title: An exploration of conditions proposed to trigger the Ebola virus glycoprotein for fusion

text: Ebolaviruses continue to inflict horrific disease and instill fear. The 2013–2016 outbreak in Western Africa caused unfathomable morbidity and mortality (over 11,000 deaths), and the second largest outbreak is on-going in the Democratic Republic of the Congo. The first stage of an Ebolavirus infection is entry, culminating in delivery of the viral genome into the cytoplasm to initiate replication. Among enveloped viruses, Ebolaviruses use a complex entry pathway: they bind to attachment factors on cell surfaces, are engulfed by macropinocytosis, and traffic through the endosomal system. En route, the receptor binding subunit of the glycoprotein (GP) is reduced from ~130 to ~19 kDa by cathepsins. This event allows cleaved GP (GP(cl)) to bind to Niemann-Pick C1 (NPC1), its endosomal receptor. The virus then fuses with a late endosomal membrane, but how this occurs remains a subject of debate. An early, but standing, observation is that entry of particles bearing GP(cl) is inhibited by agents that raise endosomal pH or inhibit cysteine proteases, suggesting the need for an additional factor(s). Yet, some have concluded that NPC1 is sufficient to trigger the fusion activity of GP(cl). Here, we re-examined this question using sensitive cell-cell and pseudovirus-cell fusion assays. We did not observe detectable GP(cl)-mediated fusion with NPC1 or its GP(cl) binding domain at any pH tested, while robust fusion was consistently observed with GP from lymphocytic choriomeningitis virus at low pH. Addition of proposed fusion-enhancing factors—cations (Ca(++) and K(+)), a reducing agent, the anionic lipid Bis(Monoacylglycero)Phosphate, and a mixture of cathepsins B and L—did not induce detectable fusion. Our findings are in line with the earlier proposal that an additional factor is required to trigger the full fusion activity of GP(cl) after binding to NPC1. We discuss caveats to our study and what the missing factor(s) might be.


title: COVID-19 y arritmias, relación y riesgo

text: Resumen La pandemia por COVID-19 tiene relación con arritmias que ocurren a través de efectos directos en el miocardio o de efectos indirectos por los tratamientos que podrían ser útiles para detener al virus. Esta revisión muestra el mal pronóstico que confiere el antecedente de arritmias o el desarrollo de estas durante el curso de la enfermedad por COVID-19, el efecto proarrítmico de algunos tratamientos y las medidas de prevención y tratamiento en caso de presentar arritmias. Abstract The COVID-19 pandemic has a relationship with arrhythmias that occur through direct effects on the myocardium, or through indirect effects of the treatments that could be used in detaining the virus. In this review, it demonstrates the poor prognosis conferred by having a history of arrhythmias or the development of these during the course of the illness due to COVID-19, the proarrhythmic effect of some treatments, and the prevention measures, and treatment in cases presenting with arrhythmias.


title: What you need to know

text: From symptoms and fatality rate to stockpiling and caring for family, Michael Le Page and Jessica Hamzelou have the answers


title: Covid-19 Outbreak and the Need for Rice Self-sufficiency in West Africa

text: In the decade since the 2008 global food crisis, West African countries have made efforts to raise domestic rice production and to make the region self-sufficient. Today, West Africa produces nearly two-thirds of Africa’s rice. The region’s rice import dependency has fallen from nearly half of local consumption in 2010 to about 30%. In spite of this improvement, the region remains the world’s second largest rice importer. The situation of Benin, Burkina Fasso, Gambia and Niger remains challenging with rice import dependency still exceeding 70%. Production in some countries has fallen even below the 2010 level due to civil strife, climatic changes and macroeconomic difficulties. Countries of the region, on average, allocate less than 5% of their budget to agriculture, less than half the share committed in the Maputo Agreement. The Covid-19 outbreak and corresponding preventive lockdowns have posed a new challenge as food supply chains were stretched; production, transportation and consumption fell sharply; and household income was affected. In addition, closure of frontiers and temporary trade disruption in major Asian rice exporters has led to increase in rice prices in the international market. In late April, rice futures rose to reach a level not surpassed since 2011. This threatens to further aggravate an already fragile food security situation in the region. The crisis again points to the need for greater efforts at the national and international level to achieve food security. West African countries will need to enhance public spending on agriculture with a greater focus on measures aimed at improving rice productivity


title: Investigating the impact of gaspers on cabin air quality in commercial airliners with a hybrid turbulence model

text: Abstract It is not clear whether turning on the gaspers in the cabins of commercial airliners actually improves the air quality. To answer this question, this study first developed a hybrid turbulence model which was suitable for predicting the air distribution in an aircraft cabin with gaspers turned on. Next, the investigation validated the model using two sets of experimental data from a cabin mockup and an actual airplane. This study then used the validated model to systematically investigate the impact of gaspers on cabin air quality in a seven-row section of the fully-occupied, economy-class cabin of Boeing 767 and 737 airplanes. The CFD calculations formed a database consisting of 9660 data points that provide information about SARS infection risk. It was found that the distribution of opened gaspers can influence the infection risk for passengers. Even though the gasper supplies clean air, it is possible for it to have a negative impact on the passengers' health. Statistically speaking, the overall effect of turning on the gaspers on the mean infection risk for the general population was neutral.


title: High‐Coverage SARS‐CoV‐2 Genome Sequences Acquired by Target Capture Sequencing

text: In this study, we designed a set of SARS‐CoV‐2 enrichment probes to increase the capacity for sequence‐based virus detection and obtain the comprehensive genome sequence at the same time. This universal SARS‐CoV‐2 enrichment probe set contains 502 120nt ssDNA biotin‐labeled probes designed based on all available SARS‐CoV‐2 viral sequences and it can be used to enrich for SARS‐CoV‐2 sequences without prior knowledge of type or subtype. Following the CDC health and safety guidelines, marked enrichment was demonstrated in a virus strain sample from a cell culture, three nasopharyngeal swab samples (cycle threshold [Ct] values: 32.36, 36.72, and 38.44) from patients diagnosed with COVID‐19 (positive control) and four throat swab samples from patients without COVID‐19 (negative controls), respectively. Moreover, based on these high‐quality sequences, we discuss the heterozygosity and viral expression during coronavirus replication, and its phylogenetic relationship with other selected high‐quality samples from The Genome Variation Map (GVM). Therefore, this universal SARS‐CoV‐2 enrichment probe system can capture and enrich SARS‐CoV‐2 viral sequences selectively and effectively in different samples, especially clinical swab samples with a relatively low concentration of viral particles. This article is protected by copyright. All rights reserved.


title: A calculus for services innovation

text: Innovation in the services area — especially in the electronic services (e-services) domain — can be systematically developed by first considering the strategic drivers and foci, then the tactical principles and enablers, and finally the operational decision attributes, all of which constitute a process or calculus of services innovation. More specifically, there are four customer drivers (i.e., collaboration, customization, integration and adaptation), three business foci (i.e., creation-focused, solution-focused and competition-focused), six business principles (i.e., reconstruct market boundaries, focus on the big picture not numbers, reach beyond existing demand, get strategic sequence right, overcome organizational hurdles and build execution into strategy), eight technical enablers (i.e., software algorithms, automation, telecommunication, collaboration, standardization, customization, organization, and globalization), and six attributes of decision informatics (i.e., decision-driven, information-based, real-time, continuously-adaptive, customer-centric and computationally-intensive). It should be noted that the four customer drivers are all directed at empowering the individual — that is, at recognizing that the individual can, respectively, contribute in a collaborative situation, receive customized or personalized attention, access an integrated system or process, and obtain adaptive real-time or just-in-time input. The developed process or calculus serves to identify the potential white spaces or blue oceans for innovation. In addition to expanding on current innovations in services and related experiences, white spaces are identified for possible future innovations; they include those that can mitigate the unforeseen consequences or abuses of earlier innovations, safeguard our rights to privacy, protect us from the always-on, interconnected world, provide us with an authoritative search engine, and generate a GDP metric that can adequately measure the growing knowledge economy, one driven by intangible ideas and services innovation.


title: Rapid and sensitive insulated isothermal PCR for point-of-need feline leukaemia virus detection

text: OBJECTIVES: Feline leukaemia virus (FeLV), a gamma retrovirus, causes diseases of the feline haematopoietic system that are invariably fatal. Rapid and accurate testing at the point-of-need (PON) supports prevention of virus spread and management of clinical disease. This study evaluated the performance of an insulated isothermal PCR (iiPCR) that detects proviral DNA, and a reverse transcription (RT)-iiPCR that detects both viral RNA and proviral DNA, for FeLV detection at the PON. METHODS: Mycoplasma haemofelis, feline coronavirus, feline herpesvirus, feline calicivirus and feline immunodeficiency virus were used to test analytical specificity. In vitro transcribed RNA, artificial plasmid, FeLV strain American Type Culture Collection VR-719 and a clinical FeLV isolate were used in the analytical sensitivity assays. A retrospective study including 116 clinical plasma and serum samples that had been tested with virus isolation, real-time PCR and ELISA, and a prospective study including 150 clinical plasma and serum samples were implemented to evaluate the clinical performances of the iiPCR-based methods for FeLV detection. RESULTS: Ninety-five percent assay limit of detection was calculated to be 16 RNA and five DNA copies for the RT-iiPCR, and six DNA copies for the iiPCR. Both reactions had analytical sensitivity comparable to a reference real-time PCR (qPCR) and did not detect five non-target feline pathogens. The clinical performance of the RT-iiPCR and iiPCR had 98.82% agreement (kappa[κ] = 0.97) and 100% agreement (κ = 1.0), respectively, with the qPCR (n = 85). The agreement between an automatic nucleic extraction/RT-iiPCR system and virus isolation to detect FeLV in plasma or serum was 95.69% (κ = 0.95) and 98.67% (κ = 0.85) in a retrospective (n = 116) and a prospective (n = 150) study, respectively. CONCLUSIONS AND RELEVANCE: These results suggested that both RT-iiPCR and iiPCR assays can serve as reliable tools for PON FeLV detection.


docid: fcqtstpk

title: Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases

text: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.


title: Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

text: BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients’ mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.


title: Estimated Burden of Community-Onset Respiratory Syncytial Virus–Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014–15

text: BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalizations in young children. We estimated the burden of community-onset RSV-associated hospitalizations among US children aged <2 years by extrapolating rates of RSV-confirmed hospitalizations in 4 surveillance states and using probabilistic multipliers to adjust for ascertainment biases. METHODS: From October 2014 through April 2015, clinician-ordered RSV tests identified laboratory-confirmed RSV hospitalizations among children aged <2 years at 4 influenza hospitalization surveillance network sites. Surveillance populations were used to estimate age-specific rates of RSV-associated hospitalization, after adjusting for detection probabilities. We extrapolated these rates using US census data. RESULTS: We identified 1554 RSV-associated hospitalizations in children aged <2 years. Of these, 27% were admitted to an intensive care unit, 6% needed mechanical ventilation, and 5 died. Most cases (1047/1554; 67%) had no underlying condition. Adjusted age-specific RSV hospitalization rates per 100 000 population were 1970 (95% confidence interval [CI],1787 to 2177), 897 (95% CI, 761 to 1073), 531 (95% CI, 459 to 624), and 358 (95% CI, 317 to 405) for ages 0–2, 3–5, 6–11, and 12–23 months, respectively. Extrapolating to the US population, an estimated 49 509–59 867 community-onset RSV-associated hospitalizations among children aged <2 years occurred during the 2014–2015 season. CONCLUSIONS: Our findings highlight the importance of RSV as a cause of hospitalization, especially among children aged <2 months. Our approach to estimating RSV-related hospitalizations could be used to provide a US baseline for assessing the impact of future interventions.


title: One-pot synthesis of glycyrrhetic acid polyglycosides based on grafting-from method using cyclic sulfite

text: Abstract Glycyrrhetic acid polyglycosides were synthesized in one-pot via cationic ring-opening condensation polymerization of cyclic sulfite (4) initiated by glycyrrhetic acid as an aglycon. Sulfite 4 worked as a practical monomer for the preparation of (1→2)-linked polysaccharide skeletons. The chemical stability of 4 was evaluated by the comparison of thermodynamic parameters with those of conventional epoxide (2). The grafting reaction of 4 from glycyrrhetic acid (5) was performed in the presence of TfOH and MS 3A in CH2Cl2 at room temperature. The polymerization degree was moderately controllable by the change of feed ratio of initiator.


title: Urbanisation and infectious diseases in a globalised world

text: Summary The world is becoming urban. The UN predicts that the world's urban population will almost double from 3·3 billion in 2007 to 6·3 billion in 2050. Most of this increase will be in developing countries. Exponential urban growth is having a profound effect on global health. Because of international travel and migration, cities are becoming important hubs for the transmission of infectious diseases, as shown by recent pandemics. Physicians in urban environments in developing and developed countries need to be aware of the changes in infectious diseases associated with urbanisation. Furthermore, health should be a major consideration in town planning to ensure urbanisation works to reduce the burden of infectious diseases in the future.


title: Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia

text: Summary Objectives To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Methods The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved. Results A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31–68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality. Conclusions The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome.


title: Forme familiale de la maladie de Kawasaki : à propos de 2 cas dans une fratrie

text: Résumé Nous présentons 2 cas de maladie de Kawasaki survenus dans une même fratrie à 7 ans d'intervalle. Ces observations soulèvent à nouveau l'hypothèse d'une prédisposition génétique de cette affection. Depuis plusieurs années, des enquêtes épidémiologiques menées au Japon évoquent l'hypothèse d'un facteur génétique sans en faire la preuve. Cette vascularite fébrile de l'enfant reste de diagnostic difficile, et donc souvent retardé, alors que l'on dispose d'un traitement efficace permettant de prévenir ses complications cardiaques, faisant toute la gravité de la maladie. L'identification de son étiologie précise, étape préalable indispensable à la mise au point d'un éventuel marqueur diagnostique spécifique, constituerait un progrès majeur. Abstract This article presents the clinical observation of 2 cases of children suffering from Kawasaki disease in the same family at a 7-year interval. This observation suggests a genetic predisposition to the disease. Epidemiological surveys conducted in Japan for some years point to a genetic factor but without proof. Childhood systemic febrile vasculitis is hard to recognise, so its diagnosis is often made lately, while there is an effective therapy, which prevents from serious cardiovascular complications. Identification of its precise cause, a necessary step before any diagnostic laboratory test, will be a major breakthrough.


title: Tracheostomy intervention in intubated COVID positive patients: A survey of current clinical practice among ENT surgeons

text: INTRODUCTION: The COVID‐19 pandemic has resulted in an unprecedented need for critical care intervention. Prolonged intubation and mechanical ventilation has resulted in the need for tracheostomy in some patients. The purpose of this international survey was to assess optimal timing, technique and outcome for this intervention. METHODS: An online survey was generated. Otorhinolaryngologists from both the United Kingdom and Abroad were polled with regards to their experience of tracheostomy in COVID‐19 positive ventilated patients. RESULTS: The survey was completed by 50 respondents from 16 nations. The number of ventilated patients totalled 3403, on average 9.7% required a tracheostomy. This was on average performed on day 14 following intubation. The majority of patients were successfully weaned (mean 7.4 days following tracheostomy). CONCLUSION: The results of this brief survey suggest that tracheostomy is of benefit in selected patients. There was insufficient data to suggest improved outcomes with either percutaneous vs an open surgical technique.


title: High Titers of IgE Antibody to Dust Mite Allergen and the Risk for Wheezing Among Asthmatic Children Infected with Rhinovirus

text: BACKGROUND: The relevance of allergic sensitization, judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear. OBJECTIVE: To examine the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden. METHODS: The children enrolled (n=287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 non-asthmatic controls. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, total IgE, allergen-specific IgE antibody, and levels of expired nitric oxide (FE(NO)). RESULTS: Sixty-four percent of wheezing children compared to 13% of children with stable asthma and 17% of the non-asthmatic controls tested positive for rhinovirus (p<0.001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were Group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides sp) were common and correlated significantly with levels of total IgE and FE(NO). The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite ≥17.5 IU/ml who tested positive for rhinovirus (odds ratio for wheezing: 31.5; 95% CI 8.3–108, p<0.001). CONCLUSIONS: High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.


title: Analysis of Resistance of Ebola Virus Glycoprotein-Driven Entry Against MDL28170, An Inhibitor of Cysteine Cathepsins

text: Ebola virus (EBOV) infection can cause severe and frequently fatal disease in human patients. The EBOV glycoprotein (GP) mediates viral entry into host cells. For this, GP depends on priming by the pH-dependent endolysosomal cysteine proteases cathepsin B (CatB) and, to a lesser degree, cathepsin L (CatL), at least in most cell culture systems. However, there is limited information on whether and how EBOV-GP can acquire resistance to CatB/L inhibitors. Here, we addressed this question using replication-competent vesicular stomatitis virus bearing EBOV-GP. Five passages of this virus in the presence of the CatB/CatL inhibitor MDL28170 were sufficient to select resistant viral variants and sequencing revealed that all GP sequences contained a V37A mutation, which, in the context of native GP, is located in the base of the GP surface unit. In addition, some GP sequences harbored mutation S195R in the receptor-binding domain. Finally, mutational analysis demonstrated that V37A but not S195R conferred resistance against MDL28170 and other CatB/CatL inhibitors. Collectively, a single amino acid substitution in GP is sufficient to confer resistance against CatB/CatL inhibitors, suggesting that usage of CatB/CatL inhibitors for antiviral therapy may rapidly select for resistant viral variants.


title: Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs

text: Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.


title: Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys

text: Abstract SARS coronavirus (SARS-CoV) administered intranasally and intratracheally to rhesus, cynomolgus and African Green monkeys (AGM) replicated in the respiratory tract but did not induce illness. The titer of serum neutralizing antibodies correlated with the level of virus replication in the respiratory tract (AGM>cynomolgus>rhesus). Moderate to high titers of SARS-CoV with associated interstitial pneumonitis were detected in the lungs of AGMs on day 2 and were resolving by day 4 post-infection. Following challenge of AGMs 2 months later, virus replication was highly restricted and there was no evidence of enhanced disease. These species will be useful for the evaluation of the immunogenicity of candidate vaccines, but the lack of apparent clinical illness in all three species, variability from animal to animal in level of viral replication, and rapid clearance of virus and pneumonitis in AGMs must be taken into account by investigators considering the use of these species in efficacy and challenge studies.


title: Duration of immunity (DOI) and booster vaccination—dealing with the issue at practice level in the UK

text: Abstract The presentation offers a UK veterinary practitioners viewpoint on issues of DOI and booster vaccination with reference to both dog and cat vaccines. The current use of vaccines and issues surrounding their use are discussed, including motivations for and against vaccinating in a climate of reduced fear of disease, and increased suspicion of vaccines. Attitudes to extended DOI and routine booster vaccinations are explored, and specific disease and prevention issues concerning leptospirosis in particular are presented. The strategy and tactics of implementation of extended DOI vaccines at general practice level are discussed based on the author's own experiences, and thoughts offered on how vaccine manufacturers might support the process at local and national levels, as well as communicating a positive message for continued routine vaccination of dogs and cats, and the advantages that extended DOI offers.


title: Dipeptidyl peptidase-4 inhibitors and the risks of autoimmune diseases in type 2 diabetes mellitus patients in Taiwan: a nationwide population-based cohort study

text: AIMS: Dipeptidyl peptidase-4, a transmembrane glycoprotein expressed in various cell types, serves as a co-stimulator molecule to influence immune response. This study aimed to investigate associations between DPP-4 inhibitors and risk of autoimmune disorders in patients with type 2 diabetes mellitus in Taiwan. METHODS: This retrospective cohort study used the nationwide data from the diabetes subsection of Taiwan National Health Insurance Research Database between January 1, 2009, and December 31, 2013. Cox proportional hazards models were developed to compare the risk of autoimmune disorders and the subgroup analyses between the DPP-4i and DPP-4i-naïve groups. RESULTS: A total of 774,198 type 2 diabetic patients were identified. The adjusted HR of the incidence for composite autoimmune disorders in DPP-4i group was 0.56 (95% CI 0.53–0.60; P < 0.001). The subgroup analysis demonstrated that the younger patients (aged 20–40 years: HR 0.47, 95% CI 0.35–0.61; aged 41–60 years: HR 0.50, 95% CI 0.46–0.55; aged 61–80 years: HR 0.63, 95% CI 0.58–0.68, P = 0.0004) and the lesser duration of diabetes diagnosed (0–5 years: HR 0.48, 95% CI 0.44–0.52; 6–10 years: HR 0.48, 95% CI 0.43–0.53; ≧ 10 years: HR 0.86, 95% CI 0.78–0.96, P < 0.0001), the more significant the inverse association of DPP-4 inhibitors with the incidence of composite autoimmune diseases. CONCLUSIONS: DPP-4 inhibitors are associated with lower risk of autoimmune disorders in type 2 diabetes mellitus patients in Taiwan, especially for the younger patients and the lesser duration of diabetes diagnosed. The significant difference was found between the four types of DPP-4 inhibitors and the risk of autoimmune diseases. This study provides clinicians with useful information regarding the use of DPP-4 inhibitors for treating diabetic patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00592-020-01533-5) contains supplementary material, which is available to authorized users.


title: The potential of putative zinc-binding motifs of haemagglutinin A (HA) protein for categorization and prediction of pathogenicity of H5 subtypes of avian influenza virus

text: In the present study, we used the potential of bioinformatics and computational analysis to predict the existence and biological relevance of zinc finger (ZF) motifs in heamagglutinin A (HA) protein of Avian Influenza (AI) virus. Sequence data of Avian Influenza (AI) virus were retrieved from accessible databases (GenBank, GISAID, IRD) and analyzed for the existence, as well as functional prediction of the putative zinc finger or ‘‘zinc-binding’’ motif(s) of HA protein. It is hypothesized that the ZF motif(s) in HA of AI can be used as a ‘‘novel’’ biomarker for categorization of the virus and/or its virulence. As a model for analysis, we used the H5 subtypes of highly pathogenic, non-pathogenic and low pathogenic avian influenza (HPAI, NPAI and LPAI) of H5N1 and H5N2 of avian and human origin. Interestingly, our method of characterization using the zinc-finger agrees with the existing classification in distinguishing between highly pathogenic and non-pathogenic or low pathogenic subtypes. The new method also clearly distinguished between low and non-pathogenic strains of H5N2 and H5N1 which are indistinguishable by the existing method that utilizes the sequence of amino acids of the proteolytic cleavage site for pathogenicity. It is hypothesized that zinc through the activities of zinc-binding proteins modulates the virulence property of the viral subtypes. Our observation further revealed that only the HA protein among the eight encoded proteins of influenza virus contain high numbers of Cys-His residues. It is expected that the information gathered from the analysis of the data will be useful to generate more research hypotheses/designs that will give further insight towards the identification and control of avian influenza virus through the molecular manipulation of zinc finger motifs present in viral HA protein.


docid: aiorjsyh

title: Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System

text: Humoral responses within the central nervous system (CNS) are common to many neurotropic viral infections, with antibody (Ab)-secreting cells (ASC) contributing to local protection. However, a role for virus-specific memory B cells (Bmem) within the CNS is poorly explored due to lack of robust phenotypic or functional identification in mice. This study takes advantage of the progeny of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice (AID(Cre)-Rosa26(tdTomato)) to monitor B cells having undergone activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) following neurotropic coronavirus infection. AID detection via tdTomato expression allowed tracking of virus-specific ASC and Bmem in priming and effector sites throughout infection. In draining lymph nodes, tdTomato-positive (tdTomato(+)) ASC were most prevalent prior to germinal center (GC) formation, but total tdTomato(+) B cells only peaked with robust GC formation at day 14 p.i. Moreover, their proportion of Bmem dominated over the proportion of ASC throughout infection. In the CNS, tdTomato(+) cells started emerging at day 14 p.i. While they initially comprised mainly Bmem, the proportions of ASC and Bmem became similar as tdTomato(+) B cells increased throughout viral persistence. Delayed tamoxifen treatment demonstrated ongoing CNS recruitment of tdTomato(+) B cells, mainly ASC, primed late during GC reactions. Overall, the data support the idea that virus-induced B cells exhibiting SHM require peripheral GC formation to emerge in the CNS. Ongoing GC reactions and regional signals further regulate dynamics within the CNS, with preferential maintenance of tdTomato(+) B cells in spinal cords relative to that in brains during viral persistence. IMPORTANCE The prevalence and role of antigen-specific Bmem in the CNS during viral encephalomyelitis is largely undefined. A lack of reliable markers identifying murine Bmem has made it difficult to assess their contribution to local antiviral protection via antigen presentation or conversion to ASC. Using reporter mice infected with neurotropic coronavirus to track virus-specific Bmem and ASC, this report demonstrates that both subsets only emerge in the CNS following peripheral GC formation and subsequently prevail. While early GC reactions supported preferential Bmem accumulation in the CNS, late GC reactions favored ASC accumulation, although Bmem outnumbered ASC in draining lymph nodes throughout infection. Importantly, virus-specific B cells undergoing sustained GC selection were continually recruited to the persistently infected CNS. Elucidating the factors governing temporal events within GCs, as well as regional CNS cues during viral persistence, will aid intervention to modulate CNS humoral responses in the context of infection and associated autoimmune pathologies.


title: Public health considerations associated with molluscan aquaculture systems: Human viruses

text: Abstract The documentation of several recent outbreaks of human virus diseases associated with the consumption of shellfish has reiterated the threat posed by these agents to the shellfish industry. This article reviews pertinent outbreaks, identifies principal viral agents involved, and delineates systems which may be at greatest risk. The results of two recent laboratory studies which sought to define environmental factors that contribute to virus accumulation by shellfish are also discussed. First, the accumulation of environmentally significant levels of feces-associated and monodispersed poliovirus by oysters (Crassostrea virginica) and clams (Mercenaria mercenaria) was investigated. The results of this study suggested that virus accumulation by mollusks may not be significant when water column concentrations are below ⋍0.01 plaque-forming units (PFU) per milliliter. The second study focused on the relative contributions of undisturbed sediments versus those in the water column in the accumulation of viruses by epifaunal and infaunal shellfish (C. virginica and M. mercenaria). Viruses were found to be most efficiently accumulated when suspended in the water column.


title: Development and application of multiplex PCR assays for detection of virus-induced respiratory disease complex in dogs

text: Canine infectious respiratory disease complex (CIRDC) viruses have been detected in dogs with respiratory illness. Canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), canine adenovirus type 2 (CAdV-2) and canine herpesvirus 1 (CaHV-1), are all associated with the CIRDC. To allow diagnosis, two conventional multiplex polymerase chain reactions (PCR) were developed to simultaneously identify four RNA and two DNA viruses associated with CIRDC. The two multiplex PCR assays were then validated on 102 respiratory samples collected from 51 dogs with respiratory illness by sensitivity and specificity determination in comparison to conventional simplex PCR and a rapid three-antigen test kit. All six viruses were detected in either individual or multiple infections. The developed multiplex PCR assays had a >87% sensitivity and 100% specificity compared to their simplex counterpart. Compared to the three-antigen test kit, the multiplex PCR assays yielded 100% sensitivity and more than 83% specificity for detection of CAdV-2 and CDV, but not for CIV. Therefore, the developed multiplex PCR modalities were able to simultaneously diagnose a panel of CIRDC viruses and facilitated specimen collection through being suitable for use of nasal or oral samples.


title: Selective and facile assay of human immunodeficiency virus protease activity by a novel fluorogenic reaction

text: Abstract A highly selective and facile assay of human immunodeficiency virus protease (HIV-PR) has been required for the screening of medicinal inhibitors and also for classifying the subtypes of HIV in the therapeutic treatment of acquired immune deficiency syndrome (AIDS). This article describes a novel assay method of HIV-PR based on the selective fluorogenic reaction of peptides. A peptide fragment generated from a substrate by the enzymatic digestion with HIV-PR could be selectively quantified by the spectrofluorometric detection after the fluorogenic reaction with catechol in the presence of sodium periodate and sodium borate (pH 7.0). This assay system uses an N-terminal acetyl peptide as the substrate and crude extracts from Escherichia coli expressing recombinant HIV-PR. The activity obtained by the proposed assay correlated with that obtained by a conventional HIV-PR assay based on fluorescence resonance energy transfer detection.


title: Highly sensitive nanomechanical assay for the stress transmission of carbon chain

text: Abstract Here, we report the first quantitative experimental study into the molecular basis of the transmission of mechanical signal that originates from biochemical reaction focusing on the length of carbon chain. We designed an experiment by using n-alkanethiols with a same carboxyl group and different chain lengths (n =1, 5, 10 and 15) to immobilize a same receptor molecule on the gold surface of a microcantilever, and detected the nanomechanical response of biochemical reaction. The sensitivity of the microcantilever was found to be greatly influenced by the chain length of linker that is between the receptor molecule and the microcantilever surface. The efficiency of stress transmission increases significantly with decreasing length of carbon chain. At the same time, we develop a label-free microcantilever sensor for highly sensitive detection of Glycyrrhizic acid (GL). The detection limit of the microcantilever sensor for GL is found to be as low as 20pg/mL for the shortest linker (n =1), which is 500 times lower than the longest linker (n =15) and 50 times lower than that of the corresponding icELISA. These findings will provide new insights into the fundamental mechanisms of stress transmission, which may be exploited for biochemical sensor and nanoactuation applications.


title: COVID‐19 pandemic and management of GIMEMA clinical trials: changes and challenges

text: With the outbreak of COVID‐19 pandemic (Wang et al, 2020), Italy ‐ and in particular the largest Northern regions ‐ became disease epicenter with a dramatic raise in infections and deaths in the month of March.


title: Matching diagnostics development to clinical need: Target product profile development for a point of care test for community-acquired lower respiratory tract infection

text: BACKGROUND: Point of care tests (POCTs) are increasingly being promoted for guiding the primary medical care of community acquired lower respiratory tract infections (CA-LRTI). POCT development has seldom been guided by explicitly identified clinical need and requirements of the intended users. Approaches for identifying POCT priorities and developing target product profiles (TPPs) for POCTs in primary medical care are not well developed, and there is no published TPP for a CA-LRTI POCT aimed at developed countries. METHODS: We conducted workshops with expert stakeholders and a survey with primary care clinicians to produce a target product profile (TPP) to guide the development of a clinically relevant and technologically feasible POCT for CA-LRTI. RESULTS: Participants with clinical, academic, industrial, technological and basic scientific backgrounds contributed to four expert workshops, and 45 practicing primary care clinicians responded to an online survey and prioritised community-acquired pneumonia (CAP) as the CA-LRTI where a new POCT was most urgently needed. Consensus was reached on a TPP document that included information on the intended niche in the clinical pathway in primary medical care; diagnostic product specification (intended use statement and test concept), and minimum and ideal user specifications. Clinicians minimum requirements of a CA-LRTI POCT included the use of minimally invasive samples, a result in less than 30 minutes, no more than a single preparation step, minimum operational requirements, and detection of common respiratory pathogens and their resistance to commonly prescribed antibiotics. CONCLUSIONS: This multidisciplinary, multistage partnership approach generated a clinically-driven TPP for guiding the development of a new POCT, and this approach as well as the TPP itself may be useful to others developing a new POCT.


title: The Arabidopsis eukaryotic translation initiation factor 3, subunit F (AteIF3f), is required for pollen germination and embryogenesis

text: Previous studies have shown that subunits E (eIF3e), F (eIF3f) and H (elF3h) of eukaryotic translation initiation factor 3 play important roles in cell development in humans and yeast. eIF3e and eIF3h have also been reported to be important for normal cell growth in Arabidopsis. However, the functions of subunit eIF3f remain largely unknown in plant species. Here we report characterization of mutants for the Arabidopsis eIF3f (AteIF3f) gene. AteIF3f encodes a protein that is highly expressed in pollen grains, developing embryos and root tips, and interacts with Arabidopsis eIF3e and eIF3h proteins. A Ds insertional mutation in AteIF3f disrupted pollen germination and embryo development. Expression of some of the genes that are essential for pollen tube growth and embryogenesis is down‐regulated in ateif3f‐1 homozygous seedlings obtained by pollen rescue. These results suggested that AteIF3f might play important roles in Arabidopsis cell growth and differentiation in combination with eIF3e and eIF3h.


title: Chapter 16 Shikimic acid as intermediary model for the production of drugs effective against influenza virus

text: Abstract This chapter explains the application of shikimic acid as preventive medicine for the outbreak of swine or Avian flu due to H1N1 virus. Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid), a natural organic compound, is generally utilized as a starting material for industrial synthesis of the antiviral oseltamivir, a drug against the H1N1 influenza virus. It is also an important intermediate in the biosynthesis of lignin, aromatic amino acids (phenylalanine, tyrosine, and tryptophan), and most alkaloids of plants and microorganisms. Plant and microbial sources are the only sources of shikimic acid. Being a deadly viral disease, influenza causes the death of around half a million people each year. A neuraminidase present on the surface of the virus is the most important factor for viral reproduction by contributing to the release of viruses from infected host cells and hence the treatment of influenza can only be possible by neuraminidase inhibitors. The neuraminidase inhibitors oseltamivir or Tamiflu derived from shikimic acid pathway have been found to be potent influenza viral neuraminidase inhibitors against most influenza strains.


docid: abepbwio

title: Synthetic lethals in HIV: ways to avoid drug resistance: Running title: Preventing HIV resistance

text: BACKGROUND: RNA viruses rapidly accumulate genetic variation, which can give rise to synthetic lethal (SL) and deleterious (SD) mutations. Synthetic lethal mutations (non-lethal when alone but lethal when combined in one genome) have been studied to develop cancer therapies. This principle can also be used against fast-evolving RNA-viruses. Indeed, targeting protein sites involved in SD + SL interactions with a drug would render any mutation of such sites, lethal. RESULTS: Here, we set up a strategy to detect intragenic pairs of SL and SD at the surface of the protein to predict less escapable drug target sites. For this, we detected SD + SL, studying HIV protease (PR) and reverse transcriptase (RT) sequence alignments from two groups of VIH(+) individuals: treated with drugs (T) or not (NT). Using a series of statistical approaches, we were able to propose bona fide SD + SL couples. When focusing on spatially close co-variant SD + SL couples at the surface of the protein, we found 5 SD + SL groups (2 in the protease and 3 in the reverse transcriptase), which could be good candidates to form pockets to accommodate potential drugs. CONCLUSIONS: Thus, designing drugs targeting these specific SD + SL groups would not allow the virus to mutate any residue involved in such groups without losing an essential function. Moreover, we also show that the selection pressure induced by the treatment leads to the appearance of new mutations, which change the mutational landscape of the protein. This drives the existence of differential SD + SL couples between the drug-treated and non-treated groups. Thus, new anti-viral drugs should be designed differently to target such groups. REVIEWERS: This article was reviewed by Neil Greenspan Csaba Pal and István Simon. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-015-0044-y) contains supplementary material, which is available to authorized users.


title: A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19

text: A high-throughput platform would greatly facilitate COVID-19 serological testing and antiviral screening. Here we report a nanoluciferase SARS-CoV-2 (SARS-CoV-2-Nluc) that is genetically stable and replicates similarly to the wild-type virus in cell culture. We demonstrate that the optimized reporter virus assay in Vero E6 cells can be used to measure neutralizing antibody activity in patient sera and produces results in concordance with a plaque reduction neutralization test (PRNT). Compared with the low-throughput PRNT (3 days), the SARS-CoV-2-Nluc assay has substantially shorter turnaround time (5 hours) with a high-throughput testing capacity. Thus, the assay can be readily deployed for large-scale vaccine evaluation and neutralizing antibody testing in humans. Additionally, we developed a high-throughput antiviral assay using SARS-CoV-2-Nluc infection of A549 cells expressing human ACE2 receptor (A549-hACE2). When tested against this reporter virus, remdesivir exhibited substantially more potent activity in A549-hACE2 cells compared to Vero E6 cells (EC50 0.115 vs 1.28 μM), while this difference was not observed for chloroquine (EC50 1.32 vs 3.52 μM), underscoring the importance of selecting appropriate cells for antiviral testing. Using the optimized SARS-CoV-2-Nluc assay, we evaluated a collection of approved and investigational antivirals and other anti-infective drugs. Nelfinavir, rupintrivir, and cobicistat were identified as the most selective inhibitors of SARS-CoV-2-Nluc (EC50 0.77 to 2.74 μM). In contrast, most of the clinically approved antivirals, including tenofovir alafenamide, emtricitabine, sofosbuvir, ledipasvir, and velpatasvir were inactive at concentrations up to 10 μM. Collectively, this high-throughput platform represents a reliable tool for rapid neutralization testing and antiviral screening for SARS-CoV-2.


title: Feline infectious peritonitis virus-associated rhinitis in a cat

text: CASE SUMMARY: This report describes a cat with initial respiratory signs prior to developing fulminant feline infectious peritonitis (FIP) after adoption from an animal shelter. Histologic examination of the tissues revealed typical lesions associated with FIP in the lung, liver, large intestine and small intestine. Histologic examination of the nasal cavity revealed pyogranulomatous rhinitis. Immunohistochemistry with monoclonal antibody FIPV3-70 targeting FIP antigen in macrophages confirmed FIP and molecular analysis identified a spike protein mutation (R793S) consistent with the presence of an FIP virus. Pathological changes, immunolabeling and molecular analysis provide evidence that respiratory infection by feline coronavirus is part of the spectrum of FIP-associated disease. RELEVANCE AND NOVEL INFORMATION: This report highlights nasal pathology associated with FIP through a combination of histopathology, immunohistochemistry and molecular characterization of the virus. Our work supports a little-appreciated role of the respiratory tract in FIP.


title: Outbreak of influenza A in a boarding school in South Africa, 2016

text: INTRODUCTION: We investigated an outbreak of influenza-like illness (ILI) at a boarding school in Eastern Cape Province, South Africa. We aimed to confirm the etiological agent, estimate attack rates and identify risk factors for illness. METHODS: We conducted a retrospective cohort study including senior school boarders (n=308). Students with ILI (cough and fever) were identified through school medical records. We also conducted a questionnaire-based cross-sectional study among senior students including boarders (n=107) and day students (n=45). We collected respiratory specimens for respiratory pathogen testing by real-time polymerase chain reaction from a subset of symptomatic students. We calculated attack rates of medically attended ILI (medILI) and identified factors associated with medILI using logistic regression. We calculated seasonal influenza vaccine effectiveness (VE) against medILI. RESULTS: Influenza A (H3N2) virus was detected in 61% (23/38) of specimens. Attack rate for medILI was 13% among boarders (39/308) in the cohort study and 20% in both day students (9/45) and boarders (21/107) in the cross-sectional study. Playing squash was associated with medILI (aOR 5.35, 95% confidence interval [95% CI]: 1.68-17.07). Of the boarders, 19% (57/308) were vaccinated before the outbreak. The adjusted VE against medILI was 18% (aOR 0.82, 95% CI 0.38-1.78). The outbreak led to cancellation of several events and the need for academic remedial sessions. CONCLUSION: We confirmed an influenza A (H3N2) virus outbreak with a high attack rate. The outbreak affected academic and sports activities. Participation in sports and social gatherings while experiencing ILI should be discouraged to reduce viral transmission and impact on school activities.


title: Inflammatory responses to infection: The Dutch contribution

text: Abstract At any given moment, our body is under attack by a large variety of pathogens, which aim to enter and use our body to propagate and disseminate. The extensive cellular and molecular complexity of our immune system enables us to efficiently eliminate invading pathogens or at least develop a condition in which propagation of the microorganism is reduced to a minimum. Yet, the evolutionary pressure on pathogens to circumvent our immune defense mechanisms is immense, which continuously leads to the development of novel pathogenic strains that challenge the health of mankind. Understanding this battle between pathogen and the immune system has been a fruitful area of immunological research over the last century and will continue to do so for many years. In this review, which has been written on the occasion of the 50th anniversary of the Dutch Society for Immunology, we provide an overview of the major contributions that Dutch immunologists and infection biologists have made in the last decades on the inflammatory response to viral, bacterial, fungal or parasitic infections. We focus on those studies that have addressed both the host and the pathogen, as these are most interesting from an immunological point of view. Although it is not possible to completely cover this comprehensive research field, this review does provide an interesting overview of Dutch research on inflammatory responses to infection.


title: A Scenario-Based Evaluation of the Middle East Respiratory Syndrome Coronavirus and the Hajj

text: Between April 2012 and June 2014, 820 laboratory-confirmed cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS-CoV in the population, with a lower reproductive number, some evidence of human-to-human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS-CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human-to-human cases, or a combination of the two. Furthermore, MERS-CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.


title: Chapter 6 Real-Time Estimation of the Case Fatality Ratio and Risk Factors of Death

text: Abstract During the course of an epidemic, estimating the risk of death and identifying risk factors of death are of utmost importance for public health assessment of the severity of infection. The real-time estimation involves a number of important statistical problems to consider, and this chapter comprehensively describes commonly used estimation methods and their pitfalls. When estimating the case fatality risk (CFR) during the course of an epidemic, the data are right-censored because of the time delay from illness onset to death. A conventional survival analysis technique is employed for addressing right censoring. Identification of risk factors of death also requires the care for censored nature of the data, and we have devised a method that combines the survival analysis and logistic regression. Ascertainment bias is always a practical issue in interpreting the absolute value of the CFR or comparing CFR between different groups, and recent studies have shown that observational effort including seroepidemiological survey has to be made to overcome this bias.


From COVID-19 Pandemic into a Brave New World


title: Preventing the dysfunction of public health centres responding to COVID‐19 by focusing on public health nurses in Japan

text: With the outbreak of COVID-19, maintaining the healthcare system is a crucial issue. In Japan, the number of COVID-19 cases is increasing rapidly day by day with a risk of overshooting initial estimations (WHO, 2020a). Public health nurses (PHNs) working in public health centers in prefectures and designated centers in cities or core cities, play a critical role in controlling COVID-19 (Yoshioka-Maeda, Honda, Iwasaki-Motegi, 2020). Providing care for COVID-19 patients, their families, and the community, the workload of PHNs has been reaching the maximum limit.


title: Academic Leadership in a Time of Crisis: The Coronavirus and COVID‐19

text: The novel coronavirus and the disease it causes, COVID‐19 is one of the most unpredictable global public health crises in recent times. Academic leaders across the United States have responded by moving their educational and associated activities online; as a sense of immediacy swept the nation. The decision to pivot to remote learning was made swiftly, particularly by those institutions operating a shared leadership model, benefitting from a greater degree of agility, innovation, and collaboration. The current article highlights three of the leadership best practices for navigating unpredictable adaptive challenges such as that posed by the coronavirus pandemic. Firstly, by utilizing a type of servant leadership, that emphasizes empowerment, involvement, and collaboration, academic leaders with emotional intelligence and emotional stability should place the interests of others above their own. Secondly, academic leaders should distribute leadership responsibilities to a network of teams throughout the organization to improve the quality of the decisions made in crisis resolution and thirdly, leaders should communicate clearly and frequently to all stakeholders through a variety of communication channels. Looking forward, the rise of the flexible “allostatic leader” with the adaptive capacity to learn and evolve in crisis, to emerge better able to address future crises, is described.


title: Rotavirus Increases Levels of Lipidated LC3 Supporting Accumulation of Infectious Progeny Virus without Inducing Autophagosome Formation

text: Replication of many RNA viruses benefits from subversion of the autophagic pathway through many different mechanisms. Rotavirus, the main etiologic agent of pediatric gastroenteritis worldwide, has been recently described to induce accumulation of autophagosomes as a mean for targeting viral proteins to the sites of viral replication. Here we show that the viral-induced increase of the lipidated form of LC3 does not correlate with an augmented formation of autophagosomes, as detected by immunofluorescence and electron microscopy. The LC3-II accumulation was found to be dependent on active rotavirus replication through the use of antigenically intact inactivated viral particles and of siRNAs targeting viral genes that are essential for viral replication. Silencing expression of LC3 or of Atg7, a protein involved in LC3 lipidation, resulted in a significant impairment of viral titers, indicating that these elements of the autophagic pathway are required at late stages of the viral cycle.


title: Anti-viral agents: potential utility in exacerbations of asthma

text: Asthma is the most common chronic respiratory disease and its prevalence is on the increase. Respiratory viral infections in early life have been suggested to increase the risk of development of asthma in later life and virus infection remains the single greatest precipitant of asthma exacerbations. The development of effective anti-viral treatments remains a key target for therapeutic intervention. Here we discuss the role of respiratory viral infection in asthma exacerbation and highlight current and potential anti-viral agents and their mechanisms of action.


title: Proteomic analysis of purified turkey adenovirus 3 virions

text: Turkey adenovirus 3 (TAdV-3) causes high mortality and significant economic losses to the turkey industry. However, little is known about the molecular determinants required for viral replication and pathogenesis. Moreover, TAdV-3 does not grow well in cell culture, thus detailed structural studies of the infectious particle is particularly challenging. To develop a better understanding of virus-host interactions, we performed a comprehensive proteomic analysis of proteinase K treated purified TAdV-3 virions isolated from spleens of infected turkeys, by utilizing one-dimensional liquid chromatography mass spectrometry. Our analysis resulted in the identification of 13 viral proteins associated with TAdV-3 virions including a novel uncharacterized TaV3gp04 protein. Further, we detected 18 host proteins in purified virions, many of which are involved in cell-to cell spread, cytoskeleton dynamics and virus replication. Notably, seven of these host proteins have not yet been reported to be present in any other purified virus. In addition, five of these proteins are known antiviral host restriction factors. The availability of reagents allowed us to identify two cellular proteins (collagen alpha-1 (VI) chain and haemoglobin) in the purified TAdV-3 preparations. These results represent the first comprehensive proteomic profile of TAdV-3 and may provide information for illustrating TAdV-3 replication and pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0214-z) contains supplementary material, which is available to authorized users.


title: Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

text: The Middle‐East and Africa Influenza Surveillance Network (MENA‐ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA‐ISN countries. Data were presented at the 8th MENA‐ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA‐ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA‐ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.


title: Infektionen mit neuem humanen Betacoronavirus 2c EMC/2012 (hCoV-EMC)

text: An unknown Coronavirus (hCoV-EMC) was first isolated retrospectively in September 2012 from sputum of a 60 year old Saudi Arabian patient, who suffered from acute respiratory failure followed by renal failure and died already in June 2012. The clinical findings were highly similar to those presented in the severe diseases seen in the SARS pandemic in 2003. Also the hCoV-E M C is genetically related to animal Coronaviruses (in bats) and caused 9 affirmed severe human infections leading to 5 deaths by now. The following article should give a short overview concerning the current knowledge about the new human Coronavirus as well as information about the official disease definition and registration procedures in Germany (Robert Koch-Institut).


title: Comparison of enzyme-linked immunosorbent assay and RT-PCR for the detection of porcine epidemic diarrhoea virus

text: Abstract Porcine epidemic diarrhoea (PED) is a contagious enteric disease of pigs caused by a coronavirus. A double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) based on the use of monoclonal antibodies was developed for the detection of porcine epidemic diarrhoea virus (PEDV). The DAS-ELISA was compared with RT-PCR in the examination of 506 specimens collected during 2006–2007 from pigs originating from different farms located in the Po valley. Both faecal samples obtained directly from the rectum of live animals showing clinical signs and intestinal samples collected from the caecum of deceased pigs were included in the study. The correlation between the two methods was higher when testing faecal samples (K =0.97, 95% CI: 0.94–1.00) than testing intestinal samples (K =0.62, 95% CI: 0.35–0.89). The use of ELISA technology provided an efficient and effective mean of evaluating the presence of coronavirus PED antigen in field samples and indicates that this procedure is a very useful tool in epidemiological studies.


Can PM(2.5) pollution worsen the death rate due to COVID-19 in India and Pakistan?


title: Survey on the implementation of the Occupational Health and Safety Act at an academic hospital in Johannesburg

text: BACKGROUND: Despite the available research findings, recommendations and the South African Occupational Health and Safety Act (OHSA) (Act 85 of 1993), there are still challenges with regard to the implementation of selected sections and regulations of the OHSA. This is evidenced by the occupational injuries and illness claims registered with the compensation fund (South Africa, Department of Labour 1993). OBJECTIVES: To determine the extent to which the OHSA was implemented at an academic hospital in Johannesburg, from the senior professional nurses and nursing managers’ perspective, and to describe recommendations in order to facilitate the implementation of the Act. METHODS: A contextual, quantitative, exploratory and descriptive survey was conducted. A purposive sampling method was used to select the participants that met the inclusion criteria. A structured Likert-scale questionnaire was used to collect data (Brink 2011). Stata version 12 was used to analyse the data. Cronbach’s alpha, with a cut-off point of 0.7 was used to test for internal consistency. Ethical considerations were strictly adhered to. Results are presented in the form of graphs, frequency distributions and tables. RESULTS: The study revealed that overall there is 93.3% non-implementation of the selected sections and regulations of the OHSA. These results have serious implications on the health and safety of employees in the workplace. CONCLUSION: The study recommends that the replication of the study should be conducted in order to determine the extent of implementation of the selected sections and regulations of the OHSA in other government institutions.


title: DESPERATE TIMES CALL FOR DESPERATE MEASURES: GOVERNMENT SPENDING MULTIPLIERS IN HARD TIMES

text: We investigate state‐dependent effects of fiscal multipliers and allow for endogenous sample splitting to determine whether the U.S. economy is in a slack state. When the endogenized slack state is estimated as the period of the unemployment rate higher than about 12%, the estimated cumulative multipliers are significantly larger during slack periods than nonslack periods and are above unity. We also examine the possibility of time‐varying regimes of slackness and find that our empirical results are robust under a more flexible framework. Our estimation results point out the importance of the heterogenous effects of fiscal policy and shed light on the prospect of fiscal policy in response to economic shocks from the current COVID‐19 pandemic. (JEL C32, E62, H20, H62)


title: First, do no harm: bilateral radial artery occlusion in a COVID-19 patient

text: OBJECTIVE: Objective of this case report is to draw attention to a less known thrombotic complication associated with COVID-19, i.e., thrombosis of both radial arteries, with possible (long-term) consequences. THE CASE: In our COVID-19 ICU a 49-year-old male patient was admitted, with past medical history of obesity, smoking and diabetes, but no reported atherosclerotic complications. The patient had been admitted with severe hypoxemia and multiple pulmonary emboli were CT-confirmed. ICU-treatment included mechanical ventilation and therapeutic anticoagulation. Preparing the insertion of a new radial artery catheter for invasive blood pressure measurement and blood sampling, we detected that both radial arteries were non-pulsating and occluded: (a) Sonography showed the typical anatomical localization of both radial and ulnar arteries. However, Doppler-derived flow-signals could only be obtained from the ulnar arteries. (b) To test collateral arterial supply of the hand, a pulse-oximeter was placed on the index finger. Thereafter, the ulnar artery at the wrist was compressed. This compression caused an immediate loss of the finger’s pulse-oximetry perfusion signal. The effect was reversible upon release of the ulnar artery. (c) To test for collateral perfusion undetectable by pulse-oximetry, we measured regional oxygen saturation (rSO(2)) of the thenar muscle by near-infrared spectroscopy (NIRS). Confirming our findings above, ulnar arterial compression demonstrated that thenar rSO(2) was dependent on ulnar artery flow. The described development of bilateral radial artery occlusion in a relatively young and therapeutically anticoagulated patient with no history of atherosclerosis was unexpected. CONCLUSIONS: Since COVID-19 patients are at increased risk for arterial occlusion, it appears advisable to meticulously check for adequacy of collateral (hand-) perfusion, avoiding the harm of hand ischemia if interventions (e.g., catheterizations) at the radial or ulnar artery are intended.


title: Demographic and seasonal characteristics of respiratory pathogens in neonates and infants aged 0 to 12 months in the Central‐East region of Tunisia

text: BACKGROUND: This study aimed to characterize the epidemiology of pathogenic respiratory agents in patients aged 0 to 12 months and hospitalized for acute respiratory infections in Tunisia between 2013 and 2014. METHODS: A total of 20 pathogens, including viruses, Mycoplasma pneumoniae, and Streptococcus pneumoniae, were detected using molecular sensitive assays, and their associations with the patient’s demographic data and season were analyzed. RESULTS: Viral infectious agents were found in 449 (87.2%) of 515 specimens. Dual and multiple infectious agents were detected in 31.4% and 18.6% of the samples, respectively. Viral infection was predominant in the pediatric environment (90.8%, P < 0.001), male patients (88.0%), and spring (93.8%). Rhinovirus was the most detected virus (51.8%) followed by respiratory syncytial virus A/B (34.4%), coronavirus group (18.5%), adenovirus (17.9%), and parainfluenza viruses 1‐4 (10.9%). Respiratory Syncytial virus A/B was significantly associated with gender (38.0% male cases vs 28.3% female cases, P = 0.02). Infections by Adenovirus, Bocavirus, and Metapneumovirus A/B increased with increasing age of patients (predominated cases aged 6‐12 months, P < 0.001). S. pneumoniae was detected in 30.9% of th tested samples. In 18.2% of the negative viral infections, only S. pneumoniae was identified. CONCLUSION: A predominance of the rhinovirus infection was observed in this study. Coronavirus subtypes were described for the first time in Tunisia. The observed different pathogenic profiles across age groups could be helpful to avoid the misclassification of patients presenting with ARIs at the triage level when no standardized protocol is available. This study will provide clues for physicians informing decisions regarding preventive strategies and medication in Tunisia.


title: Impact of 3D printed medical equipment on the management of the Covid19 pandemic

text: Very high mortality rates of coronavirus pandemic (COVID‐19) are observed around the world due to lack of medical equipment. The increased need for medical devices and personal protective equipment (PPE) has kept several healthcare professionals at risk. Fortunately, 3D printing technology allows to overcome the lack of medical supplies. This study highlights the impact of 3D printing on the combat against COVID19, and its importance in the medical product supply chain. Indeed, the existing medical equipment fabricated by 3D printing technology and its role in the management of Covid19 pandemic is presented. Moreover, the last works are examined to know whether the models of the medical equipment are free of use and whether useful informations are presented (eg, available design data and setup guidelines).


COVID-19–Associated Collapsing Glomerulopathy: An Emerging Entity


title: Control Measures for Severe Acute Respiratory Syndrome (SARS) in Taiwan

text: As of April 14, 2003, Taiwan had had 23 probable cases of severe acute respiratory syndrome (SARS), all imported. Taiwan isolated these first 23 patients with probable SARS in negative-pressure rooms; extensive personal protective equipment was used for healthcare workers and visitors. For the first 6 weeks of the SARS outbreak, recognized spread was limited to one healthcare worker and three household contacts.


title: Graduate medical education funding mechanisms, challenges, and solutions: A narrative review

text: BACKGROUND: With increased attention on the federal budget deficit, graduate medical education (GME) funding has in particular been targeted as a potential source of cost reduction. Reduced GME funding can further deteriorate the compensation of physicians during their residency training. METHODS: In order to understand the GME funding mechanisms and current challenges, as well as the value of the work accomplished by residents, we searched peer-reviewed, English language studies published between 2000 and 2019. RESULTS: Direct and indirect GME funding is intended to support resident reimbursement and the higher costs associated with supporting a teaching program. However, policy efforts have aimed to reduce federal funding for GME. Furthermore, evidence suggests that residents are inadequately compensated because their salaries do not reflect the number of hours worked and are not comparable to those of other medical staff. CONCLUSIONS: Our review suggests that creative solutions are needed to diversify GME funding and improve resident compensation.


title: Is macrophages heterogeneity important in determining COVID-19 lethality?

text: COVID-19 (coronavirus disease 2019) pandemic due to infection with SARS-CoV-2 has led to the death of thousands of adults worldwide. It is now clear that the hyper-inflammatory response triggered by SARS-CoV-2 plays a major role in disease severity and lethality of the infection. Macrophages are innate immune cells that sense and respond to infections by producing a plethora of inflammatory molecules and by interacting with other inflammatory cells. Therefore, macrophages may be diriment on eliminating pathogens and promoting organ repair. However, macrophages can be a major player of the so called cytokine storm and may be damaging to the tissues. It is believed that macrophage activation syndrome is induced by SARS-CoV to be lethal. Surprisingly and fortunately few children die from COVID-19. For instance, in Italy, out of more than 30.000 deaths for COVID-19, three are children. Therefore, we must wonder why? Are macrophages different in children compared to adults? In my opinion they are different. It has been demonstrated that macrophages populate the lung in three “developmental waves”, and it has been suggested that similar waves may be observed in other important organs, such as the heart and kidney. It is most likely that macrophages heterogeneity is involved in determining the severity. There are no doubts that macrophages are important in determining life or death in these patients. Comparing macrophages of children with those of adults with different degrees of disease severity is, therefore, mandatory.


title: Recently Discovered Human Coronaviruses

text: In marked contrast to their historical classification as relatively harmless, common cold-causing, respiratory pathogens, human coronaviruses (HCoVs) are associated with more severe clinical complications, as emphasized by the discovery of severe acute respiratory syndrome-associated CoV (SARS-CoV) in 2003. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified strains HCoV-NL63 and HCoV-HKU1, and definite proof for their etiology remains a major challenge. This article focuses on the characteristics of the five HCoVs that are known, and summarizes current knowledge of their pathogenic potential in people, with an emphasis on the interactions between these viruses and their cognate receptors on susceptible target cells.


title: On a Coupled Time-Dependent SIR Models Fitting with New York and New-Jersey States COVID-19 Data

text: This article describes a simple Susceptible Infected Recovered (SIR) model fitting with COVID-19 data for the month of March 2020 in New York (NY) state. The model is a classical SIR, but is non-autonomous; the rate of susceptible people becoming infected is adjusted over time in order to fit the available data. The death rate is also secondarily adjusted. Our fitting is made under the assumption that due to limiting number of tests, a large part of the infected population has not been tested positive. In the last part, we extend the model to take into account the daily fluxes between New Jersey (NJ) and NY states and fit the data for both states. Our simple model fits the available data, and illustrates typical dynamics of the disease: exponential increase, apex and decrease. The model highlights a decrease in the transmission rate over the period which gives a quantitative illustration about how lockdown policies reduce the spread of the pandemic. The coupled model with NY and NJ states shows a wave in NJ following the NY wave, illustrating the mechanism of spread from one attractive hot spot to its neighbor.


title: Impact of COVID‐19 on oral emergency services

text: OBJECTIVE: To retrospectively review the impact of the outbreak of coronavirus disease 2019 (COVID‐19) on services in the oral emergency room. MATERIALS AND METHODS: A statistical analysis of epidemiological characteristics and the patients’ diagnoses and treatments in the Emergency Department of Peking University Hospital of Stomatology during the outbreak of COVID‐19 in 2020 compared with those in 2019 in Beijing, China. RESULTS: There were fewer total visits in 2020 than in 2019 (P = 0.001), and the proportions of patients who were children, adolescents and elderly people were lower in 2020 than in 2019 (P < 0.001). The proportions of patients with acute toothache and infections were higher in 2020 than in 2019, and the proportions of patients with maxillofacial trauma and non‐emergencies were lower in 2020 than in 2019 (P < 0.001). Drug treatment for acute pulpitis was used more often in 2020 than in 2019, and endodontic treatment and examination consultations were less common in 2020 than in 2019 (P = 0.022). CONCLUSIONS: The outbreak of COVID‐19 affected the patient population and structure of disease types and oral services in the emergency room. The number of visits to the oral emergency room and the proportions of the patients who were children, adolescents and elderly people were reduced, meanwhile the percentage of emergency cases, except trauma, and conservative treatments increased during the outbreak of COVID‐19.


Covid-19 digestive system involvement and clinical outcomes in a large academic hospital in Milan, Italy.


title: Transmission of rhinovirus in the Utah BIG-LoVE families: Consequences of age and household structure

text: BACKGROUND: Common cold viruses create significant health and financial burdens, and understanding key loci of transmission would help focus control strategies. This study (1) examines factors that influence when individuals transition from a negative to positive test (acquisition) or a positive to negative test (loss) of rhinovirus (HRV) and other respiratory tract viruses in 26 households followed weekly for one year, (2) investigates evidence for intrahousehold and interhousehold transmission and the characteristics of individuals implicated in transmission, and (3) builds data-based simulation models to identify factors that most strongly affect patterns of prevalence. METHODS: We detected HRV, coronavirus, paramyxovirus, influenza and bocavirus with the FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC). We used logistic regression to find covariates affecting acquisition or loss of HRV including demographic characteristics of individuals, their household, their current infection status, and prevalence within their household and across the population. We apply generalized linear mixed models to test robustness of results. RESULTS: Acquisition of HRV was less probable in older individuals and those infected with a coronavirus, and higher with a higher proportion of other household members infected. Loss of HRV is reduced with a higher proportion of other household members infected. Within households, only children and symptomatic individuals show evidence for transmission, while between households only a higher number of infected older children (ages 5-19) increases the probability of acquisition. Coronaviruses, paramyxoviruses and bocavirus also show evidence of intrahousehold transmission. Simulations show that age-dependent susceptibility and transmission have the largest effects on mean HRV prevalence. CONCLUSIONS: Children are most likely to acquire and most likely to transmit HRV both within and between households, with infectiousness concentrated in symptomatic children. Simulations predict that the spread of HRV and other respiratory tract viruses can be reduced but not eliminated by practices within the home.


title: Construction of plasmids expressing Sars-CoV encoding proteins and their effects on transcription of hfgl2 prothrombinase

text: SARS coronavirus (SARS-CoV) is the etiologic agent of severe acute respiratory syndrome. The aim of this study was to construct Sars-CoV membrane (M), nucleocapsid (N) and spike 2 (S2) gene eukaryotic expression plasmids, and identify their expression in vitro. Gene fragments encoding N protein, M protein and S2 protein of SARS-CoV were amplified by PCR using cDNA obtained from lung samples of SARS patients as template, and subcloned into pcDNA3.1 vector to form eukaryotic expression plasmids. SARS-CoV protein eukaryotic expression plasmids were transfected respectively into CHO cells. Immunohistochemistry was employed to detect the expression of the structural proteins of SARS-CoV in transfected cells. SARS-CoV protein eukaryotic expression plasmids were successfully constructed by identification with digestion of restriction enzymes and sequencing. M, N and S2 proteins of SARS-CoV were detected in the cytoplasm of transfected CHO cells. It was concluded that these recombinant eukaryotic expression plasmids were constructed successfully, and SARS-CoV encoding proteins could activate transcription and expression of hfgl2 gene.


title: The Challenges for Labour Market Policy during the COVID‐19 Pandemic

text: The COVID‐19 pandemic is having a dramatic economic impact in most countries. In the UK, it has led to sharp falls in labour demand in many sectors of the economy and to initial acute labour shortages in other sectors. Much more than in a typical downturn, the current crisis is not simply a general slowdown in economic activity but also a radical short‐term shift in the mix of economic activities – of which an unknown, but possibly significant, amount will be persistent. The initial policy response has focused on cushioning the blow to families’ finances and allowing the majority of workers and firms to resume their original activities once the crisis subsides. These are crucial priorities. But there should also be a focus on reallocating some workers, either temporarily if working in shut‐down sectors or permanently by facilitating transitions to sectors and jobs offering better prospects and facing labour shortages. The phasing‐out of the furlough subsidies, which is projected to happen in Autumn 2020, brings this into even sharper focus since the alternative for many workers will be unemployment. Active labour market policy will need to be front and centre.


title: Establishing Appropriate Agency Relationships for Providers in China

text: Physicians play multiple roles in a health system. They typically serve simultaneously as the agent for patients, for insurers, for their own medical practices, and for the hospital facilities where they practice. Theoretical and empirical results have demonstrated that financial relations among these different stakeholders can affect clinical outcomes as well as the efficiency and quality of care. What are the physicians’ roles as the agents of Chinese patients? The marketization approach of China’s economic reforms since 1978 has made hospitals and physicians profit-driven. Such profit-driven behavior and the financial tie between hospitals and physicians have in turn made physicians more the agents of hospitals rather than of their patients. While this commentary acknowledges physicians’ ethics and their dedication to their patients, it argues that the current physician agency relation in China has created barriers to achieving some of the central goals of current provider-side health care reform efforts. In addition to eliminating existing perverse financial incentives for both hospitals and physicians, the need for which is already agreed upon by numerous scholars, we argue that the success of the ongoing Chinese public hospital reform and of overall health care reform also relies on establishing appropriate physician-hospital agency relations. This commentary proposes 2 essential steps to establish such physician-hospital agency relations: (1) minimize financial ties between senior physicians and tertiary-level public hospitals by establishing a separate reimbursement system for senior physicians, and (2) establishing a comprehensive physician professionalism system underwritten by the Chinese government, professional physician associations, and major health care facilities as well as by physician leadership representatives. Neither of these suggestions is addressed adequately in current health care reform activities.


title: Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study

text: Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further.


title: Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration

text: In Theiler’s murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).


title: COVID-19 in Vietnam: A lesson of pre-preparation

text: Abstract Background Vietnam was slowing the spread of COVID-19 to 200 cases by the end of March. From perspective of a relatively vulnerable healthcare systems, timely interventions were implemented to different stage of pandemic progress to limit the spread. Method The authors compiled literature on different public health measures in Vietnam in compared to the progression of COVID-19 from January to March 2020. Results Three stages of pandemic progression of COVID-19 were recorded in Vietnam. At 213 confirmed cases under treatment and isolation, a range of interventions were enforced including intensive and expansive contact, mass testing, isolation, and sterilization. Many were in place before any case were reported. Conclusion Preparation were key for Vietnam's healthcare system in the ever-changing landscape of COVID-19 pandemic.


title: Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat

text: Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.


title: Latent Profiles of the Comorbidity of Post-traumatic Stress Disorder and Generalized Anxiety Disorder among Children and Adolescents who are Potentially Infected with COVID-19

text: The present study aims to examine the comorbidity patterns of the symptoms (intrusion and avoidance) for posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD) and the role of perceived threat and courtesy stigma in distinguishing specific patterns of the symptoms for PTSD and GAD among children and adolescents who are susceptible to coronavirus disease 2019 (COVID-19) in Hubei, China. A total of 1,172 (683 female and 489 male) children and adolescents aged 8–18 years were involved in completing the measurements of PTSD, GAD, perceived threat of COVID-19, and COVID-19-related courtesy stigma. The Latent Profile Analysis identified the three profiles of the symptoms for PTSD and GAD which were labeled as Moderate PTSD, Mild Comorbidity, and Severe Comorbidity. The scores of the symptoms for PTSD, GAD, perceived threat, and stigma were different among the three profiles. The risk factors (i.e., perceived threat and stigma) that are related to comorbidity patterns were examined through a three-step method. The possibility of entry into the Severe Comorbidity Profile increased with increasing perceived threat and stigma. The mental health care interventions for children and adolescents who are susceptible to COVID-19 can be developed to reduce perceived threat and stigma.


The prevalence of livestock diseases in the South Pacific


title: Replication of feline coronaviruses in peripheral blood monocytes

text: Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. The related feline enteric coronavirus (FECV) causes mild enteritis. Why these feline coronaviruses manifest so differently in vivo is not known. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. The infection kinetics in monocytes were host dependent. Monocytes from 1 cat were resistant to both FIPV- and FECV-infection. Monocytes from the other 2 cats could initially be infected by both FIPV and FECV but FIPV infection was sustained in monocytes of only one cat. FECV-infection was never sustained and viral production was up to 100 times lower than in FIPV-infected monocytes. In CrFK cells, FIPV and FECV infection kinetics did not differ. In monocytes of a larger cat population (n = 19) the 3 infection patterns were also found. Considering all 22 investigated cats, 3/22 were not susceptible for FIPV and FECV. The rest could be infected with FECV and FIPV but 10/22 cats had monocytes that only sustained FIPV infection and 9/22 sustained neither FIPV nor FECV infection.


docid: wfptxfzs

title: Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

text: Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.