title: Coronavirus (COVID-19) Infection in Pregnancy: Does Non-contrast Chest Computed Tomography (CT) Have a Role in Its Evaluation and Management?

text: The outbreak of COVID-19 has become a globally concerning pandemic having affected more than 5 million people worldwide. The disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious. Only limited literature exists on the evaluation and management of pregnant women with suspected or confirmed COVID-19. In this short commentary, we inform the readers of the potential role of chest CT in symptomatic COVID-19 pregnant women and the related limitations.


title: The Role of Family Physicians in a Pandemic: A Blueprint

text: Pandemics are a significant stress test for a country's economic, political and health systems An effective pandemic response demands a multi-pronged and multi-layered approach, comprising surveillance, containment, border control, as well as various social and community measures In the wake of the novel coronavirus disease 2019 (COVID-19) pandemic, which has now infected more than 7 million people worldwide, strict quarantine measures are a commonplace, and a third of the world's population have now gone into some form of lockdown With the exception of border control, all these response measures involve the contributions of family physicians and general practitioners (GPs) in one way or another Primary care physicians form and lead the primary care network, which in turn forms the backbone of any healthcare system Being the first point of contact for a significant proportion of patients, primary care physicians play an essential strategic function in the fight against disease, both during peacetime and in the event of a public health crisis In this commentary, we examine and propose some of the key roles that they play in a pandemic, drawing examples from the current COVID-19 pandemic and past experiences COVID-19 has showed us that the world is grossly unprepared for a pandemic, both in terms of our global management and the structure of our current primary health care systems, and this should provide the impetus for us to improve


title: Vaccines for the prevention against the threat of MERS-CoV

text: First identified in 2012, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is listed as a new Category C Priority Pathogen. While the high mortality of MERS-CoV infection is further intensified by potential human-to-human transmissibility, no MERS vaccines are available for human use. This review explains immune responses resulting from MERS-CoV infection, describes MERS vaccine criteria, and presents available small animal models to evaluate the efficacy of MERS vaccines. Current advances in vaccine development are summarized, focusing on specific applications and limitations of each vaccine category. Taken together, this review provides valuable guidelines toward the development of an effective and safe MERS vaccine. This article is written for a Special Focus Issue of Expert Review of Vaccines on “Vaccines for Biodefence”.


title: Urban transportation energy and carbon dioxide emission reduction strategies

text: Abstract Sustainability is an urban development priority. Thus, energy and carbon dioxide emission reduction is becoming more significant in the sustainability of urban transportation systems. However, urban transportation systems are complex and involve social, economic, and environmental aspects. We present solutions for a sustainable urban transportation system by establishing a simplified system dynamics model with a timeframe of 30years (from 1995 to 2025) to simulate the effects of urban transportation management policies and to explore their potential in reducing vehicular fuel consumption and mitigating CO2 emissions. Kaohsiung City was selected as a case study because it is the second largest metropolis in Taiwan and is an important industrial center. Three policies are examined in the study including fuel tax, motorcycle parking management, and free bus service. Simulation results indicate that both the fuel tax and motorcycle parking management policies are suggested as potentially the most effective methods for restraining the growth of the number of private vehicles, the amount of fuel consumption, and CO2 emissions. We also conducted a synthetic policy consisting of all policies which outperforms the three individual policies. The conclusions of this study can assist urban transport planners in designing appropriate urban transport management strategies and can assist transport operation agencies in creating operational strategies to reduce their energy consumption and CO2 emissions. The proposed approach should be generalized in other cities to develop an appropriate model to understand the various effects of policies on energy and CO2 emissions.


title: Respiratory Syncytial Virus (RSV) Modulation at the Virus-Host Interface Affects Immune Outcome and Disease Pathogenesis

text: The dynamics of the virus-host interface in the response to respiratory virus infection is not well-understood; however, it is at this juncture that host immunity to infection evolves. Respiratory viruses have been shown to modulate the host response to gain a replication advantage through a variety of mechanisms. Viruses are parasites and must co-opt host genes for replication, and must interface with host cellular machinery to achieve an optimal balance between viral and cellular gene expression. Host cells have numerous strategies to resist infection, replication and virus spread, and only recently are we beginning to understand the network and pathways affected. The following is a short review article covering some of the studies associated with the Tripp laboratory that have addressed how respiratory syncytial virus (RSV) operates at the virus-host interface to affects immune outcome and disease pathogenesis.


title: FIV infection of IL-2-dependent and -independent feline lymphocyte lines: Host cells range distinctions and specific cytokine upregulation

text: Abstract We have analyzed the ability of three molecular clones of feline immunodeficiency virus (FIV) and an ex vivo variant to infect nine distinct specific-pathogen-free feline cell lines in tissue culture. The purpose of these studies was to elucidate mechanisms by which host cells regulate the level of virus infection and expression and to assess host cell cytokine responses to virus infection. Cells used for the analyzes included four IL-2-dependent continuous T-cell lines (104-C1, 104-C7, MCH5-4 and DB FeTs) which arose from long-term passage, followed by limiting dilution cloning of peripheral blood mononuclear cells (PBMCs); two IL-2-independent T-cell lines (104-C1DL and MCH5-4DL) which originated from two of the IL-2-dependent lines, 104-C1 and MCH5-4; respectively; Crandell feline kidney cells (CrFK); G355-5 brain-derived glial cells; and the T-cell lymphoma line, 3201. Cells were infected with FIV-PPR, FIV-34TF10, FIV 34TF10orf2rep, and a variant arising from FIV-PPR during ex vivo passage on 104-C1DL cells, termed FIV-PPRglial. Infection of the IL-2-dependent T-cell line, 104-C1, by FIV-PPR resulted in the specific and distinct upregulation of cytokine expression. In particular, these cells doubled their expression of the pleiotropic cytokines, interleukin-4 and interleukin-12 after FIV infection. Interferon-γ production also increased after infection with FIV whereas, TNFα expression remained constant. Also, a marked upregulation of MHC class II expression was noted post infection of MCH5-4 and 104-C1 cells with FIV-PPR. Similar results were obtained after infection with FIV-34TF10orf2rep, indicating that the upregulation of cytokine expression is not an isolate-specific phenomenon. Changes in cytokine and class II expression are similar to various reports for the in vivo cytokine alterations in FIV, SIV and HIV infections. The ex vivo infection of these cell lines offers a manipulable system to examine the mechanism(s) by which lentiviruses alter cytokine expression.


title: Multiplexed detection of influenza A virus subtype H5 and H9 via quantum dot-based immunoassay

text: A quantum dot-based lateral flow immunoassay system (QD-LFIAS) was developed to simultaneously detect both influenza A virus subtypes H5 and H9. Water-soluble carboxyl-functionalized quantum dots (QDs) were used as fluorescent tags. The QDs were conjugated to specific influenza A virus subtype H5 and H9 antibodies via an amide bond. When influenza A virus subtype H5 or H9 was added to the QD-LFIAS, the QD-labeled antibodies specifically bound to the H5 or H9 subtype viruses and were then captured by the coating antibodies at test line 1 or 2 to form a sandwich complex. This complex produced a bright fluorescent band in response to 365 nm ultraviolet excitation. The intensity of fluorescence can be detected using an inexpensive, low-maintenance instrument, and the virus concentration directly correlates with the fluorescence intensity. The detection limit of the QD-LFIAS for influenza A virus subtype H5 was 0.016 HAU, and the detection limit of the QD-LFIAS for influenza A virus subtype H9 was 0.25 HAU. The specificity and reproducibility were good. The simple analysis step and objective results that can be obtained within 15 min indicate that this QD-LFIAS is a highly efficient test that can be used to monitor and prevent both Influenza A virus subtypes H5 and H9.


title: First external quality assurance of antibody diagnostic for SARS-new coronavirus

text: Abstract To confirm an infection with the new coronavirus (SARS-CoV) causing the severe acute respiratory syndrome (SARS) diagnostic assays for detection of SARS-CoV specific antibody are necessary. To evaluate the diagnostic performance of laboratories an external quality assurance (EQA) study was performed in 2004. Participating laboratories (9/20) correctly detected anti-SARS antibodies in serum samples without false positive results in an immunofluorescence assay. In contrast, only 4/13 laboratories detected most of the anti-SARS antibody positive samples without false positive results using enzyme immunoassays (EIA) and/or immunoblot. The overall results clearly demonstrate that serological diagnosis of SARS-CoV remains at an early stage of development, with further technical improvements required, particularly with respect to the use of SARS specific EIAs.


title: Cancer Surgery During The Covid-19 Pandemic In Turkey

text: The coronavirus disease (Covid-19), which has spread rapidly all over the world after its appearance in December 2019, soon became a pandemic. In many places struck by the epidemic, clinical branches have prepared new guidelines for approaching the management of the disease in their area during the pandemic. Surgeons have also delayed elective surgeries. The first case of Covid-19 in Turkey was detected on March 10, 2020. After this date, 39 patients with a diagnosis of cancer were operated on in our clinic. In this study, we wanted to reveal the results of the cancer surgeries that we have performed during this period.


title: New Zealand's success

text: The country is tantalisingly close to wiping out covid-19. Does that mean life there can go back to normal? Alice Klein reports


Waiting during the time of COVID‐19


Presence of human bocavirus 1 and other viral co-infections in hospitalized children with lower respiratory tract infection in Latvia


title: Elucidating genetic diversity with oligonucleotide arrays

text: DNA microarrays, initially designed to measure gene expression levels, also provide an ideal platform for determining genetic diversity. Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. They have wide-ranging potential applications including comparative genomics, polymorphism discovery and genotyping. The identification of inheritable genetic markers also permits the analysis of quantitative traits, population studies and linkage analysis. In this review, we will discuss the application of oligonucleotide arrays, in particular high-density oligonucleotide arrays for elucidating genetic diversity and highlight some of the directions that the field may take.


COVID-19 pandemic: a stress test for interventional radiology


title: Feasibility of prone Position Coronary Angiography in a patient with COVID-19 pneumonia and refractory hypoxemia.

text: Abstract A 57-year-old woman hospitalized for a COVID-19 related refractory ARDS, developed, a few days later, antero-septal ST-elevation with acute systolic dysfunction. A coronary angiography was performed with the patient in prone (face-down) position, due to the necessity to maintain a reasonable oxygen-saturation during the examination.


title: Relationship between perception and anxiety about COVID-19 infection and risk behaviors for spreading infection: A national survey in Japan

text: BACKGROUND: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of “possible super spreaders”, suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies. METHODS: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020. FINDINGS: Thirteen-point-three percent of the participants rated “1” on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses. INTERPRETATION: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic. FUNDING: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.


title: Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus

text: BACKGROUND: Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. However, factors that affect NDV replication in host cells are poorly understood. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to elucidate the role of PKR in NDV infection. RESULTS: NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2α, in a dose-dependent manner by either the lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably decreased eIF2α phosphorylation as well as IFN-β mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2α or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2α signaling cascade in NDV infection. CONCLUSION: PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2α phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.


title: An “Old” protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses

text: Abstract Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.


title: Recomendaciones nacionales sobre donación pediátrica

text: Despite being an international reference in donation and transplantation, Spain needs to improve pediatric donation, including donation after the circulatory determination of death. The present article, a summary of the consensus report prepared by the Organización Nacional de Trasplantes and the Spanish Pediatrics Association, intends the facilitation of donation procedures in newborns and children and the analysis of associated ethical dilemma. The ethical basis for donation in children, the principles of clinical assessment of possible donors, the criteria for the determination of death in children, intensive care management of donors, basic concepts of donation after the circulatory determination of death and the procedures for donation in newborns with severe nervous system's malformation incompatible with life, as well as in children receiving palliative care are commented. Systematically considering the donation of organs and tissues when a child dies in conditions consistent with donation is an ethical imperative and must become an ethical standard, not only because of the need of organs for transplantation, but also to ensure family centered care.


title: Occupational Exposure to Blood and Body Fluids among Medical Laboratory Science Students of the University of Health and Allied Sciences during Vocational Internship in the Volta Region of Ghana

text: Medical laboratory science students (MLSS), likewise health care workers (HCW), invariably get exposed to blood and body fluids (BBF) of patients. The degree of exposure of these students is even worsened due to their inexperience, which is usually revealed during their vocational training programme. This study therefore determined the prevalence of exposure to BBF and its risk factors among MLSS at the University of Health and Allied Sciences (UHAS). A cross-sectional survey was employed using simple random sampling to enrol 178 students into the study. The study was conducted from February 1 to March 31, 2018, after the annual vocational training programme completed in August 2017. Self-administered questionnaires based on the objectives of the study were given out to participants to complete after their consent was sought. Descriptive data were reported as absolute number with percentages, whereas bivariate and multiple logistic regressions were done to describe relationship between risk factors and exposure to BBF. The study findings revealed that, out of 178 MLSS that participated, 90 (50.6%) experienced at least one exposure to BBF. Also, work experience before university education increased the chances of exposure to BBF (AOR = 7.37, 95% CI = 1.22–44.43, pvalue = 0.029) compared with those with no experience. In contrast, adequate personal protective equipment (PPE) reduced the tendencies of exposure to BBF (AOR = 0.41, 95% CI = 0.20–0.88, p value = 0.023) compared with students who had insufficient PPE. The study showed high, 50.6% (95% CI: 43.0%–58.1%), exposure to BBF. Work history and sufficient PPE were the most significantly associated risk factors. In view of this, there is the need to promote training and education on exposure to BBF particularly among experienced students and also encourage health facilities to continue providing enough PPE for students during their annual obligatory vocational internship programmes.


title: Combined inhalational and oral supplementation of ascorbic acid may prevent influenza pandemic emergency: A hypothesis

text: Abstract Occurrence of influenza pandemics is a worldwide phenomenon and a significant cause of mortality and morbidity throughout the globe. It is due to mutations in the influenza virus genetic material creating antigenic drift of pathogenic viral proteins resulting in emergence of new influenza virus strains. Therefore, the vaccines available for prevention of influenza offer no protection against influenza pandemics caused by new virus strains. Moreover, the existing drugs used to combat influenza may be ineffective to treat influenza pandemics due to the emergence of drug resistance in the pandemic virus strain. Therefore, a working strategy must be developed to combat influenza pandemics. In this review we have addressed this problem and reviewed the published studies on ascorbic acid in the common cold and influenza and laboratory studies on the effect of ascorbic acid on influenza virus. We have also correlated the clinical and laboratory studies and developed a hypothesis to prevent influenza pandemics.


title: Expression, Glycosylation, and Modification of the Spike (S) Glycoprotein of SARS CoV

text: The spike (S) glycoprotein of coronaviruses is known to be essential in the binding of the virus to the host cell at the advent of the infection process. To study the maturation pathway of the S glycoprotein of the severe acute respiratory syndrome (SARS)-coronavirus (CoV) within the host cell, a T7/vaccinia virus-based expression system coupled to immunoprecipitation with anti-S antibodies was used to test and analyze different forms of the S glycoprotein. The state of maturity of the S glycoprotein can be deduced from its sensitivity to hydrolysis by endoglycosidase H (EndoH) or N-glycosidase F (N-Gly F). A fully matured S glycoprotein will be modified with complex oligosaccharides which makes it resistant to cleavage by EndoH but not by N-Gly F. By exploiting this characteristic, it is then possible to determine which forms of the immunoprecipitated S protein are properly processed by the host cell. With this system, many different constructs of the S glycoprotein can be analyzed in parallel thus providing another method by which to study the functional domains of S involved in membrane fusion event that occurs during viral infection.


Vorwort des Editor in Chief


title: Involvement of miR-15a in G0/G1 Phase Cell Cycle Arrest Induced by Porcine Circovirus Type 2 Replication

text: Many viruses exploit the host cell division cycle to favour their own growth. Here we demonstrated that porcine circovirus type 2 (PCV2), which is a major causative agent of an emerging and important swine disease complex, PCV2-associated diseases, caused G0/G1 cell cycle arrest through degradation of cyclin D1 and E followed by reduction of retinoblastoma phosphorylation in synchronized PCV2-infected cells dependent upon virus replication. This induction of G0/G1 cell cycle arrest promoted PCV2 replication as evidenced by increased viral protein expression and progeny virus production in the synchronized PCV2-infected cells. To delineate a mechanism of miRNAs in regulating PCV2-induced G0/G1 cell cycle arrest, we determined expression levels of some relevant miRNAs and found that only miR-15a but not miR-16, miR-21, and miR-34a was significantly changed in the PCV2-infected cells. We further demonstrated that upregulation of miR-15a promoted PCV2-induced G0/G1 cell cycle arrest via mediating cyclins D1 and E degradation, in which involves PCV2 growth. These results reveal that G0/G1 cell cycle arrest induced by PCV2 may provide favourable conditions for viral protein expression and progeny production and that miR-15a is implicated in PCV2-induced cell cycle control, thereby contributing to efficient viral replication.


Biologics for psoriasis during COVID-19 outbreak


title: Serotonin syndrome in two COVID-19 patients treated with lopinavir/ritonavir

text: • Two cases of Serotonin syndrome (SS) in COVID-19 patients are presented. • Lopinavir/ritonavir (LPV/r) have been widely used during the COVID-19 pandemic. • LPV/r with duloxetine and lithium triggered SS in patient 1. • LPV/r with risperidone, and probably also morphine, triggered SS in patient 2. • A Video of patient 2 shows myoclonus and ocular clonus in the context of SS.


title: The investigation of immunomodulatory effects of adipose tissue mesenchymal stem cell educated macrophages on the CD4 T cells

text: Abstract Mesenchymal stem cells (MSCs) are strong immunomodulatory cells investigated in numerous clinical studies on fatal pathologies, such as graft versus host disease and autoimmune diseases; e.g., systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. Macrophages are one of the critical cells linking the innate and adaptive immune system, and it has been shown that MSCs can differentiate between pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype of macrophages. However, it has not yet been fully clarified whether these differentiated macrophages are functional. In this study, we compared the immunomodulatory effects on the CD4 T cells of M1, M2a and M2c macrophages with the macrophages that directly and indirectly cultured with MSCs. We analyzed the changes in CD14, CD64, CD80, CD163 and CD200R expression to evaluate macrophage phenotypes, and the changes in CD4, IFN-g, IL-4, IL-17a and FoxP3 expression to evaluate T helper subsets using the FACS method. The changes in IL-1b, IL-4, IL-10, IL-12p70, IL-17a and IFN-g in the media supernatants were analyzed using the Luminex method. We also performed WST-1 and Caspase-3 ELISA analyses to observe the proliferation and apoptosis status of the T cells. MSCs were found to differentiate macrophages into a distinctive phenotype, which was close to the M2c phenotype, but was not considered as an M2c cell due to the low expression of CD163, a characteristic marker for M2c. While MEM-D, MEM-ID and MSCs showed similar inhibitory effects on the Th2 and Th17 cells, the most significant increase in Treg cell frequencies was seen in MEM-D cells. Macrophages can alter their phenotypes and functions according to the stimuli from the environment. The fact that macrophages educated with MSCs suppressed the production of all the cytokines we evaluated even after the removal of MSCs suggests that these cells may be differentiated by MSCs into a suppressive macrophage subgroup. However, the Treg cell activation caused by direct interactions between MSCs and macrophage cells may be the most prominent observation of this study compared to previous work. As a result, according to our data, the interactions between MSCs and macrophages may lead to differentiation of macrophage cells into an immunosuppressive phenotype, and these macrophages may suppress the T lymphocyte subgroups at least as effectively as MSCs. However, our data obtained from in vitro experiments should be supported by future in vivo studies.


title: Health is global: proposals for a UK Government-wide strategy

text: Global health enables the harmonisation of international and domestic-health concerns—its outlook is much wider than a development or foreign-assistance perspective alone. Engaging globally in health requires the creation of relevant and effective partnerships to implement solutions for shared or common problems. To build on the UK's achievements and leadership in global health, the central government Department of Health is now leading the development of a UK Government-wide global strategy. This paper describes the rationale and process for developing the new UK Government-wide strategy for global health and highlights some of the issues that must be discussed.


title: YouTube as source of information on 2019 novel coronavirus outbreak: a cross sectional study of English and Mandarin content

text: Abstract Background The current 2019 novel coronavirus outbreak is rapidly evolving. YouTube has been recognized as a popular source of information in previous disease outbreaks. We analyzed the content on YouTube about n-CoV in English and Mandarin languages. Methods YouTube was searched using the terms ‘2019 novel coronavirus’, ‘Wuhan virus’ and ‘武汉病毒’ (Mandarin for Wuhan virus) on 1st and 2nd February 2020. First 50 videos in each group were analyzed. Videos in other languages, duplicate videos, those without an audio and duration >15 min were excluded .72 videos in English and 42 in Mandarin were reviewed. 2 reviewers classified the videos as useful, misleading or news based on pre specified criterion. Inter-observer agreement was evaluated with kappa coefficient. Modified DISCERN index for reliability and medical information and content index (MICI) score were used for content analysis. Results These videos attracted cumulative 21,288,856 views. 67% of English and 50% Mandarin videos had useful information. The viewership of misleading Mandarin videos was higher than the useful ones. WHO accounted for only 4% of useful videos. Mean DISCERN score for reliability was 3.12/5 and 3.25/5 for English and Mandarin videos respectively. Mean cumulative MICI score of useful videos was low (6.71/25 for English and 6.28/25 for Mandarin). Conclusions YouTube viewership during 2019 n-CoV outbreak is higher than previous outbreaks. The medical content of videos is suboptimal International health agencies are underrepresented. Given its popularity, YouTube should be considered as important platform for information dissemination.


Extracorporeal membrane oxygenation in the treatment of respiratory failure during COVID‑19


title: The Acute Chest Syndrome in Cameroonian children living with sickle cell disease

text: BACKGROUND: Although sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. METHODS: This was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization. RESULTS: Twenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm(3), 23476 (11543.7)/mm(3), 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05). CONCLUSION: ACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients’ parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.


title: Live Cell Imaging of Viral Entry

text: Viral entry encompasses the initial steps of infection starting from virion host cell attachment to viral genome release. Given the dynamic interactions between the virus and the host, many questions related to viral entry can be directly addressed by live cell imaging. Recent advances in fluorescent labeling of viral and cellular components, fluorescence microscopy with high sensitivity and spatiotemporal resolution, and image analysis enabled studies of a broad spectrum across many viral entry steps, including virus-receptor interactions, internalization, intracellular transport, genomic release, nuclear transport, and cell-to-cell transmission. Collectively, these live cell imaging studies have not only enriched our understandings of the viral entry mechanisms, but also provided novel insights into basic cellular biology processes.


title: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening

text: Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 “mortality rate”, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.


title: Natural Shocks and Marriage Markets: Fluctuations in Mehr and Dowry in Muslim Marriages

text: We examine how mehr, a conditional payment from husbands to wives in the event of divorce, and dowry, a transfer from the bride’s family to the groom at the time of marriage, have fluctuated in Bangladesh due to natural shocks. We develop a model of the marriage market in which dowry acts as a groom price, whereas mehr serves to deter inefficient divorces. Our comparative statics results show that mehr and dowry are both increasing (decreasing) in shocks that raise (lower) income. We then exploit several natural experiments in Bangladesh including the Green Revolution in the 1960s, war of independence in 1971, and famine of 1974 to explain fluctuations in the value of mehr and dowry observed in Muslim marriages. Using two household survey datasets, we find partial support for our theoretical predictions. To rule out alternative explanations, particularly the effect of legal changes, we use household survey data from the Indian state of West Bengal that experienced a similar increase in agricultural productivity but none of the legal changes affecting Bangladesh. These results demonstrate that natural shocks may affect social institutions.


title: Disaster Preparedness and Response for the Burn Mass Casualty Incident in the Twenty-first Century

text: The effective and efficient coordination of emergent patient care at the point of injury followed by the systematic resource-based triage of casualties are the most critical factors that influence patient outcomes after mass casualty incidents (MCIs). The effectiveness and appropriateness of implemented actions are largely determined by the extent and efficacy of the planning and preparation that occur before the MCI. The goal of this work was to define the essential efforts related to planning, preparation, and execution of acute and subacute medical care for disaster burn casualties. This type of MCI is frequently referred to as a burn MCI.”


title: A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor

text: Lycorine potently inhibits flaviviruses in cell culture. At 1.2-μM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 10(2)- to 10(4)-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val→Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound’s potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis.


title: Clarifying dairy calf mortality phenotypes through postmortem analysis

text: ABSTRACT Health problems can be thought of as phenotypic expressions of the complex relationships between genes, environments, and phenomes as a whole. Detailed evaluations of phenotypic expressions of illness are required to characterize important biological outcomes. We hypothesized that classifying dairy calf mortality phenotypes via a systematic postmortem analysis would identify different cause-of-death diagnoses than those derived from treatments alone. This cross-sectional study was carried out on a dairy calf ranch in the northwestern United States from June to September 2017 and focused on calves ≤90 d of age. Comparisons were made between causes of death based on 3 levels of information: on-farm treatment records alone, necropsy-based postmortem analyses in addition to treatment records, and Washington Animal Disease Diagnostic Laboratory (WADDL) results in addition to all other information. A total of 210 dairy calves were necropsied during this study, of which 122 cases were submitted to WADDL. Necropsy- and WADDL-derived mortality phenotypes were in almost perfect agreement (Cohen's κ = 0.86) when broadly categorized as diarrhea, respiratory, diarrhea and respiratory combined, or other causes. The level of agreement between on-farm treatment records and postmortem-derived results was low and varied by the level of diagnostic detail provided. There was just fair agreement (κ = 0.22) between treatment-based and necropsy-based phenotypes without WADDL input and only slight agreement (κ = 0.13) between treatment-based and corresponding necropsy-based phenotypes with WADDL input. Even for those cases in which causes of death aligned along a comparable pathologic spectrum, the lack of detail inherent to standard treatment-based causes of death failed to identify meaningful target areas for intervention. This was especially apparent for numerous cases of necrotizing enteritis and typhlitis (cecal inflammation) that were variously categorized as diarrhea and pneumonia by treatment-based diagnoses. The specificity of these lesions stood in stark contrast to the otherwise generic cause of death diagnoses derived from treatments. The findings from this study supported the hypothesis and highlighted the value of on-farm necropsies and laboratory-based diagnostics to (1) detect antemortem disease misclassifications, (2) provide detail regarding disease processes and mortality phenotypes, and (3) direct disease mitigation strategies.


title: Disruptions during a pandemic: Gaps identified and lessons learned

text: Global disruptions caused by coronavirus disease 2019 (COVID‐19) affects all walks of life, and dentistry and dental education are no exceptions. Dental education uniquely blends didactic courses and hands‐on clinical training seamlessly to prepare oral healthcare providers of the future. Apart from economical and access to care implications, closure of all the dental institutions in the United States affects their educational mission greatly, equally disturbing pre‐doctoral and graduate training. Efforts are ongoing to continue the educational mission in dental institutions by delivering scheduled course content remotely using multiple online tools. In spite of those efforts, since clinical experiences cannot be completely replaced by any available alternative method of instruction that is delivered remotely, students are missing out on valuable patient‐based clinical experiences. In this perspective article, we briefly discuss the several implications of COVID‐19, in the context of dental education. We then highlight some of the lessons we can learn from this pandemic which we hope will have several positive implications, including curricular changes, increased public health awareness and preparedness for future public health emergencies.


title: Is it Possible to Safely Maintain a Regular Vascular Practice During the C19 Pandemic?

text: Abstract Objective This study aimed to evaluate the protocol adopted during the emergency phase of the COVID-19 pandemic to maintain elective activity in a vascular surgery unit while minimising the risk of contamination to both patients and physicians, and the impact of this activity on the intensive care (IC) resources. Methods The activity of a vascular surgery unit was analysed from 8 March to 8 April 2020. Surgical activity was maintained only for acute or elective procedures obeying priority criteria. The preventive screening protocol consisted of nasopharyngeal swabs (NPS) for all patients and physicians with symptoms and for unprotected contact infected cases, and serological physician evaluations every 15 days. Patients treated in the acute setting were considered theoretically infected and the necessary protective devices were used. The number of patients and the possible infection of physicians were evaluated. The number and type of interventions and the need for post-operative IC during this period were compared with those in the same periods in 2018 and 2019. Results One hundred and fifty-one interventions were performed, of which 34 (23%) were acute/emergency. The total number of interventions was similar to those performed in the same periods in 2019 and 2018: 150 (33, of which 22% acute/emergency) and 117 (29, 25% acute/emergency), respectively. IC was necessary after 6% (17% in 2019 and 20% in 2018) of elective operations and 33% (11) of acute/emergency interventions. None of the patients treated electively were diagnosed with COVID-19 infection during hospitalisation. Of the 34 patients treated in acute/emergency interventions, five (15%) were diagnosed with COVID-19 infection. It was necessary to screen 14 (47%) vascular surgeons with NPS after contact with infected colleagues, but none for unprotected contact with patients; all were found to be negative on NPS and serological evaluation. Conclusion A dedicated protocol allowed maintenance of regular elective vascular surgery activity during the emergency phase of the COVID-19 pandemic, with no contamination of patients or physicians and minimal need for IC resources.


title: Analysing passenger network changes: The case of Hong Kong

text: Abstract Passenger throughput at Hong Kong International Airport (HKIA) has shown steady growth since its opening. Various aspects relating to HKIA have been studied in prior literature. This paper investigated changes in HKIA's passenger network for the period of 2001–2012 and used the gravity model to examine the key factors explaining its passenger traffic flows. The findings suggested that HKIA's passenger network has changed significantly and expanded to many new different destinations. Two regions (East Asia and Southeast Asia) were the most important markets for HKIA, and most key destinations connected by Hong Kong showed healthy growth. Nine factors could explain passenger traffic flows between Hong Kong and its key destinations: Hong Kong GDP per capita, GDP per capita of destinations connected by HKIA, distance, airport hub status of the destination airport, tourist destinations connected by HKIA, numbers of passenger airlines in service, bilateral trade flows, speaking a common language and having strong cultural/colonial links with Hong Kong, and the route presence of Cathay Pacific.


title: The Use of Bovine Serum Protein as an Oral Support Therapy Following Coronavirus Challenge in Calves 1

text: Abstract The objective of this experiment was to investigate the therapeutic efficacy of a supplemental bovine serum protein blend fed to calves challenged with virulent coronavirus. Twelve Holstein bull calves (approximately 3 wk of age) were allocated by initial body weight to Control (n = 5) and treated (n = 7) groups. On d 0, all calves were orally challenged with 1 × 107 plaque forming units of virulent coronavirus isolate. Infection was allowed to progress for 24h before treatment was started. On d 1, treated calves began receiving 160g of dry bovine serum powder (16g IgG) mixed into milk replacer powder (67g) at both an a.m. and p.m. feeding. Control calves received only milk replacer powder (227g) at both feedings. Response to coronavirus challenge and dietary treatment was monitored prior to a.m. and p.m. feeding by the collection of multiple clinical measures. Fecal consistency was decreased by coronavirus challenge but was not affected by dietary treatment. Mean daily rectal temperature and heart rate were not affected by dietary treatment. Average packed cell volume was higher in treated calves than in control (35.0 and 27.0%). Coronavirus challenge resulted in an immediate increase in respiration rate, decreasing by d 7. Control calves tended to have a greater average respiration rate compared with treated (28.7 vs. 26.8 breaths/min). Treated calves had a higher average feed intake than control (0.57 vs. 0.44 kg/d). These data suggest that bovine-serum supplemented milk replacer may decrease the severity of disease in young calves exposed to coronavirus.


title: Ophthalmology in the time of COVID-19: Experience from Hong Kong Eye Hospital

text: AIM: To review international guidelines and to share our infection control experience during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary eye centre in Hong Kong. METHODS: Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed. The measures at our hospital were drawn up as per international and local health authorities' guidelines and implemented with the collaboration of doctors, nurses and administrative staff. RESULTS: The aims of our infection control measures are to 1) minimize cross-infection within the hospital; 2) protect and support hospital staff; 3) ensure environmental control. To minimize the risk of cross-infection, outpatient attendance and elective surgery have been reduced by 40%, and general anesthesia procedures were reduced by 90%. Patients entering the hospital are screened for fever, travel history, contact and cluster history, and COVID-19 related symptoms. To protect and support hospital staff, we ensure provision of adequate personal protective equipment (PPE) and provide clear guidelines on the level of PPE needed, depending on the clinical situation. Other protective measures include provision of work uniforms, easy access to alcohol-based hand rub, opening new lunch areas, implementation of self-monitoring and self-reporting systems, and communication via online education and updates. Finally, environmental control is achieved by ensuring regular disinfection of the hospital premise, enhancing ventilation, and usage of disposable ophthalmic instruments. CONCLUSION: Our multi-pronged approach to infection control is, so far, successful in minimizing infection risks, while allowing the maintenance of essential ophthalmic services.


First Cases of COVID-19 in Heart Transplantation From China


title: Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies

text: The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.


title: Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus

text: Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy-choice RNA recombination. During infection, multiple subgenomic (sg) mRNAs are transcribed from a mirror set of sg negative-strand RNA templates. The sg mRNAs all possess a short 5′ common leader sequence, derived from the 5′ end of the genomic RNA. The joining of the non-contiguous ‘leader’ and ‘body’ sequences presumably occurs during minus-strand synthesis. To study whether toroviruses use a similar transcription mechanism, we characterized the 5′ termini of the genome and the four sg mRNAs of Berne virus (BEV). We show that BEV mRNAs 3–5 lack a leader sequence. Surprisingly, however, RNA 2 does contain a leader, identical to the 5′-terminal 18 residues of the genome. Apparently, BEV combines discontinuous and non-discontinous RNA synthesis to produce its sg mRNAs. Our findings have important implications for the understanding of the mechanism and evolution of nidovirus transcription.


title: Diagnostic Testing or Empirical Therapy for Patients Hospitalized with Suspected Influenza: What to Do?

text: Accumulating evidence supports the use of specific diagnostic tests and antiviral therapies for seriously ill patients with influenza. Among available diagnostic tests, reverse-transcriptase polymerase chain reaction is faster than culture and more sensitive than commercial antigen assays. Current neuraminidase inhibitors were approved on the basis of their efficacy in ambulatory patients, but seriously ill patients who receive these agents are less likely to die, even when treatment is initiated >48 h after symptom onset. For patients hospitalized with suspected influenza, it is unclear which circumstances warrant diagnostic testing and which warrant the use of empirical therapy. Rapid antigen assays may reduce the unnecessary use of other tests and medications but are relatively insensitive, thus eliminating many patients with influenza as candidates for treatment. Empirical antiviral therapy ensures that all patients receive treatment promptly, at a cost equivalent to that of diagnostic tests alone, but results in the receipt of treatment by many patients without influenza. For patients hospitalized with suspected influenza, clinicians need to combine these approaches in order to optimize patient care.


Shut down and reboot—preparing to minimise infection in a post-COVID-19 era


title: Advances in viral disease diagnostic and molecular epidemiological technologies

text: The early and rapid detection and characterization of specific nucleic acids of medico–veterinary pathogens have proven invaluable for diagnostic purposes. The integration of amplification and signal detection systems, including online real-time devices, have increased speed and sensitivity and greatly facilitated the quantification of target nucleic acids. They have also allowed for sequence characterization using melting or hybridization curves. The newer-generation molecular diagnostic technologies offer, hitherto, unparalleled detection and discrimination methodologies, which are vital for the positive detection and identification of pathogenic agents, as well as the effects of the pathogens on the production of antibodies. The development phase of the novel technologies entails a thorough understanding of accurate diagnosis and discrimination of present and emerging diseases. The development of novel technologies can only be successful if they are transferred and used in the field with a sustainable quality-assured application to allow for the optimal detection and effective control of diseases. The aim of these new tools is to detect the presence of a pathogen agent before the onset of disease. This manuscript focuses mainly on the experiences of two World Organisation for Animal Health collaborating centers in context to molecular diagnosis and molecular epidemiology of transboundary and endemic animal diseases of viral origin, food safety and zoonoses.


title: Learning from history: do not flatten the curve of antiviral research!

text: Here, we explore the dynamics of the response of the scientific community to several epidemics, including Coronavirus 2019 (COVID-19), as assessed by the numbers of clinical trials, publications, and level of research funding over time. All six prior epidemics studied [bird flu, severe acute respiratory syndrome (SARS), swine flu, Middle East Respiratory Syndrome (MERS), Ebola, and Zika] were characterized by an initial spike of research response that flattened shortly thereafter. Unfortunately, no antiviral medications have been discovered to date as treatments for any of these diseases. By contrast, the HIV/AIDS pandemic has garnered consistent research investment since it began and resulted in drugs being developed within 7 years of its start date, with many more to follow. We argue that, to develop effective treatments for COVID-19 and be prepared for future epidemics, long-term, consistent investment in antiviral research is needed.


title: Nucleotide sequence variation of the VP7 gene of two G3-type rotaviruses isolated from dogs

text: Abstract The sequence of the VP7 gene of two rotaviruses isolated from dogs in southern Italy was determined and the inferred amino acid sequence was compared with that of other rotavirus strains. There was very high nucleotide and amino acid identity between canine strain RV198/95 and other canine strains, and to the human strain HCR3A. Strain RV52/96, however, was found to have about 95% identity to the G3 serotype canine strains K9, A79-10 and CU-1 and 96% identity to strain RV198/95 and to the simian strain RRV. Therefore both of the canine strains belong to the G3 serotype. Nevertheless, detailed analysis of the VP7 variable regions revealed that RV52/96 possesses amino acid substitutions uncommon to the other canine isolates. In addition, strain RV52/96 exhibited a nucleotide divergence greater than 16% from all the other canine strains studied; however, it revealed the closest identity (90.4%) to the simian strain RRV. With only a few exceptions, phylogenetic analysis allowed clear differentiation of the G3 rotaviruses on the basis of the species of origin. The nucleotide and amino acid variations observed in strain RV52/96 could account for the existence of a canine rotavirus G3 sub-type.


Intestinal Disorders


Corona! Die Krise der Verschlankung und ihre Folgen


title: Statistically-based methodology for revealing real contagion trends and correcting delay-induced errors in the assessment of COVID-19 pandemic

text: COVID-19 pandemic has reshaped our world in a timescale much shorter than what we can understand. Particularities of SARS-CoV-2, such as its persistence in surfaces and the lack of a curative treatment or vaccine against COVID-19, have pushed authorities to apply restrictive policies to control its spreading. As data drove most of the decisions made in this global contingency, their quality is a critical variable for decision-making actors, and therefore should be carefully curated. In this work, we analyze the sources of error in typically reported epidemiological variables and usual tests used for diagnosis, and their impact on our understanding of COVID-19 spreading dynamics. We address the existence of different delays in the report of new cases, induced by the incubation time of the virus and testing-diagnosis time gaps, and other error sources related to the sensitivity/specificity of the tests used to diagnose COVID-19. Using a statistically-based algorithm, we perform a temporal reclassification of cases to avoid delay-induced errors, building up new epidemiologic curves centered in the day where the contagion effectively occurred. We also statistically enhance the robustness behind the discharge/recovery clinical criteria in the absence of a direct test, which is typically the case of non-first world countries, where the limited testing capabilities are fully dedicated to the evaluation of new cases. Finally, we applied our methodology to assess the evolution of the pandemic in Chile through the Effective Reproduction Number R(t), identifying different moments in which data was misleading governmental actions. In doing so, we aim to raise public awareness of the need for proper data reporting and processing protocols for epidemiological modelling and predictions.


title: Rotavirus infection in adults

text: Summary Rotavirus has been recognised for 30 years as the most common cause of infectious gastroenteritis in infants and young children. By contrast, the role of rotavirus as a pathogen in adults has long been underappreciated. Spread by faecal-oral transmission, rotavirus infection in adults typically manifests with nausea, malaise, headache, abdominal cramping, diarrhoea, and fever. Infection can also be symptomless. Rotavirus infection in immuno-compromised adults can have a variable course from symptomless to severe and sustained infection. Common epidemiological settings for rotavirus infection among adults include endemic disease, epidemic outbreak, travel-related infection, and disease resulting from child-to-adult transmission. Limited diagnostic and therapeutic alternatives are available for adults with suspected rotavirus infection. Because symptoms are generally self-limiting, supportive care is the rule. Clinicians caring for adults with gastroenteritis should consider rotavirus in the differential diagnosis. In this review we intend to familiarise clinicians who primarily provide care for adult patients with the salient features of rotavirus pathophysiology, clinical presentation, epidemiology, treatment, and prevention.


title: Isolation and identification of bat viruses closely related to human, porcine and mink orthoreoviruses

text: Bats have been identified as natural reservoirs of many viruses, including reoviruses. Recent studies have demonstrated the interspecies transmission of bat reoviruses to humans. In this study, we report the isolation and molecular characterization of six strains of mammalian orthoreovirus (MRV) from Hipposideros and Myotis spp. These isolates were grouped into MRV serotype 1, 2 or 3 based on the sequences of the S1 gene, which encodes the outer coat protein σ1. Importantly, we found that three of six bat MRV strains shared high similarity with MRVs isolated from diseased minks, piglets or humans based on the S1 segment, suggesting that interspecies transmission has occurred between bats and humans or animals. Phylogenetic analyses based on the 10 segments showed that the genomic segments of these bat MRVs had different evolution lineages, suggesting that these bat MRVs may have arisen through reassortment of MRVs of different origins.


title: EpiJSON: A unified data-format for epidemiology

text: Abstract Epidemiology relies on data but the divergent ways data are recorded and transferred, both within and between outbreaks, and the expanding range of data-types are creating an increasingly complex problem for the discipline. There is a need for a consistent, interpretable and precise way to transfer data while maintaining its fidelity. We introduce ‘EpiJSON’, a new, flexible, and standards-compliant format for the interchange of epidemiological data using JavaScript Object Notation. This format is designed to enable the widest range of epidemiological data to be unambiguously held and transferred between people, software and institutions. In this paper, we provide a full description of the format and a discussion of the design decisions made. We introduce a schema enabling automatic checks of the validity of data stored as EpiJSON, which can serve as a basis for the development of additional tools. In addition, we also present the R package ‘repijson’ which provides conversion tools between this format, line-list data and pre-existing analysis tools. An example is given to illustrate how EpiJSON can be used to store line list data. EpiJSON, designed around modern standards for interchange of information on the internet, is simple to implement, read and check. As such, it provides an ideal new standard for epidemiological, and other, data transfer to the fast-growing open-source platform for the analysis of disease outbreaks.


title: Baculovirus transit through insect cell membranes: A mechanistic approach

text: Baculovirus systems are used for various purposes, but the kinetics of the infection process is not fully understood yet. We investigated the dynamics of virion movement from a medium toward the interior of insect cells and established a mechanistic model that shows an excellent fit to experimental results. It also makes possible a description of the viral dynamics on the cell surface. A novel measurement method was used to distinguish between infected cells that carry virions on their surfaces, cells that carry virions in their interior, and those carrying virions both inside and on their surface. The maximum number of virions carried by a cell: 55 viruses/cell, and the time required for viral internalization, 0.8 [Formula: see text] , are reported. This information is particularly useful for assessing the infection efficacy and the required number of virions needed to infect a given cell population. Although our model specifically concerns the infection process of Sf9 insect cells by baculovirus, it describes general features of viral infection. Some of the model features may eventually be applicable in the studies towards palliation of the COVID-19 outbreak.


title: Divergent Roles of Autophagy in Virus Infection

text: Viruses have played an important role in human evolution and have evolved diverse strategies to co-exist with their hosts. As obligate intracellular pathogens, viruses exploit and manipulate different host cell processes, including cellular trafficking, metabolism and immunity-related functions, for their own survival. In this article, we review evidence for how autophagy, a highly conserved cellular degradative pathway, serves either as an antiviral defense mechanism or, alternatively, as a pro-viral process during virus infection. Furthermore, we highlight recent reports concerning the role of selective autophagy in virus infection and how viruses manipulate autophagy to evade lysosomal capture and degradation.


title: New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

text: Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS‐6620, remdesivir and pyrazofurin) are C‐nucleosides, and two of them (GS‐6620, remdesivir) also contain a phosphoramidate part. The C‐nucleoside and phosphoramidate (and for the adenine analogues the 1′‐cyano group as well) may be considered as essential attributes for their antiviral activity.


title: Pharyngitis

text: Most infectious pharyngitis has a viral cause. The use of aspirin or nonsteroidal antiinflammatory agents (NSAIAs) is advised in adults and NSAIAs in children for the treatment of pain. There are several studies that show that NSAIAs relieve pharyngitis pain better than acetaminophen. Penicillin remains the antibiotic of choice of group A beta-hemolytic streptococcal (GAS) pharyngitis. Resistance has not developed to penicillin. Patients with GAS pharyngitis should have improvement in 3 to 4 days. If not better at that time, the patient should be seen for diagnostic reconsideration or the development of a suppurative complication.


title: Resiquimod enhances mucosal and systemic immunity against avian infectious bronchitis virus vaccine in the chicken

text: Abstract Adjuvant enhancing mucosal immune response is preferred in controlling many pathogens at the portal of entry. Earlier, we reported that a toll-like-receptor 7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken. Here, we report the effect of R-848 when adjuvanted with live or inactivated avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal immunity. Specific pathogen free (SPF) chicks (n = 60) were equally divided into six groups at two weeks of age and immunized with either inactivated or live IBV vaccine adjuvanted with or without R-848. Groups that received either PBS or R-848 served as control. A booster was given on 14 days post-immunization (dpi). R-848 enhanced the antigen specific humoral and cellular immune responses when co-administered with the vaccines as evidenced by an increase in the antibody titre in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35 dpi and increased proportion of CD4+ and CD8+ T cells on 21 dpi in the flow cytometry. Interestingly, it potentiated the IgA responses in the tear and intestinal secretions when used with both live and inactivated IBV vaccines. The combination of IBV vaccine with R-848 significantly up-regulated the transforming growth factor beta 4 (TGFβ4) transcripts in the peripheral blood mononuclear cells (PBMCs) than that of the respective vaccine per se. An enhanced secretory IgA response is likely due to the up-regulation of TGFβ4, which is responsible for class switching to IgA. In conclusion, co-administration of R-848 with inactivated or live IBV vaccine enhanced the systemic as well as mucosal immune responses in the chicken.


title: MNE-NGO partnerships for sustainability and social responsibility in the global fast-fashion industry: A loose-coupling perspective

text: Stakeholders are increasingly aware of the environmental and human rights issues related to highly conspicuous fashion merchandising. To mitigate the negative responses from environmentally conscious consumer groups, fashion merchandisers have sought to partner with non-governmental organizations (NGOs). While there is a growing body of literature on sustainability and social responsibility (SSR), the increasingly popular practice of fast-fashion industry partnering with NGOs has been neglected, and so far, remained under the radar. Such partnerships may be of success, but at the same time while promising on the surface, they can actually go awry, resulting in adverse outcomes for both parties. We build upon the loose-coupling theory to explain the relationships between fast-fashion multinational enterprises (MNEs) and NGOs. We discuss three causes (casual indeterminacy; fragmented external environment; discrete internal environment) and four key benefits (adaptability to environmental changes, flexibility, innovation, and firewalls for separate identity) for loosely-coupled partnerships. We then explore the dark side of such partnerships, identifying three challenges (power imbalance, mistrust and opportunism, and misaligning goals). Finally, we offer a set of propositions as a way of advancing our knowledge of partnerships in fashion merchandising industry.


title: Risk factors for wheezing in a subtropical environment Role of respiratory viruses and allergen sensitization

text: Abstract Background Risk factors for acute wheezing among children in subtropical areas are largely unknown. Objective To investigate the role of viral infections, allergen sensitization, and exposure to indoor allergens as risk factors for acute wheezing in children 0 to 12 years old. Methods One hundred thirty-two children 0 to 12 years of age who sought emergency department care for wheezing and 65 children with no history of wheezing were enrolled in this case-control study. Detection of respiratory syncytial virus antigen, rhinovirus and coronavirus RNA, adenovirus, influenza, and parainfluenza antigens was performed in nasal washes. Total IgE and specific IgE to mites, cockroach, cat, and dog were measured with the CAP system. Major allergens from mites, cockroach, cat, and dog were quantified in dust samples by ELISA. Univariate and multivariate analyses were performed by logistic regression. Results In children under 2 years of age, infection with respiratory viruses and family history of allergy were independently associated with wheezing (odds ratio, 15.5 and 4.2; P = .0001 and P = .008, respectively). Among children 2 to 12 years old, sensitization to inhalant allergens was the major risk factor for wheezing (odds ratio, 2.7; P = .03). High-level allergen exposure, exposure to tobacco smoke, and lack of breast-feeding showed no association with wheezing. Conclusions Some risk factors for wheezing previously identified in temperate climates were present in a subtropical area, including respiratory syncytial virus infection in infants and allergy in children older than 2 years. Rhinovirus was not associated with wheezing and did not appear to be a trigger for asthma exacerbations.


title: Synthesis and structure-activity relationship studies of water-soluble β-cyclodextrin-glycyrrhetinic acid conjugates as potential anti-influenza virus agents

text: Glycyrrhetinic acid (GA) is a major constituent of the herb Glycyrrhiza glabra, and many of its derivatives demonstrate a broad spectrum of antiviral activities. In the current study, 18 water-soluble β-cyclodextrin (CD)-GA conjugates, in which GA was covalently coupled to the primary face of β-CD using 1,2,3-triazole moiety along with varying lengths of linker, were synthesized via copper-catalyzed azide-alkyl cycloaddition reaction. Benefited from the attached β-CD moiety, all these conjugates showed lower hydrophobicity (AlogP) compared with their parent compound GA. With the exception of per-O-methylated β-CD-GA conjugate (35), all other conjugates showed no significant cytotoxicity to MDCK cells, and these conjugates were then screened against A/WSN/33 (H1N1) virus using the cytopathic effect assay. The preliminary results indicated that six conjugates showed promising antiviral activity, and the C-3 and C-30 of GA could tolerate some modifications. Our findings suggested that GA could be used as a lead compound for the development of potential anti-influenza virus agents.


title: An educational programme for nursing college staff and students during a MERS- coronavirus outbreak in Saudi Arabia

text: BACKGROUND: The Middle Eastern Respiratory Syndrome Coronavirus is a serious and emerging issue in Saudi Arabia and the world. A response was required to reduce possible disease transmission between the hospital and university. College of Nursing academic staff developed a programme in response to the educational and emotional needs of participants. METHODS: A MERS-CoV Task Force responded to the rapidly unfolding epidemic. The aim was to find out what nursing staff and nursing students in the college knew about MERS- CoV. While most gaps in knowledge were addressed after an intense information seminar, other learning needs were identified and responded to. The Task Force developed mandatory information sessions for all nursing faculty, students and staff. All staff were informed by email, letters and posters. There are 28 faculty staff, 84 support staff and 480 students in the College of Nursing. The information settings all took place within the College of Nursing, Princess Nourah University, Kingdom of Saudi Arabia. Questionnaires were given to faculty, students and staff to understand their baseline knowledge. After the sessions, faculty, students and staff were asked about what was learned through the sessions, and what educational needs still needed to be addressed. Approval was sought and received by the Ethics Committee for the College of Nursing. Participants completed informed consent forms and the voluntary nature of the study was explained. RESULTS: The total number of people attending the education sessions was133, including 65 students. 18 faculty members attended and 57 support staff. Data was gathered on gaps in participant knowledge and a plan was developed to address the gaps. Policies were established around student participation in clinical and return to work practices for staff with any symptoms. CONCLUSION: In hospitals there is above average risk for exposure to infectious diseases. Student nurses travel between hospital and university, with the capacity to act as a conduit of pathogens to large, susceptible populations. Nursing colleges must respond thoroughly to protect students and staff and prevent spread of disease into the university community in the midst of an epidemic.


title: Role of Homozygous DC-SIGNR 5/5 Tandem Repeat Polymorphism in HIV-1 Exposed Seronegative North Indian Individuals

text: Despite multiple sexual exposures to HIV-1 virus, some individuals remain HIV-1 seronegative. Although several genetic factors have been related to HIV-1 resistance, the homozygosity for a mutation in CCR5 gene (the 32-bp deletion, i.e., CCR5-Delta32 allele) is presently considered the most relevant one. The C-type lectins, DC-SIGN (present on dendritic cells and macrophages) and DC-SIGNR (present on endothelial cells in liver and lymph nodes) efficiently bind and transmit HIV-1 to susceptible cell in trans, thereby augmenting the infection. A potential association of the DC-SIGN and DC-SIGNR neck domain repeat polymorphism and risk of HIV-1 infection is currently under debate. To determine the influence of host genetic factors on HIV-1 resistance, we conducted genetic risk association study in HIV-1-exposed seronegative (n = 47) individuals, HIV-1 seronegative (n = 262) healthy control, and HIV-1-infected seropositive patients (n = 168) for polymorphism in neck domain of DC-SIGN and DC-SIGNR genes. The DC-SIGN and DC-SIGNR genotypes were identified by polymerase chain reaction method in DNA extracted from peripheral blood and confirmed by sequencing. Fisher exact or χ (2) test was used for static analysis. DC-SIGN genotype and allele distribution was fairly similar in HIV-1-exposed seronegative, HIV-1 seropositive, and HIV-1 seronegative control. There was no statistical significance in the differences in the distribution of DC-SIGN genotypes. A total of 13 genotypes were found in DC-SIGNR neck repeat region polymorphism. Among all the genotypes, only 5/5 homozygous showed significant reduced risk of HIV-1 infection in HIV-1-exposed seronegative individuals (p = 0.009). A unique genotype 8/5 heterozygous was also found in HIV-1 seropositive individual, which is not reported elsewhere.


title: Global Spread of Hemorrhagic Fever Viruses: Predicting Pandemics

text: As successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. Epidemics usually occur when health systems are unprepared. During an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. As humanity recovers, policy-makers seek scientific expertise to improve their “preparedness” to face future events. Global spread of disease is exemplified by the spread of yellow fever from Africa to the Americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of Ebola virus, spread by motorbike and long haul carriers. Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Did we learn from the past epidemics? Are we prepared for the worst? The ultimate goal is to develop a resilient global health infrastructure. Besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. So far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in Southeast Asia and South America, illuminating the imperfections of our surveillance. Epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community. Pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, Geographic Information Systems (GIS), Next Generation sequencing, and Metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. Predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. Preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. At present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. For the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response.


title: Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

text: The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection.


title: Evolutionary insights into host–pathogen interactions from mammalian sequence data

text: Infections are one of the major selective pressures acting on humans, and host-pathogen interactions contribute to shaping the genetic diversity of both organisms. Evolutionary genomic studies take advantage of experiments that natural selection has been performing over millennia. In particular, inter-species comparative genomic analyses can highlight the genetic determinants of infection susceptibility or severity. Recent examples show how evolution-guided approaches can provide new insights into host–pathogen interactions, ultimately clarifying the basis of host range and explaining the emergence of different diseases. We describe the latest developments in comparative immunology and evolutionary genetics, showing their relevance for understanding the molecular determinants of infection susceptibility in mammals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users.


title: Familial acute necrotizing encephalopathy with RANBP2 mutation: The first report in Northeast Asia

text: Abstract Background Acute necrotizing encephalopathy (ANE) is a rare but rapidly progressing encephalopathy following a febrile illness, commonly a viral infection. It is characterized by the features of acute encephalopathy such as seizure, alteration of consciousness, and symmetric involvement of the bilateral thalamus on neuroimaging tests. Although most ANE cases have occurred sporadically, familial or recurrent ANE has been reported in Caucasian patients, with genetic susceptibility to ANE noted in some patients due to a RANBP2 mutation. We report the cases of two Korean siblings with typical ANE and RANBP2 mutation. Case report A 2year-old Korean girl presented with prolonged seizures and encephalopathy after two days of febrile illness. Brain computed tomography (CT) showed diffuse brain swelling and low attenuation in the bilateral thalamus. Two months later, her younger sister presented with lethargy and flurries of seizures after a Mycoplasma pneumoniae infection. Brain magnetic resonance imaging scan (MRI) showed a characteristic involvement of the bilateral thalamus, suggesting ANE. Although they received intravenous steroids and immunoglobulin, the older child died; her sister remained in a coma. Both were diagnosed with familial ANE after identifying a common missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) in the younger sister and their father. Conclusions This report is the first case of familial ANE in Northeast Asia identifying a RANBP2 mutation with poor outcome. Due to rapidly deterioration and recurrent nature of familial ANE, genetic test of RANBP2 mutation should be considered for early diagnosis. Further studies are needed to elucidate the nature of ANE.


title: Differential expression of sialic acid on porcine organs during the maturation process

text: Sialylated structures play important roles in cell communication, and change in a regulated manner during development and differentiation. In this work, we report the main glycosidic modifications that occur during the maturation of porcine tissues, involving the sialylation process as determined with lectins. Sialic acids were identified at several levels in a broad range of cell types of nervous, respiratory, genitourinary and lymphoid origin. Nevertheless, the most contrasting was the type of glycosidic linkage between 5-N-acetyl-neuraminic acid (Neu5Ac) and galactose (Gal) expressed in central nervous system (CNS). Newborn CNS abundantly expressed Neu5Acα2,3Gal, but weakly or scarcely expressed Neu5Acα2,6Gal/GalNAc. Maturation of CNS induced drastic changes in sialic acid expression. These changes include decrease or complete loss of NeuAcα2,3Gal residues, mainly in olfactory structures and brain cortex, which were replaced by their isomers Neu5Acα2,6Gal/GalNAc. In the brain cortex and cerebellum, the increase of Neu5Acα2,6Gal/GalNAc molecules was paralleled by an increase of 5-N-acetyl-9-O-acetyl-neuraminic acid (Neu5,9Ac2). In addition, terminal Gal and N-acetyl-d-galactosamine (GalNAc) residues also increased their expression in adult CNS tissues, but this was more significant in structures forming the encephalic trunk. Our results show that sialylation of porcine CNS is finely modulated throughout the maturation process.


title: Are Patients with Inflammatory Bowel Disease at Increased Risk for Covid-19 Infection?

text: Crohn’s disease [CD] and ulcerative colitis [UC], the main inflammatory bowel diseases [IBD] in humans, are chronic, immune-inflammatory diseases, the pathogenesis of which suggests a complex interaction between environmental factors and genetic susceptibility. These disabling conditions affect millions of individuals and, together with the drugs used to treat them, can put patients at risk of developing complications and other conditions. This is particularly relevant today, as coronavirus disease [Covid-19] has rapidly spread from China to countries where IBD are more prevalent, and there is convincing evidence that Covid-19-mediated morbidity and mortality are higher in subjects with comorbidities. The primary objectives of this Viewpoint are to provide a focused overview of the factors and mechanisms by which the novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infects cells and to illustrate the link between such determinants and intestinal inflammation. We also provide clues about the reasons why the overall IBD population might have no increased risk of developing SARS-CoV-2 infection and highlight the potential of cytokine blockers, used to treat IBD patients, to prevent Covid-driven pneumonia.


title: 20th International Conference on Emerging Infectious Diseases in the Pacific Rim Organized by the United States-Japan Cooperative Medical Sciences Program (USJCMSP)

text: The 20th International Conference on Emerging Infectious Diseases in the Pacific Rim to3ok place in Shenzhen, China on January 8–9, 2018 followed by meetings of the acquired immunodeficiency syndrome (AIDS)/immunology, acute respiratory infections, cancer, hepatitis, and viral diseases panels on January 10–11. The conference was organized as part of the United States-Japan Cooperative Medical Sciences Program (USJCMSP) by the Japan Agency for Medical Research and Development (AMED) and the U.S. National Institutes of Health (NIH) and was locally hosted by the Shenzhen Third People’s Hospital and the Chinese Academy of Sciences (CAS) Institute of Microbiology. The conference provides the basis for networking and fostering of collaboration opportunities between researchers in Southeast Asia and the United States based on the scientific and interactive platform of the USJCMSP and takes place in the region on an annual basis. This report summarizes the discussions and conclusions from the conference.


title: Chapter 7 Nanoparticle-based vaccines opportunities and limitations

text: Abstract Infectious diseases are the tip of the iceberg in the economic burden of the developing countries, due to the resistance of the pathogens to antibiotics and the lack of vaccines. The vaccines have become a big challenge in the last decades, where the attention has been focused on scientific challenges such as new vaccine development and adjuvants or delivery systems. The classical vaccines were developed from live-attenuated or killed organisms, such as influenza, smallpox, and BCG, as well as subunits such as Hepatitis B. The attenuated vaccines carry the risk of regaining their pathogenicity under immunosuppression conditions. The development of subunit vaccines without risk are considered as an essential need in combination with adequate delivery systems to obtain desired cell and humoral immune responses against infectious diseases. In the last decades, the use of nanoparticles as a delivery system in vaccines has received special attention to improve vaccine efficacy. These nanoparticles could be composed of lipids, metal and nonmetal inorganics, several polymers, and virus-like particles, which have been tested in research; some of them have already been approved for human and animal use. The characteristics of the nanoparticles have allowed targeting desired antigen-presenting cells to improve immunization strategies to induce protection. The main characteristics of the nanoparticles are to protect the antigens from early proteolytic degradation, control antigen release, and help antigen uptake and processing by antigen-presenting cells, and they should be safe for human and veterinary use. In addition, the nanoparticles could be modified in their physicochemical properties to target specific cells and improve vaccine efficacy. This chapter focuses on the nanoparticle-based vaccine formulations and the approaches used to realize efficient delivery of vaccines in order to induce host protective immunity against infectious diseases.


Coronavirus: Wales tests 90% of suspected patients in their own home.


title: Chapter 2 Virus Replication

text: Publisher Summary This chapter describes virus replication. Before the development of in vitro cell culture techniques, all viruses had to be propagated in their natural host. For bacterial viruses, this was a relatively simple process that permitted an earlier development of laboratory research methods than was possible with plant or animal viruses. For animal viruses, samples from affected animals were collected and used to infect other animals, initially of the same species. When consistent results were obtained, attempts were usually made to determine whether other species might also be susceptible. This chapter explains that the advent of in vitro animal cell culture brought research studies in line with those involving bacterial viruses, thereby reducing the risks associated with adventitious viruses in animal inoculation systems and enhancing diagnostic testing. Various in vitro cell culture systems are used since an artificial medium was developed to maintain cell viability outside the source species: organ cultures, explant cultures, primary cell cultures, and cell lines. Organ cultures maintain the three-dimensional structure of the tissue and are used for short-term experiments. A fundamental characteristic that separates viruses from other replicating entities is the manner in which new virus particles are synthesized. Viruses do not use binary fission; virus particles are assembled de novo from the various structural components synthesized as somewhat independent but synchronized events. The critical first step in the virus replication cycle is the binding of the virus particle to a host cell. This binding process may involve a series of interactions that define in part the host range of the virus and its tissue/organ specificity.


title: Special Issue “Equine Viruses”: Old “Friends” and New Foes?

text: The Food and Agriculture Organization of the United Nations has recently estimated that the world equid population exceeds 110 million (FAOSTAT 2017).[...].


title: Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

text: The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted.


Author reply to Letters to the Editor “COVID-19 pneumonia in Taiwan”


title: Resveratrol plus carboxymethyl-β-glucan in infants with common cold: A randomized double-blind trial

text: OBJECTIVES: To evaluate effectiveness of a nasal resveratrol/carboxymethyl-β-glucan solution compared to nasal saline solution: a) on common cold symptoms by means of a validated measure scale (CARIFS score), b) on Rhinovirus infection and CCL2, CCL5, IL8, IL6, CXCL10 and TLR2 expression in nasal swabs, c) on frequency of relapses after 30 days of follow-up. METHODS: 89 infants with respiratory infection symptoms were randomly assigned to receive either a nasal resveratrol/carboxymethyl-β-glucan solution or nasal saline solution. All patients were evaluated with CARIFS score at enrollment, after 48 h, 7 and 30 days by physicians and parents. Nasal swabs were obtained at enrollment, after 48 h and after one week. RESULTS: CARIFS score improved in both groups. Episodes of sneezing and cough were fewer in study group after 7 days of follow-up (p < 0.05). No significant differences were found on nasopharyngeal swabs in Rhinovirus detection and cytokines expression after 48 h, nor in 30 days relapses. TLR2 expression was significantly higher in Rhinovirus infected children of the study group. No adverse effects occurred. CONCLUSIONS: These data suggest that a solution containing resveratrol plus carboxymethyl-β-glucan might have a positive impact on both clinical and socio-economic burden due to infant common cold.


title: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection

text: Summary Background The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. Methods We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). Findings We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. Interpretation Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations. Published online May 9, 2003 http://image.thelancet.com/extras/03art4454web.pdf