title: In silico approach toward the identification of unique peptides from viral protein infection: Application to COVID-19

text: We describe a method for rapid in silico selection of diagnostic peptides from newly described viral pathogens and applied this approach to SARS-CoV-2/COVID-19. This approach is multi-tiered, beginning with compiling the theoretical protein sequences from genomic derived data. In the case of SARS-CoV-2 we begin with 496 peptides that would be produced by proteolytic digestion of the viral proteins. To eliminate peptides that would cause cross-reactivity and false positives we remove peptides from consideration that have sequence homology or similar chemical characteristics using a progressively larger database of background peptides. Using this pipeline, we can remove 47 peptides from consideration as diagnostic due to the presence of peptides derived from the human proteome. To address the complexity of the human microbiome, we describe a method to create a database of all proteins of relevant abundance in the saliva microbiome. By utilizing a protein-based approach to the microbiome we can more accurately identify peptides that will be problematic in COVID-19 studies which removes 12 peptides from consideration. To identify diagnostic peptides, another 7 peptides are flagged for removal following comparison to the proteome backgrounds of viral and bacterial pathogens of similar clinical presentation. By aligning the protein sequences of SARS-CoV-2 field isolates deposited to date we can identify peptides for removal due to their presence in highly variable regions that may lead to false negatives as the pathogen evolves. We provide maps of these regions and highlight 3 peptides that should be avoided as potential diagnostic or vaccine targets. Finally, we leverage publicly deposited proteomics data from human cells infected with SARS-CoV-2, as well as a second study with the closely related MERS-CoV to identify the two proteins of highest abundance in human infections. The resulting final list contains the 24 peptides most unique and diagnostic of SARS-CoV-2 infections. These peptides represent the best targets for the development of antibodies are clinical diagnostics. To demonstrate one application of this we model peptide fragmentation using a deep learning tool to rapidly generate targeted LCMS assays and data processing method for detecting CoVID-19 infected patient samples. Graphical Abstract


In memoriam: Gita Ramjee


title: Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2

text: We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression.


Et COVID-19 nous frappa de plein fouet…


title: Strategies Using Bio-Layer Interferometry Biosensor Technology for Vaccine Research and Development

text: Bio-layer interferometry (BLI) real-time, label-free technology has greatly contributed to advances in vaccine research and development. BLI Octet platforms offer high-throughput, ease of use, reliability, and high precision analysis when compared with common labeling techniques. Many different strategies have been used to immobilize the pathogen or host molecules on BLI biosensors for real-time kinetics and affinity analysis, quantification, or high-throughput titer. These strategies can be used in multiple applications and shed light onto the structural and functional aspects molecules play during pathogen-host interactions. They also provide crucial information on how to achieve protection. This review summarizes some key BLI strategies used in human vaccine research and development.


title: Challenges and opportunities in pandemic influenza planning: lessons learned from recent infectious disease preparedness and response efforts

text: Abstract The impact of the next pandemic influenza is likely to be far greater, by orders of magnitude, than most bioterrorism (BT) scenarios. A written pandemic emergency plan and establishment of emergency management teams are critical to mounting a coordinated and effective response to what will be a catastrophic event. Members of these teams should include public health, medical, emergency response and public safety officials, organized at each local, state and federal level. The tragic events of September 11, 2001 and the subsequent anthrax attacks have substantially increased funding and support for bioterrorism planning in the United States. Thus, public health officials have an unprecedented opportunity to strengthen current systems' planning efforts by promoting dual use bioterrorism/pandemic influenza plans. Combining lessons learned from the 2001 terrorist incidents, recent preevent smallpox vaccine programs and the history of past influenza pandemics, more effective strategies can be developed. For example, enhanced influenza surveillance systems can provide data that will not only provide early identification of a novel influenza strain, but will provide more timely recognition of other outbreaks of infectious diseases, including public health threats that may initially present as an influenza-like illness (ILI). In recent years, we have witnessed emerging and reemerging infectious disease threats that have presented us with challenges similar to those posed by an influenza pandemic. Such events highlight the need for advance planning to ensure an optimal response to a health emergency that is certain to be unpredictable, complex, rapidly evolving and accompanied by considerable public alarm. While advance warning for a terrorist attack is unlikely, the warning already exists for a possible new influenza strain, as evidenced by the recent cases of H5N1 in Hong Kong and the rapid global spread of cases of Severe Acute Respiratory Syndrome.


docid: ovsngppo

title: Traitors of the immune system—Enhancing antibodies in HIV infection: Their possible implication in HIV vaccine development

text: Considering recent HIV vaccine failures, the authors believe that it would be most important to find new targets for vaccine-induced immunity, and to analyze the data from previous trials, using an innovative approach. In their review article, the authors briefly summarize the significance of the antibody-dependent enhancement of infection in different viral diseases and discuss role of these types of antibodies as the obstacles for vaccine development. Findings which indicate that complement-mediated antibody-dependent enhancement (C-ADE) is present also in HIV-infected patients, are summarized. Previous results of the authors, suggesting that C-ADE plays a very important role in the progression of HIV infection are described. Data reflecting that enhancing antibodies may develop even in vaccinated animals and human volunteers, and may be responsible for the paradoxical results obtained in some subgroups of vaccinees are discussed. Finally, based on their hypothesis, the authors offer some suggestions for the future development of vaccines.


title: Collateral damage of COVID‐19 pandemic: Delayed medical care

text: During the COVID‐19 pandemic, emergency room visits have drastically decreased for non‐COVID conditions such as appendicitis, heart attack, and stroke. Patients may be avoiding seeking medical attention for fear of catching the deadly condition or as an unintended consequence of stay‐at‐home orders. This delay in seeking care can lead to increased morbidity and mortality, which has not been figured in the assessment of the extent of damage caused by this pandemic. This case illustrates an example of “collateral damage” caused by the COVID‐19 pandemic. What would have been a standard ST‐elevation myocardial infarction treated with timely and successful stenting of a dominant right coronary artery occlusion, became a much more dangerous postinfarction ventricular septal defect; all because of a 2‐day delay in seeking medical attention by an unsuspecting patient.


title: Viral etiology of Parkinson's disease: Focus on influenza A virus

text: Abstract Some clinical reports and epidemiological data suggest that a virus may play a role in the etiology of Parkinson's disease (PD). Following intracerebral injection of a neurovirululent strain of influenza A virus into mice, the virus was found to be particularly localized in neurons of the substantia nigra and hippocampus. Although efforts to detect virus particles in the brains, or antibodies in the serum or CSF of patients with PD have been generally unsuccessful, recent immunohistochemical work has revealed the presence of complement proteins and the interferon-induced MxA in association with Lewy bodies and swollen neuronal processes. Although a viral etiology for PD is not now widely accepted, we proposed such an hypothesis. Neurovirulent influenza A virus is a candidate, but some other viruses or complex infection of these viruses may be responsible for the formation of Lewy bodies and the later death of nigral neurons.


title: The challenges of public health education with a particular reference to China

text: Summary A recent seminar on public health education at the Chinese University of Hong Kong posed some key questions for the future of public health, as well as how the next generation of public health specialists should be educated. This paper summarizes some of the discussions on the future of public health education in China within the context of China's healthcare reforms and trends in global public health education.


Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: A case report


Protecting patients and healthcare personnel from COVID-19: considerations for practice and outpatient care in cardiology


title: The genetic and cultural evolution of unsustainability

text: Anthropogenic changes are accelerating and threaten the future of life on earth. While the proximate mechanisms of these anthropogenic changes are well studied (e.g., climate change, biodiversity loss, population growth), the evolutionary causality of these anthropogenic changes have been largely ignored. Anthroecological theory (AET) proposes that the ultimate cause of anthropogenic environmental change is multi-level selection for niche construction and ecosystem engineering. Here, we integrate this theory with Lotka’s Maximum Power Principle and propose a model linking energy extraction from the environment with genetic, technological and cultural evolution to increase human ecosystem carrying capacity. Carrying capacity is partially determined by energetic factors such as the net energy a population can acquire from its environment and the efficiency of conversion from energy input to offspring output. These factors are under Darwinian genetic selection in all species, but in humans, they are also determined by technology and culture. If there is genetic or non-genetic heritable variation in the ability of an individual or social group to increase its carrying capacity, then we hypothesize that selection or cultural evolution will act to increase carrying capacity. Furthermore, if this evolution of carrying capacity occurs faster than the biotic components of the ecological system can respond via their own evolution, then we hypothesize that unsustainable ecological changes will result.


Occurrence of pulmonary embolism in a patient with mild clinical expression of COVID-19 infection


title: Demonstration of viral antigen and immunoglobulin (IgG and IgM) in brain tissue of pigs experimentally infected with haemagglutinating encephalomyelitis virus

text: Abstract Haemagglutinating encephalomyelitis virus (HEV) was inoculated either orally or intranasally into ten 3-day-old gnotobiotic piglets. All infected pigs showed inappetence and listlessness, but there were no clinical signs of nervous disorder. Severe encephalomyelitis, characterized by neuronophagia, focal gliosis and perivascular cuffing, was observed in the brain stem and cerebral cortex. Nasally infected pigs, in particular, developed lesions in the area of the stria olfactoria and tractus olfactorius. Coincident with the encephalitic changes, HEV antigen was observed first in the trigeminal ganglion cells and then in degenerating neurones. Immunoglobulin (IgG and IgM)-containing cells were also found in perivascular cuffs and glial foci. They appeared at first on PID 7 and after that increased in number. These findings suggest that these encephalitic lesions are a specific immune response to HEV following its multiplication in the central nervous system.


title: Open Development and Clinical Validation Of Multiple 3D-Printed Sample-Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck

text: The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck in the way of high-sensitivity virological testing for COVID-19. To address this crisis, we designed and executed an innovative, radically cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a rigorous multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital’s drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ=0.85–0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs’ non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.


ISUOG Safety Committee Position Statement on use of personal protective equipment and hazard mitigation in relation to SARS‐CoV‐2 for practitioners undertaking obstetric and gynecological ultrasound


title: Incidental COVID-19 Pneumonia on (18)F-Fluorocholine PET/CT

text: We present the case of a patient who underwent (18)F-fluorocholine PET/CT for biochemical recurrence of prostate cancer in which bilateral pneumonia was diagnosed. In the current state of COVID-19 pandemic, a high prevalence of incidental pneumonia may be expected, even with previous clinical triage, explained by a nondefined number of patients who were asymptomatic or minimally symptomatic for infectious process. Therefore, nuclear medicine physicians should be prepared to recognize and diagnose incidental COVID-19 pneumonia manifestation on (18)F-fluorocholine PET/CT, due to the crucial epidemiological implications.


“A quick glance at selected topics in this issue” aims to highlight contents of the Journal and provide a quick review to the readers.


title: Artificial Intelligence and Echocardiography: A Primer for Cardiac Sonographers

text: Artificial intelligence (AI) is emerging as a key component in diagnostic medical imaging, including echocardiography. AI with deep learning has already been used with automated view labeling, measurements, and interpretation. As the development and use of AI in echocardiography increase, potential concerns may be raised by cardiac sonographers and the profession. This report, from a sonographer's perspective, focuses on defining AI, the basics of the technology, identifying some current applications of AI, and how the use of AI may improve patient care in the future.


title: COVID‐19 & Allogeneic Transplant: Activity and Preventive Measures for Best Outcomes in China

text: The COVID‐19 pandemic poses a great challenge to all aspects of medical activities, including haematopoietic stem cell transplantation (HSCT). To minimize the risk of infection in transplantation, we focused on preventive measures and strict screening in each section of transplantation, involving healthy donors, recipients, caregivers and medical workers. Due to the effective preventive work, our transplantation activity was not interrupted. In our centre, haploidentical donors are preferred over unrelated donors for reducing the uncertainty of COVID‐19 on the provision of stem cells, and graft compositions are advocated as fresh peripheral blood stem cells. We especially promoted telemedicine and avoided unnecessary clinic visits in the regular follow‐up after transplantation. Here, we describe the detailed preventive measures used during the outbreak of COVID‐19 in our centre to provide other countries with experience in transplantation.


title: mTOR inhibition and p53 activation, microRNAs: The possible therapy against pandemic COVID-19

text: mTOR is a serine-threonine kinase and participates in cell proliferation, cellular metabolism was found to be activated during Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and replication. During viral replication mTOR, downstream target genes such as ribosomal protein S6 kinase beta 1 (S6K1) and Eukaryotic translational initiation factor 4E-binding protein1 (4-E-BP1) are activated result in ribosome biosynthesis and efficient protein synthesis. In plasmacytoid dendritic cells (pDCs), mTOR plays a key role in the association of adapter protein myeloid differentiation primary response gene 88 (MyD88), Toll-like receptor 9 (TLR9) and interferon regulatory factor (IRF-7) leading to the transcriptional activation of type-I interferon (IFN) genes. Viruses also inactivate the interferon α (IFN-α) pathway by impairing the IRF-7 mediated activation of IFN-α gene transcription. Thus, mammalian target of rapamycin (mTOR) inhibitors can help in suppressing the early stages of viral infection and replication. Interestingly, the key tumor-suppressor p53 protein will undergo degradation by virus-encoded E3 ubiquitin ligase Ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) leading to an increased viral survival in host cells. Thus, the mTOR inhibitors and p53 activators or microRNAs that functions as p53 and can target 3′-UTR of mTOR and RPS6KB1 might effectively inhibit viral replication in the human respiratory tract and lung cells.


title: Canine Infectious Respiratory Disease

text: Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These pathogens are often highly contagious, and coinfections are common. Clinical signs are frequently mild and self-limiting; however, some individual cases progress to severe disease. Clinical diagnosis of CIRDC is often based on history of exposure and physical examination findings; however, determining the etiologic agent requires application of specific diagnostic tests, and results can be difficult to interpret because of widespread subclinical infections.


title: A Modern Approach To Traditional Chinese Medicine

text: Abstract Traditional Chinese Medicine (TCM) is consisting of many practices that are common in East Asia. These practices have been around for more than 2000 years. Many of these methods are becoming increasingly popular in the Western world, where they are classified as alternative or complementary medicine. Most of these techniques are untested and some are even considered dangerous in the modern day world, however, they are sometimes able to help, where modern medicine can not. Therefore, it would be wrong to totally reject them. The SINOPOLL project is a joint R&D effort between Thor Medical Systems LLC and their Chinese partner Shenzhen Anke. Its goal is to combine the vast traditional knowledge in TCM with modern day medical system technology. This paper gives an overview of this research, as well, as proposes several possible solutions for common problems in this field.


title: Radiologist Reporting and Operational Management for Patients with Suspected COVID-19

text: Abstract Objective Evaluate adoption and outcomes of locally-designed reporting guidelines for patients with possible COVID-19. Methods We developed a departmental guideline for radiologists that specified reporting terminology and required communication for patients with imaging findings suggestive of COVID-19, based on patient test status and imaging indication. In this retrospective study, radiology reports completed 3/1/2020-5/3/2020 that mentioned COVID-19 were reviewed. Reports were divided into patients with known COVID-19, patients with “suspected” COVID-19 (having an order indication of respiratory or infectious signs or symptoms), and “unsuspected patients” (other order indications, e.g., trauma or non-chest pain). Primary outcome was percentage of COVID-19 reports using recommended terminology; secondary outcome was percentages of suspected and unsuspected patients diagnosed with COVID-19. Relationships between categorical variables were assessed with Fisher’s exact test. Results Among 77,400 total reports, 1,083 suggested COVID-19 based on imaging findings; 774 (71%) of COVID-19 reports used recommended terminology. Of 574 patients without known COVID-19 at time of interpretation, 345 (60%) were eventually diagnosed with COVID-19, including 61% (315/516) of suspected and 52% (30/58) of unsuspected patients. Nearly all (46/58) unsuspected patients were identified at CT. Discussion Radiologists rapidly adopted recommended reporting terminology for patients with suspected COVID-19. The majority of patients for whom radiologists raised concern for COVID-19 were subsequently diagnosed with the disease, including the majority of clinically unsuspected patients. Using unambiguous terminology and timely notification about previously unsuspected patients will become increasingly critical to facilitate COVID-19 testing and contact tracing as states begin to lift restrictions.


title: Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

text: Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.


title: Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions

text: Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.


title: Cluster of acute hemorrhagic appendicitis among high school students in Wuhan, China

text: Abstract Background Features of a cluster of acute appendicitis that occurred among a high school student population in China were investigated. Methods Epidemiologic data, medical records, and histologic slides of resected appendices were examined. Results During a period between April 10, 1997, and June 11, 1997, 11 cases occurred in a high school, with 10 cases among 290 students enrolled at the time. From the end of the initial cluster until June, 2000, 20 additional cases were encountered. Female cases (6.5%) are more frequent than male cases (1.9%). There was a clustering pattern. Many patients had a history of mutual contact before the onset of symptoms. Pathologically, the resected appendices exhibited diffuse or focal hemorrhages in the lamina propria or within hyperplastic lymphoid follicles, and infiltration by eosinophils and by lymphocytes. Appendical tissues were examined using immunohistochemistry, but no etiologic agent was identified. Conclusions This cluster of acute appendicitis represented a special kind of appendicitis, with features of an infectious disease in epidemiology.


title: Discovery, diversity and evolution of novel coronaviruses sampled from rodents in China

text: Abstract Although rodents are important reservoirs for RNA viruses, to date only one species of rodent coronavirus (CoV) has been identified. Herein, we describe a new CoV, denoted Lucheng Rn rat coronavirus (LRNV), and novel variants of two Betacoronavirus species termed Longquan Aa mouse coronavirus (LAMV) and Longquan Rl rat coronavirus (LRLV), that were identified in a survey of 1465 rodents sampled in China during 2011–2013. Phylogenetic analysis revealed that LAMV and LRLV fell into lineage A of the genus Betacoronavirus, which included CoVs discovered in humans and domestic and wild animals. In contrast, LRNV harbored by Rattus norvegicus formed a distinct lineage within the genus Alphacoronavirus in the 3CLpro, RdRp, and Hel gene trees, but formed a more divergent lineage in the N and S gene trees, indicative of a recombinant origin. Additional recombination events were identified in LRLV. Together, these data suggest that rodents may carry additional unrecognized CoVs.


title: Managing Clinical Risk and Measuring Participants’ Perceptions of the Clinical Research Process

text: Meticulous study design, exacting scientific review, scrupulous data management, rigorous human subjects protection, and effective recruitment strategies are essential components of all clinical research studies that must be in place prior to the conduct of the study. Equally important to the success of the study and to the well-being and protection of study participants is the assurance that safe clinical environments are provided for the care of research participants. This chapter describes approaches to managing clinical care and clinical research quality in clinical research, as well as the application of established health care-based clinical quality methods and tools to the complex processes of clinical research. Techniques for identifying clinical risks, tools for collecting data about the quality of clinical care processes, and strategies for measuring the participants' perceptions of the research process are discussed in detail.


title: Scaling up behavioral science interventions in online education

text: Online education is rapidly expanding in response to rising demand for higher and continuing education, but many online students struggle to achieve their educational goals. Several behavioral science interventions have shown promise in raising student persistence and completion rates in a handful of courses, but evidence of their effectiveness across diverse educational contexts is limited. In this study, we test a set of established interventions over 2.5 y, with one-quarter million students, from nearly every country, across 247 online courses offered by Harvard, the Massachusetts Institute of Technology, and Stanford. We hypothesized that the interventions would produce medium-to-large effects as in prior studies, but this is not supported by our results. Instead, using an iterative scientific process of cyclically preregistering new hypotheses in between waves of data collection, we identified individual, contextual, and temporal conditions under which the interventions benefit students. Self-regulation interventions raised student engagement in the first few weeks but not final completion rates. Value-relevance interventions raised completion rates in developing countries to close the global achievement gap, but only in courses with a global gap. We found minimal evidence that state-of-the-art machine learning methods can forecast the occurrence of a global gap or learn effective individualized intervention policies. Scaling behavioral science interventions across various online learning contexts can reduce their average effectiveness by an order-of-magnitude. However, iterative scientific investigations can uncover what works where for whom.


title: Ecology of zoonoses: natural and unnatural histories

text: Summary More than 60% of human infectious diseases are caused by pathogens shared with wild or domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations with frequent cross-species transmission to people. Some of these diseases have only emerged recently. Together, these organisms are responsible for a substantial burden of disease, with endemic and enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year. Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more effective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats.


title: Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

text: Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.


title: Analysis of the mitigation strategies for COVID-19: from mathematical modelling perspective

text: In this article, a mathematical model for the transmission of COVID-19 disease is formulated and analysed. It is shown that the model exhibits a backward bifurcation at [Formula: see text] when recovered individuals do not develop a permanent immunity for the disease. In the absence of reinfection, it is proved that the model is without backward bifurcation and the disease free equilibrium is globally asymptotically stable for [Formula: see text]. By using available data, the model is validated and parameter values are estimated. The sensitivity of the value of [Formula: see text] to changes in any of the parameter values involved in its formula is analysed. Moreover, various mitigation strategies are investigated using the proposed model and it is observed that the asymptomatic infectious group of individuals may play the major role in the re-emergence of the disease in the future. Therefore, it is recommended that in the absence of vaccination, countries need to develop capacities to detect and isolate at least 30% of the asymptomatic infectious group of individuals while treating in isolation at least 50% of symptomatic patients to control the disease.


title: Update on SARS research and other possibly zoonotic coronaviruses

text: Abstract The global outbreak of severe acute respiratory syndrome (SARS) in 2003 led to an intense and effective global response that stopped the spread of the disease by July 2003. There was also an intensive and very productive research effort to identify the aetiological agent, characterise the clinical and epidemiological features of the disease, understand the pathogenesis of the disease and the molecular biology of the virus, and design antiviral drugs and vaccines to treat and prevent the disease. In parallel with the SARS research effort there have been continuous improvements in our ability to detect and characterise other novel viruses. The SARS outbreak illustrates the importance of such detection tools in the response to public health threats. Studies since the SARS outbreak suggest that many novel viruses exist in animals and some, but probably not many, will present a risk to humans.


title: Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

text: Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here, we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte-secreted factor. The injected MSCs exert their function through exosomes, extracellular vesicles of endosome origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal-progenitor-mediated organ protections.


title: Molecular diversity of coronaviruses in bats

text: Abstract The existence of coronaviruses in bats is unknown until the recent discovery of bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other bat species. Among 309 bats of 13 species captured from 20 different locations in rural areas of Hong Kong over a 16-month period, coronaviruses were amplified from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA-dependent-RNA-polymerase (pol) and helicase genes revealed six novel coronaviruses from six different bat species, in addition to the two previously described coronaviruses. Among the six novel coronaviruses, four were group 1 coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An astonishing diversity of coronaviruses was observed in bats.


title: Innovative approach for improved rFVIII concentrate

text: The development of a new recombinant factor VIII was designed and implemented to answer a number of unmet needs of patients affected by hemophilia A. Turoctocog alfa is bioengineered in a specific Chinese hamster ovary clone to present translational and posttranslational characteristics (sulphation, glycosylation) biosimilar to natural circulating forms of FVIII, with the aim to devoid any minimal change which may impact immunogenicity and antigenicity of recombinant protein. Both producer cell line and media are maintained free of any animal or human plasma derivative. Downstream processes of purification are performed by five steps (immunoaffinity chromatography, ion‐exchange chromatography, virus inactivation by means of solvent‐detergent treatment and nanofiltration, and to end with gel filtration), to provide the best possible margin of safety from known and unknown infectious agents. Large clinical trials seem to confirm the expectations placed in Turoctocog alfa in terms of high quality and safety of recombinant FVIII toward the goal of overcoming actual and future challenges of hemophilia therapy.


title: The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction

text: Abstract Virus-like particle (VLP) formation by the coronavirus E and M proteins suggests that interactions between these proteins play a critical role in coronavirus assembly. We studied interactions between the infectious bronchitis virus (IBV) E and M proteins using in vivo crosslinking and VLP assembly assays. We show that IBV E and M can be crosslinked to each other in IBV-infected and transfected cells, indicating that they interact. The cytoplasmic tails of both proteins are important for this interaction. We also examined the ability of the mutant and chimeric E and M proteins to form VLPs. IBV M proteins that are missing portions of their cytoplasmic tails or transmembrane regions were not able to support VLP formation, regardless of their ability to be crosslinked to IBV E. Interactions between the E and M proteins and the membrane bilayer are likely to play an important role in VLP formation and virus budding.


title: The Post-COVID-19 Functional Status (PCFS) Scale: a tool to measure functional status over time after COVID-19

text: We propose an ordinal tool to measure the full spectrum of functional outcomes following COVID-19. This “Post-COVID-19 Functional Status (PCFS) Scale” can be used for tracking functional status over time as well as for research purposes.


title: High‐resolution structure of HLA‐A*1101 in complex with SARS nucleocapsid peptide

text: The structure of the human MHC‐I molecule HLA‐A*1101 in complex with a nonameric peptide (KTFPPTEPK) has been determined by X‐ray crystallography to 1.45 Å resolution. The peptide is derived from the SARS‐CoV nucleocapsid protein positions 362–370 (SNP(362–370)). It is conserved in all known isolates of SARS‐CoV and has been verified by in vitro peptide‐binding studies to be a good to intermediate binder to HLA‐A*0301 and HLA‐A*1101, with IC(50) values of 70 and 186 nM, respectively [Sylvester‐Hvid et al. (2004), Tissue Antigens, 63, 395–400]. In terms of the residues lining the peptide‐binding groove, the HLA‐A*1101–SNP(362–370) complex is very similar to other known structures of HLA‐A*1101 and HLA‐A*6801. The SNP(362–370) peptide is held in place by 17 hydrogen bonds to the α‐chain residues and by nine water molecules which are also tightly bound in the peptide‐binding groove. Thr6 of the peptide (Thr6p) does not make efficient use of the middle (E) pocket. For vaccine development, there seems to be a potential for optimization targeted at this position. All residues except Thr2p and Lys9p are accessible for T‐cell recognition.


title: Impact of 2013 south Asian haze crisis: study of physical and psychological symptoms and perceived dangerousness of pollution level

text: BACKGROUND: The widespread forest fires in Indonesia in June 2013 led to widespread haze to neighbouring countries. This is the first study in the medical literature reporting the acute physical and psychological symptoms of the general population during a haze crisis. We evaluated the factors that are associated with psychological stress of haze exposure. METHODS: This study was conducted between June 21 to June 26, 2013. Participants were recruited by an online recruitment post and snowball sampling techniques. Participants were required to complete an online survey which was composed of demographics questionnaire, physical symptom checklist, perceived dangerous Pollutant Standard Index (PSI) value and views on the N-95 mask and the Impact of Event Scale-Revised (IES-R). RESULTS: A total of 298 participants returned the completed study questionnaire. The respondents reported a mean number of 4.03 physical symptoms (S.D. = 2.6). The five most common physical symptoms include mouth or throat discomfort (68.8%), nose discomfort (64.1%), eye discomfort (60.7%), headache (50.3%) and breathing difficulty (40.3%). The total IES-R score was 18.47 (S.D. = 11.69) which indicated that the study population experienced mild psychological stress but not to the extent of acute stress reaction syndrome. The perceived dangerous PSI level and number of physical symptoms were significantly associated with the mean intrusion score, mean hyper-arousal score, total mean IES-R score and total IES-R score (p < 0.05). CONCLUSIONS: Our findings suggest that a haze crisis is associated with acute physical symptoms and mild psychological stress. The number of physical symptoms and the perceived dangerous PSI values are important factors associated with psychological stress.


title: Vaccine development and therapeutic design for 2019‐nCoV/SARS‐CoV‐2: Challenges and chances

text: The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019‐nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019‐nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time‐consuming and expensive to obtain. Scientific simulations and more in‐depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti‐2019‐nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019‐nCoV. Computational‐based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS‐CoV‐2.


docid: dabjcvno

title: The 2020 coronavirus lockdown and seismic monitoring of anthropic activities in Northern Italy

text: In March/April 2020 the Italian government drastically reduced vehicle traffic and interrupted all non-essential industrial activities over the entire national territory. Italy thus became the first country in the world, with the exception of Hubei, to enact lockdown measures as a consequence of the COVID-19 outbreak and the need to contain it. Italy is also a seismically active area, and as such is monitored by a dense permanent network of seismic stations. We analyse continuous seismic data from many stations in northern and central Italy, and quantify the impact of the lockdown on seismic ambient noise, as a function of time and location. We find that the lockdown reduces ambient noise significantly in the 1–10 Hz frequency range; because natural sources of seismic noise are not affected by the lockdown, the seismic signature of anthropic noise can be characterised with unprecedented clarity, by simply comparing the signal recorded before and after the lockdown. Our results correlate well with independent evaluations of the impact of the lockdown (e.g., cell phone displacements), and we submit that ambient-noise seismology is a useful tool to monitor containment measures such as the coronavirus lockdowns.


title: Influenza and other emerging respiratory viruses

text: Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.


docid: daokmiuz

title: Characterization of DNA hybridization kinetics in a microfluidic flow channel

text: Abstract In this investigation we report on the influence of volumetric flow rate, flow velocity, complementary DNA concentration, height of a microfluidic flow channel and time on DNA hybridization kinetics. A syringe pump was used to drive Cy3-labeled target DNA through a polydimethylsiloxane (PDMS) microfluidic flow channel to hybridize with immobilized DNA from the West Nile Virus. We demonstrate that a reduction of channel height, while keeping a fixed volumetric flow rate or a fixed flow velocity, enhances mass transport of target DNA to the capture probes. Compared to a passive hybridization, the DNA hybridization in the microfluidic flow channel generates higher fluorescence intensities for lower concentration of target DNA during the same fixed period of time. Within a fixed 2min time period the fastest DNA hybridization at a 50pM concentration of target DNA is achieved with a continuous flow of target DNA at the highest flow rate and the lowest channel height.


title: Novel Circovirus from Mink, China

text: A long-established epidemic of enteritis, caused by an unidentified pathogen distinct from parvovirus, has now been recognized in mink. In 2013, we identified a novel circovirus by degenerate PCR and fully sequenced its genome. This virus differs substantially from currently known members of the genus Circovirus and represents a new species.


docid: dxgrwlra

title: COVID-19 y Argumentum ad ignorantiam o «no todo vale»


title: Collectins: Innate Immune Pattern Recognition Molecules

text: Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a C-terminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.


title: Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

text: Abstract Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1–5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.


title: PPE shortages leaving staff at risk and urgent care system in jeopardy

text: A poll by the BDA of dentists staffing the emerging network of Urgent Dental Care centres suggests a third of sites in England remain inactive, with more than half reporting that their operational status is being impacted by a lack of Personal Protective Equipment (PPE)


title: Leveraging Lifestyle Medicine Interest Groups Through the COVID-19 Pandemic

text: Lifestyle medicine domains, despite accounting for more than 78% of chronic disease risk, are infrequently taught as a part of the medical curriculum. Aspects such as nutrition are taught in less than 25% of medical schools, a statistic that continues to decline, and less than 20% of practicing physicians were required to take even a single course in exercise counseling during their medical school training. To combat this lack of training, the American College of Lifestyle Medicine annually awards the Donald A. Pegg scholarship to fund the development of Lifestyle Medicine Interest Groups (LMIGs) across medical schools worldwide. This scholarship was initiated in 2016 and utilizes private funds to support the development and expansion of LMIGs with the aim of increasing awareness of lifestyle medicine among training practitioners. There are four award winners per year. To date there are sixteen Pegg Award winners. This article will showcase the four 2019-2020 Donald A. Pegg award recipients and their impact on the LMIGs at their institutions. Furthermore, it highlights the ingenuity and adaptation of these LMIGs during the COVID-19 pandemic.


title: Preparative purification of glycyrrhizin extracted from the root of liquorice using high-speed counter-current chromatography

text: Abstract Glycyrrhizin is one of the main bioactive components in liquorice (Glycyrrhiza uralensis Fisch) which has recently been found to be highly active in inhibiting replication of the severe acute respiratory syndrome (SARS)-associated virus. The separation and purification of glycyrrhizin from a methanol–water (70:30 (v/v)) extract of liquorice roots was achieved using high-speed counter-current chromatography. The separation was performed at a preparative scale in a one-step separation with a two-phase solvent system composed of ethyl acetate–methanol–water (5:2:5 (v/v)). The lower phase was used as the mobile phase in the head-to-tail elution mode. The present method yielded 42.2mg glycyrrhizin at 96.8% purity from 130mg of the crude exact with 95.2% recovery as determined by HPLC analysis.


title: Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol

text: The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.


title: Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19

text: Abstract Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.


title: Haddon Matrix for Kidney Transplantation during COVID‐19 Pandemic: A Problem Solving Framework for Present and Future

text: Novel coronavirus disease 2019 (COVID‐19) pandemic is a public health emergency with several million worldwide and a quarter of a million and soon half a million deaths including a third in the United States alone (as of May 10, 2020).(1) It affects kidney transplantation and has caused mortality in waitlist dialysis and transplant patients.(2,3) This inevitably raises questions about the practicality and direction of transplant surgeries during this critical period.


title: Reverse Transcription Recombinase Polymerase Amplification Assay for the Detection of Middle East Respiratory Syndrome Coronavirus

text: The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42°C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS-CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV.


title: Clinical Features of COVID-19-Related Liver Damage

text: Abstract Background & Aims Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Methods We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. Results Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P=.027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09±4.79 days) than patients with normal liver function (12.76±4.14 days) (P=.021). Conclusions More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.


title: Antibodies on demand: a fast method for the production of human scFvs with minimal amounts of antigen

text: BACKGROUND: Antibodies constitute a powerful tool to study protein function, protein localization and protein-protein interactions, as well as for diagnostic and therapeutic purposes. High-throughput antibody development requires faster methodologies with lower antigen consumption. RESULTS: Here, we describe a novel methodology to select human monoclonal recombinant antibodies by combining in vitro protein expression, phage display antibody libraries and antibody microarrays. The application of this combination of methodologies permitted us to generate human single-chain variable fragments (scFvs) against two proteins: green fluorescent protein (GFP) and thioredoxin (Trx) in a short time, using as low as 5 μg of purified protein. These scFvs showed specific reactivity against their respective targets and worked well by ELISA and western blot. The scFvs were able to recognise as low as 31 ng of protein of their respective targets by western blot. CONCLUSION: This work describes a novel and miniaturized methodology to obtain human monoclonal recombinant antibodies against any target in a shorter time than other methodologies using only 5 μg of protein. The protocol could be easily adapted to a high-throughput procedure for antibody production.


title: Role of Pharmacists in Responding to Humanitarian Crisis

text: Abstract Medical and pharmaceutical responses are crucial for saving precious lives during any humanitarian crisis. These responses include provision of both supplies as well as skilled human resource. Increasing number of humanitarian crisis situations are happening due to natural (owing to global warming, climatic change, and natural geographic processes) as well as global sociopolitical scenario with rising number of unresolved conflicts, economic turmoils, and international disputes. Hence, health professional's response to humanitarian crisis have evolved as a permanent feature of the global health-care scene. Pharmacists as the essential member of health care team, are incorporated in the health system network globally, also including their presence in the emergency conditions. The role of pharmacist is transforming globally to patient-centered approach. Similarly, in emergency medicine, pharmacists have not only struggled to advance their role in the logistic management but also focussed on rationality and safety, in accordance with the needs of the population.


docid: jxgywvwx

title: Chapter 13 Recent Advances and Future Needs in Environmental Virology

text: Publisher Summary The detection of viruses in water and other environmental samples constitutes special challenges. The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. The infected cell cultures undergo observable morphological changes called cytopathogenic effects (CPEs) that are used for the detection of viruses. Even though many viruses are culturable in several cell lines and are thus detectable by the development of CPEs in cell culture, there are several viruses, like enteric waterborne adenoviruses types 40 and 41, which are difficult to culture and do not produce clear and consistent CPE. Other viruses, like waterborne caliciviruses, have not yet been successfully grown in cell cultures. Conventional cell culture assays for the detection of viruses in environmental samples have limited sensitivity and can be labor-intensive and timeconsuming. Two advances, the PCR and microarrays, have spurred the study of viruses and should be further applied to the field of environmental virology. The ability of both DNA viruses and RNA viruses to rapidly evolve means new and emerging viral pathogens will need to be addressed. Pathogen discovery and characterization, occurrence in the environment, exposure pathways, and health outcomes via environmental exposure need to be addressed. This will likely follow a new microbial risk framework that will require focused research on some important properties of viral disease transmission. The future will require models that examine community risks and provide explicit links between the models currently under development for environmental exposure and infectious disease.


title: Coronavirus HKU1 Infection in the United States

text: In 2005, a new human coronavirus, HCoV-HKU1, was identified in Hong Kong. We screened respiratory specimens collected from December 16, 2001, to December 15, 2002, from children <5 years of age who tested negative for respiratory syncytial virus, parainfluenza viruses, influenza virus, and adenovirus for HCoV-HKU1 by reverse transcription–polymerase chain reaction. Overall, 1,048 respiratory specimens from 851 children were tested, and 9 HCoV-HKU1–positive children (1%) were identified, 2 of whom had 2 positive specimens. Children who had HCoV-HKU1 infection had evidence of either upper or lower respiratory tract infection or both. Two patients had disease beyond the respiratory tract. HCoV-HKU1 was identified from December 2001 to February 2002. Sequence analyses suggest that a single strain was circulating. HCoV-HKU1 is therefore likely circulating in the United States and is associated with upper and lower respiratory tract disease.


title: Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia

text: Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.


title: Physiological Outcomes of an Internet Disease Management Program vs. In-person Counselling:A Randomized, Controlled Trial

text: ABSTRACT OBJECTIVE To compare physiological outcomes and satisfaction for followup care between an interactive diabetes internet program and Diabetes Education Centres. METHOD A randomized, controlled trial with outcomes of glycosylated hemoglobin (A1C), fasting blood glucose, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, lowdensity lipoprotein cholesterol and patient satisfaction. Enrollment was staggered, with individuals assessed at baseline, 3, 6 and 12 months. RESULTS Fifty-seven participants completed the study (20 control, 37 internet). Physiological outcomes were not statistically different between the 2 groups. However, within-group comparisons demonstrated a significant improvement in the internet group's A1C, TG and satisfaction levels from baseline to 3 and 6 months (p<0.0452, p<0.0428 and p<0.0138, respectively). CONCLUSION Although the trial was limited in sample size, it yielded significant findings for diabetes management, within group. Further research in using the internet program in other applications for diabetes management is needed.


title: Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia

text: Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.


title: IFN-γ–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations

text: Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.


docid: uxltqopq

title: BAG3: a multifaceted protein that regulates major cell pathways

text: Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain (110–124 amino acids). BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicate that BAG3 is instead expressed in several tumor types. In different tumor contexts, BAG3 protein was reported to sustain cell survival, resistance to therapy, and/or motility and metastatization. In some tumor types, down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. This review attempts to outline the emerging mechanisms that can underlie some of the biological activities of the protein, focusing on implications in tumor progression.


Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague


title: Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

text: New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73–1.0), specificity of 0.66 (95% CI 0.52–0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75–0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47–0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.


title: Epidemiology

text: Abstract Although lacking the control available to toxicity studies, epidemiology allows for much larger study sizes and is particularly useful for identifying causal factors for population-wide health concerns. Some epidemiological studies are given more credence than their toxicological counterparts because the data are seen as more accurate for ‘real-life’ situations. Also, data collected for completely different reasons can often be incorporated into an epidemiological study. The greatest difference between epidemiology and toxicology, aside from the observational/experimental basis, is the measure of exposure, which, although it would improve any study, is often difficult to incorporate into epidemiological studies because of the historical nature of exposures.


title: Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles

text: Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to "recoviruses." Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens.


title: Generation of MERS-CoV Pseudotyped Viral Particles for the Evaluation of Neutralizing Antibodies in Mammalian Sera

text: Pseudotyped viral particle production has been used extensively and broadly for many viruses to evaluate levels of neutralizing antibodies, viral entry inhibitors and vaccine immunogenicity. This assay is extremely safe and useful alternative to live virus-based assay without the need for high containment facilities. In this chapter, we describe the generation of MERS-CoV pseudotyped viral particles (MERSpp) expressing full-length spike protein using second-generation lentiviral packaging system. This platform is optimized to generate high titer of MERSpp and to test sera from different mammalian species.


docid: szrtbtoc

title: Economic review

text: Abstract Severe Acute Respiratory Syndrome (SARS) has taken its toll on Japanese companies operating in East Asia, according to a Japan External Trade Organization (JETRO) survey conducted in June.


title: Impact of weather on COVID-19 pandemic in Turkey

text: Abstract The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (°C), dew point (°C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.


title: Probing the structural dynamics of proteins and nucleic acids with optical tweezers

text: Conformational changes are an essential feature of most molecular processes in biology. Optical tweezers have emerged as a powerful tool for probing conformational dynamics at the single-molecule level because of their high resolution and sensitivity, opening new windows on phenomena ranging from folding and ligand binding to enzyme function, molecular machines, and protein aggregation. By measuring conformational changes induced in a molecule by forces applied by optical tweezers, new insight has been gained into the relationship between dynamics and function. We discuss recent advances from studies of how structure forms in proteins and RNA, including non-native structures, fluctuations in disordered proteins, and interactions with chaperones assisting native folding. We also review the development of assays probing the dynamics of complex protein–nucleic acid and protein–protein assemblies that reveal the dynamic interactions between biomolecular machines and their substrates.


title: Incidence and risk factors of lower respiratory tract illnesses during infancy in a Mediterranean birth cohort

text: Aim: To investigate the incidence rate, viral respiratory agents and determinants of lower respiratory tract illnesses (LRTIs) in infants younger than 1 year. Methods: A total of 487 infants were recruited at birth for the Asthma Multicenter Infant Cohort Study in Barcelona (Spain). Cases of LRTIs were ascertained through an active register including a home visit and viral test in nasal lavage specimens during the first year of life. Cotinine in cord blood, household aeroallergens, indoor NO(2) and maternal and neonatal IgE were measured. Other maternal and infants' characteristics were obtained from structured questionnaires. Results: The incidence rate of at least one LRTI was 38.7 infants per 100 persons‐years. The most frequently isolated viral agent was respiratory syncytial virus (44.7%). The risk of LRTIs was higher in infants with a maternal history of asthma and in those with siblings (OR = 2.4; 95% CI: 0.98–6.08 and OR = 1.8; 95% CI: 1.04–3.21, respectively). The risk of LRTIs was lower in infants who were breast fed for more than 12 weeks (OR = 0.26; 95% CI: 0.26–0.86) and in those from a low socioeconomic class (OR = 0.16; 95% CI: 0.06–0.42). Conclusion: Viral LRTIs are frequent in infants younger than 1 year of age and there is an inter‐relationship between maternal asthma, siblings, breast feeding and socioeconomic status.


title: Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features

text: Abstract The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PLpro) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PLpro is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PLpro, compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PLpro. The unique features observed in the crystal structure of the MERS-CoV PLpro should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases.


title: A Mini-Review on the Epidemiology of Canine Parvovirus in China

text: Canine viral diarrhea is a severe disease in dogs worldwide. The role of canine parvovirus (CPV) in canine viral diarrhea is a common health problem in dogs, attracting major concern from veterinarians and dog owners across China. In this mini-review, we summarize the CPV epidemiology in China, including its origin, prevalence, coinfection, and the genetic evolution of the virus. The review reveals the correlation between CPV-2 infection and seasonality, a dog's age/gender/breed/vaccination; that CPV-2 is the main causative agent of canine diarrhea in Northeast China and that coinfection with other pathogens is a common occurrence; the predominant CPV epidemic strains were the new CPV-2a, and CPV-2c has shown significant growth trends since 2010. This mini-review will provide valuable information for CPV infections across China and other countries.


title: Novel Orthopoxvirus and Lethal Disease in Cat, Italy

text: We report detection and full-genome characterization of a novel orthopoxvirus (OPXV) responsible for a fatal infection in a cat. The virus induced skin lesions histologically characterized by leukocyte infiltration and eosinophilic cytoplasmic inclusions. Different PCR approaches were unable to assign the virus to a defined OPXV species. Large amounts of typical brick-shaped virions, morphologically related to OPXV, were observed by electron microscopy. This OPXV strain (Italy_09/17) was isolated on cell cultures and embryonated eggs. Phylogenetic analysis of 9 concatenated genes showed that this virus was distantly related to cowpox virus, more closely related to to ectromelia virus, and belonged to the same cluster of an OPXV recently isolated from captive macaques in Italy. Extensive epidemiologic surveillance in cats and rodents will assess whether cats are incidental hosts and rodents are the main reservoir of the virus. The zoonotic potential of this novel virus also deserves further investigation.


title: A changing world, again. How Appreciative Inquiry can guide our growth

text: Abstract COVID-19 is an interconnecting, cascading tsunami of up-rootedness and change on many levels. The global challenge we face is twofold: 1) how do we sustain our psychological, physical, social and economic capital and wellbeing in a time of great uncertainty; and 2) how do we adapt and create a new existence in an altered reality? Appreciative Inquiry (AI) is a well-documented approach to helping individuals and systems move from a deficit-based paradigm to a strengths-based perspective. AI holds myriad potential benefits for individuals, communities, and macro systems to build resilience and promote growth during and after COVID-19. This article will provide an overview of AI and its relevance to the current situation, as well as provide specific strategies for how people and systems can use AI as they transition through the pandemic and afterward.


title: Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil

text: Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.


title: An assessment of Ebola-related stigma and its association with informal healthcare utilisation among Ebola survivors in Sierra Leone: a cross-sectional study

text: BACKGROUND: We examined the magnitude and correlates of Ebola virus disease (EVD)-related stigma among EVD survivors in Sierra Leone since their return to their communities. In addition, we determined whether EVD-related stigma is a predictor of informal health care use among EVD survivors. METHODS: We conducted a cross-sectional study among 358 EVD survivors in five districts across all four geographic regions (Western Area, Northern Province, Eastern Province and Southern Province) of Sierra Leone. Ebola-related stigma was measured by adapting the validated HIV related stigma for people living with HIV/AIDS instrument. We also measured traditional and complementary medicine (T&CM) use (as a measure of informal healthcare use). Data were analysed using descriptive statistics and regression analysis. RESULTS: EVD survivors report higher levels of internalised stigma (0.92 ± 0.77) compared to total enacted stigma (0.71 ± 0.61). Social isolation (0.96 ± 0.88) was the highest reported enacted stigma subscale. Ebola survivors who identified as Christians [AOR = 2.51, 95%CI: 1.15–5.49, p = 0.021], who perceived their health to be fair/poor [AOR = 2.58, 95%CI: 1.39–4.77. p = 0.003] and who reside in the northern region of Sierra Leone [AOR = 2.80, 95%CI: 1.29–6.07, p = 0.009] were more likely to experience internalised stigma. Verbal abuse [AOR = 1.95, 95%CI: 1.09–3.49, p = 0.025] and healthcare neglect [AOR = 2.35, 95%CI: 1.37–4.02, p = 0.002] were independent predictors of T&CM use among EVD survivors. CONCLUSION: Our findings suggest EVD-related stigma (internalised and enacted) is prevalent among EVD survivors since their return to their communities. Religiosity, perceived health status and region were identified as independent predictors of internalised stigma. Verbal abuse and healthcare neglect predict informal healthcare use. EVD survivor-centred and community-driven anti-stigma programs are needed to promote EVD survivors’ recovery and community re-integration.


title: Electronic data interchange usage in China's healthcare organizations: the case of Beijing's hospitals

text: China has long since realized the potential benefits of adopting electronic data exchange. In particular, the Chinese government is promoting the usage of electronic data interchange (EDI) in healthcare organizations. However, little research has described the current status of EDI usage in these organizations. This study investigates the extent of EDI usage in Beijing's hospitals along four dimensions: volume, diversity, breadth, and depth. The results from 57 hospitals show that EDI usage is in its very early stages. The study provides possible reasons for the low EDI usage from cultural, economic, and technological perspectives, analyzes the differences of EDI usage in the different levels of China's hospitals, and suggests strategies to promote EDI usage in China's healthcare organizations.


Coronavirus uses as binding site in humans angiotensin‐converting enzyme 2 functional receptor that is involved in arterial blood pressure control and fibrotic response to damage and is a drug target in cardiovascular disease. Is this just a phylogenetic coincidence?


title: Comment on ‘Two cases of COVID‐19 presenting with a clinical picture resembling chilblains: first report from the Middle East’: pernio unrelated to COVID‐19

text: Dear editor, we have read with interest Dr´s Alramthan and Aldaraji contribution to the spectrum of COVID-19 clinical manifestations.1 Since COVID-19 outbreak begin, new symptoms have been described.2 Some of them, were not initially highlighted and could be a distinguishing feature of COVID-19 infection, like anosmia or ageusia.3 Therefore, it is believed that a newly reported one, so-called acute acro-ischemia is another novel clinical manifestation of COVID-19 infection.4.


docid: nqqbqzmu

title: Human parechovirus: sepsis-like illness with pulmonary infection


title: The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

text: Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo.


Author’s Reply: Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling All Asymptomatic Patients Before Surgical Treatment