title: COVID-19 and pneumonia: a role for the uPA/uPAR system

text: Here, we highlight recent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system that suggest its potential role as a main orchestrator of fatal progression to pulmonary, kidney, and heart failure in patients with coronavirus. Patients with prolonged background inflammation can present with aberrant inflammatory reactions, well recognized as the main factors that can result in death and probably sustained by a dysregulated uPA/uPAR system. SuPAR, the soluble form of uPAR, represents a biomarker of disease progression, and its levels correlate well with comorbidities associated with the death of patients with coronavirus. New drugs that regulate the uPA/uPAR system could help treat the severe complications of highly pathogenic human coronaviruses (hCoVs), including pandemic coronavirus 2019 (COVID-19).


title: Bacterial Biofilm and its Role in the Pathogenesis of Disease

text: Recognition of the fact that bacterial biofilm may play a role in the pathogenesis of disease has led to an increased focus on identifying diseases that may be biofilm-related. Biofilm infections are typically chronic in nature, as biofilm-residing bacteria can be resilient to both the immune system, antibiotics, and other treatments. This is a comprehensive review describing biofilm diseases in the auditory, the cardiovascular, the digestive, the integumentary, the reproductive, the respiratory, and the urinary system. In most cases reviewed, the biofilms were identified through various imaging technics, in addition to other study approaches. The current knowledge on how biofilm may contribute to the pathogenesis of disease indicates a number of different mechanisms. This spans from biofilm being a mere reservoir of pathogenic bacteria, to playing a more active role, e.g., by contributing to inflammation. Observations also indicate that biofilm does not exclusively occur extracellularly, but may also be formed inside living cells. Furthermore, the presence of biofilm may contribute to development of cancer. In conclusion, this review shows that biofilm is part of many, probably most chronic infections. This is important knowledge for development of effective treatment strategies for such infections.


title: The value of superstitions

text: Abstract This paper estimates the value of superstitions by studying the auctions of vehicle license plates. We show that the value of superstitions is economically significant, which justifies their persistence in human civilization. We also document the changes of the value of superstitions across different types of plates, across different policy regimes, and across different macroeconomic environments. Interestingly, some of the changes are rather consistent with economic intuition.


title: Identification of multiple potential viral diseases in a large urban center using wastewater surveillance

text: Viruses are linked to a multitude of human illnesses and can disseminate widely in urbanized environments causing global adverse impacts on communities and healthcare infrastructures. Wastewater-based epidemiology was employed using metagenomics and quantitative polymerase chain reaction (qPCR) assays to identify enteric and non-enteric viruses collected from a large urban area for potential public health monitoring and outbreak analysis. Untreated wastewater samples were collected from November 2017 to February 2018 (n = 54) to evaluate the diversity of human viral pathogens in collected samples. Viruses were classified into virus types based on primary transmission routes and reviewed against viral associated diseases reported in the catchment area. Metagenomics detected the presence of viral pathogens that cause clinically significant diseases reported within the study area during the sampling year. Detected viruses belong to the Adenoviridae, Astroviridae, Caliciviridae, Coronaviridae, Flaviviridae, Hepeviridae, Herpesviridae, Matonaviridae, Papillomaviridae, Parvoviridae, Picornaviridae, Poxviridae, Retroviridae, and Togaviridae families. Furthermore, concentrations of adenovirus, norovirus GII, sapovirus, hepatitis A virus, human herpesvirus 6, and human herpesvirus 8 were measured in wastewater samples and compared to metagenomic findings to confirm detected viral genus. Hepatitis A virus obtained the greatest average viral load (1.86 × 10(7) genome copies/L) in wastewater samples compared to other viruses quantified using qPCR with a 100% detection rate in metagenomic samples. Average concentration of sapovirus (1.36 × 10(6) genome copies/L) was significantly greater than norovirus GII (2.94 × 10(4) genome copies/L) indicating a higher burden within the study area. Findings obtained from this study aid in evaluating the utility of wastewater-based epidemiology for identification and routine monitoring of various viruses in large communities. This methodology has the potential to improve public health responses to large scale outbreaks and viral pandemics.


title: Dobrava, but not Saaremaa, hantavirus is lethal and induces nitric oxide production in suckling mice

text: Abstract Hantaviruses are the causative agents of HFRS and HCPS (hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome), two severe, and often fatal human diseases. Mortality from HFRS varies between hantaviruses; Hantaan and Dobrava show the highest, Seoul intermediate, and Puumala low mortality. Saaremaa, genetically closely related to Dobrava, is also known to induce HFRS, with low or no mortality. In this study, mice were inoculated with Dobrava and Saaremaa viruses to test for infectibility, lethality, viremia, nitric oxide production and antibody responses. Out of suckling mice intracerebrally inoculated with 50, 500 and 5000 focus-forming units of Dobrava virus, respectively, 1/8, 2/8 and 7/8 died within 18–26 days. In all but one of the lethally infected mice high levels of replicating virus were detected, and most were positive for neutralizing antibodies and showed elevated levels of nitric oxide production. All suckling mice intracerebrally inoculated with 50, 500, or 5000 focus-forming units of Saaremaa virus survived and all seroconverted. Clearly lower viral titers were observed for the Saaremaa virus-inoculated mice, also when sacrificed at day 18 after infection, compared to those in mice that died following Dobrava virus infection. Dobrava, Saaremaa, Puumala and Hantaan virus infections of adult mice were asymptomatic, and the anti-nucleocapsid protein IgG2a/IgG1-titer ratio was higher in mice inoculated with Dobrava virus than in those inoculated with Saaremaa virus. Elevated nitric oxide production was not detected in asymptomatically infected mice, and iNOS−/− mice, like normal mice, cleared viremia. In conclusion, we show that Dobrava virus and Saaremaa virus induce distinct differences in terms of survival, viremia, nitric oxide production and antibody responses in mice.


The use of dexamethasone in the treatment of COVID-19


title: Activation of virus‐specific major histocompatibility complex class II‐restricted CD8(+) cytotoxic T cells in CD4‐deficient mice

text: Acute enteritic or respiratory disease is a consequence of coronavirus infection in man and rodents. Mouse hepatitis virus, stain A59 (MHV‐A59) causes acute hepatitis in mice and rats and induces a response of major histocompatibility complex (MHC) class II‐restricted CD4(+) cytotoxic T cells, protecting mice against acute infection. In the present study we show that MHV‐A59 infection of mice that lack a functional CD4 gene activates effector cells of the CD8(+) phenotype. These cytotoxic T cells lyse virus‐infected target cells in a MHC class II‐restricted fashion. The results indicate that CD8(+) T cells have the potential to utilize MHC class II as restriction element, illustrating that the immune system can effectively deal with evading microorganisms, such as viruses which down‐regulate MHC class I.


title: The assessment of data sources for influenza virologic surveillance in New York State

text: BACKGROUND: Following the 2013 USA release of the Influenza Virologic Surveillance Right Size Roadmap, the New York State Department of Health (NYSDOH) embarked on an evaluation of data sources for influenza virologic surveillance. OBJECTIVE: To assess NYS data sources, additional to data generated by the state public health laboratory (PHL), which could enhance influenza surveillance at the state and national level. METHODS: Potential sources of laboratory test data for influenza were analyzed for quantity and quality. Computer models, designed to assess sample sizes and the confidence of data for statistical representation of influenza activity, were used to compare PHL test data to results from clinical and commercial laboratories, reported between June 8, 2013 and May 31, 2014. RESULTS: Sample sizes tested for influenza at the state PHL were sufficient for situational awareness surveillance with optimal confidence levels, only during peak weeks of the influenza season. Influenza data pooled from NYS PHLs and clinical laboratories generated optimal confidence levels for situational awareness throughout the influenza season. For novel influenza virus detection in NYS, combined real‐time (rt) RT‐PCR data from state and regional PHLs achieved ≥85% confidence during peak influenza activity, and ≥95% confidence for most of low season and all of off‐season. CONCLUSIONS: In NYS, combined data from clinical, commercial, and public health laboratories generated optimal influenza surveillance for situational awareness throughout the season. Statistical confidence for novel virus detection, which is reliant on only PHL data, was achieved for most of the year.


title: Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis

text: Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within.


title: Identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana

text: Abstract Here, we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana. In March 2019, 14 employees of Chongqing Bosai Mining Company, China, working in a manganese mining of Guyana, had unexplained fever, and two of them died. We obtained lung and brain tissues as well as the blood samples from the two deceased cases (patient No. 1 and 2), and bronchoscopy lavages and cerebrospinal fluid samples from one severe case (patient No. 3), respectively. All samples were tested by pathological examination, high-throughput sequencing, and real-time PCR. Pathological detection showed the presence of spore-like structures in the lung tissue of patient No. 1, indicating a fungal infection in this patient. Nanopore sequencing identified the existing of H. capsulatum in the lung tissue sample within 13 h. Next-generation sequencing identified specific fragments of H. capsulatum in all of the samples tested (lung, brain and blood serum from the deceased cases, and plasma from the severe case). Real-time PCR assays did not reveal any viral infection related to transmission from bat feces. We conclude that H. capsulatum was the causative pathogen of this disease cluster based on epidemiologic, clinical, pathological and nucleic acid evidence.


title: Lectin Switching During Dengue Virus Infection

text: Dengue virus receptors are relatively poorly characterized, but there has been recent interest in 2 C-type lectin molecules, dendritic cell–specific intercellular adhesion molecule 3 (ICAM-3)–grabbing nonintegrin (DC-SIGN) and its close homologue liver/lymph node–specific ICAM-3–grabbing integrin (L-SIGN), which can both bind dengue and promote infection. In this report we have studied the interaction of dengue viruses produced in insect cells, tumor cell lines, and primary human dendritic cells (DCs) with DC-SIGN and L-SIGN. Virus produced in primary DCs is unable to interact with DC-SIGN but remains infectious for L-SIGN–expressing cells. Skin-resident DCs may thus be a site of initial infection by insect-produced virus, but DCs will likely not participate in large-scale virus replication during dengue infection. These results reveal that differential glycosylation of dengue virus envelope protein is highly dependent on cell state and suggest that studies of virus tropism using virus prepared in insect cells or tumor cell lines should be interpreted with caution.


title: Report from the Medical Library Association’s InSight Initiative Summit 1: Engaging Users in a Disruptive Era

text: At the Medical Library Association’s Insight Initiative Summit 1, held March 6–7, 2018, academic and hospital librarians and publishing industry partners came together to discuss their shared role in engaging users of health sciences information in an era in which “disruptors” such as pirate websites, scientific collaboration networks, and preprint servers pose threats to traditional means of access to scholarly content. Through a mixture of keynote talks, themed panel discussions, and small-group problem-solving exercises, the summit program raised important questions, sparked conversation, and provided insight into the need for both libraries and publishing organizations to improve their user experience, lower their barriers to access, and offer value to users that cannot be provided by competitors, including helping authors and students become informed, responsible advocates for and consumers of scholarly publications. The key takeaways from the summit are expected to impact libraries’ and publishers’ strategies and stimulate the cocreation of enduring materials to enhance user engagement in disseminating and discovering scientific and medical information.


title: Mixed Viral Infections Circulating in Hospitalized Patients with Respiratory Tract Infections in Kuwait

text: The aim of this study was to determine the frequency of viral mixed detection in hospitalized patients with respiratory tract infections and to evaluate the correlation between viral mixed detection and clinical severity. Hospitalized patients with respiratory tract infections (RTI) were investigated for 15 respiratory viruses by using sensitive molecular techniques. In total, 850 hospitalized patients aged between 3 days and 80 years were screened from September 2010 to April 2014. Among the 351 (47.8%) patients diagnosed with viral infections, viral mixed detection was identified in 49 patients (14%), with human rhinovirus (HRV) being the most common virus associated with viral mixed detection (7.1%), followed by adenovirus (AdV) (4%) and human coronavirus-OC43 (HCoV-OC43) (3.7%). The highest combination of viral mixed detection was identified with HRV and AdV (2%), followed by HRV and HCoV-OC43 (1.4%). Pneumonia and bronchiolitis were the most frequent reason for hospitalization with viral mixed detection (9.1%). There were statistical significance differences between mixed and single detection in patients diagnosed with bronchiolitis (P = 0.002) and pneumonia (P = 0.019). Our findings might indicate a significant association between respiratory virus mixed detection and the possibility of developing more severe LRTI such as bronchiolitis and pneumonia when compared with single detection.


docid: pepenzvw

title: Transcriptome Analysis Reveals Dynamic Gene Expression Profiles in Porcine Alveolar Macrophages in Response to the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important swine pathogens and causes reproductive failure in sows and respiratory disease in growing pigs. PRRSV mainly infects porcine alveolar macrophages (PAMs), leading to the subversion of innate and adaptive immunity of pigs. The transcriptome analysis of gene expression profiles in PRRSV-infected PAMs is essential for understanding the pathogenesis of PRRSV. Here we performed next-generation RNA sequencing and a comprehensive bioinformatics analysis to characterize the dynamic transcriptome landscapes in PAMs following PRRSV infection. Totally 38222 annotated mRNAs, 12987 annotated long noncoding RNAs (lncRNAs), and 17624 novel lncRNAs in PRRSV-infected PAMs were identified through a transcripts computational identification pipeline. The differentially expressed mRNAs and lncRNAs during PRRSV infection were characterized. Several differentially expressed transcripts were validated using qRT-PCR. Analyses on dynamic overrepresented GO terms and KEGG pathways in PRRSV-infected PAMs at different time points were performed. Meanwhile the genes involved in IFN-related signaling pathways, proinflammatory cytokines and chemokines, phagocytosis, and antigen presentation and processing were significantly downregulated, indicating the aberrant function of PAMs during PRRSV infection. Moreover, the differentially and highly expressed lncRNA XR_297549.1 was predicted to both cis-regulate and trans-regulate its neighboring gene, prostaglandin-endoperoxide synthase 2 (PTGS2), indicating its role in inflammatory response. Our findings reveal the transcriptome profiles and differentially expressed mRNAs and lncRNAs in PRRSV-infected PAMs in vitro, providing valuable information for further exploration of PRRSV pathogenesis.


title: Rhinovirus Associated Severe Respiratory Failure in Immunocompetent Adult Patient

text: Rhinovirus infection is typically associated with the common cold and has rarely been reported as a cause of severe pneumonia in immunocompetent adults. A 55-year-old previous healthy woman, who consumed half a bottle of alcohol daily, presented with respiratory failure after one week of upper respiratory infection symptoms. Radiography revealed bilateral, diffuse ground glass opacity with patchy consolidation in the whole lung field; bronchoalveolar lavage fluid analysis indicated that rhinovirus was the causative organism. After five days of conservative support, the symptoms and radiographic findings began to improve. We report this rare case of rhinovirus pneumonia in an otherwise healthy host along with a review of references.


A Framework to Deal with Uncertainty in the Age of COVID-19


title: High percentage of smudge cells in a patient with COVID19: Rediscovering their utility

text: We present a patient with SARS‐CoV‐2 infection, with an unexpected presence of lymphocytosis. Examination of blood film revealed mature small lymphocytes associated with high percentage of smudge cells (63%). A peripheral flow cyometry evidenced a CD5 negative CLL. A high percentage of smudge cells is associated with CLL diagnosis and has an important prognostic value: better survival and prolonged time to first treatment. It is a useful index in developing countries with low access to molecular testing.


title: The history of respiratory disease management

text: Abstract Lung diseases have shifted from infections – tuberculosis, pneumonia – to diseases of dirty air – chronic obstructive pulmonary disease, asthma and lung cancer. New diseases have emerged from industrial pollution and HIV, while better imaging has revealed others previously unrecognized. Scientific advances in microbiology, imaging and clinical measurement have improved diagnosis and allowed better targeted treatment. Advances in treatment have been dramatic, the most important being drugs (antibiotics, cortisone, β2-adrenoreceptor agonists), ventilatory support (from iron lung to nasal positive-pressure ventilation), inhaled therapy (metered dose inhalers, nebulizers) and lung surgery (resections, video-assisted thoracoscopic surgery, transplantation). Delivery of care has shifted from sanatoria for the rich but nothing at all for the poor, to hospitals and universal coverage. Generalists have turned into super-specialists and doctors have been joined by growing numbers of professions allied to medicine (PAMs). Management of lung disease has vastly improved but the impact of disease remains.


Post COVID-19 diabetes care—lessons and challenges


COVID-19 testing in Africa: lessons learnt


title: Role of pattern recognition receptors and interferon-beta in protecting bat cell lines from encephalomyocarditis virus and Japanese encephalitis virus infection

text: Abstract Bats are potential natural hosts of Encephalomyocarditis virus (EMCV) and Japanese encephalitis virus (JEV). Bats appear to have some unique features in their innate immune system that inhibit viral replication causing limited clinical symptoms, and thus, contributing to the virus spill over to humans. Here, kidney epithelial cell lines derived from four bat species (Pteropus dasymallus, Rousettus leschenaultii, Rhinolophus ferrumequinum, and Miniopterus fuliginosus) and two non-bat species (Homo sapiens and Mesocricetus auratus) were infected with EMCV and JEV. The replication of EMCV and JEV was lower in the bat cell lines derived from R. leschenaultii, R. ferrumequinum, and M. fuliginosus with a higher expression level of pattern recognition receptors (PRRs) (TLR3, RIG-I, and MDA5) and interferon-beta (IFN-β) than that in the non-bat cell lines and a bat cell line derived from P. dasymallus. The knockdown of TLR3, RIG-I, and MDA5 in Rhinolophus bat cell line using antisense RNA oligonucleotide led to decrease IFN-β expression and increased viral replication. These results suggest that TLR3, RIG-I, and MDA5 are important for antiviral response against EMCV and JEV in Rhinolophus bats.


docid: ymsozgry

title: An analysis of International Health Regulations Emergency Committees and Public Health Emergency of International Concern Designations

text: INTRODUCTION: Nine events have been assessed for potential declaration of a Public Health Emergency of International Concern (PHEIC). A PHEIC is defined as an extraordinary event that constitutes a public health risk to other states through international spread and requires a coordinated international response. The WHO Director-General convenes Emergency Committees (ECs) to provide their advice on whether an event constitutes a PHEIC. The EC rationales have been criticised for being non-transparent and contradictory to the International Health Regulations (IHR). This first comprehensive analysis of EC rationale provides recommendations to increase clarity of EC decisions which will strengthen the IHR and WHO’s legitimacy in future outbreaks. METHODS: 66 EC statements were reviewed from nine public health outbreaks of influenza A, Middle East respiratory syndrome coronavirus, polio, Ebola virus disease, Zika, yellow fever and coronavirus disease-2019. Statements were analysed to determine which of the three IHR criteria were noted as contributing towards the EC’s justification on whether to declare a PHEIC and what language was used to explain the decision. RESULTS: Interpretation of the criteria were often vague and applied inconsistently. ECs often failed to describe and justify which criteria had been satisfied. DISCUSSION: Guidelines must be developed for the standardised interpretation of IHR core criteria. The ECs must clearly identify and justify which criteria have contributed to their rationale for or against PHEIC declaration. CONCLUSION: Striving for more consistency and transparency in EC justifications would benefit future deliberations and provide more understanding and support for the process.


docid: qxkxjxsz

title: Porcine epidemic diarrhea: A retrospect from Europe and matters of debate

text: Abstract A retrospect is given on the emergence of porcine epidemic diarrhea (PED) during the early seventies in Europe. While, at first, it appeared as a disease affecting feeder pigs, fattening- and adult swine, it later also became pathogenic for neonatal and suckling pigs hereby drastically increasing its economic impact. Isolation of the causative virus revealed a new porcine coronavirus, the origin of which has never been clarified. Pathogenesis studies with the prototype strain CV777 showed severe villous atrophy in neonatal pigs and the virus-animal interactions showed many similarities with transmissible gastro-enteritis virus (TGEV), another porcine coronavirus. Disease patterns in field outbreaks showed muchvariation but, while farm related factors played a role, possible genetic variations of virus strains in Europe have not been examined and are thus unknown. CV777 in experimental pigs caused diarrheal disease and mortality rates similar to those later encountered in Asia and more recently with the “original” US strains even though genomic typing of the prototype European strain have shown that it belongs to the S-INDEL strains. In Europe, PED has become endemic during the eighties and nineties and subsequently regressed so that, after 2000, swine populations in many countries have largely become seronegative. Sporadic outbreaks have recently reappeared showing a large variety of clinical outcomes.


title: Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases

text: During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York City’s Ebola active monitoring program over a 16-month period in 2014–2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at “low (but not zero) risk” and “some or high risk”: 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.


Conduite à tenir pour le suivi des patients atteints d’uvéite au cours de la pandémie Covid-19


title: On the role of governmental action and individual reaction on COVID-19 dynamics in South Africa: A mathematical modelling study

text: Mathematical models proffer a rational basis to epidemiologists and policy makers on how, where and when to control an infectious disease. Through mathematical models one can explore and provide solutions to phenomena which are difficult to measure in the field. In this paper, a mathematical models has been used to explore the role of government and individuals reaction to the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The proposed framework incorporates all the relevant biological factors as well as the effects of individual behavioral reaction and government action such as travel restrictions, social distancing, hospitalization, quarantine and hygiene measures. Understanding the dynamics of this highly contagious SARS-CoV-2, which at present does not have any therapy assist the policy makers on evaluating the effectiveness of the control measures currently being implemented. Moreover, policy makers can have insights on short-and-long term dynamics of the disease. The proposed conceptual framework was combined with data on cases of coronavirus disease (COVID-19) in South Africa, March 2020 to early May 2020. Overall, our work demonstrated optimal conditions necessary for the infection to die out as well as persist.


title: Lower respiratory tract viral infections in pediatric abdominal organ transplant recipients: A single hospital inpatient cohort study

text: Respiratory viral infections are a major cause of morbidity and mortality in solid organ transplant recipients. Early detection of a viral etiology of a LRTI in a febrile transplant recipient can theoretically reduce the use of antibiotics, trigger modification of immunosuppression and prompt appropriate isolation procedures to reduce nosocomial infections. We retrospectively evaluated pediatric abdominal organ transplant recipients hospitalized with respiratory illnesses to determine the viral pathogens identified by various methods including multiplex RT‐PCR performed on nasopharyngeal or endotracheal aspirates. Among 30 symptomatic subjects (median age, 2.5 yr) evaluated using this methodology, 25 (83%) were positive for at least one virus. Rhinovirus was the most frequently identified virus (14 subjects). RSV was identified in five subjects with associated mortality of 40%. Parainfluenza, influenza, metapneumovirus, and adenovirus were also identified. This study indicates that rhinovirus is a significant cause of morbidity in this single center cohort of pediatric abdominal organ transplant recipients.


title: Why do many pheasants released in the UK die, and how can we best reduce their natural mortality?

text: Around 60% of pheasants released for shooting in the UK, an estimated 21 million birds, do not end up at their intended fate: being shot. This constitutes wastage, raising economic, environmental and ethical questions. We review what is known of the fates of released pheasants and consider why they do not directly contribute to the numbers harvested. We focus on four main explanations: predation, disease, starvation and dispersal, and highlight other important causes of mortality. For each explanation, we attempt to attribute levels of loss and identify timings or conditions when such losses may be heaviest. We review factors that exacerbate losses and methods available to mitigate them. Opportunities for amelioration may arise at all stages of the rearing and release of pheasants and involve changes to the conditions under which eggs are produced, the way young pheasants are reared or the management of the environment into which they are released. We found few studies investigating impacts of post-release management techniques on pheasant survival outside of the breeding season within a UK context. We found that a number of less commonly deployed practices focusing on early-life, pre-release management may improve survival. Given the scale of pheasant releasing in the UK, even improvements in survival of 1% would mean that ~ 350,000 fewer birds die of natural causes. Complementing current post-release management with proven novel pre-release management interventions could reduce the number of pheasants required for release, whilst maintaining current shooting levels. Lowering release numbers would lower financial costs, benefit the environment and reduce some ethical concerns over the release and shooting of reared pheasants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10344-018-1199-5) contains supplementary material, which is available to authorized users.


title: Molecular study of porcine transmissible gastroenteritis virus after serial animal passages revealed point mutations in S protein

text: Porcine respiratory coronavirus is related genetically to porcine transmissible gastroenteritis virus with a large deletion in S protein. The respiratory virus is a mutated form that may be a consequence of the gastroenteritis virus’s evolution. Intensive passages of the virus in its natural host may enhance the appearance of mutations and therefore may contribute to any attenuated form of the virus. The objective of this study was to characterize the porcine transmissible gastroenteritis virus TMK22 strain after passages in piglets from 1992 until 2007. A typical experimental infection, molecular characterization, and serological analysis were also carried out to further characterize and to evaluate any significant difference between strains. The sequence analysis showed two amino acid deletions and loss of an N-glycosylation site in transmissible gastroenteritis virus S protein after passages in piglets. Although these deletions were positioned at the beginning of the antigenic site B of S protein, no clinical differences were observed in piglets infected experimentally either with the native virus or the mutated one. Serological tests did not show any antibody reactivity difference between the two strains. In this article, we report that the S protein deletion did not affect the virus’s pathogenicity. The variety of the virus’s evolutionary forms may be a result, not only of the multiple passages in natural hosts, but also of other factors, such as different pathogens co-infection, nutrition, immunity, and others. Further studies need to be carried out to characterize the mutated strain.


title: Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study in the Netherlands

text: OBJECTIVES: To identify the factors that influence the hand hygiene compliance of final year medical students, using a theoretical behavioural framework. DESIGN: Cross-sectional survey assessing self-reported compliance and its behavioural correlates. SETTING: Internships of medical students in the Netherlands. PARTICIPANTS: 322 medical students of the Erasmus Medical Center were recruited over a period of 12 months during the Public Health internship, which is the final compulsory internship after an 18-month rotation schedule in all major specialities. PRIMARY AND SECONDARY OUTCOME MEASURES: Behavioural factors influencing compliance to hand hygiene guidelines were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models. Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, self-efficacy, knowledge, risk perception and habit on hand hygiene compliance. RESULTS: We included 313 students in the analysis (response rate 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R(2)=0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. CONCLUSIONS: Targeting medical students’ behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career.


title: The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors

text: The baculovirus expression vector system (BEVS) platform has become an established manufacturing platform for the production of viral vaccines and gene therapy vectors. Nine BEVS‐derived products have been approved – four for human use (Cervarix®, Provenge®, Glybera® and Flublok®) and five for veterinary use (Porcilis® Pesti, BAYOVAC CSF E2®, Circumvent® PCV, Ingelvac CircoFLEX® and Porcilis® PCV). The BEVS platform offers many advantages, including manufacturing speed, flexible product design, inherent safety and scalability. This combination of features and product approvals has previously attracted interest from academic researchers, and more recently from industry leaders, to utilize BEVS to develop next generation vaccines, vectors for gene therapy, and other biopharmaceutical complex proteins. In this review, we explore the BEVS platform, detailing how it works, platform features and limitations and important considerations for manufacturing and regulatory approval. To underscore the growth in opportunities for BEVS‐derived products, we discuss the latest product developments in the gene therapy and influenza vaccine fields that follow in the wake of the recent product approvals of Glybera® and Flublok®, respectively. We anticipate that the utility of the platform will expand even further as new BEVS‐derived products attain licensure. Finally, we touch on some of the areas where new BEVS‐derived products are likely to emerge.


title: Biology and pathogenesis of cytomegalovirus in periodontal disease

text: Human periodontitis is associated with a wide range of bacteria and viruses and with complex innate and adaptive immune responses. Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Treponema denticola, cytomegalovirus and other herpesviruses are major suspected pathogens of periodontitis, and a combined herpesvirus–bacterial periodontal infection can potentially explain major clinical features of the disease. Cytomegalovirus infects periodontal macrophages and T‐cells and elicits a release of interleukin‐1β and tumor necrosis factor‐α. These proinflammatory cytokines play an important role in the host defense against the virus, but they also have the potential to induce alveolar bone resorption and loss of periodontal ligament. Gingival fibroblasts infected with cytomegalovirus also exhibit diminished collagen production and release of an increased level of matrix metalloproteinases. This article reviews innate and adaptive immunity to cytomegalovirus and suggests that immune responses towards cytomegalovirus can play roles in controlling, as well as in exacerbating, destructive periodontal disease.


Exposure to media and fear and worry about COVID‐19


title: Trajectory of the COVID-19 pandemic: chasing a moving target

text: The spread of COVID-19 has already taken a pandemic form, affecting over 180 countries in a matter of three months The full continuum of disease ranges from mild, self-limiting illness to severe progressive COVID-19 pneumonia, multiorgan failure, cytokine storm and death Younger and healthy population is now getting affected than before Possibilities of airborne and fecal oral routes of transmission has increased the concern In the absence of any specific therapeutic agent for coronavirus infections, the most effective manner to contain this pandemic is probably the non-pharmacological interventions (NPIs) The damage due to the pandemic disease is multifaceted and crippling to economy, trade, and health of the citizens of the countries The extent of damage in such scenarios is something that is beyond calculation by Gross Domestic Product rate or currency value of the country Unfortunately, unlike many other diseases, we are still away from the target antiviral drug and vaccine for severe acute respiratory syndrome (SARS-CoV-2) infection The prime importance of NPIs like social distancing, staying in home, work from home, self-monitoring, public awareness, self-quarantine, etc are constantly being emphasized by CDC, WHO, health ministries of all countries and social media houses This is time of introspection and learning from our mistakes Countries like China and South Korea who were initially the most hit countries could contain the disease spread by liberal testing of their population, stringent quarantine of people under investigation and isolation of the positive cases Rest of the countries need to act urgently as well to bring an immediate halt in the community transmission


title: Personal protective equipment (PPE) for both anesthesiologists and other airway managers: principles and practice during the COVID-19 pandemic

text: Healthcare providers are facing a coronavirus disease pandemic. This pandemic may last for many months, stressing the Canadian healthcare system in a way that has not previously been seen. Keeping healthcare providers safe, healthy, and available to work throughout this pandemic is critical. The consistent use of appropriate personal protective equipment (PPE) will help assure its availability and healthcare provider safety. The purpose of this communique is to give both anesthesiologists and other front-line healthcare providers a framework from which to understand the principles and practices surrounding PPE decision-making. We propose three types of PPE including: 1) PPE for droplet and contact precautions, 2) PPE for general airborne, droplet, and contact precautions, and 3) PPE for those performing or assisting with high-risk aerosol-generating medical procedures.


title: COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020

text: During January 26–February 10, 2020, an outbreak of 2019 novel coronavirus disease in an air-conditioned restaurant in Guangzhou, China, involved 3 family clusters. The airflow direction was consistent with droplet transmission. To prevent the spread of the virus in restaurants, we recommend increasing the distance between tables and improving ventilation.


title: A proposed lung ultrasound and phenotypic algorithm for the care of COVID-19 patients with acute respiratory failure

text: Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-020-01704-6) contains supplementary material, which is available to authorized users.


Spine Surgery and COVID-19: Early experiences from Singapore


title: Antibody against adult diarrhoea rotavirus among healthy adult population in China

text: Abstract This paper deals with a method of using unknown serum as the first antibody to coat wells of the microtiter plate directly in application of the sandwich ELISA method with double antibodies for the assay of the antibody against adult diarrhoea rotavirus. This method was used for assay of the antibody against adult rotavirus in 1,380 sera of healthy adults obtained from some provinces and cities of China, of which 141 showed a positive result with a total positive rate of 10.2%. The infection rate varied in different regions. In order to confirm the accuracy of these results a blocking test was carried out on 25 positive specimens, and the results revealed that the P/N ratios after blocking were all lower than those before blocking. Seventeen of these 25 positive serum specimens were obtained from rural areas of Qian'an County, Hebei Province where epidemic adult diarrhoea had occurred two years ago. The antibody against adult diarrhoea rotavirus was not detected in 50 adult sera from Xizang Autonomous Region. Only one out of 50 adult sera from Hainan Island was positive for the antibody.


title: First report of feline bocavirus associated with severe enteritis of cat in Northeast China, 2015

text: Feline bocavirus (FBoV) is a newly identified bocavirus of cats in the family Parvoviridae. A novel FBoV HRB2015-LDF was first identiﬁed from the cat with severe enteritis in Northeast China, with an overall positive rate of 2.78% (1/36). Phylogenetic and homologous analysis of the complete genome showed that FBoV HRB2015-LDF was clustered into the FBoV branch and closely related to other FBoVs, with 68.7–97.5% identities. And the genes of VP1, NPA and NS1 shared 70.7–97.6, 72.4–98.6 and 67.2–98.0% nucleotide identities with other FBoVs, respectively. The results suggested that the FBoVs could be divided into two distinct lineages, and the difference of nucleotide identities was >20–30% between the lineages.


title: Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents

text: An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known, although only a few of these models have been used to study anti-poxvirus agents. We will review those MPXV small animal models that have been developed thus far for the study of therapeutic agents.


title: Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data

text: This paper investigates the profile of COVID-19 cases in Hong Kong, highlighting the unique age structure of confirmed cases compared to other territories. While the majority of cases in most territories around the world have fitted an older age profile, our analysis shows that positive cases in Hong Kong have been concentrated among younger age groups, with the largest incidence of cases reported in the 15–24 age group. This is despite the population’s rapidly aging structure and extremely high levels of population density. Using detailed case data from Hong Kong’s Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong’s high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Combined with community action and targeted and aggressive early policy measures taken to contain the virus, these factors may have contributed to the uniquely younger age structure of COVID-19 cases in the city. Consequently, this young profile of confirmed cases may have prevented fatalities in the territory. Recent research has highlighted the importance of a demographic approach to understanding COVID-19 transmission and fatality rates. The experience in Hong Kong shows that while an older population age structure may be important for understanding COVID-19 fatality, it is not a given. From a social science perspective at least, there is ‘no easy answer’ to why one area should experience COVID-19 differently from another.


title: Ecosystem dynamics, biological diversity and emerging infectious diseases

text: Abstract In this article, we summarize the major scientific developments of the last decade on the transmission of infectious agents in multi-host systems. Almost sixty percent of the pathogens that have emerged in humans during the last 30–40years are of animal origin and about sixty percent of them show an important variety of host species besides humans (3 or more possible host species). In this review, we focus on zoonotic infections with vector-borne transmission and dissect the contrasting effects that a multiplicity of host reservoirs and vectors can have on their disease dynamics. We discuss the effects exerted by host and vector species richness and composition on pathogen prevalence (i.e., reduction, including the dilution effect, or amplification). We emphasize that, in multiple host systems and for vector-borne zoonotic pathogens, host reservoir species and vector species can exert contrasting effect locally. The outcome on disease dynamics (reduced pathogen prevalence in vectors when the host reservoir species is rich and increased pathogen prevalence when the vector species richness increases) may be highly heterogeneous in both space and time. We then ask briefly how a shift towards a more systemic perspective in the study of emerging infectious diseases, which are driven by a multiplicity of hosts, may stimulate further research developments. Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective.


title: Protein Microarrays: Novel Developments and Applications

text: Protein microarray technology possesses some of the greatest potential for providing direct information on protein function and potential drug targets. For example, functional protein microarrays are ideal tools suited for the mapping of biological pathways. They can be used to study most major types of interactions and enzymatic activities that take place in biochemical pathways and have been used for the analysis of simultaneous multiple biomolecular interactions involving protein-protein, protein-lipid, protein-DNA and protein-small molecule interactions. Because of this unique ability to analyze many kinds of molecular interactions en masse, the requirement of very small sample amount and the potential to be miniaturized and automated, protein microarrays are extremely well suited for protein profiling, drug discovery, drug target identification and clinical prognosis and diagnosis. The aim of this review is to summarize the most recent developments in the production, applications and analysis of protein microarrays.


title: Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG

text: Abstract The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. • To protect all healthcare professionals against the risks of infection with SARS-CoV-2. • To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.


title: Human Organs-on-Chips for Virology

text: While conventional in vitro culture systems and animal models have been used to study the pathogenesis of viral infections and to facilitate development of vaccines and therapeutics for viral diseases, models that can accurately recapitulate human responses to infection are still lacking. Human organ-on-a-chip (Organ Chip) microfluidic culture devices that recapitulate tissue–tissue interfaces, fluid flows, mechanical cues, and organ-level physiology have been developed to narrow the gap between in vitro experimental models and human pathophysiology. Here, we describe how recent developments in Organ Chips have enabled re-creation of complex pathophysiological features of human viral infections in vitro.


title: Multi-scale computational modelling in biology and physiology

text: Abstract Recent advances in biotechnology and the availability of ever more powerful computers have led to the formulation of increasingly complex models at all levels of biology. One of the main aims of systems biology is to couple these together to produce integrated models across multiple spatial scales and physical processes. In this review, we formulate a definition of multi-scale in terms of levels of biological organisation and describe the types of model that are found at each level. Key issues that arise in trying to formulate and solve multi-scale and multi-physics models are considered and examples of how these issues have been addressed are given for two of the more mature fields in computational biology: the molecular dynamics of ion channels and cardiac modelling. As even more complex models are developed over the coming few years, it will be necessary to develop new methods to model them (in particular in coupling across the interface between stochastic and deterministic processes) and new techniques will be required to compute their solutions efficiently on massively parallel computers. We outline how we envisage these developments occurring.


title: Genomic characterization of a novel bat-associated Circovirus detected in European Miniopterus schreibersii bats

text: Circoviruses are small circular DNA viruses causing severe pig and poultry disease, recently identified in various bat species worldwide. We report the detection and full-genome molecular characterization of a novel bat-associated Circovirus identified in faecal samples of Miniopterus schreibersii bats (Schreiber’s bent-winged bats) from Sardinia, Italy. Full-genomic sequencing revealed a new putative member of Circoviridae family, with a genome size of 2063 nt. Sequencing allowed the characterization of the two major ORFs, inversely arranged, encoding replicase and capsid proteins, as well as the finding of a polythymidine tract within the genome, and highlighted phylogenetic relationships of the novel virus. This is the first report of circovirus in European bats. Giving the high level of genetic diversity of bat circoviruses, it is paramount to further investigate the relationships between these viruses and bats.


title: Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses

text: BACKGROUND: The recent Ebola virus (EBOV) epidemic highlights the need for efficacious virucidal products to help prevent infection and limit the spread of Ebola virus disease. However, there is limited data on the efficacy of virucidal products against EBOV, because the virus has a high biosafety level and is only available in a few laboratories worldwide. The virucidal efficacy of antiseptics and disinfectants can be determined using the European Standard EN14476:2013/FprA1:2015. Modified vaccinia virus Ankara (MVA) was introduced in 2014 as a reference virus for the claim ‘virucidal active against enveloped viruses for hygienic hand rub and hand wash’. For EBOV, also an enveloped virus, the suitability of MVA as a surrogate needs to be proven. The aim of this study was to test the in vitro efficacy of four povidone iodine (PVP-I) formulations against EBOV: 4 % PVP-I skin cleanser; 7.5 % PVP-I surgical scrub; 10 % PVP-I solution; and 3.2 % PVP-I and 78 % alcohol solution. The formulations were tested with MVA to define the test conditions, and as a secondary objective the suitability of MVA as a surrogate for enveloped viruses like EBOV was assessed. METHODS: According to EN14476, a standard suspension test was used for MVA. Large-volume plating was used for EBOV to increase test sensitivity and exclude potential after-effects. All products were tested under clean (0.3 g/L BSA) and dirty (3.0 g/L BSA + 3.0 mL/L erythrocytes) conditions with MVA for 15, 30, and 60 s. The concentration-contact time values obtained with MVA were verified for EBOV. RESULTS: Viral titres of MVA and EBOV were reduced by >99.99 % to >99.999 % under clean and dirty conditions after application of the test products for 15 seconds. CONCLUSIONS: All products showed excellent virucidal efficacy against EBOV, demonstrating the important role PVP-I can play in helping to prevent and limit the spread of Ebola virus disease. The efficacy against both test viruses after 15 s is helpful information for the implementation of guidance for people potentially exposed to EBOV, and confirms the excellent virucidal efficacy of PVP-I against enveloped viruses. MVA was found to be a suitable surrogate for enveloped viruses like EBOV.


title: Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

text: The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.


Supresión de angiotensia II en la infección por el virus SARS-CoV-2: una propuesta terapeútica


title: Early and late HHV-6 gene transcripts in multiple sclerosis lesions and normal appearing white matter

text: Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the aetiology of which is believed to have both genetic and environmental components. We have investigated one of the candidate viruses for the environmental component of multiple sclerosis, the neurotropic human herpesvirus 6 (HHV-6). Utilizing fluorescent in situ hybridization (FISH) techniques, we have examined human post-mortem tissues for the presence of immediate early and late viral gene expression in multiple sclerosis patient normal appearing white matter (NAWM), lesional tissue and normal control brain samples. HHV-6 gene transcription was detected in all tissue samples and was restricted to oligodendrocytes, as determined by double mRNA FISH analysis. Quantitative analysis of viral mRNA expression indicated that both NAWM and lesional multiple sclerosis samples exhibited significantly higher levels of HHV-6 expression compared with the normal control samples. Lesional samples exhibited the highest levels of viral gene expression, with NAWM exhibiting an intermediate level between lesional and control tissues. Immunofluorescence against early and late HHV-6 proteins verified active translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis of nested polymerase chain reactions using extracted genomic DNA and cDNA confirmed the presence of the HHV-6 genome in all individuals, with the active expression profile mirroring the FISH results. The frequent high level of HHV-6 infection in multiple sclerosis samples suggests a possible role in pathogenesis.


title: A chromosome-scale genome assembly of Isatis indigotica, an important medicinal plant used in traditional Chinese medicine: An Isatis genome

text: Isatis indigotica (2n = 14) is an important medicinal plant in China. Its dried leaves and roots (called Isatidis Folium and Isatidis Radix, respectively) are broadly used in traditional Chinese medicine for curing diseases caused by bacteria and viruses such as influenza and viral pneumonia. Various classes of compounds isolated from this species have been identified as effective ingredients. Previous studies based on transcriptomes revealed only a few candidate genes for the biosynthesis of these active compounds in this medicinal plant. Here, we report a high-quality chromosome-scale genome assembly of I. indigotica with a total size of 293.88 Mb and scaffold N50 = 36.16 Mb using single-molecule real-time long reads and high-throughput chromosome conformation capture techniques. We annotated 30,323 high-confidence protein-coding genes. Based on homolog searching and functional annotations, we identified many candidate genes involved in the biosynthesis of main active components such as indoles, terpenoids, and phenylpropanoids. In addition, we found that some key enzyme-coding gene families related to the biosynthesis of these components were expanded due to tandem duplications, which likely drove the production of these major active compounds and explained why I. indigotica has excellent antibacterial and antiviral activities. Our results highlighted the importance of genome sequencing in identifying candidate genes for metabolite synthesis in medicinal plants.


title: Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

text: The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins.


title: Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection

text: ABSTRACT Importance: It is postulated that myocardial injury may be common in Coronavirus Disease (COVID-19) reflected by troponin elevation. The nature, degree and mechanism of myocardial injury in affected patients in the United States are unknown. Objective: To describe the severity and trends of myocardial injury in a large cohort of hospitalized patients with confirmed COVID-19. Design: Retrospective cohort study of data captured between February 27th and April 12th, 2020. Setting: Patients were admitted to one of five hospitals in the Mount Sinai Health System (MSHS) in New York City. Data was collected from the electronic health record (EHR) databases within the hospital system. Participants: We included all patients with confirmed COVID-19 admitted to the aforementioned hospitals during the study period who had at least one troponin-I measured within 24 hours of admission. Exposure(s) (for observational studies): SARS-CoV-2 infection as confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcome(s) and Measure(s): During the study period, 2736 patients met the inclusion criteria. Demographics, medical history, admission labs, and all troponin-I measurements during hospitalization were recorded for each patient. Admission troponin levels were characterized as mildly elevated (between one and three times the upper limit of normal) and elevated (above three times the upper limit of normal). Results: The median age was 66.4 years, with 59.6% men and 40.7% over age 70. In those patients with elevated troponins, cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, were more prevalent as were conditions of chronic kidney disease, hypertension and diabetes. Inflammatory markers were higher among patients with more substantial troponin elevations as well. Patients who had lower hemoglobin, hypo- or hypertension, or tachycardia generally presented with higher troponins. Conclusions and Relevance: Myocardial injury, manifesting as troponin elevation appears to be common among patients hospitalized with COVID-19 but present at generally low levels. Patients with a history of CVD are more likely to have myocardial injury than patients without CVD or risk factors for CVD. Troponin elevation among patients hospitalized with COVID-19 likely represents non-ischemic or secondary myocardial injury.


COVID‐19 and elective cosmetic procedures: Asymptomatic transmission in epidemic area and subsequent burdens


Commentary on: A Novel solution to the PPE crisis during the Coronavirus pandemic (COVID-19)


docid: kzaowysv

title: Passive immunity to porcine epidemic diarrhea virus following immunization of pregnant gilts with a recombinant orf virus vector expressing the spike protein

text: Passive immunity is critical for protection of neonatal piglets against porcine epidemic diarrhea virus (PEDV). Here, we investigated the immunogenicity of an orf virus (ORFV) vector expressing the full-length spike (S) protein of PEDV (ORFV-PEDV-S) in pregnant gilts and its ability to confer passive immunity and protection in piglets. Three doses of ORFV-PEDV-S were given to two groups of PEDV-negative pregnant gilts, with the last dose being administered two weeks prior to farrowing. One of the two groups immunized with the ORFV-PEDV-S recombinant virus was also exposed to live PEDV orally on day 31 post-immunization (pi). Antibody responses were assessed in serum, colostrum and milk of immunized gilts, and passive transfer of antibodies was evaluated in piglet sera. The protective efficacy of ORFV-PEDV-S was evaluated after challenge of the piglets with PEDV. PEDV-specific IgG, IgA and neutralizing antibody (NA) responses were detected in ORFV-PEDV-S-immunized and ORFV-PEDV-S-immunized/PEDV-exposed gilts. PEDV NA, IgG and IgA were detected in the serum of piglets born to immunized gilts, demonstrating the transfer of antibodies through colostrum and milk. Piglets born to immunized gilts showed reduced morbidity and a marked reduction in mortality after PEDV challenge in comparison to control piglets. Piglets born to gilts that received ORFV-PEDV-S and were exposed to live PEDV showed stronger NA responses and lower clinical scores when compared to piglets born to gilts immunized with ORFV-PEDV-S alone. These results demonstrate the potential of ORFV as a vaccine delivery platform capable of eliciting passive immunity against PEDV.


title: The Progression of Computed Tomographic (CT) Images in Patients with Coronavirus Disease (COVID-19) Pneumonia The CT progression of COVID-19 pneumonia

text: • Of the 49 patients, 89.8% (44/49) patients had a typical transition from early stage to advanced stage, and then from advanced stage to dissipating stage. • With the evidence of fibrosis for progression of CT results, 42.9% (21/49) patients developed fibrosis whereas 57.1% (28/49) patients demonstrated no definite fibrosis. • Patients with fibrosis in follow CT were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), and higher rate of ICU admission (19.0% [4/21] vs. 3.6% [1/28]) than that of those without fibrosis.


title: COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review

text: Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysiological mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV- 2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicinebased narrative review, the following pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.


title: Acute respiratory infection and bacteraemia as causes of non-malarial febrile illness in African children: a narrative review

text: The replacement of “presumptive treatment for malaria” by “test before treat” strategies for the management of febrile illness is raising awareness of the importance of knowing more about the causes of illness in children who are suspected to have malaria but return a negative parasitological test. The most common cause of non-malarial febrile illness (NMFI) in African children is respiratory tract inflection. Whilst the bacterial causes of NMFI are well known, the increasing use of sensitive techniques such as polymerase chain reaction (PCR) tests is revealing large numbers of viruses that are potential respiratory pathogens. However, many of these organisms are commonly present in the respiratory tract of healthy children so causality and risk factors for pneumonia remain poorly understood. Inflection with a combination of viral and bacterial pathogens is increasingly recognised as important in the pathogenesis of pneumonia. Similarly, blood stream inflections with organisms typically grown by aerobic culture are well known but a growing number of organisms that can be identified only by PCR, viral culture, or serology are now recognised to be common pathogens in African children. The high mortality of hospitalised children on the first or second day of admission suggests that, unless results are rapidly available, diagnostic tests to identify specific causes of illness will still be of limited use in guiding the potentially life saving decisions relating to initial treatment of children admitted to district hospitals in Africa with severe febrile illness and a negative test for malaria. Malaria control and the introduction of vaccines against Haemophilus influenzae type b and pneumococcal disease are contributing to improved child survival in Africa. However, increased parasitological testing for malaria is associated with increased use of antbiotics to which resistance is already high.


title: Interaction of certain monoterpenoid hydrocarbons with the receptor binding domain of 2019 novel coronavirus (2019-nCoV), transmembrane serine protease 2 (TMPRSS2), cathepsin B, and cathepsin L (CatB/L) and their pharmacokinetic properties

text: As of June 2020, the coronavirus disease 19 (COVID-19) caused by the 2019 new type coronavirus (2019-nCoV) infected more than 7,000,000 people worldwide and caused the death of more than 400,000 people. The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B (CatB), and cathepsin L (CatL)]. As a result of the relative binding capacity index (RBCI) analysis, carvone was found to be the most effective molecule against all targets when binding energy and predicted (theoretical) IC50 data were evaluated together. It was found to exhibit drug-likeness property according to the Lipinski’s rule-of-five. Carvone has also been determined to be able to cross the blood-brain barrier (BBB) effectively, not a substrate for P-glycoprotein (P-gp), not to inhibit any of the cytochrome P molecules, and to have no toxic effects even on liver cells. In addition, the LD50 dose of carvone in rats was 1.707 mol/kg. Due to its interaction profile with target proteins and excellent pharmacokinetic properties, it has been concluded that carvone can be considered as an alternative agent in drug development studies against 2019-nCoV.


title: Pediatric Mycoplasma pneumoniae Infection Presenting with Acute Cholestatic Hepatitis and Other Extrapulmonary Manifestations in the Absence of Pneumonia

text: Mycoplasma pneumoniae infections mainly involve respiratory tract; however, also can manifestate other symptoms by site involved. Extrapulmonary manifestations of M. pneumoniae infection are rarely known to occur without pneumonia. Herein we report a case of a 9-year-old boy who presented with acute cholestatic hepatitis in the absence of pneumonia. Rhabdomyolysis, skin rash, and initial laboratory results suspicious of disseminated intravascular coagulopathy were also observed in this patient. M. pneumoniae infection was identified by a 4-fold increase in immunoglobulin G antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. This is the first pediatric case in Korea of M. pneumoniae infection presenting with acute cholestatic hepatitis in the absence of pneumonia.


Good and Bad News about Ebola


title: Serological Screening for Coronavirus Infections in Cats

text: Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded.


docid: bijtwbro

title: Responding to the COVID-19 outbreak in Singapore: Staff Protection and Staff Temperature and Sickness Surveillance Systems

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by novel coronavirus (SARS-CoV-2), and first reported in Wuhan, China, in December 2019. Since the severe acute respiratory syndrome (SARS) outbreak in 2003, Tan Tock Seng Hospital (TTSH) in Singapore has routinely fit-tested staff for high filtration N95 respirators, and established web-based staff surveillance systems. The routine systems were enhanced in response to Singapore’s first imported COVID-19 case on January 23,2020. METHODS: We conducted a cross-sectional study, from January 23,2020 to February 23,2020, among healthcare workers to evaluate the effectiveness of the staff protection and surveillance strategy in TTSH, a 1600-bed multidisciplinary acute-care hospital co-located with the 330-bed National Centre for Infectious Diseases (NCID). As of February 23,2020, TTSH/NCID has managed 76% of confirmed COVID-19 cases in Singapore. The hospital adopted a multi-pronged approach to protect and monitor staff with potential COVID-19 exposures:(1) Risk-based personal protective equipment, (2) Staff fever and sickness surveillance, and (3) Enhanced medical surveillance of unwell staff. RESULTS: A total of 10,583 staff were placed on hospital-wide fever and sickness surveillance, with 1,524 frontline staff working in COVID-19 areas under close surveillance. Among frontline staff, a median of eight staff illness episodes was seen per day, and almost 10% (n=29) resulted in hospitalization. None of the staff was found to be infected with COVID-19. CONCLUSIONS: A robust staff protection and health surveillance system that is routinely implemented during non-outbreak periods and enhanced during the COVID-19 outbreak is effective in protecting frontline staff from the infection.


title: Genetic diversity of the Yokose virus, XYBX1332, isolated from bats (Myotis daubentonii) in China

text: BACKGROUND: Yokose virus was first isolated from bats (Miniopterus fuliginosus) collected in Yokosuka, Japan, in 1971, and is a new member of the family Flaviviridae, genus Flavivirus. In this study, we isolated a Yokose virus from a serum sample of Myotis daubentonii (order Chiroptera, family Vespertilionidae) collected in Yunnan province, China in 2013. METHODS: The serum specimens of bat were used to inoculate in BHK-21 and Vero E6 cells for virus isolation. Then the viral complete genome sequence was obtained and was used for phylogenetic analysis performed by BEAST software package. RESULTS: The virus was shown to have cytopathic effects in mammalian cells (BHK-21 and Vero E6). Genome sequencing indicated that it has a single open reading frame (ORF), with a genome of 10,785 nucleotides in total. Phylogenetic analysis of the viral genome suggests that XYBX1332 is a Yokose virus (YOKV) of the genus Flavivirus. Nucleotide and amino acid homology levels of the ORF of XYBX1332 and Oita-36, the original strain of YOKV, were 72 and 82%, respectively. The ORFs of XYBX1332 and Oita-36 encode 3422 and 3425 amino acids, respectively. In addition, the non-coding regions (5′- and 3′-untranslated regions [UTRs]) of these two strains differ in length and the homology of the 5′- and 3′-UTRs was 81.5 and 78.3%, respectively. CONCLUSION: The isolation of YOKV (XYBX1332) from inland China thousands of kilometers from Yokosuka, Japan, suggests that the geographical distribution of YOKV is not limited to the islands of Japan and that it can also exist in the inland areas of Asia. However, there are large differences between the Chinese and Japanese YOKV strains in viral genome.


title: The 3 B's of cancer care amid the COVID‐19 pandemic crisis: “Be safe, be smart, be kind”—A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer

text: Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis.


Espen expert statements and practical guidance on clinical nutrition in COVID-19 patients


title: Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: an overview

text: During the past two decades, antibodies, antibody derivatives and vaccines have been developed for therapeutic and diagnostic applications in human and veterinary medicine. Numerous species of dicot and monocot plants have been genetically modified to produce antibodies or vaccines, and a number of diverse transformation methods and strategies to enhance the accumulation of the pharmaceutical proteins are now available. Veterinary applications are the specific focus of this article, in particular for pathogenic viruses, bacteria and eukaryotic parasites. We focus on the advantages and remaining challenges of plant-based therapeutic proteins for veterinary applications with emphasis on expression platforms, technologies and economic considerations.


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title: Structure–activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors

text: Abstract Human rhinovirus 3C protease (HRV 3Cpro) is known to be a promising target for development of therapeutic agents against the common cold because of the importance of the protease in viral replication as well as its expression in a large number of serotypes. To explore non-peptidic inhibitors of HRV 3Cpro, a series of novel heteroaromatic esters was synthesized and evaluated for inhibitory activity against HRV 3Cpro, to determine the structure–activity relationships. The most potent inhibitor, 7, with a 5-bromopyridinyl group, had an IC50 value of 80nM. In addition, the binding mode of a novel analog, 19, with the 4-hydroxyquinolinone moiety, was explored by molecular docking, suggesting a new interaction in the S1 pocket.


title: Chapter 3 Disastrous Disasters A Polemic on Capitalism, Climate Change, and Humanitarianism

text: Abstract The way people have thought about disasters has changed in almost immeasurable ways. They are no longer considered as “Acts of God” but caused either by natural hazards or by human actions. This shift in thinking has led to different ways of dealing with disasters. What is becoming apparent is that more and more disasters are being produced by human actions. We cause them but seem unable to find the political will to stop doing so. Further, the role of humanitarian agencies has changed. At one time bodies such as the Red Cross would be associated with helping the injured in the battlefield. The nature of present-day warfare or complex emergencies and terrorism means that humanitarian bodies are dealing with many vulnerable refugees and internally displaced people. The following polemic reflects on these changes.


title: Deep learning COVID-19 detection bias: accuracy through artificial intelligence

text: BACKGROUND: Detection of COVID-19 cases’ accuracy is posing a conundrum for scientists, physicians, and policy-makers. As of April 23, 2020, 2.7 million cases have been confirmed, over 190,000 people are dead, and about 750,000 people are reported recovered. Yet, there is no publicly available data on tests that could be missing infections. Complicating matters and furthering anxiety are specific instances of false-negative tests. METHODS: We developed a deep learning model to improve accuracy of reported cases and to precisely predict the disease from chest X-ray scans. Our model relied on convolutional neural networks (CNNs) to detect structural abnormalities and disease categorization that were keys to uncovering hidden patterns. To do so, a transfer learning approach was deployed to perform detections from the chest anterior-posterior radiographs of patients. We used publicly available datasets to achieve this. RESULTS: Our results offer very high accuracy (96.3%) and loss (0.151 binary cross-entropy) using the public dataset consisting of patients from different countries worldwide. As the confusion matrix indicates, our model is able to accurately identify true negatives (74) and true positives (32); this deep learning model identified three cases of false-positive and one false-negative finding from the healthy patient scans. CONCLUSIONS: Our COVID-19 detection model minimizes manual interaction dependent on radiologists as it automates identification of structural abnormalities in patient’s CXRs, and our deep learning model is likely to detect true positives and true negatives and weed out false positive and false negatives with > 96.3% accuracy.


title: Coronavirus nCOVID-19: A Pandemic Disease and the Saudi precautions

text: Now nCOVID-19 has a foothold in many countries, and the threat of a pandemic situation has risen. Recently a novel coronavirus (nCOVID-19) has first emerged in China, causing multiple symptoms in humans and closely related to those caused by SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The nCOVID-19 has reported in Wuhan city of China has recently infected over six million people and at least 0.4 million confirmed deaths all over the world, while 2.8 million people has recovered from this deadly virus. Many instances of this respiratory syndrome coronavirus infection have already reported in more than 216 countries and territories. In contrast, the majority of cases reported in the USA, Brazil, Russia, Spain, UK, Italy, France and many more countries. In today's context, the coronavirus is one of the significant issues faced by the world with plenty of cases. In these circumstances, rapid reviews which recommended by WHO (World Health Organization), and these recommendations are very significant, helpful and cover current data with different preventive measures developed by the Saudi CDC (Saudi Centre for Disease Prevention and Control). This review article describes the possible modes of transmission so that proper preventive actions should be taking. Importantly, this work mentioned the animal reservoir through which may infect humans, and it must be identified to break the transmission chain. In additions, this review paper briefly discussed the spread of the coronavirus in the Arabian Peninsula and what precaution measures are in place by each country to limit the spreading of this virus. Taking into consideration the preventive measures by pharmacists as part of health care professions, however, the number of infected people, especially those with close contact with nCOVID-19 patients, are rise day by day and currently seems unstoppable.


Detection of multiple respiratory viruses by real-time polymerase chain reaction in infants attending an outpatient clinic


title: Using patient-collected clinical samples and sera to detect and quantify the severe acute respiratory syndrome coronavirus (SARS-CoV)

text: BACKGROUND: Severe acute respiratory syndrome (SARS) caused a large outbreak of pneumonia in Beijing, China, in 2003. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect and quantify SARS-CoV in 934 sera and self-collected throat washes and fecal samples from 271 patients with laboratory-confirmed SARS managed at a single institution. RESULTS: SARS-CoV detection rates in sera were highest in the first 9 days of illness, whereas detection was highest in throat washes 5–14 days after onset of symptoms. The highest SARS-CoV RT-PCR rates (70.4–86.3%) and viral loads (log(10 )4.5–6.1) were seen in fecal samples collected 2–4 weeks after the onset of clinical illness. Fecal samples were frequently SARS-CoV RT-PCR positive beyond 40 days, and occasional sera still had SARS-CoV detected after 3 weeks of illness. CONCLUSION: In the context of an extensive outbreak with major pressure on hospital resources, patient self-collected samples are an alternative to nasopharyngeal aspirates for laboratory confirmation of SARS-CoV infection.


title: Network theory and SARS: predicting outbreak diversity

text: Abstract Many infectious diseases spread through populations via the networks formed by physical contacts among individuals. The patterns of these contacts tend to be highly heterogeneous. Traditional “compartmental” modeling in epidemiology, however, assumes that population groups are fully mixed, that is, every individual has an equal chance of spreading the disease to every other. Applications of compartmental models to Severe Acute Respiratory Syndrome (SARS) resulted in estimates of the fundamental quantity called the basic reproductive number R 0 —the number of new cases of SARS resulting from a single initial case—above one, implying that, without public health intervention, most outbreaks should spark large-scale epidemics. Here we compare these predictions to the early epidemiology of SARS. We apply the methods of contact network epidemiology to illustrate that for a single value of R 0 , any two outbreaks, even in the same setting, may have very different epidemiological outcomes. We offer quantitative insight into the heterogeneity of SARS outbreaks worldwide, and illustrate the utility of this approach for assessing public health strategies.


title: Surfactant Proteins A and D: Trimerized Innate Immunity Proteins with an Affinity for Viral Fusion Proteins

text: Innate recognition of viruses is an essential part of the immune response to viral pathogens. This is integral to the maintenance of healthy lungs, which are free from infection and efficient at gaseous exchange. An important component of innate immunity for identifying viruses is the family of C-type collagen-containing lectins, also known as collectins. These secreted, soluble proteins are pattern recognition receptors (PRRs) which recognise pathogen-associated molecular patterns (PAMPs), including viral glycoproteins. These innate immune proteins are composed of trimerized units which oligomerise into higher-order structures and facilitate the clearance of viral pathogens through multiple mechanisms. Similarly, many viral surface proteins form trimeric configurations, despite not showing primary protein sequence similarities across the virus classes and families to which they belong. In this review, we discuss the role of the lung collectins, i.e., surfactant proteins A and D (SP-A and SP-D) in viral recognition. We focus particularly on the structural similarity and complementarity of these trimeric collectins with the trimeric viral fusion proteins with which, we hypothesise, they have elegantly co-evolved. Recombinant versions of these innate immune proteins may have therapeutic potential in a range of infectious and inflammatory lung diseases including anti-viral therapeutics.


title: Quick crossword #53

text: Set by Richard Smyth


Lettre à l’éditeur: “Les lentilles de contact et leur rôle protecteur contre le SARS COV 2”


title: Exchange rate pass-through in deflation: The case of Taiwan

text: Abstract This paper incorporates deflation in an analysis of the relationship between the exchange rate pass-through and inflation. Using a nonlinear model based on monthly data of Taiwan's import prices from 1981 to 2008, we find that the degree of exchange rate pass-through is increasing in deflation. The increase becomes smaller when the price of oil is excluded. Evidence for pass-through increasing in deflation has not previously been found in the existing literature and presents a new understanding of the pricing behavior of firms. Poor profits in deflation cause firms to pass through most of the cost of exchange rate changes to their products to avoid exiting the market.


title: COVID-19 and Health-Related Authority Allocation Puzzles

text: COVID-19-related controversies concerning the allocation of scarce resources, travel restrictions, and physical distancing norms each raise a foundational question: How should authority, and thus responsibility, over healthcare and public health law and policy be allocated? Each controversy raises principles that support claims by traditional wielders of authority in “federal” countries, like federal and state governments, and less traditional entities, like cities and sub-state nations. No existing principle divides “healthcare and public law and policy” into units that can be allocated in intuitively compelling ways. This leads to puzzles concerning (a) the principles for justifiably allocating “powers” in these domains and (b) whether and how they change during “emergencies.” This work motivates the puzzles, explains why resolving them should be part of long-term responses to COVID-19, and outlines some initial COVID-19-related findings that shed light on justifiable authority allocation, emergencies, emergency powers, and the relationships between them.


title: Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients

text: In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33–1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16–0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.


title: Protein Palmitoylation and Its Role in Bacterial and Viral Infections

text: S-palmitoylation is a reversible, enzymatic posttranslational modification of proteins in which palmitoyl chain is attached to a cysteine residue via a thioester linkage. S-palmitoylation determines the functioning of proteins by affecting their association with membranes, compartmentalization in membrane domains, trafficking, and stability. In this review, we focus on S-palmitoylation of proteins, which are crucial for the interactions of pathogenic bacteria and viruses with the host. We discuss the role of palmitoylated proteins in the invasion of host cells by bacteria and viruses, and those involved in the host responses to the infection. We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. The role of the palmitoyl moiety present in bacterial lipopolysaccharide and lipoproteins, contributing to infectivity and affecting recognition of bacteria by innate immune receptors, is also discussed.


title: Enhanced identification of viral and atypical bacterial pathogens in lower respiratory tract samples with nucleic acid amplification tests

text: The advantages of nucleic acid amplification tests (NAT) over conventional methods for the detection of pathogens in lower respiratory tract samples have not been established. NAT for respiratory pathogens were performed on 439 endotracheal tube (ETT) and bronchoalveolar lavage (BAL) samples. A potential pathogen was detected in 87 samples. Of 22 samples that tested positive by conventional methods, 15 tested positive for the same pathogen by NAT, 1 tested positive for a different pathogen, 2 had co‐infections identified only by NAT, and 4 tested negative by NAT. An additional 73 pathogens were detected by NAT in 65 samples including 30 pathogens that were missed by conventional methods (19 adenovirus, 6 respiratory syncytial virus, 3 parainfluenza virus 1–4, 2 influenza A), 41 pathogens not routinely identified by conventional methods in most laboratories (23 rhinovirus, 8 human coronavirus OC43, 5 human metapneumovirus (hMPV), 2 human coronavirus 229E, 2 human coronavirus NL63, 1 Chlamydophila pneumoniae) and 2 pathogens from samples where no respiratory virus testing was requested (1 influenza A, 1 parainfluenza virus). Four of 52 patients who had multiple BAL samples submitted on the same day had negative and positive results by NAT on different samples. NAT improves detection of potential pathogens from ETT and BAL samples. J. Med. Virol. 78:702–710, 2006. © 2006 Wiley‐Liss, Inc.