title: NK cells: A double edge sword against SARS-CoV-2

text: Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).


title: Virus–host interaction in feline immunodeficiency virus (FIV) infection

text: Abstract Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus–host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections.


title: Glycosylation and oligomerization of the spike protein of marburg virus

text: Abstract The oligosaccharide side chains of the glycoprotein of Marburg virus (MW 170,000) have been analyzed by determining their sensitivity to enzymatic degradation and their reactivity with lectins. It was found that they consist of N- and O-glycans. Studies employing chemical cross-linking showed that the glycoprotein is present as a homotrimer in the viral envelope.


title: Surveillance strategy for early detection of unusual infectious disease events

text: New pathogens continue to emerge, and the increased connectedness of populations across the globe through international travel and trade favors rapid dispersal of any new disease. The ability to respond to such events has increased but the question is what ‘preparedness’ means at the level of the clinician. Clinicians deal with patients with unexplained illness on a daily basis, and even with syndromes highly indicative of infectious diseases, the cause of illness is often not detected, unless extensive and costly diagnostic work-ups are done. This review discusses innovations in diagnostics and surveillance aimed at early detection of unusual disease. Risk based approaches are promising, but optimal preparedness planning requires multidisciplinary partnerships across domains, and a global translational research agenda to develop tools, systems, and evidence for interventions.


title: Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins

text: The crystal structure of the reovirus attachment protein, σ1, reveals a fibre‐like structure that is remarkably similar to that of the adenovirus attachment protein, fibre. Both proteins are trimers with head‐and‐tail morphology. They share unique domain structures and functional properties including defined regions of flexibility within the tail and an unusual symmetry mismatch with the pentameric viral capsid protein into which they are inserted. Moreover, the receptors for reoviruses and adenoviruses, junctional adhesion molecule 1 and coxsackievirus and adenovirus receptor, respectively, also share key structural and functional properties. Although reoviruses and adenoviruses belong to different virus families and have few properties in common, the observed similarities between σ1 and fibre point to a conserved mechanism of attachment and an ancient evolutionary relationship. Copyright © 2003 John Wiley & Sons, Ltd.


title: Early Cytokine mRNA Expression Profiles Predict Morbillivirus Disease Outcome in Ferrets

text: Severe immunosuppression is a hallmark of Morbillivirus infections. To study the underlying mechanisms, we have developed a ferret model of canine distemper virus infection. The model reproduces all clinical signs of measles, but the lack of ferret-specific reagents has limited the characterization of the cellular immune response. Towards this, we cloned ferret cytokines and established semi-quantitative real-time PCR assays. To demonstrate the utility of these assays we compared the cytokine profiles elicited by lethal and non-lethal strains during the prodromal phase. We observed a general lack of cytokine induction in animals that later succumbed to the disease, whereas survivors mounted a robust and sustained response. The newly developed cytokine assays strengthen and expand the ferret model not only for Morbillivirus pathogenesis studies but also for several other human respiratory viruses including influenza and SARS.


title: Aerosol emission and superemission during human speech increase with voice loudness

text: Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm(3)) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as “speech superemitters,” consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.


title: Role of Telecom Network to Manage COVID-19 in India: Aarogya Setu

text: Concerted Research, Development and Innovation have enabled telecom and Internet reach most of the 1.3 billion people in India at a price-point that they can afford. This telecom network is being used for a whole lot of application today providing a large variety of services like education, health care, financial inclusion and disaster management. In almost all crisis situation like that created by coronavirus, one finds that telecom network can be leveraged to offer help to the needy, administration and coordinators to better manage the disaster. Aarogya Setu for smartphones and Aarogya Setu for feature phones are two such efforts, which are potentially going to help in this difficult situation.


title: In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis

text: BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician. We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 10(4) colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.


title: Potential Triggers of MS

text: MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. The primary cause of this CNS disease remains elusive. Here we will address our current understanding of the role of viruses as potential environmental triggers for MS. Virus infections can act peripherally (outside the CNS) or within the CNS. The association of viral infections with demyelinating disease, in both animals and humans, will be discussed, as will the potential contributions of peripheral infection with Torque Teno virus, infection outside of and/or within the CNS with Epstein-Barr virus and infection within the CNS with Human Herpesvirus 6 to MS. An experimental animal model, Theiler’s murine encephalomyelitis virus infection of susceptible strains of mice is an example of viral infections of the CNS as a prerequisite for demyelination. Finally, the proposition that multiple virus infections, which first prime the immune system and then trigger the disease, as a model where infections outside of the CNS lead to inflammatory changes within the CNS, are required for the development of a MS-like disease is explored.


title: Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

text: Abstract Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CLpro of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R1 or R4 destabilizes the oxyanion hole in the 3CLpro. Interestingly, 3f, 3g and 3m could inhibit both NA and 3CLpro and serve as a starting point to develop broad-spectrum antiviral agents.


title: Dengue research: a bibliometric analysis of worldwide and Arab publications during 1872–2015

text: BACKGROUND: Dengue is an important emerging and re-emerging arboviral infection globally as a rapidly growing and widespread public health problem, with transmission occurring in more than 128 countries in Asia, Americas, southeast Africa, western Pacific, and eastern Mediterranean regions. Therefore, the aim of this study was to characterize and quantify the scientific output of dengue research in Arab countries relative to that worldwide by using a bibliometric analysis. METHODS: The standardized search approach based on the use of the the keyword “dengue” in the title, abstract, and keyword field was used to get research output related to dengue at a global level. All data related to dengue were collected from the past to December 31, 2015. RESULTS: A total of 19,581 dengue-related documents identified in the Scopus database. The results show that the study of dengue exhibits an overall upward trend from 1872 to 2015 with peak publications in 2014. The leading countries in dengue research were the USA (4,709; 24.05 %), India (1,942; 9.92 %), Brazil (1,530; 7.81 %), Thailand (1,260; 6.43 %), the UK (1,129; 5.77 %), and France (1,087; 5.55 %). Only 226 (1.16 % of the overall global research effort in the dengue field) articles were published from the Arab region. The total number of citations for all publications was 352,710, with an average of 18.0 citations per publication. Furthermore, the h-index for all extracted data related to dengue research was 186. Kingdom of Saudi Arabia (KSA) was the most productive country in Arab region with 102 documents representing 45.1 %. Furthermore, the h-index for all extracted data related to dengue research was 27. The USA was Arab’s most main cooperative partner (46, 20.4 %), followed by India (36, 15.9 %). CONCLUSIONS: The amount of literature related to dengue research has considerably increased over the last decade. This bibliometric analysis has demonstrated the leading role that the USA, India, Brazil, Thailand, the UK, and France play in dengue research. The Arab world produced fewer publications related to dengue with lower quality than other world countries.


title: Reaction Cycles of Halogen Species in the Immune Defense: Implications for Human Health and Diseases and the Pathology and Treatment of COVID-19

text: There is no vaccine or specific antiviral treatment for COVID-19. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. It is therefore challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.


COVID-19 - Journal de Bord – 11/04/2020: Masque chirurgical et autres protections


title: Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma

text: Background Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. Objective To study whether RSV or RV types are differentially associated with the future use of asthma control medication. Methods Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. Results A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03). Conclusions Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.


title: Generation and characterisation of monoclonal antibodies against influenza virus A, subtype H5N1

text: Abstract The emergence of highly pathogenic avian influenza A virus (HPAIV) subtype H5N1 in 1997 has since resulted in large outbreaks in poultry and in transmission from poultry to humans, mostly in southeast Asia, but also in several European countries. Effective diagnosis and control measures are essential for the management of HPAIV infections. To develop a rapid diagnostic test, a panel of murine monoclonal antibodies (mAbs) against influenza virus A subtype H5 was generated. Eleven mAbs were produced and characterised according to their reactivity by indirect and sandwich ELISA and western blotting against different H5 subtypes representing past and viruses currently circulating. Ten out of 11 mAbs reacted strongly with the haemagglutinin (HA) protein of H5 viruses, whereas one mAb reacted with the M1 protein. Targeted HA protein epitopes seemed to be conformational. One hybridoma clone binds to a linear epitope of the M1 protein. One specific mAb reacts with HPAIV H5 in the immunofluorescence test, and two antibodies neutralised H5 viruses. On the basis of the results, the set of seven mAbs is appropriate for developing diagnostic tests. With the generated mAbs, a sandwich ELISA was developed recognising all H5N1 strains tested but no other influenza viruses. With this ELISA, as little as 0.005 HA units or 0.1ng/ml H5N1 was detected, surpassing other ELISA tests. The novel reagents have the potential to improve significantly available rapid antigen detection systems.


title: The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

text: Abstract The physiological and pharmacological role of nucleic acids structures folded into the non canonical G-quadruplex conformation have recently emerged. Their activities are targeted at vital cellular processes including telomere maintenance, regulation of transcription and processing of the pre-messenger or telomeric RNA. In addition, severe conditions like cancer, fragile X syndrome, Bloom syndrome, Werner syndrome and Fanconi anemia J are related to genomic defects that involve G-quadruplex forming sequences. In this connection G-quadruplex recognition and processing by nucleic acid directed proteins and enzymes represents a key event to activate or deactivate physiological or pathological pathways. In this review we examine protein-G-quadruplex recognition in physiologically significant conditions and discuss how to possibly exploit the interactions’ selectivity for targeted therapeutic intervention.


title: Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan

text: BACKGROUND: Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. METHODS: Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. RESULTS: The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. CONCLUSIONS: The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.


title: Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

text: BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can cause acute inflammation. Long noncoding RNAs (lncRNAs) play important roles in a number of biological process including inflammation response. However, whether lncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells (IPECs) is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of lncRNAs in Mock and TGEV-infected porcine intestinal epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 106 lncRNAs were differentially expressed. Many differentially expressed lncRNAs act as elements to competitively attach microRNAs (miRNAs) which target to messenger RNA (mRNAs) to mediate expression of genes that related to toll-like receptors (TLRs), NOD-like receptors (NLRs), tumor necrosis factor (TNF), and RIG-I-like receptors (RLRs) pathways. Functional analysis of the binding proteins and the up/down-stream genes of the differentially expressed lncRNAs revealed that lncRNAs were principally related to inflammatory response. Meanwhile, we found that the differentially expressed lncRNA TCONS_00058367 might lead to a reduction of phosphorylation of transcription factor p65 (p-p65) in TGEV-infected IPEC-J2 cells by negatively regulating its antisense gene promyelocytic leukemia (PML). CONCLUSIONS: The data showed that differentially expressed lncRNAs might be involved in inflammatory response induced by TGEV through acting as miRNA sponges, regulating their up/down-stream genes, or directly binding proteins.


Isolation of a Coronavirus from Urinary Tract Tumours of Endemic Balkan Nephropathy Patients


title: Reverse Transcription Loop-Mediated Isothermal Amplification for Rapid Detection of Transmissible Gastroenteritis Virus

text: Transmissible gastroenteritis virus (TGEV) is the causative agent of porcine transmissible gastroenteritis, and sensitive detection methods are required for preventing the disease. In this article, reverse transcription-loop-mediated isothermal amplification (RT-LAMP) was developed to detect TGEV. Three pairs of primers targeting the nucleocapsid (N) gene of TGEV were synthesized and used in the RT-LAMP. The optimization, sensitivity, and specificity of the RT-LAMP were evaluated. Our results showed that the RT-LAMP amplified the N gene with high specificity, efficiency, and rapidity at isothermal condition. The optimal reaction condition was achieved at 60°C for 30 min. The RT-LAMP assay was more sensitive than gel-based RT-PCR and PCR. It had a higher sensitivity than enzyme-linked immunosorbent assay (ELISA) using the equal virus templates. In addition, the established RT-LAMP differentiated TGEV from porcine epidemic diarrhea virus, porcine rotavirus, porcine pseudorabies virus, porcine reproductive and respiratory syndrome virus, and avian infectious bronchitis virus. The approach is suitable for detecting TGEV for field diagnostics or in less-equipped laboratories due to its convenience and simplicity.


Association of Viral and Bacterial Respiratory Infection with Exacerbations of Wheezing in Young Asthmatic Children


title: Induction of Cyclooxygenase-2 Expression by Hepatitis B Virus Depends on Demethylation-associated Recruitment of Transcription Factors to the Promoter

text: BACKGROUND: The hepatitis B virus (HBV) is a major etiological factor of inflammation and damage to the liver resulting in hepatocellular carcinoma. Transcription factors play important roles in the disordered gene expression and liver injury caused by HBV. However, the molecular mechanisms behind this observation have not been defined. RESULTS: In this study, we observed that circulating prostaglandin (PGE) 2 synthesis was increased in patients with chronic hepatitis B infection, and detected elevated cyclooxygenase (COX)-2 expression in HBV- and HBx-expressing liver cells. Likewise, the association of HBx with C/EBPβ contributed to the induction of COX-2. The COX-2 promoter was hypomethylated in HBV-positive cells, and specific demethylation of CpG dinucleotides within each of the two NF-AT sites in the COX-2 promoter resulted in the increased binding affinity of NF-AT to the cognate sites in the promoter, followed by increased COX-2 expression and PGE2 accumulation. The DNA methylatransferase DNMT3B played a key role in the methylation of the COX-2 promoter, and its decreased binding to the promoter was responsible for the regional demethylation of CpG sites, and for the increased binding of transcription factors in HBV-positive cells. CONCLUSION: Our results indicate that upregulation of COX-2 by HBV and HBx is mediated by both demethylation events and recruitment of multiple transcription factors binding to the promoter.


title: AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses

text: Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Therefore, we have developed AVPdb, available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated resource of experimentally verified AVPs targeting over 60 medically important viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we have separately provided HIV inhibiting peptides in ‘HIPdb’. AVPdb contains detailed information of 2683 peptides, including 624 modified peptides experimentally tested for antiviral activity. In modified peptides a chemical moiety is attached for increasing their efficacy and stability. Detailed information include: peptide sequence, length, source, virus targeted, virus family, cell line used, efficacy (qualitative/quantitative), target step/protein, assay used in determining the efficacy and PubMed reference. The database also furnishes physicochemical properties and predicted structure for each peptide. We have provided user-friendly browsing and search facility along with other analysis tools to help the users. Entering of many synthetic peptide-based drugs in various stages of clinical trials reiterate the importance for the AVP resources. AVPdb is anticipated to cater to the needs of scientific community working for the development of antiviral therapeutics.


title: Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets

text: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine causing high mortality rates in piglets. PEDV outbreaks have occurred continuously in most swine-producing Asian countries and have recently emerged in the United States, leading to large economic losses for both the Asian and US pig industries. The spike (S) protein of PEDV consists of the S1 and S2 domains, responsible for virus binding and fusion, respectively. The involvement of the S1 domain in specific high-affinity interactions with the cellular receptor and induction of neutralizing antibodies in the natural host makes it a logical target for the development of effective vaccines and therapeutics against PEDV. Passive immunization by oral administration of egg yolk antibodies (IgY) obtained from immunized chickens provides an alternative source of specific antibodies for the prevention and treatment of PEDV in newborn piglets. In this study, we produced an IgY against the PEDV S1 protein and investigated its immunoprophylactic effect in neonatal piglets. A codon-optimized PEDV S1 gene consisting of amino acid residues 25–749 was synthesized and used to establish a stable porcine cell line constitutively expressing a recombinant PEDV S1 protein containing the chicken immunoglobulin Fc fragment at its C-terminus. The purified recombinant S1 protein was found to mediate potent immune responses in immunized hens. We next tested the ability of oral passive immunization with anti-PEDV S1 IgY to protect piglets against PEDV. Specific chicken IgY against the S1 protein was orally administered to neonatal piglets, and their responses subsequent to a virulent PEDV challenge were monitored. The results showed that oral administration of anti-PEDV S1 IgY efficiently protects neonatal piglets against PEDV, suggesting its potential as a prophylactic or therapeutic agent against acute PEDV infection.


title: Transcutaneous Administration of Dengue Vaccines

text: In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications.


title: The impact of biosensing in a pandemic outbreak: COVID-19

text: Abstract COVID-19 pandemic outbreak is the most astounding scene ever experienced in the XXI century. In this opinionated review, we underscore the crucial role of biosensing to handle with such situations. As a matter of fact, testing accelerates life-saving decisions on treatment and isolation of COVID-19 patients in an early stage, and thereby, decelerating or even preventing the spread of such emerging infectious diseases. Meanwhile, it is also proven that a timely and broad application of testing leads to lower mortality rates in countries like Germany or South Korea. Besides, biosensors are also powerful tools for effective assessment of clinical progress and to provide alertness on severity or critical trends of infection. In view hereof, we critically discuss the state-of-the-art biosensing devices for COVID-19 testing. We spot the urgent needs and highlight innovative diagnostic approaches for targeting various COVID-19 related biomarkers. Finally, we outline our recommendations on biosensors and biosensing-related issues towards pandemic outbreaks.


title: Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts

text: Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.


title: Early Onset Noninfectious Pulmonary Syndromes after Hematopoietic Cell Transplantation

text: This article reviews the noninfectious pulmonary syndromes that cause morbidity and mortality early after hematopoietic cell transplantation with an emphasis on risk factors, clinical manifestations, treatment, and outcomes. The first section covers idiopathic pneumonia syndrome and its subtypes: peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, delayed pulmonary toxicity syndrome, and cryptogenic organizing pneumonia. The second section covers pulmonary toxicities of chemotherapies and immunosuppressive agents used in this setting. The final section covers less common syndromes, including pulmonary alveolar proteinosis, venous thromboembolism, pulmonary cytolytic thrombi, pulmonary venoocclusive disease, and transfusion-related acute lung injury.


title: A multivariate CAR model for mismatched lattices

text: Abstract In this paper, we develop a multivariate Gaussian conditional autoregressive model for use on mismatched lattices. Most current multivariate CAR models are designed for each multivariate outcome to utilize the same lattice structure. In many applications, a change of basis will allow different lattices to be utilized, but this is not always the case, because a change of basis is not always desirable or even possible. Our multivariate CAR model allows each outcome to have a different neighborhood structure which can utilize different lattices for each structure. The model is applied in two real data analysis. The first is a Bayesian learning example in mapping the 2006 Iowa Mumps epidemic, which demonstrates the importance of utilizing multiple channels of infection flow in mapping infectious diseases. The second is a multivariate analysis of poverty levels and educational attainment in the American Community Survey.


title: Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2

text: We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.


Characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the COVID-19 outbreak


title: Trends in the utilization of computed tomography and cardiac catheterization among children with congenital heart disease

text: Background/Purpose Pediatric cardiac computed tomography (CT) is a noninvasive imaging modality used to clearly demonstrate the anatomical detail of congenital heart diseases. We investigated the impact of cardiac CT on the utilization of cardiac catheterization among children with congenital heart disease. Methods The study sample consisted of 2648 cardiac CT and 3814 cardiac catheterization from 1999 to 2009 for congenital heart diseases. Diagnoses were categorized into 11 disease groups. The numbers of examination, according to the different modalities, were compared using temporal trend analyses. The estimated effective radiation doses (mSv) of CT and catheterization were calculated and compared. Results The number of CT scans and interventional catheterizations had a slight annual increase of 1.2% and 2.7%, respectively, whereas that of diagnostic catheterization decreased by 6.2% per year. Disease groups fell into two categories according to utilization trend differences between CT and diagnostic catheterization. The increased use of CT reduces the need for diagnostic catheterization in patients with atrioventricular connection disorder, coronary arterial disorder, great vessel disorder, septal disorder, tetralogy of Fallot, and ventriculoarterial connection disorder. Clinicians choose either catheterization or CT, or both examinations, depending on clinical conditions, in patients with semilunar valvular disorder, heterotaxy, myocardial disorder, pericardial disorder, and pulmonary vein disorder. The radiation dose of CT was lower than that of diagnostic cardiac catheterization in all age groups. Conclusion The use of noninvasive CT in children with selected heart conditions might reduce the use of diagnostic cardiac catheterization. This may release time and facilities within the catheterization laboratory to meet the increasing demand for cardiac interventions.


title: Challenging loop—mediated isothermal amplification (LAMP) technique for molecular detection of Toxoplasma gondii

text: Abstract Objective To compare analytical sensitivity and specificity of a newly described DNA amplification technique, LAMP and nested PCR assay targeting the RE and B1 genes for the detection of Toxoplasma gondii (T. gondii) DNA. Methods The analytical sensitivity of LAMP and nested-PCR was obtained against10-fold serial dilutions of T. gondii DNA ranging from 1 ng to 0.01 fg. DNA samples of other parasites and human chromosomal DNA were used to determine the specificity of molecular assays. Results After testing LAMP and nested-PCR in duplicate, the detection limit of RE-LAMP, B1-LAMP, RE-nested PCR and B1-nested PCR assays was one fg, 100 fg, 1 pg and 10 pg of T. gondii DNA respectively. All the LAMP assays and nested PCRs were 100% specific. The RE-LAMP assay revealed the most sensitivity for the detection of T. gondii DNA. Conclusions The obtained results demonstrate that the LAMP technique has a greater sensitivity for detection of T. gondii. Furthermore, these findings indicate that primers based on the RE are more suitable than those based on the B1 gene. However, the B1-LAMP assay has potential as a diagnostic tool for detection of T. gondii.


title: Proteomics and disease: opportunities and challenges

text: Since the human genome was sequenced, there has been intense activity to understand the function of the 30 000 identified genes; attention has now turned to the products of genes — proteins. Proteomics is the large‐scale study of the structure and function of proteins; it includes the rapidly evolving field of disease proteomics, which aims to identify proteins involved in human disease and to understand how their expression, structure and function cause illness. Proteomics has identified proteins that offer promise as diagnostic or prognostic markers, or as therapeutic targets in a range of illnesses, including cancer, immune rejection after transplantation, and infectious diseases such as tuberculosis and malaria; it has the potential to allow patient‐tailored therapy. Some major challenges remain, both technical (eg, detecting “low‐abundance” proteins, and maintaining sample stability) and in data management (eg, correlating changes in proteins with disease processes).


COVID-19, adulto mayor y edadismo: errores que nunca han de volver a ocurrir


title: Advances in microfluidics in combating infectious diseases

text: Abstract One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed.


title: Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect

text: The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people(1). Current therapy relies upon a combination of pegylated interferon-α and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus(2,3). The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B(4). Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature08960) contains supplementary material, which is available to authorized users.


title: A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a)

text: The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.


title: American Society for Surgery of the Hand (ASSH) Presidential Address Themes, 1964-2018: Revisiting Our History as We Move Forward

text: Abstract The American Society for Surgery of the Hand (ASSH) was established in 1946. Since then, significant advances have been made in diagnosis and treatment of conditions affecting the upper extremity. However, there has been little documentation regarding how the largest and oldest society dedicated to hand surgery has evolved over time. Further, an understanding of the history of the ASSH and the specialty of hand surgery should be emphasized in resident and fellow education. The authors aim to provide a historical overview of the ASSH through the speeches of ASSH past presidents which sheds light on future directions and long-term goals. Presidential addresses from 1961 to 2018 (courtesy of ASSH Chase Library historical archives) were reviewed. The overall percentage of ASSH presidents by specialty was 67% orthopaedic, 25% plastic surgery, and 8% general surgery. The most common speech theme overall was “how to be a good hand surgeon” (31%). The most common speech themes were as follows by decade: 1960’s, “history and the current state of ASSH”; 1970’s and 80’s “assessments of how to be a good surgeon” and “goals for ASSH”; 1990’s, “healthcare and governmental regulation”; 2000’s, “how to be a better hand surgeon”; 2010’s “goals for ASSH”. In earlier years, there was more of a focus on education and technical skill development in the ASSH. Work-life balance, introduced in the 1990s, has become more of a focus in the past 20 years. Revisiting the history of the ASSH and its goals allows us to reflect on the progress made while recognizing what is important as we look into the future. Further, as we strive to make progress in the field of hand surgery during the current pandemic, valuable tools surface that will allow the specialty to strengthen its education, research, and patient care delivery in the future.


title: Current Smoking is Not Associated with COVID-19

text: Despite the main complications of SARS-CoV-2 infection regard lung involvement, the prevalence of current smoking in COVID-19 patients is very low even if one might have anticipated that opposite. Thus, the epidemiological data seem to question the role of coexisting active smoking as a risk factor for COVID-19 pneumonia.


title: The Role of Public Health Nursing in Emergency Preparedness and Response

text: Public health services are vital to homeland security and defense, and nurses make up the majority of public health care workers. This article identifies issues in preparing for bioterrorism and describes the role of public health nurses in bioterrorism preparedness.


title: Genetic characteristics of canine bocaviruses in Korean dogs

text: Abstract To survey for canine bocavirus (CBoV) infection, 83 Korean dogs showing several clinical signs were collected in different provinces from January 2013 to July 2014. Using polymerase chain reaction (PCR) and in situ hybridization, CBoVs were detected in intestine and/or lung samples of 8 dogs (9.6%). To reveal the genetic characteristics of CBoVs, partial or complete regions of CBoVs were sequenced. In phylogenetic trees, 8 CBoVs fell into three clusters. The CBoV strains 13D226-1, 13D250, and 14Q216 were closely related to the CBoV HK831F strain, and the CBoV 14D142 strain was related to the CBoV HK882F strain. Lastly, CBoV 13D003, 13D095, 14D193, and 14Q209 strains were related to CBoV Dis-023, Dis-040, and Dis-046 strains. Interestingly, no canine pathogens were found in dogs in which four CBoVs (13D003, 13D0095, 14D142, and 14D193 strains) were detected and three of them (13D003, 13D095, and 14D193 strains) had a unique deletion (18 nucleotides) in the VP2 gene. Further, the open reading frame 4 (ORF4) region was absent in these 4CBoVs, but found in the other strains, which indicates that the absence of the ORF4 region rather than a unique deletion may have an influence on the pathogenesis of CBoV in dogs.


title: Sustainable Model for Public Health Emergency Operations Centers for Global Settings

text: Capacity to receive, verify, analyze, assess, and investigate public health events is essential for epidemic intelligence. Public health Emergency Operations Centers (PHEOCs) can be epidemic intelligence hubs by 1) having the capacity to receive, analyze, and visualize multiple data streams, including surveillance and 2) maintaining a trained workforce that can analyze and interpret data from real-time emerging events. Such PHEOCs could be physically located within a ministry of health epidemiology, surveillance, or equivalent department rather than exist as a stand-alone space and serve as operational hubs during nonoutbreak times but in emergencies can scale up according to the traditional Incident Command System structure.


title: Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria

text: Studies of lactic acid bacteria (LAB) as delivery vehicles have focused mainly on the development of mucosal vaccines, with much effort being devoted to the generation of genetic tools for antigen expression in different bacterial locations. Subsequently, interleukins have been co-expressed with antigens in LAB to enhance the immune response that is raised against the antigen. LAB have also been used as a delivery system for a range of molecules that have different applications, including anti-infectives, therapies for allergic diseases and therapies for gastrointestinal diseases. Now that the first human trial with a Lactococcus strain that expresses recombinant interleukin-10 has been completed, we discuss what we have learnt, what we do not yet understand and what the future holds for therapy and prophylaxis with LAB.


title: Antibody Testing Against Canine Coronavirus by Immunoperoxidase Plaque Staining

text: The application of the immunoperoxidase (IP) plaque staining procedure (IP test) to the diagnosis of canine coronavirus (CCV) infection was investigated. The IP test did not react with sera from either 15 specific pathogen-free (SPF) dogs or 7 SPF dogs immunized with a multivalent vaccine, including canine parvovirus type 2, canine distemper virus, canine adenovirus type 2, and canine parainfluenza virus. To compare the IP test with the neutralizing test (NT), sera from 240 healthy dogs and from 3 experimentally CCV-infected dogs were examined. All 60 sera positive for NT antibody were positive for IP antibody, and all 180 sera negative for NT antibody were negative for IP antibody in the healthy dogs. The IP titres showed similar changes with time after CCV inoculation to those of the NT titres in the experimentally infected dogs. These findings indicate that the IP test specifically detected anti-CCV antibodies. When the IP test and NT were compared in dogs with diarrhoeic signs. 2.1% of 48 sera and 20.3% of 74 sera, which were all negative for NT antibody, were positive for IP antibody in the dogs of under one year of age and at least one year of age, respectively. The difference between the IP and NT titres (log(10) [reciprocal of IP titre] – log(10) [reciprocal of NT titre]) for the diarrhoeic dogs of under one year of age (2.350±0.931) was significantly larger than that for the healthy dogs (0.982±0.447) (p<0.0001), the NT titre being negative or very low, despite a high IP titre in many diarrhoeic dogs. Hence, the IP test is more able to detect anti-CCV antibodies, especially in dogs showing clinical signs. The IP-positivity rate was significantly higher in the diarrhoeic dogs of under one year of age (48.7%) than in the healthy dogs (25.0%) (χ(2) = 19.844, p<0.0001), suggesting that CCV may contribute to diarrhoea in many juvenile dogs.


title: Frequent Travelers and Rate of Spread of Epidemics

text: A small proportion of air travelers make disproportionately more journeys than the rest of travelers. They also tend to interact predominantly with other frequent travelers in hotels and airport lounges. This group has the potential to accelerate global spread of infectious respiratory diseases. Using an epidemiologic model, we simulated exportation of cases from severe acute respiratory syndrome–like and influenza-like epidemics in a population for which a small proportion travel more frequently than the rest. Our simulations show that frequent travelers accelerate international spread of epidemics only if they are infected early in an outbreak and the outbreak does not expand rapidly. If the epidemic growth rate is high, as is likely for pandemic influenza, heterogeneities in travel are frequently overwhelmed by the large number of infected persons in the majority population and the resulting high probability that some of these persons will take an international flight.


title: Identification of conserved lentiviral sequences as landmarks of genomic flexibility

text: Abstract Considering that recombinations produce quasispecies in lentivirus spreading, we identified and localized highly conserved sequences that may play an important role in viral ontology. Comparison of entire genomes, including 237 human, simian and non-primate mammal lentiviruses and 103 negative control viruses, led to identify 28 Conserved Lentiviral Sequences (CLSs). They were located mainly in the structural genes forming hot spots particularly in the gag and pol genes and to a lesser extent in LTRs and regulatory genes. The CLS pattern was the same throughout the different HIV-1 subtypes, except for some HIV-1-O strains. Only CLS 3 and 4 were detected in both negative control HTLV-1 oncornaviruses and D-particle-forming simian viruses, which are not immunodeficiency inducers and display a genetic stability. CLSs divided the virus genomes into domains allowing us to distinguish sequence families leading to the notion of ‘species self’ besides that of ‘lentiviral self’. Most of acutely localized CLSs in HIV-1s (82%) corresponded to wide recombination segments being currently reported. To cite this article: M.L.J. Moncany et al., C. R. Biologies 329 (2006).


title: Gene expression profiles in rat intestine identify pathways for 1,25-dihydroxyvitamin D3 stimulated calcium absorption and clarify its immunomodulatory properties

text: Abstract Microarray technology has been used to discover 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) induced gene expression changes in rat small intestine in vivo. Here, we report gene expression changes related to intestinal absorption or transport, the immune system and angiogenesis in response to 1,25-(OH)2D3. Vitamin D deficient rats were intrajugularly given vehicle or vehicle containing 730ng of 1,25-(OH)2D3/kg of body weight. Intestinal mRNA was harvested from duodenal mucosa at 15min, 1, 3, and 6h post-injection and studied by Affymetrix microarrays. Genes significantly affected by 1,25-(OH)2D3 were confirmed by quantitative RT-PCR with remarkable agreement. The most strongly affected gene in intestine was CYP24 with 97-fold increase at 6h post-1,25-(OH)2D3 treatment. Intestinal calcium absorption genes: TRPV5, TRPV6, calbindin D9k, and Ca2+ dependent ATPase all were up-regulated in response to 1,25-(OH)2D3, supporting the currently accepted mechanism of 1,25-(OH)2D3 induced transcellular calcium transport. However, a 1,25-(OH)2D3 suppression of several intra-/intercellular matrix modeling proteins such as sodium/potassium ATPase, claudin 3, aquaporin 8, cadherin 17, and RhoA suggests a vitamin D regulation of tight junction permeability and paracellular calcium transport. Several other genes related to the immune system and angiogenesis whose expression was changed in response to 1,25-(OH)2D3 provided evidence for an immunomodulatory and anti-angiogenic role of 1,25-(OH)2D3.


title: A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury

text: INTRODUCTION: Clinical observations and animal models provide evidence that the development of acute lung injury (ALI), a phenomenon of acute diffuse lung inflammation in critically ill patients, is influenced by genetic factors. Association studies are the main tool for exploring common genetic variations underlying ALI susceptibility and/or outcome. We aimed to assess the quality of positive genetic association studies with ALI susceptibility and/or outcome in adults in order to highlight their consistency and major limitations. METHODS: We conducted a broad PubMed literature search from 1996 to June 2008 for original articles in English supporting a positive association (P ≤ 0.05) of genetic variants contributing to all-cause ALI susceptibility and/or outcome. Studies were evaluated based on current recommendations using a 10-point quality scoring system derived from 14 criteria, and the gene was considered as the unit of replication. Genes were also categorized according to biological processes using the Gene Ontology. RESULTS: Our search identified a total of 29 studies reporting positive findings for 16 genes involved mainly in the response to external stimulus and cell signal transduction. The genes encoding for interleukin-6, mannose-binding lectin, surfactant protein B, and angiotensin-converting enzyme were the most replicated across the studies. On average, the studies had an intermediate quality score (median of 4.62 and interquartile range of 3.33 to 6.15). CONCLUSIONS: Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI.


title: Silent hypoxia: A harbinger of clinical deterioration in patients with COVID-19

text: Patients infected with the SARS-CoV-2 virus can present with a wide variety of symptoms including being entirely asymptomatic. Despite having no or minimal symptoms, some patients may have markedly reduced pulse oximetry readings. This has been referred to as “silent” or “apathetic” hypoxia (Ottestad et al., 2020 [1]). We present a case of a 72-year-old male with COVID-19 syndrome who presented to the emergency department with minimal symptoms but low peripheral oxygen saturation readings. The patient deteriorated over the following days and eventually died as a result of overwhelming multi-organ system failure. This case highlights the utility of peripheral oxygen measurements in the evaluation of patients with SARS-CoV-2 infection. Self-monitoring of pulse oximetry by patients discharged from the emergency department is a potential way to identify patients needing to return for further evaluation.


Coronaviruses: a group with unique features


title: The dimer interface of the SARS coronavirus nucleocapsid protein adapts a porcine respiratory and reproductive syndrome virus-like structure

text: We have employed NMR to investigate the structure of SARS coronavirus nucleocapsid protein dimer. We found that the secondary structure of the dimerization domain consists of five α helices and a β-hairpin. The dimer interface consists of a continuous four-stranded β-sheet superposed by two long α helices, reminiscent of that found in the nucleocapsid protein of porcine respiratory and reproductive syndrome virus. Extensive hydrogen bond formation between the two hairpins and hydrophobic interactions between the β-sheet and the α helices render the interface highly stable. Sequence alignment suggests that other coronavirus may share the same structural topology.


title: The Aftermath of COVID‐19 in Dermatology Practice: What's next?

text: The rapidly increasing number of COVID‐19 patients and evidence of human‐to‐human transmission even within the asymptomatic incubation period prompted the attention of the entire world. The field of dermatology and procedural dermatology is not exempt from this global issue. We cannot deny the fact that this situation will have a lasting impact on the health‐seeking behaviours of our patients. It is necessary for dermatologists and dermatologic surgeons to be aware of the potential risks and precautions when re‐emerging their practices after COVID‐19.


title: Emerging infectious bronchitis virus (IBV) in Egypt: Evidence for an evolutionary advantage of a new S1 variant with a unique gene 3ab constellation

text: Infectious bronchitis virus (IBV), a gamma-coronavirus, causes infectious bronchitis (IB), a major respiratory disease of chicken. Its high mutation rate in conjunction with recombination of the RNA genome constantly creates IBV variants that are difficult to control by currently available vaccines. In this study, we addressed the question whether small-scale holdings might harbor IBV variants that serve as a reservoir for newly emerging variants. Egyptian IBV isolate EGY/NR725/2016 (NR725/16) from a small-scale broiler farm was assigned to genotype I, clade 23 (S1:GI-23), based on partial S1 gene sequences and corroborated by full genome sequencing. Analysis of the S1 gene established three subclades for historical IBV strains (S1:GI-23.1, S1:GI-23.2.1 and S1:GI-23.2.2) and confirmed NR725/16 as being part of a separate fourth subclade (S1:GI-23.3). Samples from the years 2018 and 2019 revealed that the new subclade prevails in Egypt, carrying fixed mutations within the hypervariable regions (HVR) 1-3 of the S1 protein that affect two neutralization sensitive epitopes at sites 294F, 297S and 306Y (48.2) and 329R (62.1). In addition, recombination was recognized in isolate NR 725/16, with intra-subtype mixing for the entire genes 3ab and E and inter-subtype mixing for the entire gene 6b with a close match to QX like viruses of genotype GI-19. Further analysis of gene 3ab detected the homologous gene pool to NR725/16 in samples from 2013 (3ab:C) and closely related 3ab genotypes in IBV Egyptian isolates from 2016, 2018 and 2019. These data prove a flourishing exchange between poultry holdings with a common gene pool. The continued circulation of viruses harboring genes S1:GI-23.3 and 3ab:C indicates an evolutionary advantage of this combination possibly by combining antigenic escape with modulated pathogenicity to facilitate IBV spread in the vaccinated poultry population in Egypt.


Murine Hepatitis Virus Strain 1 as a Model for Severe Acute Respiratory Distress Syndrome (Sars)


title: The COVID-19 pandemic and airline cash flow

text: The novel coronavirus pandemic has had a seismic impact on the travel industry. With a steep drop in demand and flight cancelations on international routes, airlines have reduced capacity on a scale that we have never seen before. In the current environment, airlines are strapped for cash, and cashflow is a prerequisite for survival. As airlines navigate through the resumption of flights in a Covid-19 and post-Covid-19 era, this paper recommends an approach for airlines to generate cashflow from corporations for their mutual benefit.


title: An alternative −1/+2 open reading frame exists within viral Npro(1–19) region of bovine viral diarrhea virus SD-1

text: Abstract We previously reported the engineering of an Npro-disrupted bovine viral diarrhea virus (BVDV), BSD1-Npro/eGFP2A (Fan and Bird, 2008a). Here, we report that BSD1-Npro/eGFP2A survives a single nucleotide missing in its C-terminal eGFP region. By using our established reverse genetics system for BVDV, we confirm that the viral mutant is rescued through a −1/+2 ORF initiated in the Npro(1–19)/eGFP region of the mutant viral genome. We furthermore uncover that this event occurs in the Npro(1–19) region of BVDV strain SD-1. The rescued viral mutant showed dramatic reductions in levels of both viral RNA and viral protein in host cells. Although the mutant is similar to the native strain in viral kinetics, the peak yield of the mutant is decreased dramatically. These findings reveal the existence of an alternative −1/+2 ORF in the Npro(1–19) region during the replication of BVDV and open a new avenue to understand the life cycle and pathogenesis of pestiviruses.


title: How to link patients with suspicious COVID-19 to health system from the community pharmacies? A route proposal

text: Abstract Colombia confirmed its first case of the COVID-19 on March 6th, 2020. On March 16th, 2020, 54 cases have been confirmed (36 imported and 18 associated), therefore, Colombia is at highest alert, and it is now trying to avoid or minimize the last stage of “community transmission”. We present a route proposal that shows how the community pharmacist may develop his responsibility to contribute to the early detection and appropriate referral of possible cases of the COVID-19. In the route have been considered three possible entrances depending on the needs of the users: anti-flu drugs, symptoms related to COVID-19 infection or the request for items for hygiene and prevention of transmission such as alcohol and face masks. Later, self-care education should be given, and the possible cases should be reported to the telephone lines designated by the mayor or the governor, continuing the healthcare process. Community pharmacies and pharmacy staff play a crucial role in minimizing the stage of “community transmission” of COVID-19, through properly detection and management of possible cases and customer education.


title: Chapter 37 Microbial Forensics in Australia—The Australian Federal Police Perspective

text: Publisher Summary The threat posed by terrorism remains many years ahead. Bioterrorism remains a real threat, but because actual incidents remain at a low level, complacency is a constant enemy; hence the continuing background of false alarms may indeed be beneficial, encouraging responding agencies to keep practiced and alert. The Australian Federal Police (AFP) model of an integrated intelligence and forensic approach is a useful model for other nations of similar size or maturity to consider as a measured contribution to a whole of government approach to threats posed by bioterrorism. The Australian microbial forensic capability is reliant on the combined and coordinated efforts of numerous government facilities, departments, and agencies within law enforcement and public health at the state, territory, and commonwealth levels, as well as the private sector. It is a shining example of how a coordinated effort can provide a comprehensive capability that does well to protect the Australian community. The AFP and Australian Chemical, Biological, Radiological and Nuclear Data Center also work closely with international law enforcement partners in the United Kingdom, Canada, and the United States. The contribution of these and other international partners can be understated in the ongoing united effort to protect the citizens and assets of Australia and other countries against bioterrorism.


title: Interstitial Pneumonia Associated with the Influenza Vaccine: A Report of Two Cases

text: Although the influenza vaccine is relatively safe and effective, serious complications can develop in rare cases. We encountered two cases of interstitial pneumonia that developed after vaccination during the 2014-2015 influenza season. Overall, nine cases, including the two presented here, have been recorded in PubMed and the Cochrane library; eight patients were treated with corticosteroids, and all nine survived, suggesting a good prognosis. Interstitial pneumonia is rare; however, we found an increase in its incidence after 2009. Therefore, clinicians must be aware of the possibility of this complication and duly educate all patients in advance.


title: Thromboelastographic Results and Hypercoagulability Syndrome in Patients With Coronavirus Disease 2019 Who Are Critically Ill

text: This cohort study examines the association of thromboelastographic results with hypercoagulability among patients with coronavirus disease 2019 who have been admitted to an intensive care unit.


title: A framework for capturing the interactions between laypersons’ understanding of disease, information gathering behaviors, and actions taken during an epidemic

text: Abstract This paper provides a description of a methodological framework designed to capture the inter-relationships between the lay publics’ understanding of health-related processes, information gathering behaviors, and actions taken during an outbreak. We developed and refined our methods during a study involving eight participants living in severe acute respiratory syndrome (SARS)-affected areas (Hong Kong, Taiwan, and Toronto). The framework is an adaptation of narrative analysis, a qualitative method that is used to investigate a phenomenon through interpretation of the stories people tell about their experiences. From our work, several hypotheses emerged that will contribute to future research. For example, our findings showed that many decisions in an epidemic are carefully considered and involve use of significant information gathering. Having a good model of lay actions based on information received and beliefs held will contribute to the development of more effective information support systems in the event of a future epidemic.


title: The Possible of Immunotherapy for COVID-19: a Systematic Review

text: The novel coronavirus (2019-nCoV) is an emerging pathogen that was first described in late December 2019 and causes a severe respiratory infection in humans. Since the outbreak of COVID-19, international attention has raised to develop treatment and control options such as types of immunotherapies. The immunotherapy is an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. These methods include several types of vaccines, monoclonal antibody candidates, and etc. This systematic review article was designed to evaluate the existing evidence and experience related to immunotherapy for 2019-nCoV. Web of Science (ISI), PubMed, and Scopus databases were used to search for suitable keywords such as 2019-nCoV, novel coronavirus, Immunotherapy, interleukin, vaccine and the related words for relevant publications up to 24.3.2020. The present systematic review was performed based on PRISMA protocol. Data extraction and quality valuation of articles were performed by two reviewers. 51 articles were the results of the search and based on the inclusions and exclusions criteria, 7 articles were included in the final review. As a conclusion of these studies demonstrated that although no serious research has been done on this subject at the time of writing this article, similar studies on the related viruses showed notable results. So immunotherapy for this virus can also be a suitable option.


Doctor–patient communication in surgical practice during the coronavirus (COVID‐19) pandemic


title: Reaching the Hispanic Community About COVID-19 Through Existing Chronic Disease Prevention Programs

text: Publicly available data on racial and ethnic disparities related to coronavirus disease 2019 (COVID-19) are now surfacing, and these data suggest that the novel virus has disproportionately sickened Hispanic communities in the United States. We discuss why Hispanic communities are highly vulnerable to COVID-19 and how adaptations were made to existing infrastructure for Penn State Project ECHO (Extension for Community Healthcare Outcomes) and Better Together REACH (a community–academic coalition using grant funds from Racial and Ethnic Approaches to Community Health) to address these needs. We also describe programming to support COVID-19 efforts for Hispanic communities by using chronic disease prevention programs and opportunities for replication across the country.


title: Novel Fractional Order SIDARTHE Mathematical Model of The COVID-19 Pandemic

text: Nowadays, COVID-19 has put a significant responsibility on all of us around the world from its detection to its remediation. The globe suffer from lockdown due to COVID-19 pandemic. The researchers are doing their best to discover the nature of this pandemic and try to produce the possible plans to control it. One of the most effective method to understand and control the evolution of this pandemic is to model it via an efficient mathematical model. In this paper, we propose to model the COVID-19 pandemic by fractional order SIDARTHE model which not appear in the literature before. The existence of a stable solution of the fractional order COVID-19 SIDARTHE model is proved and the fractional order necessary conditions of four proposed control strategies are produced. The sensitivity of the fractional order COVID-19 SIDARTHE model to the fractional order and the infection rate parameters are displayed. All studies are numerically simulated using MATLAB software via fractional order differential equation solver.


title: Predicting the anticipated emotional and behavioral responses to an avian flu outbreak

text: BACKGROUND: The purpose of this study was to develop a model to predict the emotional and behavioral responses to an avian flu outbreak. METHODS: The participants were 289 university students ranging in age, income, and ethnic backgrounds. They were presented with scenarios describing avian flu outbreaks affecting their community. They reported their anticipated emotional responses (positive emotion, negative emotion) and behavioral responses (helping, avoidance, sacrifice, illegal behavior) as if the scenarios were actually occurring. They also were assessed on individual differences expected to predict their responses. RESULTS: Participants were only modestly familiar with the avian flu and anticipated strong emotional and behavioral responses to an outbreak. Path analyses were conducted to test a model for predicting responses. The model showed that age, sex, income, spirituality, resilience, and neuroticism were related to responses. Spirituality, resilience, and income predicted better emotional responses, and neuroticism and female sex predicted worse emotional responses. Age, sex, income, and spirituality had direct effects on behavior. The emotional responses were directly related to each behavior and mediated the effects of individual differences. CONCLUSION: Emotional responses may be important in predicting behavior after an outbreak of avian flu, and personal characteristics may predict both emotional and behavioral responses.


title: Rapid and real-time detection technologies for emerging viruses of biomedical importance

text: The development of technologies with rapid and sensitive detection capabilities and increased throughput have become crucial for responding to greater number threats posed by emerging and re-emerging viruses in the recent past. The conventional identification methods require time-consuming culturing, and/ or detection of antibodies, which are not very sensitive and specific. The recent advances in molecular biology techniques in the field of genomics and proteomics greatly facilitate the rapid identification with more accuracy. We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. dengue, Japanese encephalitis, chikungunya, west Nile, severe acute respiratory syndrome virus (SARS) etc. Both these techniques are capable of detection and differentiation as well as quantifying viral load with higher sensitivity, rapidity, specificity. One of the most important advantages of LAMP is its field applicability, without requirement of any sophisticated equipments. Both these assays have been extensively evaluated and validated with clinical samples of recent epidemics from different parts of India. The establishment of these real time molecular assays will certainly facilitate the rapid detection of viruses with high degree of precision and accuracy in future.


title: Evolution of Viruses

text: The study of virus evolution has historically been concerned with disease and its emergence and has not been integrated into the general study of evolution. Yet viruses dominate our planet and their evolution is a broad and applied field that can be studied in the real time (such HIV in human disease) and can also be applied to biotechnological problems. Virus evolution is very similar, but not identical, to host evolution. Darwinian principles apply, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution, distinguish virus evolution. In RNA viruses, high error rates have led to the quasispecies concept in which collective populations are the basis of evolution. These populations provide viruses with high capacities for adaptation. Yet some RNA viruses show remarkable evolutionary stability. With DNA viruses, especially of bacteria, extensive recombination defines vast dynamic and ancient genetic pools. Temperate viruses can directly affect host gene pools by stable colonization. DNA viruses can be genetically complex and have evolved many unique viral genes. The retroviruses show both quasispecies-based rapid evolution and host-linked slow coevolution (e.g., endogenous retroviruses). Thus, virus evolution impacts all life and viral emergence continues to threaten human health.


title: Care in the time of coronavirus: Ethical considerations in head and neck oncology

text: As COVID‐19 continues to challenge the practice of head and neck oncology, clinicians are forced to make new decisions in the setting of the pandemic that impact the safety of their patients, their institutions, and themselves. The difficulty inherent in these decisions is compounded by potentially serious ramifications to the welfare of patients and health‐care staff, amid a scarcity of data on which to base informed choices. This paper explores the risks of COVID‐19 incurred while striving to uphold the standard of care in head and neck oncology. The ethical problems are assessed from the perspective of the patient with cancer, health‐care provider, and other patients within the health‐care system. While no single management algorithm for head and neck cancer can be universally implemented, a detailed examination of these issues is necessary to formulate ethically sound treatment strategies.


title: MERS coronavirus: Data gaps for laboratory preparedness

text: Abstract Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, many questions remain on modes of transmission and sources of virus. In outbreak situations, especially with emerging organisms causing severe human disease, it is important to understand the full spectrum of disease, and shedding kinetics in relation to infectivity and the ability to transmit the microorganism. Laboratory response capacity during the early stages of an outbreak focuses on development of virological and immunological methods for patient diagnosis, for contact tracing, and for epidemiological studies into sources, modes of transmission, identification of risk groups, and animal reservoirs. However, optimal use of this core public health laboratory capacity requires a fundamental understanding of kinetics of viral shedding and antibody response, of assay validation and of interpretation of test outcomes. We reviewed available data from MERS-CoV case reports, and compared this with data on kinetics of shedding and immune response from published literature on other human coronaviruses (hCoVs). We identify and discuss important data gaps, and biases that limit the laboratory preparedness to this novel disease. Public health management will benefit from standardised reporting of methods used, details of test outcomes by sample type, sampling date, in relation to symptoms and risk factors, along with the currently reported demographic, clinical and epidemiological findings.


title: The NSP2 Proteins of Mouse Hepatitis Virus and Sars Coronavirus are Dispensable for Viral Replication

text: The results presented here demonstrate that the MHV and SARS-CoV nsp2 proteins are not required for the production of infectious virus, for polyprotein expression or processing, or for viral replication complex formation in cell culture. The nsp2 protein domain resides in a region of the coronavirus replicase that is relatively nonconserved across coronaviruses. In fact, the size and amino acid sequence variability of nsp2 across the different coronaviruses has led some investigators to speculate that the nsp2 protein, along with the nsp1 and nsp3 proteins, may play host- and/or cell-specific roles in the virus life cycle. While this may be the case, it should be noted that nsp2, in some form, exists in all coronaviruses studied to date and likely plays a pivotal role in the viral life cycle. A previous study from our laboratory identified a coronavirus replicase protein that plays an important role in viral pathogenesis. Such may prove to be the case for nsp2, as well. Alternatively, beacuse nsp2 exists as a detectable precursor protein nsp2-3 prior to processing of nsp2 and nsp3 into mature proteins, nsp2 may play a critical adaptor/regulatory role for nsp3 function. Importantly, the viruses produced in this study provide a system by which the role of the nsp2 protein in viral infection can be characterized.


title: Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein

text: Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV) has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER), with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+) concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.


Should we stop aspirin prophylaxis in pregnant women diagnosed with COVID‐19?


title: Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS)

text: Summary We did a case-control study in five Hong Kong hospitals, with 241 non-infected and 13 infected staff with documented exposures to 11 index patients with severe acute respiratory syndrome (SARS) during patient care. All participants were surveyed about use of mask, gloves, gowns, and hand-washing, as recommended under droplets and contact precautions when caring for index patients with SARS. 69 staff who reported use of all four measures were not infected, whereas all infected staff had omitted at least one measure (p=0·0224). Fewer staff who wore masks (p=0·0001), gowns (p=0·006), and washed their hands (p=0·047) became infected compared with those who didn't, but stepwise logistic regression was significant only for masks (p=0·011). Practice of droplets precaution and contact precaution is adequate in significantly reducing the risk of infection after exposures to patients with SARS. The protective role of the mask suggests that in hospitals, infection is transmitted by droplets.


title: High prevalence of non-productive FeLV infection in necropsied cats and significant association with pathological findings

text: Abstract Applying a combination of semi-nested PCR and immunohistology (IHC), the presence of exogenous feline leukemia virus infection was studied in 302 necropsied cats with various disorders. 9% showed the classical outcome of persistent productive FeLV infection which was represented by FeLV antigen expression in different organs. 152 cats (50%) harboured exogenous FeLV-specific proviral sequences in the bone marrow but did not express viral antigen. These cats were considered as horizontally but non-productively infected. Statistical evaluation showed a significant association of non-productive horizontal FeLV infection with a variety of parameters. Non-productively infected cats were statistically significantly older and more often originated from animal shelters than cats without exogenous FeLV infection. Furthermore, some pathological disorders like anemia, panleukopenia, and purulent inflammation showed significant association with non-productive FeLV infection. No significant association was found with lymphosarcoma, known for a long time to be induced by productive FeLV infection.


title: A mathematical model for simulating the transmission of Wuhan novel Coronavirus

text: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probable be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from a seafood market (reservoir) to people, we simplified the model as Reservoir-People transmission network model. The basic reproduction number (R0) was calculated from the RP model to assess the transmissibility of the 2019-nCoV.


title: Assessing health systems in Guinea for prevention and control of priority zoonotic diseases: A One Health approach

text: To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts.


title: Avian coronavirus infectious bronchitis attenuated live vaccines undergo selection of subpopulations and mutations following vaccination

text: In this study, we were interested in determining if high titered egg adapted modified live infectious bronchitis virus (IBV) vaccines contain spike gene related quasispecies that undergo selection in chickens, following vaccination. We sequenced the spike glycoprotein of 12 IBV vaccines (5 different serotypes from 3 different manufacturers) directly from the vaccine vial, then compared that sequence with reisolated viruses from vaccinated and contact-exposed birds over time. We found differences in the S1 sequence within the same vaccine serotype from different manufacturers, differences in S1 sequence between different vaccine serials from the same manufacturer, and intra-vaccine differences or quasispecies. Comparing the sequence data of the reisolated viruses with the original vaccine virus, we were able to identify in vivo selection of viral subpopulations as well as mutations. To our knowledge, this is the first report showing selection of a more fit virus subpopulation as well as mutations associated with replication of modified live IBV vaccine viruses in chickens. This information is important for our understanding of how attenuated virus vaccines, including potential vaccines against the SARS-CoV, can ensure long-term survival of the virus and can lead to changes in pathogenesis and emergence of new viral pathogens. This information is also valuable for the development of safer modified live coronavirus vaccines.


title: The interaction of nonstructural protein 9 with retinoblastoma protein benefits the replication of genotype 2 porcine reproductive and respiratory syndrome virus in vitro

text: Abstract The nonstructural protein 9 (Nsp9) of porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA-dependent RNA polymerase (RdRp) that plays a vital role in viral replication. This study first demonstrated that the Nsp9 of genotype 2 PRRSV interacted with cellular retinoblastoma protein (pRb), and Nsp9 co-localized with pRb in the cytoplasm of PRRSV-infected MARC-145 cells and pulmonary alveolar macrophages (PAMs). Next, the overexpression of truncated pRb was shown to inhibit the PRRSV replication and silencing the pRb gene could facilitate the PRRSV replication in MARC-145 cells. Finally, the pRb level was confirmed to be down-regulated in PRRSV-infected MARC-145 cells, and Nsp9 was shown to promote the pRb degradation by proteasome pathway. These findings indicate that the interaction of Nsp 9 with pRb benefits the replication of genotype 2 PRRSV in vitro, helping to understand the roles of Nsp9 in the replication and pathogenesis of PRRSV.


title: Differential regulation of innate and adaptive immune responses in viral encephalitis

text: Abstract Viral encephalitis is a global health concern. The ability of a virus to modulate the immune response can have a pivotal effect on the course of disease and the fate of the infected host. In this study, we sought to understand the immunological basis for the fatal encephalitis following infection with the murine coronavirus, mouse hepatitis virus (MHV)-JHM, in contrast with the more attenuated MHV-A59. Distinct glial cell cytokine and chemokine response patterns were observed within 3 days after infection, became progressively more polarized during the course of infection and with the infiltration of leukocytes. In the brain, MHV-JHM infection induced strong accumulation of IFNβ mRNA relative to IFNγ mRNA. This trend was reversed in MHV-A59 infection and was accompanied by increased CD8 T cell infiltration into brain compared to MHV-JHM infection. Increased apoptosis appeared to contribute to the diminished presence of CD8 T cells in MHV-JHM-infected brain with the consequence of a lower potential for IFNγ production and antiviral activity. MHV-JHM infection also induced sustained mRNA accumulation of the innate immune response products interleukin (IL)-6 and IL-1. Furthermore, high levels of macrophage-inflammatory protein (MIP)-1α, MIP-1β, and MIP-2 mRNA were observed at the onset of MHV-JHM infection and correlated with a marked elevation in the number of macrophages in the brain on day 7 compared to MHV-A59 infection. These observations indicate that differences in the severity of viral encephalitis may reflect the differential ability of viruses to stimulate innate immune responses within the CNS and subsequently the character of infiltrating leukocyte populations.


title: Necessity to critically review the automatic results of the Xpert Flu assay

text: Abstract While using the Xpert Flu assay we became aware of false-negative results. The study aimed to analyze the causes of these false-negative results. One hundred fifty-nine respiratory specimens were tested in the Xpert Flu assay and in multiplex reverse transcription–polymerase chain reactions (RT-PCRs) for respiratory viruses. Discordant specimens were tested in the Influenza A/B r-gene assay. One hundred fifty-two (96%) and 151 (95%) specimens yielded concordant results for influenza A and B, respectively. Fifteen specimens tested negative in the Xpert Flu assay and positive in a multiplex RT-PCR. Positive results were confirmed for 12 of these specimens in the Influenza A/B r-gene assay. Xpert Flu assay amplification curves and endpoints suggested that the false-negative results were mainly due to erroneous automatic result interpretation. We report false-negative results of the Xpert Flu assay due to erroneous automatic result interpretation. Careful analysis of amplification curves and endpoints is needed to avoid reporting of false-negative results.