title: Detection of selected viral pathogens in dogs with canine infectious respiratory disease in Austria

text: OBJECTIVES: To assess the prevalence of canine parainfluenza virus, canine adenovirus type 2, canine distemper virus, canine respiratory coronavirus and influenza virus A infections in: (1) privately‐owned or, (2) kennelled dogs showing signs consistent with canine infectious respiratory disease and, (3) clinically healthy dogs in Vienna, Austria. MATERIALS AND METHODS: Prospectively, nasal and tonsillar swabs from 214 dogs affected with infectious respiratory disease, and 50 healthy control dogs were tested for nucleic acids specific to the various viral infections. Concurrent bronchoalveolar lavage fluid from 31 dogs with chronic respiratory disease was investigated for the same viral pathogens. Additionally, anti‐canine respiratory coronavirus antibody concentrations were measured in paired blood samples from 30 acutely diseased dogs. RESULTS: Canine respiratory coronavirus (7.5%) and canine parainfluenza virus (6.5%) were the most commonly detected viruses in samples from the upper airways of dogs with respiratory infections. Serological results showed a significant seroconversion in response to coronavirus in 50% of the examined cases. None of the samples was positive for influenza virus A‐specific nucleic acid. Canine coronavirus‐specific nucleic acid was detected in 4.0% of healthy dogs. CLINICAL SIGNIFICANCE: Canine coronavirus should be considered as a clinically relevant cause of infectious respiratory disease in crowded dog populations. For sample collection, the nasal mucosa can be recommended as the favoured site. Analysis of paired serum samples aids verification of canine coronavirus infection in respiratory disease.


title: Analogies between SARS-CoV-2 infection dynamics and batch chemical reactor behavior

text: The pandemic infection of SARS-CoV-2 presents analogies with the behavior of chemical reactors. Susceptible population (A), active infected population (B), recovered cases (C) and deaths (D) can be assumed to be molecules of chemical compounds and their dynamics seem well aligned with those of composition and conversions in chemical syntheses. Thanks to these analogies, it is possible to generate pandemic predictive models based on chemical and physical considerations and regress their kinetic parameters, either globally or locally, to predict the peak time, entity and end of the infection with certain reliability. These predictions can strongly support the emergency plans decision making process. The model predictions have been validated with data from Chinese provinces that already underwent complete infection dynamics. For all the other countries, the evolution is re-regressed and re-predicted every day, updating a pandemic prediction database on Politecnico di Milano’s webpage based on the real-time available data.


Coronavirus Disease (COVID-19) in the Middle East: A Call for a Unified Response


title: A Streamlined CyTOF Workflow To Facilitate Standardized Multi-Site Immune Profiling of COVID-19 Patients

text: Mass cytometry (CyTOF) represents one of the most powerful tools in immune phenotyping, allowing high throughput quantification of over 40 single parameters at single-cell resolution. However, wide deployment of CyTOF-based immune phenotyping studies are limited by complex experimental workflows and the need for specialized CyTOF equipment and technical expertise. Furthermore, differences in cell isolation and enrichment protocols, antibody reagent preparation, sample staining and data acquisition protocols can all introduce technical variation that can potentially confound integrative analyses of large data-sets of samples processed across multiple labs. Here, we present a streamlined whole blood CyTOF workflow which addresses many of these sources of experimental variation and facilitates wider adoption of CyTOF immune monitoring across sites with limited technical expertise or sample-processing resources or equipment. Our workflow utilizes commercially available reagents including the Fluidigm MaxPar Direct Immune Profiling Assay (MDIPA), a dry tube 30-marker immunophenotyping panel, and SmartTube Proteomic Stabilizer, which allows for simple and reliable fixation and cryopreservation of whole blood samples. We validate a workflow that allows for streamlined staining of whole blood samples with minimal processing requirements or expertise at the site of sample collection, followed by shipment to a central CyTOF core facility for batched downstream processing and data acquisition. We further demonstrate the application of this workflow to characterize immune responses in a cohort of hospitalized COVID-19 patients, highlighting key disease-associated changes in immune cell frequency and phenotype.


title: Reflections on pandemics, past and present

text: The author reflects on her personal experiences during the 2009 H1N1 influenza, acquired immune deficiency syndrome (AIDS), and severe acute respiratory syndrome (SARS) pandemics. The roles played by the Centers for Disease Control and Prevention related to pregnancy-associated influenza during the 2009 pandemic are described. Risk communication principles are summarized and resources provided.


title: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy

text: BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (≥ 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥ 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (≥ 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 ± 1.9 vs. 2.5 ± 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (≥ 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (≥ 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.


The Fight against the 2019-nCoV Outbreak: an Arduous March Has Just Begun


title: Reverse microbial etiology: A research field for predicting and preventing emerging infectious diseases caused by an unknown microorganism

text: Abstract To predict, detect, prepare for, and prevent potential emerging infectious diseases caused by unknown microorganisms in the future, we have proposed the research field of reverse microbial etiology. We isolate and classify unknown microorganisms and assesse their ability to cause infection, an outbreak, or epidemic. We suggest a list of potential pathogens and propose a preparation, prevention, and control strategy to protect global health and global economy and to ensure global security.


The role of oral bacteria in COVID-19


The Four Horsemen of the Apocalypse: Tropical Medicine in the Fight against Plague, Death, Famine, and War


title: School-Based Telemedicine Interventions for Asthma: A Systematic Review

text: BACKGROUND: School health systems are increasingly investing in telemedicine platforms to address acute and chronic illnesses. Asthma, the most common chronic illness in childhood, is of particular interest given its high burden on school absenteeism. OBJECTIVES: Conduct a systematic review evaluating impact of school-based telemedicine programs on improving asthma-related outcomes. DATA SOURCES: PubMed, Cochrane CENTRAL, CINAHL, ERIC, PsycINFO, Embase, and Google Scholar STUDY ELIGIBILITY CRITERIA: Original research, including quasi-experimental studies, without restriction on the type of telemedicine. PARTICIPANTS: School-aged pediatric patients with asthma and their families. INTERVENTIONS: School-based telemedicine. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently screened each abstract, conducted full-text review, assessed study quality, and extracted information. A third author resolved disagreements. RESULTS: Of 371 articles identified, 7 were included for the review. Outcomes of interest were asthma symptom-free days, asthma symptom frequency, quality-of-life, healthcare utilization, school absences, and spirometry. 4/7 studies reported significant increases in symptom-free days and/or decrease in symptom frequency. 5/6 reported increases in at least one quality-of-life metric, 2/7 reported a decrease in at least one healthcare utilization metric, 1/3 showed reductions in school absences, and 1/2 reported improvements in spirometry measures. LIMITATIONS: Variability in intervention designs and outcome measures make comparisons and quantitative analyses across studies difficult. Only 2/7 studies were randomized controlled trials. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: High-quality evidence supporting the use of school-based telemedicine programs to improve patient outcomes is limited. While available evidence suggests benefit, only two comparative trials were identified, and the contribution of telemedicine to these studies’ results is unclear.


title: The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study

text: BACKGROUND: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. METHODS: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). FINDINGS: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. INTERPRETATION: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19. FUNDING: None.


title: Prevalence of chronic comorbidities in chikungunya: A systematic review and meta-analysis

text: Abstract Background Epidemiologic evidence suggests that patients with chikungunya virus (CHIKV) infection may be at risk of severe disease complications when they also have comorbidities such as obesity, diabetes, cardiac diseases, and/or asthma. However, the prevalence of these co-existing medical conditions in severe CHIKV cases has not been systematically reported. Objective The aim of the present study is to conduct a systematic review and meta-analysis to describe the prevalence of chronic comorbidities in CHIKV and evaluate their possible contributions to disease severity. Methods A search strategy was developed for online databases. Search terms used were “Chikungunya” AND “Diabetes, Hypertension, Stroke, Cardiovascular Diseases, Coronary Artery Diseases, Obesity, OR Asthma”. Only 11 articles documenting the frequency of comorbidities in CHIKV were included. Meta-analyses were conducted to evaluate the overall prevalence of comorbidities in the CHIKV infection and stratify the estimates by severity. Results Among 2,773 CHIKV patients, hypertension was the most prevalent comorbidity (31.3%; 95%CI: 17.9-48.8%) followed by diabetes (20.5%; 95%CI: 12.7-31.3%), cardiac diseases (14.8%; 95%CI: 8.1-25.5%) and asthma (7.9%; 95%CI: 3.3-17.7). There was 4- to 5-fold significant increased prevalence of diabetes, hypertension and cardiac diseases in CHIKV patients over 50 years of age compared to their younger counterparts. Severe CHIKV cases had a significantly higher proportion of diabetes than non-severe cases (p<0.05). CHIKV patients with diabetes had OR of 1.2 (95%CI: 1.05-1.48; p =0.0135) for developing severe infection outcome compared to those with no diabetes. Conclusion Hypertension, diabetes and cardiac diseases may contribute to the severe outcome of CHIKV. Diabetic subjects may be at higher risk of severe infection. These findings may be relevant in developing public health measures and practices targeting CHIKV patients with comorbidities to avert the severe outcome of the infectious disease.


COVID‐19 and mycoplasma pneumoniae coinfection


title: Generation of bat-derived influenza viruses and their reassortants

text: Two novel influenza A virus-like genomes were detected in fruit bats in Central and South America. However, the biological properties of these bat-derived influenza viruses (BatIVs) are still largely unknown since infectious viral particles have never been isolated from the infected host species. In this study, a reverse genetics approach was used to generate infectious BatIV particles entirely from plasmids encoding full-length sequences in eight gene segments. We inoculated BatIV particles into various cell cultures including bat-derived cell lines and found that BatIVs infected particular bat-derived cells efficiently but not the other cell lines tested. Reassortant viruses between the two BatIVs were also successfully generated and their replication in the susceptible bat cell lines was confirmed. These findings suggest a limited host range and reassortment potential of BatIVs in nature, providing fundamental information for understanding of the ecology of BatIVs.


CRISPR enhancement, coronavirus source and a controversial appointment.


title: 9 Natural persistence of food- and waterborne viruses

text: Abstract: This chapter summarises data on the persistence of food-and waterborne viruses in the natural environment and discusses the different factors which can affect this persistence. Conventional and alternative methods by which persistence can be studied are described, and the natural factors influencing virus persistence outside the host organism are discussed. Available data concerning virus persistence in water, soil, on surfaces and in food products are reviewed.


title: Provider Decisions to Treat Respiratory Illnesses with Antibiotics: Insights from a Randomized Controlled Trial

text: RATIONALE: Lower respiratory tract illness (LRTI) frequently causes adult hospitalization and antibiotic overuse. Procalcitonin (PCT) treatment algorithms have been used successfully in Europe to safely reduce antibiotic use for LRTI but have not been adopted in the United States. We recently performed a feasibility study for a randomized clinical trial (RCT) of PCT and viral testing to guide therapy for non-pneumonic LRTI. OBJECTIVE: The primary objective of the current study was to understand factors influencing PCT algorithm adherence during the RCT and evaluate factors influencing provider antibiotic prescribing practices for LRTI. STUDY DESIGN: From October 2013-April 2014, 300 patients hospitalized at a community teaching hospital with non-pneumonic LRTI were randomized to standard or PCT-guided care with viral PCR testing. Algorithm adherence data was collected and multivariate stepwise logistic regression of clinical variables used to model algorithm compliance. 134 providers were surveyed anonymously before and after the trial to assess knowledge of biomarkers and viral testing and antibiotic prescribing practices. RESULTS: Diagnosis of pneumonia on admission was the only variable significantly associated with non-adherence [7% (adherence) vs. 26% (nonadherence), p = 0.01]. Surveys confirmed possible infiltrate on chest radiograph as important for provider decisions, as were severity of illness, positive sputum culture, abnormal CBC and fever. However, age, patient expectations and medical-legal concerns were also at least somewhat important to prescribing practices. Physician agreement with the importance of viral and PCT testing increased from 42% to 64% (p = 0.007) and 49% to 74% (p = 0.001), respectively, after the study. CONCLUSIONS: Optimal algorithm adherence will be important for definitive PCT intervention trials in the US to determine if PCT guided algorithms result in better outcomes than reliance on traditional clinical variables. Factors influencing treatment decisions such as patient age, presence of fever, patient expectations and medical legal concerns may be amenable to education to improve PCT algorithm compliance for LRTI.


title: Persistent infection of SARS coronavirus in colonic cells in vitro

text: Severe acute respiratory syndrome coronavirus (SARS‐CoV) can produce gastrointestinal symptoms. The intestinal tract is the only extrapulmonary site where viable viruses have been detected. This study examined seven established human intestinal cell lines, DLD‐1, HCT‐116, HT‐29, LoVo, LS‐180, SW‐480 and SW‐620, for their permissiveness to SARS‐CoV infection. The results showed that only LoVo cells were permissive to SARS‐CoV infection as evident by positive findings from indirect immunofluorescence staining for intracellular viral antigens, in situ hybridization for intracellular viral RNA, and electron microscopy for intracellular viral particles. In contrast to Vero cells, SARS‐CoV did not produce cytopathic effects on LoVo cells. However, LoVo cells were found to be highly permissive for productive infection with a high viral titre (>3 × 10(7) viral copies/ml) produced in culture supernatant following a few days of incubation. SARS‐CoV established a stable persistent chronic infection that could be maintained after multiple passages. Being a cell line of human origin, LoVo cells could be a useful in vitro model for studying the biology and persistent infection of SARS‐CoV. Our results on the expression of angiotensin‐converting enzyme 2 (ACE2), a recently identified cellular receptor for SARS‐CoV, in these cell lines indicated that it might not be the sole determinant for cells to be susceptible to SARS‐CoV infection. J. Med. Virol. 74:1–7, 2004. © 2004 Wiley‐Liss, Inc.


title: Development and characterization of a Rift Valley fever virus cell–cell fusion assay using alphavirus replicon vectors

text: Abstract Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell–cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expression of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by β-galactosidase α-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell–cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell–cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion.


title: DNA nanomedicine: Engineering DNA as a polymer for therapeutic and diagnostic applications

text: Abstract Nanomedicine, the application of nanotechnology to medicine, encompasses a broad spectrum of fields including molecular detection, diagnostics, drug delivery, gene regulation and protein production. In recent decades, DNA has received considerable attention for its functionality and versatility, allowing it to help bridge the gap between materials science and biological systems. The use of DNA as a structural nanoscale material has opened a new avenue towards the rational design of DNA nanostructures with different polymeric topologies. These topologies, in turn, possess unique characteristics that translate to specific therapeutic and diagnostic strategies within nanomedicine.


title: Evolving competition between low-cost carriers and full-service carriers: The case of South Korea

text: Abstract This study explores the impact of domestic low-cost carriers (LCCs) on regional tourism and aviation industries. In particular, it articulates the changing competitive dynamics between LCCs and full-service carriers (FSCs). The Lotka-Volterra (LV) model, utilising the newly proposed moving-window concept, is used for the assessment of the influence of LCCs on the South Korean and airline industry. Analysis results demonstrate that the competitive dynamics between LCCs and FSCs are not static and have evolved over time. The study proposes an efficient and effective change analysis and enables strategic planning for aviation industries.


title: Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants

text: The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies.


title: Antiviral activity of Carbenoxolone disodium against dengue virus infection

text: As one of the most important mosquito‐borne viral diseases, dengue infection is now becoming a global concern due to its rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus (DENV) infection. Glycyrrhetinic acid (GNa) and its related derivatives have been reported to inhibit a broad spectrum of viruses. However, it is unknown whether Carbenoxolone disodium (CBX), one of the GNa derivatives, affects DENV infection. Here, we found that the production of infectious DENV particles was significantly decreased by CBX treatment in DENV‐permissive cells, while the viral RNA and viral protein synthesis were not affected. Moreover, results from time‐of‐addition study showed that the inhibitory effect of CBX on DENV was exhibited by targeting the virus itself, not the host cells. Directly incubating DENV with CBX resulted in a remarkable reduction of virus titer and virus infectivity. Furthermore, DENV RNA from progeny virions in the supernatants was significantly decreased by CBX treatment in a dose‐dependent manner. Taken together, these data indicate that the antiviral activity of CBX against DENV may be mainly due to a virucidal effect exerted by the compound itself. Our work, for the first time, demonstrates that CBX has antiviral activity against DENV infection, providing useful information for development of potential therapeutic interventions against dengue. J. Med. Virol. 89:571–581, 2017. © 2016 Wiley Periodicals, Inc.


title: Reproductive technologies in swine

text: This chapter highlights the importance of reproductive technologies that are applied to porcine breeds. Nowadays the porcine industry, part of a high technological and specialized sector, offers high-quality protein food. The development of the swine industry is founded in the development of breeding/genetics, nutrition, animal husbandry, and animal health. The implementation of reproductive technologies in swine has conducted to levels of productivity never reached before. In addition, the pig is becoming an important species for biomedicine. The generation of pig models for human disease, xenotransplantation, or production of therapeutic proteins for human medicine has in fact generated a growing field of interest.


title: The reaction of elderly Asian tourists to avian influenza and SARS

text: Several cases of the H5N1 virus, or bird flu, have recently been discovered in Asia. In some isolated cases, the virus was found to have been transmitted from animals to human beings. However, most research suggested that the virus has low virulence in man. In 2005, the World Health Organisation urged vigilance, since as with other forms of influenza, the virus could mutate into form more easily communicable among human beings. As a result, some countries, issued travel alerts to their citizens to avoid all-but-essential travel to the affected areas. Visitors to Asian countries were told to avoid contact with and the consumption of poultry. This study investigates the impact of the avian influenza on elderly tourists in Asia, evaluating its findings in light of the earlier SARS outbreak in the region. It concludes that neither of these diseases significantly discouraged this group of tourists from undertaking their planned itineraries.


title: Hospital Resource Utilization and Patient Outcomes Associated with Respiratory Viral Testing in Hospitalized Patients

text: Testing patients for respiratory viruses should guide isolation precautions and provide a rationale for antimicrobial drug therapies, but few studies have evaluated these assumptions. To determine the association between viral testing, patient outcomes, and care processes, we identified adults hospitalized with respiratory symptoms from 2004 through 2012 at a large, academic, tertiary hospital in Canada. Viral testing was performed in 11% (2,722/24,567) of hospital admissions and was not associated with reduced odds for death (odds ratio 0.90, 95% CI 0.76–1.10) or longer length of stay (+1 day for those tested). Viral testing resulted in more resource utilization, including intensive care unit admission, but positive test results were not associated with less antibiotic use or shorter duration of isolation. Results suggest that health care providers do not use viral test results in making management decisions at this hospital. Further research is needed to evaluate the effectiveness of respiratory infection control policies.


title: Viral-associated glomerulopathies in children

text: Viral infections associate temporally with the onset of many glomerular diseases, particularly in children. In other cases of glomerulonephritis, when infection is clinically silent, viral syndromes can still be implicated as a trigger. However, strong evidence for viral causality in most glomerular disease is still lacking. While numerous case reports in children document the occurrence of specific forms of glomerular disease after seroconversion to a wide range of viruses, relatively few reports provide pathologic evidence of viral infection associated with glomerular lesions on kidney biopsy. Strong associations between hepatitis viruses and glomerular injury have been acknowledged in adults, but hepatitis C virus appears not to be an etiology in children. In the context of treating glomerular diseases, when diagnosed, the treatment of hepatitis B virus, cytomegalovirus and human immunodeficiency virus in children with membranoproliferative, membranous and collapsing glomerulopathy plays an important role. Otherwise, there is no evidence suggesting that the identification of a viral infection in a child with glomerulopathy should change the management of the infection or the glomerulonephritis. Therefore, additional research into this topic is very much needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00467-015-3057-y) contains supplementary material, which is available to authorized users.


title: Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia

text: Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases’ surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.


title: Pickering Emulsions: Versatility of Colloidal Particles and Recent Applications

text: Abstract The versatility of colloidal particles endows the particle-stabilized or Pickering emulsions with unique features and can potentially enable the fabrication of a wide variety of derived materials. We review the evolution and breakthroughs in the research on the use of colloidal particles for the stabilization of Pickering emulsions in recent years for the particle categories of inorganic particles, polymer-based particles, and food-grade particles. Moreover, based on the latest works, several emulsions stabilized by the featured particles and their derived functional materials, including enzyme immobilized emulsifiers for interfacial catalysis, 2D colloidal materials stabilized emulsions as templates for porous materials, and Pickering emulsions as adjuvant formulations, are also summarized. Finally, we point out the gaps in the current research on the applications of Pickering emulsions, and suggest future directions for the design of particulate stabilizers and preparation methods for Pickering emulsions and their derived materials.


title: Real Time PCR TaqMan assays for detection of polyomaviruses KIV and WUV in clinical samples

text: Abstract Recently, polyomaviruses KI and WU were identified in the airways of patients with acute respiratory symptoms. The epidemiology and pathogenesis of these two viruses are not fully understood, and the development of molecular assays, such as Real Time PCR, was useful for examining their biology and role in different clinical syndromes. The evaluation of different target regions for the amplification of polyomaviruses KI and WU, comparing published primer/probe sets and sets designed in the laboratory is described and was used for testing 175 clinical specimens (84 stools and 91 tonsils). The results showed that the laboratory designs were more sensitive for the detection of polyomaviruses KI and WU DNA in clinical samples. The choice of the primer/probe set, and primarily of the region for amplification, may be relevant for understanding the pathogenic role of viruses such as polyomaviruses KI and WU.


title: Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle

text: BACKGROUND: Escherichia coli serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of E. coli O157:H7 is the eaeA gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic E. coli with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of E. coli O157:H7 in cattle. RESULTS: Cattle were orally inoculated with either milk (control), milk with live attenuated Salmonella enterica serovar Dublin (vector), or milk with live attenuated recombinant S. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with E. coli O157:H7 to evaluate whether vaccination with the recombinant S. Dublin expressing intimin would reduce the level of E. coli O157:H7 fecal shedding. During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing S. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding S. Dublin from day 28 to day 63. All calves were challenged with E. coli O157:H7 on day 98 to determine the effect on fecal shedding of E. coli O157:H7. The amount of E. coli O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of E. coli O157:H7 from the feces in the vaccinated calves. The magnitude of fecal E. coli O157:H7 shedding did not correlate with the presence of intimin-specific fecal IgA. CONCLUSION: Oral vaccination with live attenuated recombinant S. Dublin expressing intimin reduced enteric colonization and fecal shedding of E. coli O157:H7. However, the transient clearance of E. coli O157:H7 was not associated with an enhanced IgA-mediated mucosal immune response.


Alterations in smell or taste – Classic COVID-19?


Metformin, Neutrophils and COVID-19 Infection


title: Symptomatic comparison in efficacy on patients with benign prostatic hyperplasia treated with two therapeutic approaches

text: Summary Objectives A randomised controlled trial was performed to compare the symptomatic effects on patients with benign prostatic hyperplasia (BPH) treated by two therapeutic approaches – the Western medicine (WM) and traditional Chinese medicine (TCM). Methods Four primary outcome measures, namely the quality of life (QOL), maximum urine flow ratio (UFR), International Prostate Symptom Score (IPSS) and prostate volumes, as well as four urethra-related and 35 non-urethra-related symptoms, were investigated to evaluate the effects on 31 BPH patients subjected to WM (Terazosin Hydrochloride Hytrin, THH) and 30 cases to TCM (herbal Saxifrage tablet, HST). The effects of both treatments are compared by the two-sample Kolmogorov–Smirnov test. The contributions of symptoms for four assessments are analysed by the logistic regression model and the Chow test. Results The effect of TCM is weaker than that of WM in the assessment of the IPSS score (p <0.05), and both treatments are similar in the prostate volumes, the maximum UFR and the QOL assessments (p >0.05), as well as in the effective number of urethra-related or non-urethra-related symptoms before and after treatment (p >0.05). By comparing the linear regression models, different urethra-related and non-urethra-related symptom patterns associated with TCM and WM therapies are detected for four assessments, especially for the prostate volume assessment (p <0.01). Conclusion TCM (HST) is a potentially effective treatment in improving the QOL, prostate volumes and maximum UFR for patients with BPH, though it is less effective in ameliorating the IPSS score when compared with WM (THH). The non-urethra-related symptoms experienced by BPH patients might be one of the parameters to further achieve the tailored diagnosis and treatment for BPH.


Experience of a global laboratory network in responding to infectious disease epidemics


title: A survey of optometry leadership: Participation in disaster response

text: Abstract Background A study was completed to assess the academic and state-level professional optometry leadership views regarding optometry professionals as surge responders in the event of a catastrophic event. Methods A cross-sectional survey was conducted using a 21-question, self-administered, structured questionnaire. All U.S. optometry school deans and state optometric association presidents were mailed a questionnaire and instructions to return it by mail on completion; 2 repeated mailings were made. Descriptive statistics were produced and differences between deans and association presidents were tested by Fisher exact test. Results The questionnaire response rate was 50% (25 returned/50 sent) for the state association presidents and 65% (11/17) for the deans. There were no statistically significant differences between the leadership groups for any survey questions. All agreed that optometrists have the skills, are ethically obligated to help, and that optometrists should receive additional training for participation in disaster response. There was general agreement that optometrists should provide first-aid, obtain medical histories, triage, maintain infection control, manage a point of distribution, prescribe medications, and counsel the “worried well.” Starting intravenous lines, interpreting radiographs, and suturing were less favorably supported. There was some response variability between the 2 leadership groups regarding potential sources for training. Conclusions The overall opinion of optometry professional leadership is that with additional training, optometrists can and should provide an important reserve pool of catastrophic event responders.


title: Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring

text: COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted. In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19. Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m(2), no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 μg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed. In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.


title: COVID-19 outbreak: an elusive enemy

text: Abstract A novel coronavirus, officially termed as severe acute respiratory syndrome (SARS)-CoV-2, emerged in Wuhan, China, toward the end of 2019. Just four months later, more than 100,000 people were diagnosed with COVID-19, the resulting disease. The genetic analysis of SARS-CoV-2 revealed that this virus is a new Betacoronavirus, closely related to bat-derived SARS-like coronaviruses. Clinical data from hospitals in China have revealed that approximately 10% of the infected patients have severe disease requiring intensive care. Since containment of the outbreak may have partially failed due to asymptomatic transmission, it is imperative to accelerate the development of rapid point-of-care diagnostic tests, vaccines, and therapeutics for the COVID-19 epidemic. A novel coronavirus — officially named as severe acute respiratory syndrome (SARS)-CoV-2 by the authorities — emerged in Wuhan, China, toward the end of 2019 [1, 2]. Just four months later, more than 100,000 cases have been diagnosed with the resulting disease, COVID-19, in more than 100 countries at the time of writing this paper [3]. Not only does mainland China have the most number of reported cases (94.4%), but its case-fatality rate is also relatively higher than that of other countries as of February 28, 2020 (China: 3.5%, 2,791 deaths among 78,961 confirmed cases; other countries: 1.4%, 67 deaths among 4,691 confirmed cases) [4]. In an attempt to restrict the outbreak, China quickly implemented an unprecedented measure of quarantining 35 million people in Wuhan and several other cities, but its impact on slowing the global spread of the virus now seems inadequate. In fact, the number of cases in local human-to-human transmission kept soaring in several countries as of March 25, 2020: Italy 63,927 cases, United States of America 42,164 cases, and Spain 33,089 cases [3]. In Japan, 1,128 cases were confirmed based on positive viral nucleic acid test results, and the overall case-fatality rate was 3.7% (i.e., 42 deaths) [3].


title: Genetic, transcriptome, proteomic and epidemiological evidence for blood brain barrier disruption and polymicrobial brain invasion as determinant factors in Alzheimer’s disease

text: Multiple pathogens have been detected in Alzheimer’s disease (AD) brains. A bioinformatics approach was used to assess relationships between pathogens and AD genes (GWAS), the AD hippocampal transcriptome and plaque or tangle proteins. Host/pathogen interactomes (C.albicans, C.Neoformans, Bornavirus, B.Burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, C.Pneumoniae, P.Gingivalis, H.Pylori, T.Gondii, T.Cruzi) significantly overlap with misregulated AD hippocampal genes, with plaque and tangle proteins and, except Bornavirus, Ebola and HERV-W, with AD genes. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi or protozoa in immunocompetent blood cells. AD genes are enriched in bone marrow and immune locations and in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance. The age of AD patients implies resistance to infections afflicting the younger. APOE4 protects against malaria and hepatitis C, and immune/inflammatory gain of function applies to APOE4, CR1, TREM2 and presenilin variants. 30/78 AD genes are expressed in the blood brain barrier (BBB), which is disrupted by AD risk factors (ageing, alcohol, aluminium, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolaemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption and smoking). The BBB and AD benefit from statins, NSAIDs, oestrogen, melatonin and the Mediterranean diet. Polymicrobial involvement is supported by the upregulation of pathogen sensors/defenders (bacterial, fungal, viral) in the AD brain, blood or CSF. Cerebral pathogen invasion permitted by BBB inadequacy, activating a hyper-efficient immune/inflammatory system, betaamyloid and other antimicrobial defence may be responsible for AD which may respond to antibiotic, antifungal or antiviral therapy.


title: Other Inhibitors of Viral Enzymes and Functions

text: Until the end of the 1970s, the mainstays of antiviral chemotherapy were nucleoside analogues that targeted virus polymerase, in particular, the herpesvirus DNA polymerase. The scourge of HIV triggered an unprecedented commitment to identify novel antivirals, and these efforts transformed antiviral therapy into the modern, sophisticated treatment form described in this book, with targets such as the reverse transcriptase and the protease as well as the entry of the human immunodeficiency virus. As the regulation of human pathogenic virus growth cycles became more understandable, the realisation grew that these pathogens had more than one Achilles heel that might be suitable targets for small molecules with antiviral activity. This chapter addresses those “other” targets as well as other approaches to the tried and tested polymerase inhibitors, the so-called non-nucleoside inhibitors of reverse transcriptase.


title: Low serum selenium concentrations in French patients with measles

text: Abstract Objective Selenium deficiency adversely affects the clinical outcome of measles in the tropics. In developed countries, serum selenium level has never been investigated during acute measles. The aim of this study was to determine serum selenium concentrations in French patients with acute measles and to seek correlations with clinical and virological findings. Patients and methods We studied serum selenium concentrations in 94 French patients with acute measles and in 99 healthy controls matched for age and sex. Results The mean of selenium concentration was significantly lower in the patients than in the controls (46.4±14.1μg/L versus 86.5±13.9μg/L, P <0.0001). In the patients, selenium concentrations were not associated with age, sex, vaccination status, clinical signs or specific antibody responses. Selenium levels did not differ significantly between patients with uncomplicated measles (45.8±14.2μg/L) and patients with complications (52.7±13.2μg/L) (P =0.15). Conclusion Acute measles is associated with significant reduction of selenium level that did not seem to negatively affect the course of the disease suggesting compensating mechanisms in patients from developed countries against the disease.


title: Primary and Secondary Human Bocavirus 1 Infections in a Family, Finland

text: Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The mother’s nasopharyngeal samples intermittently showed HBoV1 DNA; the grandmother had HBoV1 reinfection. Findings in this family lead to consideration of HBoV virulence, latency, and reactivation.


title: Community-based screening and testing for Coronavirus in Cape Town, South Africa: Short report

text: Corona Virus Infectious Disease 2019 (COVID-19) was first reported in Cape Town in March 2020 and the transmission was soon observed in local communities. Cape Town has many vulnerable communities because of poverty, overcrowding and comorbidities, although it has a relatively small elderly population. Amongst the unique and early responses to the pandemic in South Africa has been the strategy of community screening and testing (CST). This process has been drawn from health department’s prior adoption of a community-orientated primary care (COPC) approach, which relies on teams of community health workers working in delineated communities to prevent disease and provide early interventions for those at higher risk. The COPC principles were applied in the CST programme, which involved collaboration between facility and community-based teams, linking public health and primary care approaches, careful mapping of cases in highly vulnerable communities, targeted screening around cases, testing of those that screened positive, health education and linkage to primary care. The overall aim was to slow down transmission through early identification and isolation of diagnosed cases. Key challenges involved the designing of a screening tool with appropriate sensitivity and specificity as well as the logistics of staffing, transport, consumables, data collection and capture, security, ablutions and personal protective equipment. Key opportunities included synergies between CST and evolving commitment to COPC in the health system. Key threats were the deteriorating security situation in the most vulnerable communities because of loss of income, food insecurity and CST distrust as well as increasing turn-around-times for test results.


title: Ondanks de regels zoeken naar een waardig afscheid

text: Als iemand met (een verdenking op) covid-19 overlijdt, is passend afscheid nemen bijna onmogelijk. ‘Het blijft moeilijk dat er zoveel beperkingen zijn aan sociaal contact, zeker in de stervensfase.’


title: The impact of point-of-care testing for influenza A and B on patient flow and management in a medical assessment unit of a general hospital

text: OBJECTIVES: Timely implementation of influenza infection control and treatment can significantly reduce the impact on Hospital resources and patient management when demand is at peak. Turnaround times of Laboratory based screening tests for the diagnosis of influenza may have an impact on the implementation of infection control measures and treatment. In this study the objectives included determining the correlation between the Abbott ID NOW point-of-care testing (POCT) instrument using the Influenza A&B2 test and the laboratory based GeneXpert Flu+RSV kit. In addition the impact of the POCT instrument on the prescription of antivirals and antibiotics was evaluated by comparing with practice when the instrument was not in place. RESULTS: The results of the correlation study with a cohort of 54 patients revealed the Abbott ID NOW POCT has 92% sensitivity for the detection of Influenza A, while specificity was 100% for both Influenza A and B. The impact of the POCT instrument on the frequency of prescription of antivirals and amount of antibiotics consumed (33% reduction in antibiotic consumption in a cohort of 65 (2017) and 61 (2018)) was significant. In addition the average patient length of Hospital stay was significantly reduced from 5.26 days to 3.73 days.


title: Anti-influenza virus activity of high-mannose binding lectins derived from genus Pseudomonas

text: Abstract Lectin PFL binding high-mannose glycan derived from Pseudomonas fluorescens and other homologous lectins: PML derived from Pseudomonas mandelii and PTL derived from Pseudomonas taiwanensis were examined for antiviral activity. The cDNA of these lectin genes were synthesized, cloned, expressed in Escherichia coli. The expressed lectins were purified by gel filtrations, and supplied to cultures infected with several strains of influenza virus. These three lectins have inhibited propagation of influenza viruses with a similar extent, 50% of inhibition-dose was around ten nanomolar concentration. An immunofluorescent microscopy, a microarray analysis, and several infection experiments with different time periods of lectin addition or using the competitor substrates indicated that binding of these lectins with high-mannose glycan on HA protein of influenza virus could block the virus entry into the host cells, thereby resulting in inhibition of the virus propagation. These Pseudomonas-derived lectins would be protential and attractive antiviral agents targeting glycoproteins of enveloped viruses including influenza virus.


title: Homeless problems in Taiwan: Looking beyond legality toward social issues

text: Abstract Encouraged by the public policy, citizens in Taiwan have traditionally enjoyed a high percentage of home ownership. Therefore, it has been perplexing and enigmatic to witness the growing homeless population sleeping outside in public areas in recent years. Public actions have been called for to deal with the problem. However, the approach of these public actions has depended on how the problem of homelessness has been defined. This paper presents a historical context of how homelessness has been presented in policy discourses. Further, on the basis of a survey conducted in 2004, this paper describes the profile of the homeless and discusses why the homeless began sleeping on the streets. Finally, an outreach worker narrates his story about working with the homeless in Taipei City, the capital of Taiwan. The paper also includes policy implications in terms of appropriate public actions to be taken in response to the homelessness problem in Taiwan.


title: Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

text: In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584).


title: CHEER: hierarCHical taxonomic classification for viral mEtagEnomic data via deep leaRning

text: The fast accumulation of viral metagenomic data has contributed significantly to new RNA virus discovery. However, the short read size, complex composition, and large data size can all make taxonomic analysis difficult. In particular, commonly used alignment-based methods are not ideal choices for detecting new viral species. In this work, we present a novel hierarchical classification model named CHEER, which can conduct read-level taxonomic classification from order to genus for new species. By combining k-mer embedding-based encoding, hierarchically organized CNNs, and carefully trained rejection layer, CHEER is able to assign correct taxonomic labels for reads from new species. We tested CHEER on both simulated and real sequencing data. The results show that CHEER can achieve higher accuracy than popular alignment-based and alignment-free taxonomic assignment tools. The source code, scripts, and pre-trained parameters for CHEER are available via GitHub:https://github.com/KennthShang/CHEER.


title: Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

text: BACKGROUND: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. METHODS: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. RESULTS: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. CONCLUSIONS: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells.


title: Synthesis and Biological Evaluation of Quinolinone Compounds as SARS CoV 3CL(pro) Inhibitors

text: SARS CoV 3CL(pro) is known to be a promising target for development of therapeutic agents against the severe acute respiratory syndrome (SARS). A quinolinone compound 1 was selected via virtual screening, and it was synthetized and tested for enzymatic inhibition in vitro. Compound 1 showed potent inhibitory activity (IC(50)=0.44 µmol/L) toward SARS CoV 3CL(pro). Further work on a series of quinolinone derivatives resulted in the discovery of the most potent compound 23, inhibiting SARS CoV 3CL(pro) with an IC(50) of 36.86 nmol/L. The structure‐activity relationships were also discussed.


title: Differential surface expression and possible function of 9-O- and 7-O-acetylated GD3 (CD60 b and c) during activation and apoptosis of human tonsillar B and T lymphocytes

text: The disialoganglioside GD3 (CD60 a) and its O-acetylated variants have previously been described as surface molecules of human T lymphocytes of the peripheral blood system. Here we report the expression of the 9-O-, and 7-O-acetylated disialoglycans of GD3 (CD60 b and CD60 c respectively) on human tonsillar lymphocytes. CD60 b and c are surface-expressed on activated germinal centre B cells and colocalize in raft-like structures on the cell surface together with the cytoplasmic tyrosine kinase Lyn and Syk. Addition of CD60 b and c mAb together with anti-IgM/IL-4 to in vitro cultivated tonsillar B cells resulted in a costimulatory effect. During spontaneous and staurosporine-induced apoptosis a distinct population of activated annexin V+/CD60 b+/CD60 c- B cells was observed. CD60 b and c are also found on cells of the extrafollicular T cell area. On tonsillar T cells, CD60 b mAb had a costimulatory effect together with PHA while CD60 c mAb alone was sufficient to induce proliferation. In further contrast to B cells, during apoptosis a distinct CD60 b+ T cell subpopulation was not observed. Together, surface-expressed CD60 b and c are differently expressed on tonsillar B and T cells and may be involved in the regulation of activation and apoptosis of lymphocytes in secondary lymphatic tissue.


title: The intrinsic vulnerability of networks to epidemics

text: Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks’ structural properties, so that the same pathogen can generate different epidemic dynamics on different networks. Here we ask whether there are general properties that make a contact network intrinsically vulnerable to epidemics (that is, regardless of specific epidemiological parameters). By conducting simulations on a large set of modelled networks, we show that, when a broad range of network topologies is taken into account, the effect of specific network properties on outbreak magnitude is stronger than that of fundamental pathogen features such as transmission rate, infection duration, and immunization ability. Then, by focusing on a large set of real world networks of the same type (potential contacts between field voles, Microtus agrestis), we showed how network structure can be used to accurately assess the relative, intrinsic vulnerability of networks towards a specific pathogen, even when those have limited topological variability. These results have profound implications for how we prevent disease outbreaks; in many real world situations, the topology of host contact networks can be described and used to infer intrinsic vulnerability. Such an approach can increase preparedness and inform preventive measures against emerging diseases for which limited epidemiological information is available, enabling the identification of priority targets before an epidemic event.


title: Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients

text: PURPOSE: Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality. METHODS: Narrative review. RESULTS: We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population. CONCLUSION: We provide state-of the art review of available knowledge of critically ill SOT patients with infections.


Distributive food systems to build just and liveable futures


title: Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc

text: The enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH) is responsible for the synthesis of N-glycolylneuraminic acid (Neu5Gc), a sialic acid present on the cell surface proteins of most deuterostomes. The CMAH gene is thought to be present in most deuterostomes, but it has been inactivated in a number of lineages, including humans. The inability of humans to synthesize Neu5Gc has had several evolutionary and biomedical implications. Remarkably, Neu5Gc is a xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red meats, may promote inflammation, arthritis, and cancer. Likewise, xenotransplantation of organs producing Neu5Gc can result in inflammation and organ rejection. Therefore, knowing what animal species contain a functional CMAH gene, and are thus capable of endogenous Neu5Gc synthesis, has potentially far-reaching implications. In addition to humans, other lineages are known, or suspected, to have lost CMAH; however, to date reports of absent and pseudogenic CMAH genes are restricted to a handful of species. Here, we analyze all available genomic data for nondeuterostomes, and 322 deuterostome genomes, to ascertain the phylogenetic distribution of CMAH. Among nondeuterostomes, we found CMAH homologs in two green algae and a few prokaryotes. Within deuterostomes, putatively functional CMAH homologs are present in 184 of the studied genomes, and a total of 31 independent gene losses/pseudogenization events were inferred. Our work produces a list of animals inferred to be free from endogenous Neu5Gc based on the absence of CMAH homologs and are thus potential candidates for human consumption, xenotransplantation research, and model organisms for investigation of human diseases.


title: Food waste management during the COVID-19 outbreak: a holistic climate, economic and nutritional approach

text: Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the “strong fluctuations and short-term changes” on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (−8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.


title: Correction to: Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

text: The acknowledgement section in the original article was published incorrectly.


title: Case–control study of pathogens involved in piglet diarrhea

text: BACKGROUND: Diarrhea in piglets directly affects commercial swine production. The disease results from the interaction of pathogens with the host immune system and is also affected by management procedures. Several pathogenic agents such as Campylobacter spp., Clostridium perfringens, Escherichia coli, Salmonella spp., group A rotavirus (RV-A), coronaviruses (transmissible gastroenteritis virus; porcine epidemic diarrhea virus), as well as nematode and protozoan parasites, can be associated with disease cases. RESULTS: All bacterial, viral, protozoan, and parasitic agents here investigated, with the exception of Salmonella spp. as well as both coronaviruses, were detected in varying proportions in piglet fecal samples, and positive animals were equally distributed between case and control groups. A statistically significant difference between case and control groups was found only for Cystoisospora suis (p = 0.034) and Eimeria spp. (p = 0.047). When co-infections were evaluated, a statistically significant difference was found only for C. perfringens β2 and C. suis (p = 0.014). CONCLUSIONS: The presence of pathogens in piglets alone does not determine the occurrence of diarrhea episodes. Thus, the indiscriminate use of antibiotic and anthelminthic medication should be re-evaluated. This study also reinforces the importance of laboratory diagnosis and correct interpretation of results as well as the relevance of control and prophylactic measures.


title: Chopping the tail: how preventing superspreading can help to maintain COVID-19 control

text: Disease transmission is notoriously heterogeneous, and SARS-CoV-2 is no exception. A skewed distribution where few individuals or events are responsible for the majority of transmission can result in explosive, superspreading events, which produce rapid and volatile epidemic dynamics, especially early or late in epidemics. Anticipating and preventing superspreading events can produce large reductions in overall transmission rates. Here, we present a compartmental (SEIR) epidemiological model framework for estimating transmission parameters from multiple imperfectly observed data streams, including reported cases, deaths, and mobile phone-based mobility that incorporates individual-level heterogeneity in transmission using previous estimates for SARS-CoV-1 and SARS-CoV-2. We parameterize the model for COVID-19 epidemic dynamics by estimating a time-varying transmission rate that incorporates the impact of non-pharmaceutical intervention strategies that change over time, in five epidemiologically distinct settings—Los Angeles and Santa Clara Counties, California; Seattle (King County), Washington; Atlanta (Dekalb and Fulton Counties), Georgia; and Miami (Miami-Dade County), Florida. We find the effective reproduction number [Formula: see text] dropped below 1 rapidly following social distancing orders in mid-March, 2020 and remained there into June in Santa Clara County and Seattle, but climbed above 1 in late May in Los Angeles, Miami, and Atlanta, and has trended upward in all locations since April. With the fitted model, we ask: how does truncating the tail of the individual-level transmission rate distribution affect epidemic dynamics and control? We find interventions that truncate the transmission rate distribution while partially relaxing social distancing are broadly effective, with impacts on epidemic growth on par with the strongest population-wide social distancing observed in April, 2020. Given that social distancing interventions will be needed to maintain epidemic control until a vaccine becomes widely available, “chopping off the tail” to reduce the probability of superspreading events presents a promising option to alleviate the need for extreme general social distancing.


Proposal of the French Society of Vascular Medicine for the prevention, diagnosis and treatment of venous thromboembolic disease in out-patients with COVID 19


title: Exosome Function: From Tumor Immunology to Pathogen Biology

text: Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multi-vesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intra-cellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.


title: Recent developments in carbon-based two-dimensional materials: synthesis and modification aspects for electrochemical sensors

text: This review (162 references) focuses on two-dimensional carbon materials, which include graphene as well as its allotropes varying in size, number of layers, and defects, for their application in electrochemical sensors. Many preparation methods are known to yield two-dimensional carbon materials which are often simply addressed as graphene, but which show huge variations in their physical and chemical properties and therefore on their sensing performance. The first section briefly reviews the most promising as well as the latest achievements in graphene synthesis based on growth and delamination techniques, such as chemical vapor deposition, liquid phase exfoliation via sonication or mechanical forces, as well as oxidative procedures ranging from chemical to electrochemical exfoliation. Two-dimensional carbon materials are highly attractive to be integrated in a wide field of sensing applications. Here, graphene is examined as recognition layer in electrochemical sensors like field-effect transistors, chemiresistors, impedance-based devices as well as voltammetric and amperometric sensors. The sensor performance is evaluated from the material’s perspective of view and revealed the impact of structure and defects of the 2D carbon materials in different transducing technologies. It is concluded that the performance of 2D carbon-based sensors is strongly related to the preparation method in combination with the electrical transduction technique. Future perspectives address challenges to transfer 2D carbon-based sensors from the lab to the market. [Figure: see text]


title: Respiratory virus of severe pneumonia in South Korea: Prevalence and clinical implications

text: BACKGROUND: Severe viral pneumonia is associated with a high mortality rate. However, due to the vulnerability of critically ill patients, invasive diagnostic methods should be performed with caution in the intensive care unit (ICU). It would be helpful if the prevalence, risk factors, and clinical impact of virus detection are elucidated. METHODS: We evaluated patients with severe pneumonia between January 1(st) 2008 and December 31(st) 2015. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for 8 respiratory viruses when viral pathogen could not be excluded as the origin of severe pneumonia. The baseline characteristics, laboratory results, microbiological findings, and clinical outcomes of the patients were analyzed. RESULTS: Of the 2,347 patients admitted to the medical ICU, 515 underwent RT-PCR for respiratory viruses, 69 of whom had positive results. The detection rate was higher during the winter, with a community onset, in patients with history of recent chemotherapy, and low platelet count. Additional bronchoscopic sampling along with upper respiratory specimen increased the yield of viral detection. Respiratory syncytial virus was the most common pathogen detected, while influenza A was the most common virus with bacterial coinfection. Respiratory virus detection led to changes in clinical management in one-third of the patients. CONCLUSIONS: The detection of viral pathogens in patients with severe pneumonia is not rare, and can be more common in certain group of patients. Invasive sampling for RT-PCR can be helpful, and such detection can lead to positive changes in clinical management.


title: COVID-19-related Complications and Decompression Illness Share Main Features. Could the SARS-CoV2-related complications rely on blood foaming ?

text: A study by Saraiva et al. (2011) demonstrated the presence of Angiotensin II receptors on the erythrocyte membrane. This little-known information should be deemed as crucial as the SARS-CoV-2 relationships with oxygen saturation and the Renine Angiotensin System but it currently remains unexploited. The pulmonary and cardiovascular systems are involved in any typical complications of COVID-19 but numerous other unrelated symptoms may occur. To fill the gap, we shall first emphasize some similarities between the complications of this infectious disease and Decompression Illness (DCI), which involves bubbles formation. We theorized that the Angiotensin II clearance by the red blood cells could trigger the release of its oxygen content in the bloodstream. The following foam would worsen the widespread endotheliitis, worsen the gas exchange, trigger the coagulation process, the inflammation process and the complement pathway as typically occurs in DCI. At the end, we propose a plausible mechanism.


title: A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain

text: Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal ‘tail’. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed ‘helix-closed’ and ‘helix-open’) in virus-infected cells. ‘Helix-closed’ conformations appear to enhance dsRNA binding, and ‘helix-open’ conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.


title: RAAS inhibitors do not increase the risk of COVID-19

text: According to five new studies, therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with an increased risk of severe disease or in-hospital death among patients with COVID-19.


title: Absencing/presencing risk: Rethinking proximity and the experience of living with major technological hazards

text: Abstract There is now a substantial body of sociocultural research that has investigated the ways in which specific communities living in physical proximity with a variety of polluting or hazardous technological installations experience and respond to their exposure to the associated risk. Much of this research has sought to understand the apparent acceptance or acquiescence displayed by local populations towards established hazards of the kind that are typically resisted when the subject of siting proposals. However, recent theoretical contributions, produced largely outside the field of risk research, have problematised the objective distinction between proximity and distance. In this paper we explore the potential of some of these ideas for furthering our understanding of the relationship between place and the constitution of risk subjectivities. To do this we re-examine a number of existing sociocultural studies that are predicated on a localised approach and conceptualise the relationship of physically proximate sources of risk to everyday experience in terms of practices of ‘presencing’ and ‘absencing’. We conclude with some thoughts on the methodological and substantive implications of this reworking of proximity for future research into risk subjectivities.


title: Seasonal distribution of febrile seizure and the relationship with respiratory and enteric viruses in Korean children based on nationwide registry data

text: Abstract Purpose The seasonal distribution patterns of febrile seizures and of respiratory and enteric viral pathogens are similar. In this study, we analyzed trends in febrile seizures and viral infection in Korean children, using big data from the Korean Health Insurance Review and Assessment Service (HIRA). Methods We analyzed children younger than 6 years who visited the hospital and were diagnosed with febrile seizures from 2009 to 2016, using medical records in the HIRA database. A total of 666,136 medical records of children with a main or subdiagnosis of febrile seizure from 2008 to 2016 were included. Of these records, patients younger than 1 month and records before 2009 were excluded. Finally, 558,130 records were extracted. Results The medical records included 315,774 male children and 242,356 (43.4%) female children, with a mean age of 2.31 ± 1.31 years. The annual incidence of febrile seizure was 25.4 per 1000 person-years (27.9 for boys and 22.7 for girls). The ratio of male to female children was 1.30: 1, and records of 1-year-old children comprised the highest proportion (n = 210,400, 33.70%). The total monthly number of patients was highest in May (n = 64,969, 11.6%), and peaks were formed from April to July. The fewest patients were seen in October (n = 34,424, 6.17%). The most common viral pathogens were influenza in April and enterovirus during May–July. Conclusion The seasonal distribution of febrile seizures was high from late spring to summer, and influenza virus and enterovirus were most frequently associated.


title: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus

text: Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.


title: European Society For Emergency Medicine position paper on emergency medical systems’ response to COVID-19

text: The 2019 novel coronavirus acute respiratory epidemic is creating a stressed situation in all the health systems of the affected countries. Emergency medical systems and specifically the emergency departments as the front line of the health systems are suffering from overload and severe working conditions, the risk of contagion and transmission of the health professionals adds a substantial burden to their daily work. Under the perspective of European Society For Emergency Medicine, the recommendations provided by the health authorities are reviewed focus on the emergency department’s activity.


title: Planning for smallpox outbreaks

text: Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.


SC Johnson awards more than $1 million in cash and product to Asia Pacific groups battling COVID‐19


title: Increased ATP generation in the host cell is required for efficient vaccinia virus production

text: To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.


title: Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents?

text: Monoclonal antibodies (mAbs) are increasingly being considered as agents to fight severe viral diseases. So far, they have essentially been selected and used on the basis of their virus-neutralizing activity and/or cell-killing activity to blunt viral propagation via direct mechanisms. There is, however, accumulating evidence that they can also induce long-lasting protective antiviral immunity by recruiting the endogenous immune system of infected individuals during the period of immunotherapy. Exploiting this property may revolutionize antiviral mAb-based immunotherapies, with benefits for both patients and healthcare systems.


title: Three clusters of bovine kobuvirus isolated in Korea, 2008–2010

text: Fecal samples (n = 107) were collected from cattle with ascertained or suspected diarrheal disease on Korean farms during 2008–2010. Of these, 37 samples tested positive for bovine kobuvirus. The 37 positive samples came from 32 cattle that exhibited diarrhea and five cattle that were non-diarrhetic. The majority of the virus-positive feces samples were from calves under 1 month of age (n = 25). Nine of the 37 cattle infected with bovine kobuvirus were confirmed to have a co-infection with other viruses including bovine rotavirus (n = 3), bovine coronavirus (n = 1), bovine viral diarrhea virus (n = 1), and both bovine coronavirus and bovine viral diarrhea virus (n = 4). A neighbor-joining tree grouped 36 of the Korean kobuvirus strains (with the exception of the KB8 strain) into three clusters (G1, G3, and G4), while strains derived from Thailand and Japan (except the U1 strain) were included in the G2 cluster. The results indicated that Korean bovine kobuvirus has diverse lineages regardless of disease status and species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-011-0593-9) contains supplementary material, which is available to authorized users.


title: Les vaccins dans la prévention des infections associées aux soins

text: Résumé Les infections associées aux soins (IAS) constituent un véritable problème de santé publique. Escherichia coli, Staphylococcus aureus, Clostridium difficile sont les plus souvent à l’origine des IAS. L’antibiorésistance fréquente complique encore la prise en charge et des impasses thérapeutiques existent à présent. Les mesures d’hygiène hospitalière bien qu’essentielles sont insuffisantes pour diminuer drastiquement les IAS. Ainsi, des stratégies alternatives à l’antibiothérapie s’avèrent nécessaires pour prévenir et traiter les IAS. Parmi celles-ci, la vaccination et l’immunisation passive sont probablement les plus prometteuses. Nous avons fait une mise au point sur les vaccins disponibles et en développement clinique pour lutter contre les IAS, chez les patients à risque d’IAS et les soignants. L’intérêt de la vaccination grippale et rotavirus chez les patients pour prévenir ces IAS virales a été examiné. Le développement d’un vaccin anti-S. aureus, déjà émaillé de 2 échecs est complexe. Toutefois, ces échecs ont permis d’améliorer les connaissances sur l’immunité anti-S. aureus. La mise à disposition d’un vaccin préventif anti-C. difficile semble plus proche. Pour les autres bactéries gram négatif responsables d’IAS, le développement est moins avancé. La vaccination des patients à risques d’IAS pose également des problèmes de réponse vaccinale qu’il faudra résoudre pour utiliser cette stratégie. Ainsi, la vaccination des soignants, de par l’effet de groupe permet également de prévenir les IAS. Nous faisons ici le point sur l’intérêt de la vaccination des soignants contre la rougeole, la coqueluche, la grippe, la varicelle, l’hépatite B pour réduire les IAS avec des vaccins déjà disponibles. Summary The burden of healthcare-associated infections (HAIs) is global and major. Escherichia coli, Staphylococcus aureus, Clostridium difficile are the most frequent associated pathogens. Infection control measures are crucial but not sufficient to stem the burden of HAIs. Due to antimicrobial resistance, lack of therapeutic options for treatment of totally-drug resistant organism is also observed. Therefore, alternative strategies to antimicrobial drugs are urgently needed to prevent and treat HAI. Among these strategies, vaccines and passive immunization are probably one of the most attractive. In this review, we will discuss licensed and non-licensed vaccines for HAIs at-risk patients and HCWs to prevent HAI. The benefit of Influenza and rotavirus vaccines in patients to prevent these viral IAS is reviewed. The development of an S. aureus vaccine, previously associated to failures, seem to be complicated. These failures allow however a better knowledge of S. aureus immunity. For C. difficile, the goal of obtaining a preventive vaccine seems to be near. Development of vaccines to prevent gram negative bacteria involved in IAS remain challenging and confined in early phases of development. Vaccination of at risk patients is however challenging due to the poor immune response to vaccines usually obtained. Therefore, immunization of healthcare workers (HCWs) is crucial to prevent IAS as it is associated to herd immunity. We also review here the benefit of HCWs immunization against measles, pertussis, influenza, varicella and hepatitis B to prevent HAIs.


Preferential Infection of Mature Dendritic Cells by the JHM Strain of Mouse Hepatitis Virus


title: The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines

text: Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy.