth, and Life-Years: Opposing Discriminatory Approaches to the Allocation of Resources During the COVID-19 Pandemic and Other Health System Catastrophes

text: These authors share thoughts about discriminatory approaches to the allocation of resources during health care catastrophes, such as the COVID-19 pandemic. They argue that, although prioritization of resources is critical, fairness requires giving each patient his or her due based on clinical criteria applied to the individual rather than assumptions that favor or disfavor groups.


Global rheumatology in the time of COVID-19


title: Mechanism of 3D domain swapping in bovine seminal ribonuclease

text: 3D domain swapping (3D‐DS) is a complex protein aggregation process for which no unique mechanism exists. We report an analysis of 3D‐DS in bovine seminal ribonuclease, a homodimeric protein whose subunits are linked by two disulfide bridges, based on NMR and biochemical studies. The presence of the covalent bonds between the subunits stabilizes the unswapped dimer, and allows distinct evaluation of the structural and dynamic effects of the swapping with respect to the dimerization process. In comparison with the monomeric subunit, which, in solution has a compact structure without any propensity for local unfolding, both swapped and unswapped dimers show increased flexibility. NMR analysis, together with urea denaturation and hydrogen–deuterium exchange data, indicates that the two dimers have increased conformational fluctuations. Furthermore, we found that the rate‐limiting step of both the swapping and unswapping pathways is the detachment of the N‐terminal helices from the monomers. These results suggest a new general mechanism in which a dimeric intermediate could facilitate 3D‐DS in globular proteins. STRUCTURED DIGITAL ABSTRACT: http://www.uniprot.org/uniprot/P00669 and http://www.uniprot.org/uniprot/P00669 http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407 by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0077 (http://www.ebi.ac.uk/intact/interaction/EBI-8870415).


title: Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review

text: Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure—that is, the higher the risk the longer the distancing period. Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.


title: Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma

text: BACKGROUND: Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma. METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG ≤5 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after >10-15 days. After 15-22 days the “true” positivity rates were 94.4% for IgM and 100% for IgG. The “false” positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients. CONCLUSIONS: This study shows high “true” vs. low “false” positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs.


title: Duplex real-time RT-PCR assay for detection and subgroup-specific identification of human respiratory syncytial virus

text: Abstract Human respiratory syncytial virus (HRSV) is a leading cause of acute respiratory illness in young children worldwide. Reliable detection and identification of HRSV subgroup A and B infections are essential for accurate disease burden estimates in anticipation of licensure of novel HRSV vaccines and immunotherapies. To ensure continued reliability, molecular assays must remain current with evolving virus strains. We have developed a HRSV subgroup-specific real-time RT-PCR (rRT-PCR) assay for detection and subgroup identification using primers and subgroup-specific probes targeting a conserved region of the nucleoprotein gene combined in a single duplex reaction using all genome sequence data currently available in GenBank. The assay was validated for analytical sensitivity, specificity, reproducibility, and clinical performance with a geographically diverse collection of viral isolates and respiratory specimens in direct comparison with an established pan-HRSV rRT-PCR reference test. The assay was sensitive, reproducibly detecting as few as 5–10 copies/reaction of target RNA. The assay was specific, showing no amplification with a panel of 16 other common respiratory pathogens or predicted by in silico primer/probe analysis. The duplex rRT-PCR assay based on the most current available genome sequence data permits rapid, sensitive and specific detection and subgroup identification of HRSV.


title: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis

text: Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80–2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58–3.10) and 2.32 (95% CI: 1.70–3.17) in age <50 years and ⩾50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72–7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40–12.17) and 2.66 (95% CI: 1.27–5.57) in age <50 years and ⩾50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.


title: Chikungunya virus capsid protein contains nuclear import and export signals

text: BACKGROUND: Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. METHODS: EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. RESULTS: Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. CONCLUSIONS: We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its nuclear import and, vice versa, by CRM1-dependent nuclear export.


title: A brief report on the normal range of forehead temperature as determined by noncontact, handheld, infrared thermometer

text: BACKGROUND: Noncontact forehead temperature measurement by handheld infrared thermometer was used as a screening tool for fever. However, the accuracy data and normal range of forehead temperature determined by this method were not available. METHODS: The temperature readings from 3 handheld infrared thermometers were validated against an electronic thermometer. Normal range of forehead temperature was determined by measuring the forehead temperature in 1000 apparently healthy subjects. RESULTS: Significant differences were detected in readings obtained by the 3 different handheld infrared thermometers (analysis of covariance, P < .001) The most accurate one was chosen, and the normal range of forehead temperature in 1000 subjects detected by this method was 31.0°C to 35.6°C. CONCLUSIONS: Our study shows that commercially available, handheld infrared thermometers require individual validation. Forehead temperature in excess of 35.6°C is suggestive of fever. Further studies are required to confirm accuracy of this value in detecting fever.


title: A Simulation Framework to Investigate in vitro Viral Infection Dynamics

text: Virus infection is a complex biological phenomenon for which in vitro experiments provide a uniquely concise view where data is often obtained from a single population of cells, under controlled environmental conditions. Nonetheless, data interpretation and real understanding of viral dynamics is still hampered by the sheer complexity of the various intertwined spatio-temporal processes. In this paper we present a tool to address these issues: a cellular automata model describing critical aspects of in vitro viral infections taking into account spatial characteristics of virus spreading within a culture well. The aim of the model is to understand the key mechanisms of SARS-CoV infection dynamics during the first 24 hours post infection. Using a simulated annealing algorithm we tune free parameters with data from SARS-CoV infection of cultured lung epithelial cells. We also interrogate the model using a Latin Hypercube sensitivity analysis to identify which mechanisms are critical to the observed infection of host cells and the release of measured virus particles.


title: 3.8 Protein and Nucleic Acid Folding: Domain Swapping in Proteins

text: Abstract Among thousands of homo-oligomeric protein structures, there is a small but growing subset of ‘domain-swapped’ proteins. The term ‘domain swapping,’ originally coined by D. Eisenberg, describes a scenario in which two or more polypeptide chains exchange identical units for oligomerization. This type of assembly could play a role in disease-related aggregation and amyloid formation or as a specific mechanism for regulating function. This chapter introduces terms and features concerning domain swapping, summarizes ideas about its putative mechanisms, reports on domain-swapped structures collected from the literature, and describes a few notable examples in detail.


title: Cataloguing the response by emergency veterinary hospitals during the COVID‐19 pandemic via weekly surveys

text: BACKGROUND: The COVID‐19 pandemic has presented veterinary emergency hospitals with unique challenges. Rapid online surveys represent an efficient way of collating responses to rapidly shifting circumstances. METHODS: Fifty, 24‐h small animal emergency veterinary hospital representatives were recruited to participate in weekly surveys in April 2020 to catalog changes due to COVID‐19 pandemic. KEY FINDINGS: The majority of emergency veterinary hospitals surveyed reported significant changes to day‐to‐day operations as a result of the COVID‐19 pandemic. SIGNIFICANCE: Reporting of weekly survey results provides useful information on how emergency veterinary hospitals with similar challenges are responding to the COVID‐19 pandemic.


title: Mesenchymal stem cell derived extracellular vesicles: promising immunomodulators against autoimmune, autoinflammatory disorders and SARS-CoV-2 infection

text: Discovery of novel and broad-acting immunomodulators is of critical importance for the prevention and treatment of disorders occurring due to overexuberant immune responseincluding SARS-CoV-2 triggered cytokine storm leading to lung pathology and mortality during the ongoing viral pandemic. Mesenchymal stem/stromal cells (MSCs), highly regarded for their regenerative capacities, also possessesremarkable immunoregulatory functions affecting all types of innate and adaptive immune cells. Owing to that, MSCs have been heavily investigated in clinic for the treatment of autoimmune and inflammatory diseases along with transplant rejection. Extensive research in the last decaderevealed that MSCs carry out most of their functions through paracrine factors which are soluble mediators and extracellular vesicles (EVs). EVs, including exosomes and microvesicles, are an efficient way of intercellular communication due to their unique ability to carry biological messages such as transcription factors, growth factors, cytokines, mRNAs and miRNAs over long distances. EVs originate through direct budding of the cell membrane or the endosomal secretion pathway and they consist of the cytosolic and membrane components of their parent cell. Therefore, they are able to mimic the characteristics of the parent cell, affecting the target cells upon binding or internalization. EVs secreted by MSCs are emerging as a cell-free alternative to MSC-based therapies. MSC EVs are being tested in preclinical and clinical settings where they exhibit exceptional immunosuppressivecapacity. They regulate the migration, proliferation, activation and polarization of various immune cells, promoting a tolerogenic immune response while inhibiting inflammatory response. Being as effective immunomodulators as their parent cells, MSC EVs are also preferable over MSC-based therapies due to their lower risk of immunogenicity, tumorigenicity and overall superior safety. In this review, we present the outcomes of preclinical and clinical studies utilizing MSC EVs as therapeutic agents for the treatment of a wide variety of immunological disorders.


title: Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease

text: BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection. METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1. CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.


title: Knocking down Disease with siRNAs

text: Knocking down expression of disease-related genes using small interfering RNAs (siRNAs) has potential for treating a variety of illnesses. This Essay will examine the opportunities for harnessing RNA interference (RNAi) for therapy, as well as the obstacles and possible ways to circumvent them.


title: Intestinal Microbiota of Dogs and Cats: a Bigger World than We Thought

text: Gut microbes play a crucial role in the regulation of host health, but the true complexity of the gastrointestinal microbiota has been underestimated using traditional culture techniques. Recent molecular-phylogenetic and metagenomic studies have revealed a highly diverse microbial community in the canine and feline gastrointestinal tract of healthy animals, consisting of bacteria, archaea, fungi, protozoa, and viruses. Alterations in microbial communities have also been reported in dogs and cats with chronic enteropathies, notably increases in Proteobacteria and depletions of Firmicutes. This review summarizes the current information about the intestinal microbial ecosystem in dogs and cats.


title: Brazil's vulnerability to COVID-19 quantified by a spatial metric

text: • We propose an easy-to-apply index that can support decision-makers to identify the most vulnerable regions to this dangerous pandemic disease. • The impact of the lack of resources in the country-side regions to fight SARSCoV-2 can be assuaged by shielding the most vulnerable regions. • Our results can support countries to prepare the reopening of their economic and social activity in the next months while controlling COVID-19 in their regions.


title: Spectrum of Viruses and Atypical Bacteria in Intercontinental Air Travelers with Symptoms of Acute Respiratory Infection

text: Respiratory infections after air travel are frequent, but epidemiological data are incomplete. Using sensitive polymerase chain reactions, we studied the spectrum of atypical bacteria and respiratory viruses in travelers fulfilling the case definition of severe acute respiratory syndrome. A pathogen was identified in 67 travelers (43.2%). Influenza and parainfluenza viruses were most prevalent, at 14.2% and 15.5%, respectively. Prevalences of adenoviruses, human metapneumovirus, coronaviruses, and rhinoviruses ranged between 2.6% and 4.8%. Human bocavirus, respiratory syncytial virus, and Legionella, Mycoplasma, and Chlamydophila species were absent or appeared at frequencies of <1%. To our knowledge, these are the first specific baseline data for the mentioned agents in the context of air travel.


title: Acute interstitial pneumonia triggered by strenuous exercise

text: Abstract Acute interstitial pneumonia (AIP) is a rare and severe form of idiopathic interstitial lung disease. Treatment is primarily supportive with supplemental oxygenation and mechanical ventilation. Prognosis is poor, but long-term survival is possible after recovery from AIP. We present a case of a 48-years-old previously healthy female who was admitted due to acute shortness of breath and respiratory failure which started three days after she ran a half-marathon. After excluding infectious causes and connective-tissue diseases, a presumptive diagnosis of AIP was made based on clinical and radiological characteristics. The patient was successfully treated with high-dose corticosteroids and mycophenolate mofetil.


title: Rapid Identification of Known and New RNA Viruses from Animal Tissues

text: Viral surveillance programs or diagnostic labs occasionally obtain infectious samples that fail to be typed by available cell culture, serological, or nucleic acid tests. Five such samples, originating from insect pools, skunk brain, human feces and sewer effluent, collected between 1955 and 1980, resulted in pathology when inoculated into suckling mice. In this study, sequence-independent amplification of partially purified viral nucleic acids and small scale shotgun sequencing was used on mouse brain and muscle tissues. A single viral agent was identified in each sample. For each virus, between 16% to 57% of the viral genome was acquired by sequencing only 42–108 plasmid inserts. Viruses derived from human feces or sewer effluent belonged to the Picornaviridae family and showed between 80% to 91% amino acid identities to known picornaviruses. The complete polyprotein sequence of one virus showed strong similarity to a simian picornavirus sequence in the provisional Sapelovirus genus. Insects and skunk derived viral sequences exhibited amino acid identities ranging from 25% to 98% to the segmented genomes of viruses within the Reoviridae family. Two isolates were highly divergent: one is potentially a new species within the orthoreovirus genus, and the other is a new species within the orbivirus genus. We demonstrate that a simple, inexpensive, and rapid metagenomics approach is effective for identifying known and highly divergent new viruses in homogenized tissues of acutely infected mice.


title: Logarithmic versus Linear Visualizations of COVID-19 Cases Do Not Affect Citizens’ Support for Confinement

text: The SARS-CoV-2 virus was first identified in Wuhan, China, in late December 2019, and it quickly spread to many countries. By March 2020, the virus had triggered a global pandemic (World Health Organization, 2020). In response to this crisis, governments have implemented unprecedented public health measures. The success of these policies will largely depend on the public's willingness to comply with new rules. A key factor in citizens’ willingness to comply is their understanding of the data that motivate government action. In this study, we examine how different ways of presenting these data visually can affect citizen's perceptions, attitudes and support for public policy.


title: Procalcitonin levels in COVID-19 patients

text: Coronavirus disease 2019 (COVID-19) is turning into a pandemic. Here, we analyzed 95 patients infected with SARS-CoV-2. Sixty-two moderate patients, 21 severe patients and 12 critical patients (6 patients died) were included in our study. Our results showed that the mean serum levels of procalcitonin in severe patients were over 4 times higher than those in moderate patients, and they were over 8 times higher in critical patients than in moderate patients. For the discharged patients, both high-normal procalcitonin levels and abnormal procalcitonin levels decreased during recovery. However, in the death cases, the serum levels of procalcitonin increased as the disease worsened. We demonstrate that procalcitonin may be an indicator of severity and may contribute to determining the severity of patients infected with COVID-19; moreover, serial procalcitonin measurements may be useful in predicting prognosis.


title: A data-driven network model for the emerging COVID-19 epidemics in Wuhan, Toronto and Italy

text: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic threatens the health of humans and causes great economic losses. Predictive modelling and forecasting the epidemic trends are essential for developing countermeasures to mitigate this pandemic. We develop a network model, where each node represents an individual and the edges represent contacts between individuals where the infection can spread. The individuals are classified based on the number of contacts they have each day (their node degrees) and their infection status. The transmission network model was respectively fitted to the reported data for the COVID-19 epidemic in Wuhan (China), Toronto (Canada), and the Italian Republic using a Markov Chain Monte Carlo (MCMC) optimization algorithm. Our model fits all three regions well with narrow confidence intervals and could be adapted to simulate other megacities or regions. The model projections on the role of containment strategies can help inform public health authorities to plan control measures.


Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic


title: A philosophy of health: life as reality, health as a universal value

text: Emphases on biomarkers (e.g. when making diagnoses) and pharmaceutical/drug methods (e.g. when researching/disseminating population level interventions) in primary care evidence philosophies of health (and healthcare) that reduce health to the biological level. However, with chronic diseases being responsible for the majority of all cause deaths and being strongly linked to health behavior and lifestyle; predominantly biological views are becoming increasingly insufficient when discussing this health crisis. A philosophy that integrates biological, behavioral, and social determinants of health could benefit multidisciplinary discussions of healthy publics. This manuscript introduces a Philosophy of Health by presenting its first five principles of health. The philosophy creates parallels among biological immunity, health behavior change, social change by proposing that two general functions—precision and variation—impact population health at biological, behavioral, and social levels. This higher-level of abstraction is used to conclude that integrating functions, rather than separated (biological) structures drive healthy publics. A Philosophy of Health provides a framework that can integrate existing theories, models, concepts, and constructs.


title: Safety and Effectiveness of Rosiglitazone in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease

text: Background/Purpose Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD. Methods Taiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate amino-transferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%. Results Out of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 ± 2.4 kg (p<0.001). Conclusion Rosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.


title: Porcine Hemagglutinating Encephalomyelitis Virus and Respiratory Disease in Exhibition Swine, Michigan, USA, 2015

text: Acute outbreaks of respiratory disease in swine at agricultural fairs in Michigan, USA, in 2015 raised concern for potential human exposure to influenza A virus. Testing ruled out influenza A virus and identified porcine hemagglutinating encephalomyelitis virus as the cause of influenza-like illness in the affected swine.


title: Improved safety of endoscopic vessel harvesting during the COVID-19 pandemic

text: Abstract The COVID-19 pandemic has necessitated that operating room procedures be modified to ensure the safety of staff and patients. Specifically, procedures that have the potential to create aerosolization must be reassessed, given the risk of viral transmission via aerosolization. We present the use of a non-sealed endoscopic vessel harvesting(EVH) approach during coronary surgery that does not necessitate the use of CO2 insufflation and utilizes suction through an ultra low particulate filter, thus mitigating the risk of possible viral transmission via aerosolization or surgical smoke production. This approach is technically feasible and can minimize the risk of viral transmission during EVH.


title: The porcine dendritic cell family

text: Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. As with the more extensively studied murine and human DCs, porcine DC can be generated from bone marrow haematopoietic cells or monocytes, and have been analysed in various immunological and non-immunological tissues. Both conventional DC (cDC) and plasmacytoid DC (pDC) have been characterized. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. These have been characterized in terms of the induction of DC maturation and pro-inflammatory, Th1-like or Th2-like cytokines secretion. Porcine pDC most effectively sense virus infections and are characterized by their capacity to produce large quantities of IFN-α and the pro-inflammatory cytokines TNF-α, IL-6 and IL-12. As such, the DC family as a whole is a powerful ally in the host battle against pathogen attack. Nevertheless, DC in particular tissue environments or under particular stimuli can down-regulate immune response development. This is not only important for preventing over-activation of the immune system and also for ensuring tolerance against self or “friendly” substances including food components, but may also be used as a mechanism of pathogens to evade immune responses.


title: Impact of severe acute respiratory syndrome on the status of lung cancer chemotherapy patients and a correlation of the signs and symptoms

text: Abstract Our aim was to describe the impact of severe acute respiratory syndrome (SARS) on the status and chemotherapy of non-small-cell lung cancer (NSCLC) patients who had entered clinical trials, and to review how to differentiate the signs and symptoms of SARS from lung cancer and its treatment-related toxicities. A prospective case series involving 79 NSCLC patients who were enrolled in clinical trials undergoing chemotherapy at Taipei Veterans General Hospital, between April 1 and July 15, 2003, was studied. Whether or not there existed a delay, omission, or refusal of scheduled chemotherapy, was recorded. Whether or not our patients had been suspected of or treated as having SARS, was recorded. The patients filled out questionnaires regarding lung cancer treatment and the risk of getting SARS from the hospital. Among these patients, five were placed in an isolation unit to rule out SARS infection during this period of time, and no patient was documented to have suffered from a SARS infection after examinations. Of 373 scheduled chemotherapy injections in 79 patients, a delay in treatment occurred only 10 times. Three patients refused further chemotherapy because of a fear of getting SARS if they visited the hospital. Fifty-eight patients responded to our questionnaires. Thirty-seven patients (63.8%) were afraid of visiting hospital during this SARS infection period. Twenty-one patients (36.2%) felt that a SARS infection was more severe and fatal than their lung cancer. In conclusion, SARS is a new disease entity that is highly contagious. Its clinical manifestations overlap with the signs and symptoms of lung cancer. Thus, a clear differentiation between the two conditions is needed, especially for those patients who are under active anti-cancer treatment.


title: An outbreak of acute respiratory disease caused by a virus associated RNA II gene mutation strain of human adenovirus 7 in China, 2015

text: Human adenovirus 7 (HAdV-7) strains are a major cause of acute respiratory disease (ARD) among adults and children, associated with fatal pneumonia. An ARD outbreak caused by HAdV-7 that involved 739 college students was reported in this article. To better understand the underlying cause of this large-scale epidemic, virus strains were isolated from infected patients and sequence variations of the whole genome sequence were detected. Evolutionary trees and alignment results indicated that the major capsid protein genes hexon and fibre were strongly conserved among serotype 7 strains in China at that time. Instead, the HAdV-7 strains presented three thymine deletions in the virus associated RNA (VA RNA) II terminal region. We also found that the mutation might lead to increased mRNA expression of an adjacent gene, L1 52/55K, and thus promoted faster growth. These findings suggest that sequence variation of VA RNA II gene was a potential cause of such a severe HAdV-7 infection and this gene should be a new-emerging factor to be monitored for better understanding of HAdV-7 infection.


title: Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication

text: BACKGROUND: Infectious bronchitis virus (IBV) is a pathogenic chicken coronavirus. Currently, vaccination against IBV is only partially protective; therefore, better preventions and treatments are needed. Plants produce antimicrobial secondary compounds, which may be a source for novel anti-viral drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses. RESULTS: Dose–response cytotoxicity curves on Vero cells using trypan blue staining determined the highest non-cytotoxic concentrations of each plant extract. To screen for IBV inhibition, cells and virus were pretreated with extracts, followed by infection in the presence of extract. Viral cytopathic effect was assessed visually following an additional 24 h incubation with extract. Cells and supernatants were harvested separately and virus titers were quantified by plaque assay. Variations of this screening protocol determined the effects of a number of shortened S. nigra extract treatments. Finally, S. nigra extract-treated virions were visualized by transmission electron microscopy with negative staining. Virus titers from infected cells treated with R. rosea and N. sativa extracts were not substantially different from infected cells treated with solvent alone. However, treatment with S. nigra extracts reduced virus titers by four orders of magnitude at a multiplicity of infection (MOI) of 1 in a dose-responsive manner. Infection at a low MOI reduced viral titers by six orders of magnitude and pretreatment of virus was necessary, but not sufficient, for full virus inhibition. Electron microscopy of virions treated with S. nigra extract showed compromised envelopes and the presence of membrane vesicles, which suggested a mechanism of action. CONCLUSIONS: These results demonstrate that S. nigra extract can inhibit IBV at an early point in infection, probably by rendering the virus non-infectious. They also suggest that future studies using S. nigra extract to treat or prevent IBV or other coronaviruses are warranted.


title: Systemic Capillary Leak Syndrome secondary to Covid-19

text: Abstract Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute COVID-19 infection who presented with hemoconcentration, shock and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.


title: Les techniques de séquençage de l’ADN : une révolution en marche. Première partie

text: Summary DNA sequencing is an essential tool in molecular biology and applied biosciences. Described in the late 1970s, this method had enormously increased the possibilities of genetic research. DNA sequencing is now routinely used in molecular biology laboratories. This technology has allowed sequencing of various and important genomes as the human one. Numerous innovations to improve DNA sequencing have been realized and new technologies have been described. The main objective of this article made up of two parts is to present the actual sequencing methodologies and the main evolutions in progress in this field. Individual human sequencing is not so far. In addition to ethical questions that will rise, other questions need to be considered. For example, how will we interpret the many genetic variants in regard to predisposition to disease and to phenotype ? Many studies in progress will answer these questions. In any case, a revolution is in motion. Résumé Le séquençage d’ADN est devenu un outil essentiel en biologie moléculaire tant en médecine que dans de nombreuses autres disciplines des sciences de la vie. Le séquençage a été décrit il y a environ 30 ans et n’a cessé d’évoluer depuis cette période. Cette méthode est devenue une technique courante dans les laboratoires de biologie moléculaire. Les connaissances acquises grâce à cette méthode et la possibilité de séquencer des génomes de grande taille, tel que le génome humain, ont amené les chercheurs à développer des techniques de séquençage de plus en plus sophistiquées. Cet article, composé de deux parties, présente les techniques actuellement utilisées pour séquencer l’ADN, qu’il soit humain ou d’autre origine, et les méthodes de séquençage en développement. Ces dernières constituent un réel bouleversement. Le séquençage à l’échelle individuelle n’est plus loin. En dehors des problèmes éthiques qu’elle soulève, cette révolution pose de nouvelles questions, par exemple : comment interpréterons-nous les nombreuses variations génétiques observées chez un individu, quelles en seront les conséquences sur ses prédispositions génétiques aux maladies et autres risques, quels en seront les retentissements sur le phénotype ? De nombreuses études en cours cherchent les réponses. Dans tous les cas, la révolution est en marche.


title: Differentially expressed non-coding RNAs induced by transmissible gastroenteritis virus potentially regulate inflammation and NF-κB pathway in porcine intestinal epithelial cell line

text: BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can activate NF-κB pathway in porcine intestinal epithelial cells and result in severe inflammation. Non-coding RNAs (ncRNAs) are not translated into proteins and play an important role in many biological and pathological processes such as inflammation, viral infection, and mitochondrial damage. However, whether ncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of mRNAs, miRNAs, and circRNAs in Mock- and TGEV-infected intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 523 mRNAs, 65 microRNAs (miRNAs), and 123 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed differentially expressed mRNAs were linked to inflammation-related pathways, including NF-κB, Toll-like receptor, NOD-like receptor, Jak-STAT, TNF, and RIG-I-like receptor pathways. The interactions among mRNA, miRNA, and circRNA were analyzed. The data showed that ssc_circ_009380 and miR-22 might have interaction relationship. Dual-luciferase reporter assay confirmed that miR-22 directly bound to ssc_circ_009380. We also observed that overexpression of miR-22 led to a reduction of p-IκB-α and accumulation of p65 in nucleus in TGEV-infected IPEC-J2 cells. In contrast, inhibition of miR-22 had the opposite effects. Moreover, silencing of ssc_circ_009380 inhibited accumulation of p65 in nucleus and phosphorylation of IκB-α. CONCLUSIONS: The data revealed that differentially expressed mRNAs and ncRNAs were primarily enriched in inflammation-related pathways and ssc_circ_009380 promoted activation of NF-κB pathway by binding miR-22 during TGEV-induced inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5128-5) contains supplementary material, which is available to authorized users.


Is MERS another SARS?


Vaping during the COVID‐19 pandemic: NOT GOOD!!


title: Development and evaluation of a rapid nucleic acid amplification method to detect influenza A and B viruses in human respiratory specimens

text: Abstract Isothermal nucleic acid amplification methods can potentially shorten the amount of time required to diagnose influenza. We developed and evaluated a novel isothermal nucleic acid amplification method, RT-SIBA to rapidly detect and differentiate between influenza A and B viruses in a single reaction tube. The performance of the RT-SIBA Influenza assay was compared with two established RT-PCR methods. The sensitivities of the RT-SIBA, RealStar RT-PCR, and CDC RT-PCR assays for the detection of influenza A and B viruses in the clinical specimens were 98.8%, 100%, and 89.3%, respectively. All three assays demonstrated a specificity of 100%. The average time to positive result was significantly shorter with the RT-SIBA Influenza assay (<20 min) than with the two RT-PCR assays (>90 min). The method can be run using battery-operated, portable devices with a small footprint and therefore has potential applications in both laboratory and near-patient settings.


title: Purification and characterization of HIV–human protein complexes

text: Abstract To fully understand how pathogens infect their host and hijack key biological processes, systematic mapping of intra-pathogenic and pathogen–host protein–protein interactions (PPIs) is crucial. Due to the relatively small size of viral genomes (usually around 10–100 proteins), generation of comprehensive host–virus PPI maps using different experimental platforms, including affinity tag purification-mass spectrometry (AP-MS) and yeast two-hybrid (Y2H) approaches, can be achieved. Global maps such as these provide unbiased insight into the molecular mechanisms of viral entry, replication and assembly. However, to date, only two-hybrid methodology has been used in a systematic fashion to characterize viral–host protein–protein interactions, although a deluge of data exists in databases that manually curate from the literature individual host–pathogen PPIs. We will summarize this work and also describe an AP-MS platform that can be used to characterize viral-human protein complexes and discuss its application for the HIV genome.


title: Antimicrobial therapy of community-acquired pneumonia

text: Community-acquired pneumonia (CAP) is a common disorder that is potentially life-threatening, especially in older adults and patients with comorbid disease. Despite substantial progress in therapeutic options, CAP remains a primary cause of death from infectious disease in the United States. The mainstay of treatment for most patients is appropriate antimicrobial therapy This article reviews the principles for initial antimicrobial therapy, highlights some of the differences in approaches to antimicrobial drug selection in selected guidelines, and includes new recommendations for empiric and pathogen-directed therapy of CAP.


title: Proof by synthesis of Tobacco mosaic virus

text: BACKGROUND: Synthetic biology is a discipline that includes making life forms artificially from chemicals. Here, a DNA molecule was enzymatically synthesized in vitro from DNA templates made from oligonucleotides representing the text of the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious DNA molecule of that seminal reference sequence exists, so the goal was to synthesize it and then build viral chimeras. RESULTS: RNA was transcribed from synthetic DNA and encapsidated with capsid protein in vitro to make synthetic virions. Plants inoculated with the virions did not develop symptoms. When two nucleotide mutations present in the original sequence, but not present in most other TMV sequences in GenBank, were altered to reflect the consensus, the derivative synthetic virions produced classic TMV symptoms. Chimeras were then made by exchanging TMV capsid protein DNA with Tomato mosaic virus (ToMV) and Barley stripe mosaic virus (BSMV) capsid protein DNA. Virus expressing ToMV capsid protein exhibited altered, ToMV-like symptoms in Nicotiana sylvestris. A hybrid ORF6 protein unknown to nature, created by substituting the capsid protein genes in the virus, was found to be a major symptom determinant in Nicotiana benthamiana. Virus expressing BSMV capsid protein did not have an extended host range to barley, but did produce novel symptoms in N. benthamiana. CONCLUSIONS: This first report of the chemical synthesis and artificial assembly of a plant virus corrects a long-standing error in the TMV reference genome sequence and reveals that unnatural hybrid virus proteins can alter symptoms unexpectedly.


title: Religion and culture: Potential undercurrents influencing hand hygiene promotion in health care

text: BACKGROUND: Health care–associated infections affect hundreds of millions of patients worldwide each year. The World Health Organization's (WHO) First Global Patient Safety Challenge, “Clean Care is Safer Care,” is tackling this major patient safety problem, with the promotion of hand hygiene in health care as the project's cornerstone. WHO Guidelines on Hand Hygiene in Healthcare have been prepared by a large group of international experts and are currently in a pilot-test phase to assess feasibility and acceptability in different health care settings worldwide. METHODS: An extensive literature search was conducted and experts and religious authorities were consulted to investigate religiocultural factors that may potentially influence hand hygiene promotion, offer possible solutions, and suggest areas for future research. RESULTS: Religious faith and culture can strongly influence hand hygiene behavior in health care workers and potentially affect compliance with best practices. Interesting data were retrieved on specific indications for hand cleansing according to the 7 main religions worldwide, interpretation of hand gestures, the concept of “visibly dirty” hands, and the use of alcohol-based hand rubs and prohibition of alcohol use by some religions. CONCLUSIONS: The impact of religious faith and cultural specificities must be taken into consideration when implementing a multimodal strategy to promote hand hygiene on a global scale.


title: Parkinson's disease: a dual‐hit hypothesis

text: Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non‐motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose – hence the term ‘dual‐hit’.


title: COVID‐19: THE ‘INVISIBLE ENEMY’ AND CONTINGENT RACISM: Reflections of an Italian anthropologist conducting fieldwork in Greece

text: In this article, the author provides a narrative of her experience as an Italian undertaking fieldwork in Greece while the epidemic was in full swing. She reflects on representations of ‘the invisible enemy’: an empty category, she claims, which has been contingently filled and morally loaded, resting on pre‐existing categories, such as stereotypical representations of nations. The invisibility of ‘the enemy’ has in fact been rendered visible through what she refers to as contingent racism; this includes the ubiquitous and hence powerful use of irony and satire at the expense of China and Italy, but also expands to the use of banal and convenient tropes of accusation and derision among European Union member states, bringing back to the fore the North‐South divide and its power imbalances. The author suggests that the Covid‐19 crisis has ultimately provoked a veritable epidemic of contingent racism on multiple levels by stirring stereotypes and cultural prejudices which are rooted in time and rapidly renewed; its effect is all but contingent, and likely to accompany us far beyond the Covid‐19 crisis itself.