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Comparison of genomic and amino acid sequences of eight Japanese encephalitis virus isolates from bats
We compared nucleotide and deduced amino acid sequences of eight Japanese encephalitis virus (JEV) isolates derived from bats in China. We also compared the bat JEV isolates with other JEV isolates available from GenBank to determine their genetic similarity. We found a high genetic homogeneity among the bat JEVs isolated in different geographical areas from various bat species at different time periods. All eight bat JEV isolates belonged to genotype III. The mean evolutionary rate of bat JEV isolates was lower than those of isolates of other origin, but this difference was not statistically significant. Based on these results, we presume that the bat JEV isolates might be evolutionarily conserved. The eight bat JEV isolates were phylogenetically similar to mosquito BN19 and human Liyujie isolates of JEV. These results indicate that bats might be involved in natural cycle of JEV.
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The cell receptor level is reduced during persistent infection with influenza C virus
Persistent influenza C virus infection of MDCK cells perpetuates the viral genome in a cell-associated form. Typically, virus production remains at a low level over extended periods, in the absence of lytic effects of replication. In this study, we demonstrate that persistently infected cells are very restricted in permissiveness for superinfection. By reconstitution experiments, using bovine brain gangliosides as artificial receptors, the degree of super-infection was markedly increased. Analysis of cellular receptor expression revealed reduced concentrations of sialoglycoproteins in general and a limited presentation of the major receptor gp40. Cocultures of persistently infected and uninfected cells (the latter carrying normal receptor levels) initiated a transient rise in virus titers. This kind of induction of virus synthesis appeared to be mainly receptor-linked, since a receptor-deprived subline, MDCK II, did not give rise to a similar effect. Susceptibility of MDCK II cocultures could be partly restored by ganglioside treatment. In accordance to related virus systems, these findings on influenza C virus suggest a role of cell receptor concentrations in the regulation of long-term persistence.
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Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2‐step entry mechanism
Entry of enveloped viruses into host cells is mediated by their surface envelope glycoproteins (Env). On the surface of the virus, Env is in a metastable, prefusion state, primed to catalyze the fusion of the viral and host membranes. An external trigger is needed to promote the drastic conformational changes necessary for the fusion subunit to fold into the low‐energy, 6‐helix bundle. These triggers typically facilitate pH‐independent entry at the plasma membrane or pH‐dependent entry in a low‐pH endosomal compartment. The α‐retrovirus avian sarcoma leukosis virus (ASLV) has a rare, 2‐step entry mechanism with both pH‐dependent and pH‐independent features. Here, we present the 2.0‐Å‐resolution crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural and biophysical studies indicated that unlike other pH‐dependent or pH‐independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two histidine residues (His490 and His492) in the chain reversal region confer stability at low pH. A structural comparison of class I viral fusion proteins suggests that the presence of a positive charge, either a histidine or arginine amino acid, stabilizes a helical dipole moment and is a signature of fusion proteins active at low pH. The structure now reveals key residues and features that explain its 2‐step mechanism, and we discuss the implications of the ASLV TM structure in the context of general mechanisms required for membrane fusion.—Aydin, H., Smrke, B.M., Lee, J. E. Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2‐step entry mechanism. FASEB J. 27, 5059–5071 (2013). http://www.fasebj.org
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Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon‐ω therapy
OBJECTIVES: Recombinant feline interferon‐ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon‐ω therapy are lacking. This study aimed to determine whether interferon‐ω therapy influences acute phase protein concentrations namely serum amyloid‐A, α‐1‐glycoprotein and C‐reactive protein. METHODS: A single‐arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon‐ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid‐A and C‐reactive protein were measured by specific enzyme‐linked immunosorbent assay kits and α‐1‐glycoprotein by single radial immunodiffusion. RESULTS: All the acute phase proteins significantly increased in cats undergoing interferon‐ω therapy (D0/D65: P<0·05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be reasonable predictors of innate‐immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon‐ω therapy.
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Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps
[Image: see text] Recent crystal structure data for protein–protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.
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Open season
SARS caught China unawares. But the ensuing struggle to characterize and contain the virus has put the country's work on infectious diseases back on target. Apoorva Mandavilli reports.
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Décision kinésithérapique: Mohamed S. 25 ans: Effets délétères et utiles du confinement COVID-19 dans un contexte de sclérose en plaques en Tunisie
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COVID-19 and Mental Health: An Iranian Perspective
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Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes
Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.
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A case of acute acquired obstructive hydrocephalus in a cat with suspected ischaemic cerebellar infarct
CASE SUMMARY: A case of acquired acute obstructive hydrocephalus that developed as a complication of an ischaemic infarct in the vascular territory of the rostral cerebellar artery is described in an adult domestic shorthair cat. The clinical findings, diagnostic investigations, treatment and prognosis are reported. MRI findings are described in detail. RELEVANCE AND NOVEL INFORMATION: This is the first report of obstructive hydrocephalus as a complication of an ischaemic infarct in the region of the rostral cerebellar artery in a cat. MRI findings are described in detail with regard to the recognition of the early signs of obstructive hydrocephalus. A brief review of the literature is included, as this complication has been frequently reported in humans.
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A survey of recommended practices made by veterinary practitioners to cow-calf operations in the United States and Canada
ABSTRACT Practicing veterinarians (n = 148) who service commercial beef cow-calf herds responded to a survey describing general recommendations made to their clients in terms of vaccine protocol, health, and production practices. Responding veterinarians represented 35 states in the United States and 3 provinces in Canada. More than 50% of responding veterinarians devote over 50% of their practice to service commercial cow-calf producers. The largest group (33%) of veterinarians have been in practice for over 30 yr. Thirty-nine percent of responding veterinarians serviced more than 10,000 cows. Genetic advice is provided by 54% of practicing veterinarians. When vaccinating at branding, the most common recommended vaccines are clostridial (96%), infectious bovine rhinotracheitis (IBR; 94%), bovine respiratory syncytial virus (BRSV; 91%), parainfluenza-3 (PI-3; 90%), and bovine viral diarrhea (BVD) Types 1 and 2 (78 and 77%, respectively). When vaccinating before weaning, the most common recommended vaccines are IBR (99%), BRSV (98%), BVD Types 1 and 2 (96%), PI-3 (93%), clostridial (77%), and Mannheimia haemolytica (77%). When vaccinating after weaning, the most common recommended vaccines are BVD Type 2 (97%), IBR (97%), BVD Type 1 (96%), BRSV (96%), and PI-3 (91%). Over 60% of responding veterinarians recommended that the last preventative vaccine should be administered to cattle 7 to 21 d before shipping. The largest number of respondents (38%) recommended that the earliest age their clients should wean their calves is 90 to 120 d. Castrating bull calves at an age of 0 to 7 d was recommended by 34% of respondents. Calf nutrition is considered as extremely important during a preconditioning program by 82% of responding veterinarians.
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A Practical Protocol for Carbohydrate Microarrays
We have established a high-throughput biochip platform for constructing carbohydrate microarrays. Using this technology, carbohydrate-containing macromolecules of diverse structures, including polysaccharides, natural glycoconjugates, and mono- and oligosaccharides coupled to carrier molecules, can be stably immobilized on a glass chip without chemical modification. Here, we describe a practical protocol for this technology. We hope that anyone who has access to a standard cDNA microarray facility will be able to explore this technology for his or her own research interest. We also provide an example to illustrate that the carbohydrate microarray is also a discovery tool; this is particularly useful for identifying immunologic sugar moieties, including complex carbohydrates of cancer cells and sugar signatures of previously unrecognized microbial pathogens.
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Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds
Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.
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China's Belt and Road Initiative: Incorporating public health measures toward global economic growth and shared prosperity
Abstract The unprecedented globalization of trade, travel, climate change, protectionism, and geopolitical populism, as well as pandemic health threats are no longer issues for a single nation. In the field of public health, China's Belt and Road Initiative (BRI) offers immense opportunities for partnership and collective actions involving multiple countries to combat globalization-linked infectious and/or chronic diseases, emerging pandemics, and outbreaks of potential threats to both laboratory information management systems and health information management. The national and global health challenges have increasingly proved that economic prosperity cannot be achieved when huge knowledge and capacity gaps exist in health systems. There is thus a need for public health initiatives aimed at strengthening the health systems beyond sovereign borders to influence global geo-economics. We highlight situational insights that offer approaches and strategies for increasing public health investment and capacity development in the countries along the Belt and Road, enhancing public and global health cooperation alongside participation in disease control and elimination, promoting public health governance and data sharing for pandemic threats, and building shared values and benefits in public health through Sino-African cooperation and the BRI. Our approach also examines the values of the China's BRI in relation to public health, projections and initiatives for increasing new investment and development capacity in public health systems, and enhanced public and global health cooperation and participation toward the BRI's framework and scope.
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Membrane binding proteins of coronaviruses
Coronaviruses (CoVs) infect many species causing a variety of diseases with a range of severities. Their members include zoonotic viruses with pandemic potential where therapeutic options are currently limited. Despite this diversity CoVs share some common features including the production, in infected cells, of elaborate membrane structures. Membranes represent both an obstacle and aid to CoV replication – and in consequence – virus-encoded structural and nonstructural proteins have membrane-binding properties. The structural proteins encounter cellular membranes at both entry and exit of the virus while the nonstructural proteins reorganize cellular membranes to benefit virus replication. Here, the role of each protein in membrane binding is described to provide a comprehensive picture of their role in the CoV replication cycle.
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Bats host major mammalian paramyxoviruses
The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.
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COVID‐19 and telemedicine in hemophilia in a patient with severe hemophilia A and orthopedic surgery
We describe the case of a patient with severe hemophilia A who underwent major orthopedic surgery managed postoperatively by telemedicine (TM). The case is a splendid example of the implementation of TM and good collaboration between a Comprehensive Hemophilia Treatment Center (CHTC) and a local hospital.
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Viral detection by electron microscopy: past, present and future
Viruses are very small and most of them can be seen only by TEM (transmission electron microscopy). TEM has therefore made a major contribution to virology, including the discovery of many viruses, the diagnosis of various viral infections and fundamental investigations of virus—host cell interactions. However, TEM has gradually been replaced by more sensitive methods, such as the PCR. In research, new imaging techniques for fluorescence light microscopy have supplanted TEM, making it possible to study live cells and dynamic interactions between viruses and the cellular machinery. Nevertheless, TEM remains essential for certain aspects of virology. It is very useful for the initial identification of unknown viral agents in particular outbreaks, and is recommended by regulatory agencies for investigation of the viral safety of biological products and/or the cells used to produce them. In research, only TEM has a resolution sufficiently high for discrimination between aggregated viral proteins and structured viral particles. Recent examples of different viral assembly models illustrate the value of TEM for improving our understanding of virus—cell interactions.
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Recommandations du Comité Lithiase de l’Association Française d’Urologie pour la prise en charge des calculs urinaires durant la crise sanitaire liée à la pandémie à COVID-19
Abstract For the first time, faced with a crisis with an exceptional magnitude due to the COVID-19 pandemic responsible for saturation of emergency services and intensive care units, the urolithiasis committee of the French Urology Association designed the recommendations for care and treatment of stone-forming patients and their treatment during crisis.
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They're back! Post-financialization diversification benefits of commodities
Abstract Do alternative assets such as commodities improve portfolio diversification? The empirical evidence is generally positive but mixed, and almost exclusively focuses on U.S. data. Using several distinct commodity indexes over the period 1993–2019, we investigate the case of an investor in Canada, a commodity-currency country where equities are already exposed to commodity beta. We use spanning tests and several out-of-sample performance measures for both risk-averse and disappointment-averse investors. Overall, we find that while the diversification potential of commodities was limited in Canada before and during financialization, the post-financialization period offers new opportunities. The evidence suggests that portfolio performance is significantly improved using some, but not all, commodity indexes. Thus, the choice of a relevant commodity index matters as a vehicle for diversification. Finally, compounding an international component to the sectorial diversification of the portfolio can significantly improve its performance.
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SARS in Hospital Emergency Room
Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.
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Coronaviruses: Molecular Biology☆
Abstract Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona – Latin for ‘crown’), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido – Latin for ‘nest’) of 3′ co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002–03 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate before it was controlled by public health measures of isolation of infected individuals and contacts. Middle East Respiratory Syndrome CoV (MERS-CoV), first reported in 2012, is likely transmitted from camels to humans with potentially fatal consequences. To date, there are no approved vaccines or direct acting antiviral drugs to combat coronavirus infections in humans. The emergence or re-emergence of CoVs from animal reservoirs is a potential concern for public health.
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Microbial Forensics☆
Abstract Biothreats are a high priority concern for public safety and national security. The field of microbial forensics was developed to analyze evidence associated with biological crimes in which microbes or their toxins are used as weapons. Microbial forensics is the scientific discipline dedicated to analyzing evidence from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release for attribution purposes. Microbial forensics combines the practices of epidemiology with the characterization of microbial and microbial-related evidence to assist in determining the specific source of the sample, as individualizing as possible, and/or the methods, means, processes and locations involved to determine the identity of the perpetrator(s) of an attack.
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Preparation and Response to COVID-19 outbreak in Singapore: A Case Report
Abstract The COVID-19 pandemic has an overwhelming impact on the nursing profession. Nurses play a vital role before and during pandemics, with nurse leaders taking the lead in preparation for outbreaks. In response to an outbreak, early recognition and preparation for the increasing threat, managing staffing challenges together with the well-being of nurses are of utmost importance. Strategies to promote physical distancing while not compromising continuing nursing education and patient care are also essential. With prompt actions and coordinated efforts, risk of spreading the virus within the healthcare sector can be kept at the minimum. As nurses are in the frontline of healthcare, their confidence in being well-supported by the hospital should be maintained. This case report describes the preparation and response of the nurses in Singapore General Hospital to the COVID-19 outbreak in Singapore.
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Dysphagia in COVID‐19 –multilevel damage to the swallowing network?
We read with great interest the article “COVID‐19: what if the brain had a role in causing the deaths?” by Tassorelli and co‐workers, in which the authors generate and summarize hypotheses how SARS‐CoV‐2 may enter the peripheral and central nervous system and cause life‐threatening complications [1]. With this letter we would like to contribute to this discussion by highlighting how different complications of COVID‐19 may result in damage to central and peripheral parts of the swallowing network leading to dysphagia in critically ill COVID‐survivors.
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Oxigenoterapia de alto flujo y posición de prono con respiración espontanea en neumonía por SARS-CoV-2
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Multiplex Platforms for the Identification of Respiratory Pathogens: Are They Useful in Pediatric Clinical Practice?
Respiratory tract infections (RTIs) are extremely common especially in the first year of life. Knowledge of the etiology of a RTI is essential to facilitate the appropriate management and the implementation of the most effective control measures. This perspective explains why laboratory methods that can identify pathogens in respiratory secretions have been developed over the course of many years. High-complexity multiplex panel assays that can simultaneously detect up to 20 viruses and up to four bacteria within a few hours have been marketed. However, are these platforms actually useful in pediatric clinical practice? In this manuscript, we showed that these platforms appear to be particularly important for epidemiological studies and clinical research. On the contrary, their routine use in pediatric clinical practice remains debatable. They can be used only in the hospital as they require specific equipment and laboratory technicians with considerable knowledge, training, and experience. Moreover, despite more sensitive and specific than other tests routinely used for respiratory pathogen identification, they do not offer significantly advantage for detection of the true etiology of a respiratory disease. Furthermore, knowledge of which virus is the cause of a respiratory disease is not useful from a therapeutic point of view unless influenza virus or respiratory syncytial virus are the infecting agents as effective drugs are available only for these pathogens. On the other hand, multiplex platforms can be justified in the presence of severe clinical manifestations, and in immunocompromised patients for whom specific treatment option can be available, particularly when they can be used simultaneously with platforms that allow identification of antimicrobial resistance to commonly used drugs. It is highly likely that these platforms, particularly those with high sensitivity and specificity and with low turnaround time, will become essential when new drugs effective and safe against most of the respiratory viruses will be available. Further studies on how to differentiate carriers from patients with true disease, as well as studies on the implications of coinfections and identification of antimicrobial resistance, are warranted.
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Assessment of infectious risk in clinical xenotransplantation: The lessons for clinical allotransplantation
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Global Burden of Infectious Diseases
Systematic efforts to quantify and monitor the burden of specific health conditions in populations, at the national level, started in the mid-1950s for malaria, poliomyelitis, and influenza in the United States. Comprehensive surveillance of morbidity and mortality for dozens of conditions has since been well established in the United States and in other industrialized countries. However, despite the clear need for epidemiological data to inform health policies, reliable and comprehensive health statistics are not available in many developing countries. International efforts to assess and monitor the burden of certain diseases have been limited in the past to a small number of infectious diseases in the context of global eradication programs – smallpox, poliomyelitis, guinea worm, and, more recently, HIV/AIDS, severe acute respiratory syndrome (SARS), and avian flu influenza A (H5N1). The Global Burden of Disease Study (GBD), published in 1996, filled an important gap in our knowledge of population health status. It created a common metric, the disability-adjusted life year (DALY), to estimate morbidity and mortality for eight regions that collectively span the world’s population, generating comparable information on incidence and prevalence in global health. However, patterns of disease, disability, and risk factors have since changed significantly and new data on their distribution are available. Furthermore, the unprecedented money and attention now pouring into international health has made an accurate assessment of global health patterns a matter of utmost urgency. The new Global Burden of Diseases, Injuries, and Risk Factors (GBD 2005) project, which began in 2007, represents the first major effort at a systematic revision of estimates in health for every region in the world comprehensively, and will ensure that that the global health community bases its research and policies on complete, valid, and reliable information. Burden of disease estimates provided in this article are for 2001 – the year for which the most recent estimates of the global burden of disease and risk factors are currently available. Causes of deaths were categorized into three main groups: group I (infectious diseases and maternal, perinatal, and nutritional conditions), group II (noncommunicable diseases), and group III (injuries). Accordingly, estimates of the global burden of infectious diseases are provided in the context of the overall burden from other conditions, diseases, and injuries. The relative importance of the burden of infectious diseases was forecasted to change by 2020. As the epidemiological transition progresses worldwide, a decline in the burden of infectious diseases is expected as the burden of noncommunicable diseases and injuries gradually increases. The pace of the epidemiological transition, however, varies greatly among regions so that the projected decreases in the burden of infectious diseases are expected to vary between regions. Trends in the global burden due to specific infectious diseases projected to 2020 also vary among specific conditions. The global burden of HIV/AIDS, for instance, is expected to greatly increase, whereas the global burden due to respiratory infections and diarrheal diseases is expected to decrease. Contrary to expectations, the global burden of malaria has increased in recent years.
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Chapter 10 Cold-Chain Systems in China and Value-Chain Analysis
Abstract Cold supply chains or cold-chain systems are emerging rapidly in China. This chapter presents an overview of cold-chain systems in China, including those in fresh agricultural products, frozen processed products, and biopharmaceutical products. The rapid growth of the cold-chain supply systems emphasizes the need to establish integrated systems. We attempt to explain the integration of cold supply chains in China. This chapter is based on case studies of cold-chain companies in China within the framework of value-chain analysis. Recent integrations of cold-chain suppliers in China are reviewed along with the rationales behind the integration in terms of value creation. The findings will be of use for cold-chain practitioners and policy-makers to understand the observed behaviors of cold-chain systems. Practitioners will also be able to use the findings to guide supply chain integration decisions. This study will guide policy-makers and other stakeholders to manage the sustainable development of cold-chain systems.
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The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics
The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics. Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies. We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development. The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics. Future applications of the model are also explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.
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Theophylline-induced mesenteric periarteritis in F344/N rats
The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall.
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Procedure 36 Genosensor on gold thin-films with enzymatic electrochemical detection of a SARS virus sequence
Publisher Summary This chapter presents a procedure for the construction of a hybridization-based genosensor for a SARS (severe acute respiratory syndrome) virus sequence on a 100nm sputtered gold film, which works as immobilization and transduction surface. The chapter tests the sensitivity and the selectivity of the SARS genosensor using complementary strands of SARS virus and three-base mismatch strands. Genosensor construction include following steps: a drop of 5 mL of 1.02 mM thiolated probe deposited on the gold film and maintain at 37°C for 20 min or at 41°C for 12 h; it is cleaned with 0.1M Tris-HCl buffer; further a15 mL drop of a 2% 1-hexanethiol solution is deposited on the gold film and maintained for 10 min and again cleaned with a 2×SSC buffer solution pH 7. From the results of hybridization assay and recording of the analytical signal no significant difference found between the analytical signal obtained for a 3.03nM solution of the complementary target strand and three-base mismatch strand. The limit of detection, calculated as the concentration corresponding to a signal which is three times the standard deviation of the intercept, results to be 5 pM. This means an improvement of various orders of magnitude when compared with limits of detection reported in the bibliography for DNA assays.
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Comparative Genomic Analysis of Classical and Variant Virulent Parental/Attenuated Strains of Porcine Epidemic Diarrhea Virus
Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9−26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation.
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Patients get viral infections: so, do vines
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Teicoplanin potently blocks the cell entry of 2019-nCoV
Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.
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Diagnostic Testing in Central Nervous System Infection
Patients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broad-range diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.
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Human Adenovirus 14a: A New Epidemic Threat
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Testing for SARS‐CoV‐2: the day the world turned its attention to the clinical laboratory
In the last few months, an unprecedented number of laboratory tests for COVID‐19 have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID‐19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the U.S. and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID‐19. We will first address the detection of Sars‐Cov‐2 directly by either nucleic acid amplification tests (NAAT) or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.
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Reverse Genetics for Type I Feline Coronavirus Field Isolate To Study the Molecular Pathogenesis of Feline Infectious Peritonitis
Feline infectious peritonitis (FIP), one of the most important lethal infections of cats, is caused by feline infectious peritonitis virus (FIPV), the high-virulence biotype of feline coronaviruses (FCoVs). FIPVs are suggested to emerge from feline enteric coronaviruses (FECVs) by acquiring mutations in specific genes in the course of persistent infections. Although numerous studies identified mutations predicted to be responsible for the FECV-FIPV biotype switch, the presumed roles of specific genetic changes in FIP pathogenesis have not been confirmed experimentally. Reverse genetics systems established previously for serotype I and the less common serotype II FCoVs were based on cell culture-adapted FIPV strains which, however, were shown to be unsuitable for FIP pathogenesis studies in vivo. To date, systems to produce and manipulate recombinant serotype I field viruses have not been developed, mainly because these viruses cannot be grown in vitro. Here, we report the first reverse genetics system based on a serotype I FECV field isolate that is suitable to produce high-titer stocks of recombinant FECVs. We demonstrate that these recombinant viruses cause productive persistent infections in cats that are similar to what is observed in natural infections. The system provides an excellent tool for studying FCoVs that do not grow in standard cell culture systems and will greatly facilitate studies into the molecular pathogenesis of FIP. Importantly, the system could also be adapted for studies of other RNA viruses with large genomes whose production and characterization in vivo are currently hampered by the lack of in vitro propagation systems.
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SARS-CoV-2 in Pregnancy: A Comprehensive Summary of Current Guidelines
Since the declaration of the global pandemic of COVID-19 by the World Health Organization on 11 March 2020, we have continued to see a steady rise in the number of patients infected by SARS-CoV-2. However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG, and CatSalut have released guidelines for the care of these patients. We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers, and healthcare institutions. We included 15 papers from 10 societies through a literature search of direct review of society’s websites and their journal publications up till 20 April 2020. Recommendations specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into Tables. The summary of guidelines for the management of COVID-19 in pregnancy across different perinatal societies is fairly consistent, with some variation in the strength of recommendations. It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy.
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Experimental Evaluation of Musca domestica (Diptera: Muscidae) as a Vector of Newcastle Disease Virus
House flies, Musca domestica L. (Diptera: Muscidae), were examined for their ability to harbor and transmit Newcastle disease virus (family Paramyxoviridae, genus Avulavirus, NDV) by using a mesogenic NDV strain. Laboratory-reared flies were experimentally exposed to NDV (Roakin strain) by allowing flies to imbibe an inoculum consisting of chicken embryo-propagated virus. NDV was detected in dissected crops and intestinal tissues from exposed flies for up to 96 and 24 h postexposure, respectively; no virus was detected in crops and intestines of sham-exposed flies. The potential of the house fly to directly transmit NDV to live chickens was examined by placing 14-d-old chickens in contact with NDV-exposed house flies 2 h after flies consumed NDV inoculum. NDV-exposed house flies contained ≈10(4) 50% infectious doses (ID(50)) per fly, but no transmission of NDV was observed in chickens placed in contact with exposed flies at densities as high as 25 flies per bird. Subsequent dose–response studies demonstrated that oral exposure, the most likely route for fly-to-chicken transmission, required an NDV (Roakin) dose ≥10(6) ID(50). These results indicate that house flies are capable of harboring NDV (Roakin) but that they are poor vectors of the virus because they carry an insufficient virus titer to cause infection.
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VIGOR, an annotation program for small viral genomes
BACKGROUND: The decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. It is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. Among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. However, accurate gene prediction is a challenge that persists for decoding a newly sequenced genome. Therefore, accurate and efficient gene prediction programs are highly desired for rapid and cost effective surveillance of RNA viruses through full genome sequencing. RESULTS: We have developed VIGOR (Viral Genome ORF Reader), a web application tool for gene prediction in influenza virus, rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding regions based on sequence similarity searches and can accurately detect genome specific features such as frame shifts, overlapping genes, embedded genes, and can predict mature peptides within the context of a single polypeptide open reading frame. Genotyping capability for influenza and rotavirus is built into the program. We compared VIGOR to previously described gene prediction programs, ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user friendly web-based genome annotation program for five different viral agents, influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the first gene prediction program for rotavirus and rhinovirus for public access. VIGOR is able to accurately predict protein coding genes for the above five viral types and has the capability to assign function to the predicted open reading frames and genotype influenza virus. The prediction software was designed for performing high throughput annotation and closure validation in a post-sequencing production pipeline.
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Commentary: “Murder on the Orient Express of Pandemic: COVID was found guilty, but was it the murder?”
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Will the Higher-Income Country Blueprint for COVID-19 Work in Low- and Lower Middle-Income Countries?
Strategies to radically suppress incidence of COVID-19, as used in higher-income countries, may be unrealistic and counterproductive in most low- and lower middle-income countries. Instead, strategies should be tailored to the setting, balancing expected benefits, potential harms, and feasibility.
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Co-infections in people with COVID-19: a systematic review and meta-analysis
Abstract Objectives : In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19. Methods : We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. . Results : Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92∙2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74∙7% versus 4%, 95% CI 1-9, I2= 91∙7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62∙3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections. Conclusions : A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.
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Psychiatric‐mental health nursing leadership during coronavirus disease 2019 (COVID‐19)
This editorial presents a commentary on the impacts of COVID-19 on patient and nurse mental wellness. Implications for the psychiatric-mental health nursing workforce are discussed.
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Acro‐ischemia and COVID‐19 infection: clinical and histopathological features
With the COVID‐19 pandemic we are facing a changing world. This new coronavirus (SARS‐CoV‐2) poses new challenges to dermatologists too. Some of us are in the field, others are describing skin aspects related to this infection, either directly or indirectly caused (e.g: dermatoses resulting from prolonged contact with personal protective equipment and excessive personal hygiene). Still, cutaneous manifestations are uncommonly reported and the majority has no clinical or histological pictures.
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COVID-19 prevention and multiple sclerosis management: the SAFE pathway for the post-peak
BACKGROUND: We hereby report on our experience from Naples (South Italy), where the peak of coronavirus disease 2019 (COVID-19) has already passed. METHODS: Assuming that COVID-19 will be circulating until vaccination and/or herd immunity is achieved (possibly not earlier than 2021), we have developed a protocol for the long-term management of multiple sclerosis (MS). RESULTS: We have defined a pathway for the access to the MS Centre with logistic, preventative and clinical recommendations, and have also included 14-day self-isolation and COVID-19 testing before some disease modifying treatments. DISCUSSION: Overall, we believe our experience could be helpful for MS management in the upcoming months.
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Recent progress in the discovery of inhibitors targeting coronavirus proteases
Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. The fatal outbreak of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) highlights the threat posed by this unique virus subfamily. However, no specific drugs have been approved to treat CoV-associated diseases to date. The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. This review summarizes the recent advances in biological and structural studies, together with the development of inhibitors targeting CoV proteases, particularly main proteases (M(pro)s), which could help develop effective treatments to prevent CoV infection. [Image: see text]
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Print Media Response to SARS in New Zealand
To examine the media response to severe acute respiratory syndrome, we reviewed New Zealand's major newspaper (261 articles for 3 months). While important accurate health messages were frequently included, some were missed (e.g., hand washing in only 2% of articles). No incorrect information was identified, and health spokespersons were accurately quoted.
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Specific bacteriophage of Bordetella bronchiseptica regulates B. bronchiseptica-induced microRNA expression profiles to decrease inflammation in swine nasal turbinate cells
BACKGROUND: Respiratory diseases in pigs are the main health concerns for swine producers. Similar to the diseases in human and other animals, respiratory diseases are primary related to morbidity and are the result of infection with bacteria, viruses, or both. B. bronchiseptica causes serious respiratory diseases in the swine airway track. However, the B. bronchiseptica-specific bacteriophage has diverse advantages such as decreasing antibiotic overuse and possible therapeutic potential against bacteria. OBJECTIVE: The objects of this study were to investigate the therapeutic effect of specific B. bronchiseptica bacteriophages and to identify genes related to bacteriophage signaling utilizing RNA microarrays in swine nasal turbinate cells. METHODS: Bor-BRP-1 phages were applied 24 h prior to B.bronchiseptica infection (1 × 10(7) cfu/ml) at several concentrations of bacterial infection. Cells were incubated to detect cytokines and 24 h to detect mucin production. And real-time quantitative PCR was performed to examine related genes expression. To determine the change of total gene expression based on B.bronchiseptica and Bor-BRP-1 treatment, we performed RNA sequencing experiments. RESULTS: The results showed that B. bronchiseptica induced increased expression of several inflammatory genes such as IL-1β, IL-6, and Muc1 in a dose-dependent manner. However, Bor-BRP-1 induced reduction of gene expression compared to the B. bronchiseptica induction group. In addition, microarrays detected Bor-BRP-1-altered inflammatory gene expression against B. bronchiseptica, reducing B. bronchiseptica-induced airway inflammation in swine epithelial cells. CONCLUSION: These results suggest that the specific bacteriophage has a therapeutic potential to defend against B. bronchiseptica infection by altering inflammatory gene expression profiles.
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Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders
Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.
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COVID-19: Role of Integrated Regional Health System Towards Controlling Pandemic in the Community, Intermediate and Long-Term Care
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Examining User’s Initial Trust Building in Mobile Online Health Community Adopting
Due to the high perceived risk, it is critical to foster users’ initial trust in the promotion of mobile online health community (MOHC) adoption. The present study focused on the role of two different trust elements and examined the initial trust building process based on elaboration likelihood model and trust transfer theory. The results indicated that initial trust in MOHC context was composed of two interrelated components: health service provider (doctor) and underlying technology (MOHC platform). Especially, the initial trust in MOHC platform exerted greater effects on adopting intention. Both performance-based cue (doctors’ information quality and interaction quality) and transfer-based cue (trust in the offline doctors’ health service) positively shaped the initial trust in doctor. Meanwhile, only the performance-based cue (MOHC platform’s information quality and service quality) has significant positive association with initial trust in MOHC platform. However, interpersonal recommend is insignificantly related to the initial trust in doctor. Trust in the mobile internet service is insignificantly related to the initial trust in MOHC platform.
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The “Common Cold” in Frail Older Persons: Impact of Rhinovirus and Coronavirus in a Senior Daycare Center
OBJECTIVE: To evaluate the incidence and impact of rhino‐virus and Coronavirus infections in older persons attending daycare. DESIGN: Prospective descriptive study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS: Frail older persons and staff members of the daycare centers who developed signs or symptoms of an acute respiratory illness MEASUREMENTS: Demographic, medical, and physical findings were recorded on subjects at baseline and during respiratory illness. Nasopharyngeal specimens for viral culture as well as acute and convalescent sera for Coronavirus 229E enzyme immunoassay (EIA) were obtained for all illnesses. RESULTS: During the 44 months of study, 352 older persons experienced 522 illnesses. Thirty‐five (7%) of 522 cultures were positive for rhinovirus and 37 (8%) of 451 serologies were positive for Coronavirus 229E infection. The clinical syndromes associated with rhinovirus and Coronavirus infection were similar and characterized by nasal congestion, cough, and constitutional symptoms. No patient died or was hospitalized, but approximately 50% had evidence of lower respiratory tract involvement. The average illness lasted 14 days. During the same period, 113 staff developed 338 respiratory illnesses. Eight percent were identified as Coronavirus and 9% as rhinovirus. Cough, sputum production, and constitutional symptoms were significantly more common among older persons. CONCLUSIONS: Rhinovirus and Coronavirus 229E are common causes of moderately debilitating acute respiratory illnesses among older persons attending daycare.
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Exploring Australian Hajj Tour Operators’ Knowledge and Practices Regarding Pilgrims’ Health Risks: A Qualitative Study
BACKGROUND: Travel agents are known to be one of the main sources of health information for pilgrims, and their advice is associated with positive health behaviors. OBJECTIVE: This study aimed to investigate travel agents’ health knowledge, what health advice they provide to the pilgrims, and their sources of health information. METHODS: In-depth interviews were conducted among specialist Hajj travel agents in Sydney, Australia. Thematic analysis was undertaken. RESULTS: Of the 13 accredited Hajj travel agents, 9 (69%) were interviewed. A high level of awareness regarding gastrointestinal infections, standard hygiene methods, and the risk of injury was noted among the participants and was included in advice provided to pilgrims. However, very limited knowledge and provision of advice about the risk of respiratory infections was identified. Knowledge of the compulsory meningococcal vaccine was high, and all participated travel agents reported influenza vaccine (a recommended vaccine) as a second “compulsory” vaccine for Hajj visas. Conversely, participants reported very limited knowledge about other recommended vaccines for Hajj. The Ministry of Hajj website and personal Hajj experience were the main sources of information. CONCLUSIONS: This study identifies a potential path for novel health promotion strategies to improve health knowledge among Hajj travel agents and subsequently among Hajj pilgrims.
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Comparative Evaluation of Six Commercialized Multiplex PCR Kits for the Diagnosis of Respiratory Infections
The molecular diagnosis of respiratory infection can be performed using different commercial multiplex-based PCR kits whose performances have been previously compared individually to those of conventional techniques. This study compared the practicability and the diagnostic performances of six CE-marked kits available in 2011 on the French market, including 2 detecting viruses and atypical bacteria (from Pathofinder and Seegene companies) and 4 detecting only viruses (from Abbott, Genomica, Qiagen and Seegene companies). The respective sensitivity, specificity, accuracy and agreement of each multiplex technique were calculated by comparison to commercial duplex PCR tests (Argene/bioMérieux) used as gold standard. Eighty-eight respiratory specimens with no pathogen (n = 11), single infections (n = 33) or co-infections (n = 44) were selected to cover 9 viruses or groups of viruses and 3 atypical bacteria. All samples were extracted using the NUCLISENS® easyMAG™ instrument (bioMérieux). The overall sensitivity ranged from 56.25% to 91.67% for viruses and was below 50% with both tests for bacteria. The overall specificity was excellent (>94% for all pathogens). For each tested kit, the overall agreement with the reference test was strong for viruses (kappa test >0.60) and moderate for bacteria. After the extraction step, the hands-on time varied from 50 min to 2h30 and the complete results were available in 2h30 to 9 h. The spectrum of tested agents and the technology used to reveal the PCR products as well as the laboratory organization are determinant for the selection of a kit.
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Activation of the Renin-angiotensin-aldosterone system is associated with Acute Kidney injury in COVID-19
Abstract The pathophysiology of acute kidney injury (AKI) in COVID-19 patients is still poorly understood. SARS-CoV2 has been suggested to modulate the renin-angiotensin-aldosterone system (RAAS). In this series of COVID-19 critically ill patients, we report evidence of activation of the RAAS in COVID-19 patients with AKI.
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Evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks in the healthcare setting
BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. In particular, MERS continues to pose a significant threat in the Middle East since 2012. Currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. However, there are some MERS vaccines in the preclinical stage of development. We sought to evaluate the potential impact of targeted vaccination strategies for mitigating SARS and MERS outbreaks in healthcare settings using simple mathematical models and detailed historic transmission trees describing the progression of past nosocomial outbreaks of SARS and MERS. RESULTS: Our findings suggest that vaccination strategies targeting patients and healthcare workers, which have been disproportionately affected during past outbreaks, and assuming two vaccination coverage levels at 50 and 75% have the potential to avert nearly 50% or more of MERS or SARS cases. CONCLUSION: Our modeling results informed by historic outbreak data for SARS and MERS suggest that vaccination strategies targeting patients could be an effective measure to mitigate and prevent outbreaks in the healthcare setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0112-6) contains supplementary material, which is available to authorized users.
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Assessment of iodine‐treated filter media for removal and inactivation of MS2 bacteriophage aerosols
Aims: To investigate the performance of an iodine‐releasing filter medium for use as a protective device against airborne pathogens. Methods and Results: The filter’s physical and viable removal efficiencies (VRE) were investigated with challenges of MS2 bacteriophage aerosols, and the infectivity of MS2 collected on the filter was analysed. To test a proposed inactivation mechanism, media containing thiosulfate or bovine serum albumin (BSA) were put in impingers to quench and consume I(2) released from the filter. In direct plating experiments, treated filters presented significantly higher VREs than did untreated filters; however, collection in excess BSA decreased VRE by half and in thiosulfate the apparent VRE decreased drastically. No significant difference in infectivity of retained viruses on treated and untreated filters was observed at the same environmental condition. Conclusions: Evidence presented herein for competition by dissolved I(2) in infectivity assays supports a mechanism of induced displacement and capture of I(2.) It also requires that dissociation of iodine from the filter and capture of iodine by MS2 aerosols as they pass through the filter be factored in the design of the assessment methodology. The filter’s strong retention capability minimizes reaerosolization but also makes it difficult to discriminate the antimicrobial effect at the surface. Significance and Impact of the Study: This study shows the direct plating assay method to be sensitive to interference by iodine‐releasing materials. This requires reevaluation of earlier reports of VRE measurements.
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Uptake of Virtual Visits in A Geriatric Primary Care Clinic During the COVID‐19 Pandemic
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Why communities must be at the centre of the Coronavirus disease 2019 response: Lessons from Ebola and human immunodeficiency virus in Africa
As the Coronavirus disease 2019 (COVID-19) pandemic has spread globally, with no effective treatment or vaccine yet available, governments in many countries have put in place social interventions to control the outbreak. The various lockdown measures may have devastating impacts on economies and livelihoods. This approach risks undermining public trust in government responses and therefore undermines efforts to promote behaviour change, which is key to the success of social interventions. Important lessons can be drawn from past Ebola outbreaks and the human immunodeficiency virus pandemic on how communities should be central to COVID-19 responses. Communities are complex and only their members can inform public health experts about their lived realities, the community’s understanding of the outbreak and what will work locally to reduce transmission. The public should be encouraged to take positive actions to ensure their own health and well-being, rather than made to feel powerless. Communities should be supported to develop their own response plans, community leaders should be recognised as vital assets, community representatives should have equal inclusion in strategic meetings and greater empathy should be built into decision-making processes.
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A Computational Vaccine Designing Approach for MERS-CoV Infections
The aim of this study was to use IEDB software to predict the suitable MERS-CoV epitope vaccine against the most known world population alleles through four selecting proteins such as S glycoprotein and envelope protein and their modification sequences after the pandemic spread of MERS-CoV in 2012. IEDB services is one of the computational methods; the output of this study showed that S glycoprotein, envelope (E) protein, and S and E protein modified sequences of MERS-CoV might be considered as a protective immunogenic with high conservancy because they can elect both neutralizing antibodies and T-cell responses when reacting with B-cell, T-helper cell, and cytotoxic T lymphocyte. NetCTL, NetChop, and MHC-NP were used to confirm our results. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover most of the world population in more than 60 geographical regions. According to AllerHunter results, all those selected different protein showed non-allergen; this finding makes this computational vaccine study more desirable for vaccine synthesis.
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Revisiting the melamine contamination event in China: implications for ethics in food technology
Food technology is a burgeoning field of applied science, invading many areas of the food industry and making contributions to economic advancement; however, little research has focused on ethical aspects in this field. This article attempts to fill this knowledge gap by revisiting the tainted milk event in China in 2008, followed by a detailed discussion of the application of food technology ethics in industrial contexts. Through the lesson learnt in the Chinese food industry, it is hoped that more global concerns on ethical issues in food technology will be raised, thereby creating a more humane food production industry.
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Lung ultrasound in the diagnosis of COVID-19 infection - A case series and review of the literature
COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spreading worldwide has become a serious challenge for the entire health care system as regards infection prevention, rapid diagnosis, and treatment. Lung ultrasound (LUS) is a dynamically developing diagnostic method used in intensive care, cardiology and nephrology, it can also be helpful in diagnosing and monitoring pneumonia. Interstitial pneumonia appears to be the most common clinical manifestation of coronavirus infection. We present 4 case reports of COVID-19 involving the lungs, in which transthoracic lung ultrasound was successfully utilized as a constituent of bedside diagnostics and a review of the literature concerning potential use of LUS in COVID-19 diagnostics. The possibility to perform this examination repeatedly, its non-invasiveness and high sensitivity make it an important element of care provided for patients with viral pneumonia.
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Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro
Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and a nuclear export sequence, induces a shutdown of host transcription and nucleocytoplasmic trafficking. Here we show that infection with VEEV causes a dysregulation of cell cycling and a delay in the G(0)/G(1) phase in Vero cells and U87MG astrocytes. Cells infected with VEEV encoding a capsid NLS mutant or treated with the capsid-importin α interaction inhibitor G281-1485 were partially rescued from this cell cycle dysregulation. Pathway analysis of previously published RNA-sequencing data from VEEV infected U87MG astrocytes identified alterations of canonical pathways involving cell cycle, checkpoint regulation, and proliferation. Multiple cyclins including cyclin D1, cyclin A2 and cyclin E2 and other regulators of the cell cycle were downregulated in infected cells in a capsid NLS dependent manner. Loss of Rb phosphorylation, which is a substrate for cyclin/cdk complexes was also observed. These data demonstrate the importance of capsid nuclear localization and/or importin α binding for inducing cell cycle arrest and transcriptional downregulation of key cell cycle regulators.
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The 7 Ps marketing mix of home-sharing services: Mining travelers’ online reviews on Airbnb
The 7 Ps model is a very useful tool in helping service firms solve managerial issues in marketing. Guided by the 7 Ps marketing mix framework, a big-data, supervised machine learning analysis was performed with 1,148,062 English reviews of 37,092 Airbnb listings in San Francisco and New York City. The results disclose similar patterns in both markets, where travelers shared their experience about Service Product and Physical Evidence most often; Price and Promotion were the least mentioned elements. Furthermore, through a series of comparisons of Airbnb’s 7 Ps marketing mix among the listings managed by different types of hosts, multi-unit and single-unit hosts seem to offer similar services with a small observable difference; whereas superhosts and the ordinary hosts deliver different services. This study makes valuable methodological contributions and provides practical marketing insights for hoteliers and the hosts and webmasters on home-sharing websites. Policymakers should pay special attention to multi-unit hosts.
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Combating Heightened Social Isolation of Nursing Home Elders: The Telephone Outreach in the COVID-19 Outbreak Program
OBJECTIVE: Social isolation and loneliness—common concerns in older adults—are exacerbated by the COVID-19 pandemic. To address social isolation in nursing home residents, the Yale School of Medicine Geriatrics Student Interest Group initiated a Telephone Outreach in the COVID-19 Outbreak (TOCO) Program that implements weekly phone calls with student volunteers. METHODS: Local nursing homes were contacted; recreation directors identified appropriate and interested elderly residents. Student volunteers were paired with elderly residents and provided phone call instructions. RESULTS: Three nursing homes opted to participate in the program. Thirty elderly residents were paired with student volunteers. Initial reports from recreation directors and student volunteers were positive: elderly residents look forward to weekly phone calls and express gratitude for social connectedness. CONCLUSIONS: The TOCO program achieved initial success and promotes the social wellbeing of nursing home residents. We hope to continue this program beyond the COVID-19 pandemic in order to address this persistent need in a notably vulnerable patient population.
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COVID-19: Drug Targets and Potential Treatments
[Image: see text] Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.
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Severe COVID‐19 in a patient with chronic graft‐versus‐host disease after hematopoietic stem cell transplant successfully treated with ruxolitinib
Graft‐versus‐host disease (GVHD) is a common complication of hematopoietic stem cell transplant, which is known to be mediated by cytotoxic T‐cell effectors and dysregulated inflammatory cytokines. Similarly, the lung injury observed in severe COVID‐19 cases appears to be related to a massive production of pro‐inflammatory cytokines. The selective JAK1/2 inhibitor ruxolitinib has shown promising results in the context of GVHD, and different trials are currently underway in patients with severe COVID‐19; nevertheless, no clinical observation of safety or efficacy of treatment with ruxolitinib in this context has been published yet. We describe a first case of severe COVID‐19 developed after hematopoietic stem cell transplantation in a patient with a concomitant chronic GVHD (cGVHD), in which a treatment with ruxolitinib was administered with good tolerance and positive outcome.
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Air transportation, population density and temperature predict the spread of COVID-19 in Brazil
There is evidence that COVID-19, the disease caused by the betacoronavirus SARS-CoV-2, is sensitive to environmental conditions. However, such conditions often correlate with demographic and socioeconomic factors at larger spatial extents, which could confound this inference. We evaluated the effect of meteorological conditions (temperature, solar radiation, air humidity and precipitation) on 292 daily records of cumulative number of confirmed COVID-19 cases across the 27 Brazilian capital cities during the 1st month of the outbreak, while controlling for an indicator of the number of tests, the number of arriving flights, population density, proportion of elderly people and average income. Apart from increasing with time, the number of confirmed cases was mainly related to the number of arriving flights and population density, increasing with both factors. However, after accounting for these effects, the disease was shown to be temperature sensitive: there were more cases in colder cities and days, and cases accumulated faster at lower temperatures. Our best estimate indicates that a 1 °C increase in temperature has been associated with a decrease in confirmed cases of 8%. The quality of the data and unknowns limit the analysis, but the study reveals an urgent need to understand more about the environmental sensitivity of the disease to predict demands on health services in different regions and seasons.
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Hospitaliser les patients âgés en chambre individuelle : un rempart contre la COVID-19 et les infections nosocomiales
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QT prolongation in a diverse, urban population of COVID-19 patients treated with hydroxychloroquine, chloroquine, or azithromycin
PURPOSE: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients. METHODS: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias. RESULTS: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1–3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1–8.7). Adjusting for race/ethnicity yielded no significant associations. CONCLUSIONS: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.
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Genotypic Diversity and Epidemiology of Human Rhinovirus Among Children With Severe Acute Respiratory Tract Infection in Shanghai, 2013–2015
Human rhinovirus (HRV), and particularly HRV-C, is increasingly recognized as a cause of severe acute respiratory infections (SARIs). However, little is known about the genotypic diversity and epidemiology of HRV among children with SARI. Thus, we investigated the genotypic diversity and epidemiology of HRV in children with SARI in China over a 2-year period. In total 1,003, nasopharyngeal aspirates were collected from children hospitalized with SARI in Shanghai from 2013 to 2015. HRV was screened for by a PCR method targeting the viral 5′ UTR and was genotyped by sequencing of the VP4–VP2 region of the HRV genome. We also screened for 15 other common respiratory viruses to assess the prevalence of co-infection with HRV. The patient demographic and clinical data were reviewed. HRV was detected in 280 (27.9%) of the 1,003 specimens: HRV-A in 140 (14.0%), HRV-B in 21 (2.1%), HRV-C in 56 (5.6%), and HRV-untyped in 63 (6.3%). A phylogenetic analysis identified 77 genotypes (43 HRV-A, 10 HRV-B, and 24 HRV-C), among which A78, A12, A89, B70, C2, C6, and C24 predominated. HRV-A was detected mainly in winter 2013 and autumn 2014, while HRV-C detection peaked in autumn 2013 and 2014. The detection frequency of HRV-A was highest in patients <5 years old. Most HRV co-infections involved adenovirus, human bocavirus, and/or human respiratory syncytial virus. In conclusion, HRV-A and -C predominate in children with SARI in Shanghai. Among the 77 genotypes detected, A78, A12, A89, B70, C2, C6, and C24 were the most frequent. The HRV species responsible for SARIs differs according to season and age.
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Chapter 6 Low-Density TaqMan® Array Cards for the Detection of Pathogens
Abstract Real-time PCR assays have revolutionised diagnostic microbiology over the past 15 years or more. Adaptations and improvements over that time frame have led to the development of multiplex assays. However, limitations in terms of available fluorophores has meant the number of assays which can be combined has remained in single figures. This latter limitation has led to the focus tending to be on individual pathogens and their detection. This chapter describes the development of TaqMan® Array Cards (TACs), technology which allows the detection of multiple pathogens (up to 48 targets) from a single nucleic acid extract, utilising small volumes and real-time PCR. This in turn lends itself to a syndromic approach to infectious disease diagnosis. Using the examples of TACs we have developed in our own laboratory, as well as others, we explain the design, optimisation and use of TACs for respiratory, gastrointestinal and liver infections. Refinement of individual assays is discussed as well as the incorporation of appropriate internal and process controls onto the array cards. Finally, specific examples are given of instances where the assays have had a direct, positive impact on patient care.
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Respiratory source control using a surgical mask: An in vitro study
Cough etiquette and respiratory hygiene are forms of source control encouraged to prevent the spread of respiratory infection. The use of surgical masks as a means of source control has not been quantified in terms of reducing exposure to others. We designed an in vitro model using various facepieces to assess their contribution to exposure reduction when worn at the infectious source (Source) relative to facepieces worn for primary (Receiver) protection, and the factors that contribute to each. In a chamber with various airflows, radiolabeled aerosols were exhaled via a ventilated soft-face manikin head using tidal breathing and cough (Source). Another manikin, containing a filter, quantified recipient exposure (Receiver). The natural fit surgical mask, fitted (SecureFit) surgical mask and an N95-class filtering facepiece respirator (commonly known as an “N95 respirator”) with and without a Vaseline-seal were tested. With cough, source control (mask or respirator on Source) was statistically superior to mask or unsealed respirator protection on the Receiver (Receiver protection) in all environments. To equal source control during coughing, the N95 respirator must be Vaseline-sealed. During tidal breathing, source control was comparable or superior to mask or respirator protection on the Receiver. Source control via surgical masks may be an important adjunct defense against the spread of respiratory infections. The fit of the mask or respirator, in combination with the airflow patterns in a given setting, are significant contributors to source control efficacy. Future clinical trials should include a surgical mask source control arm to assess the contribution of source control in overall protection against airborne infection.
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Employing drug delivery strategies to create safe and effective pharmaceuticals for COVID‐19
The outbreak of the novel SARS-CoV-2 pathogen and corresponding coronavirus disease 2019 (COVID-19) have had an enormous impact on both global health and the daily lives of billions of people worldwide. With a proven vaccine at least a year from being fully tested for safety and efficacy, there may be an opportunity to rapidly repurpose existing drugs in order to prevent SARS-CoV-2 infections and improve outcomes for patients already infected with COVID-19. At present, more than 40 different drugs are being explored for efficacy against COVID-19, including antivirals and immune modulating compounds. Unfortunately, many of these drugs are associated with side effects that limit their use to the most severe cases and thereby prevent their use as prophylactics. This commentary describes drug formulation strategies that can be used to maintain the efficacy of these drugs through controlled release, targeted delivery, and non-viral nucleic acid delivery. If successful, these approaches could enable the expanded use of drugs to reduce the mortality of this devastating disease and equip healthcare providers with the tools to accelerate our recovery from this pandemic and improve our response to the next outbreak of a novel pathogenic virus. The author has no conflicts of interest to declare. This article is protected by copyright. All rights reserved.
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Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses
Porcine circovirus 2 (PCV2) is the etiological agent that causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are present in every major swine-producing country in the world. PCV2 infections may downregulate the host immune system and enhance the infection and replication of other pathogens. However, the exact mechanisms of PCVD/PCVAD are currently unknown. To date, many studies have reported that several cofactors, such as other swine viruses or bacteria, vaccination failure, and stress or crowding, in combination with PCV2, lead to PCVD/PCVAD. Among these cofactors, co-infection of PCV2 with other viruses, such as porcine reproductive and respiratory syndrome virus, porcine parvovirus, swine influenza virus and classical swine fever virus have been widely studied for decades. In this review, we focus on the current state of knowledge regarding swine co-infection with different PCV2 genotypes or strains, as well as with PCV2 and other swine viruses.
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“Therapeutic” Facemasks
There must be pathophysiological reason why “cold” viruses like SARS-CoV-2 show proclivity to nasal cavity, oral cavity, pharyngeal cavity and upper airways which have lower temperature than core body temperature. Henceforth, facemasks’ “therapeutic” role against SARS-CoV-2 must be explored because personal “therapeutic” environments may get created under facemasks due to rebreathing of ∼95°F “hot” and ∼80% “humid” exhalations which may constantly mitigate SARS-CoV-2 inside nasal cavity, oral cavity, pharyngeal cavity and upper airways.
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Childhood severe acute respiratory syndrome, coronavirus infections and asthma
Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus. Children appear to be less susceptible to the SARS coronavirus, although the other non‐SARS coronaviruses can cause respiratory infections in adults and in children of all ages. The exact reasons as to why SARS preferentially affects adults, and not children, are still unknown. Many hypotheses exist and need to be explored. During the outbreak of SARS, there did not appear to be an increase in asthma exacerbations in children.
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Catastrophe Compassion: Understanding and Extending Prosociality Under Crisis
ABSTRACT How do people behave when disasters strike? Popular media accounts depict panic and cruelty, but in fact, individuals often cooperate with and care for one another during crises. I summarize evidence for such “catastrophe compassion,” discuss its roots, and consider how it might be cultivated in more mundane times.
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El ambiente, los desplazamientos y el riesgo cardiovascular en la pandemia de COVID-19
Resumen La pandemia por COVID-19 ha desencadenado un impacto tremendo en la humanidad debido a las implicaciones culturales, económicas y sociales que este tipo de infecciones ha ocasionado. Quizá preguntas iniciales, mirando en retrospectiva corta, acerca de los hechos que comenzaron esta infección, darían una luz para prevenir eventos de esta índole en el futuro. ¿Cuáles fueron las circunstancias que desencadenaron la pandemia?, ¿fue una serie de transmisiones zoonóticas que produjeron la infección en los humanos?, ¿ha tenido algo que ver el ambiente? El desafío de las grandes potencias para mantener la hegemonía, dará curso a una plétora de investigaciones acerca de la biología del virus, las variables epidemiológicas y las enfermedades crónicas de riesgo cardiovascular. En este manuscrito se analizan algunos de estos cuestionamientos. Abstract The COVID-19 pandemic has had a tremendous impact on humanity due to the cultural, financial, and social implications caused by this type of infection. Perhaps some initial questions, looking at the short-term retrospective, about the facts that started this infection, could shed some light on preventing events of this kind in the future. What were the circumstances that triggered the pandemic? Was it a series of zoonotic transmissions that produced the infection in humans? Is it something to do with the environment? The challenge of the major powers to maintain dominance, will give rise to a plethora of studies on the biology of the virus, the epidemiological variables, and the chronic diseases of cardiovascular risk. Some of these questions are analysed in this article.
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RFID analytics for hospital ward management
In this paper, we present an RFID-enabled platform for hospital ward management. Active RFID tags are attached to individuals and assets in the wards. Active RFID readers communicate with the tags continuously and automatically to keep track of the real-time information about the locations of the tagged objects. The data regarding the locations and other transmitted information are stored in the ward management system. This platform enables capabilities of real-time monitoring and tracking of individuals and assets, reporting of ward statistics, and providing intelligence and analytics for hospital ward management. All of these capabilities benefit hospital ward management by enhanced patient safety, increased operational efficiency and throughput, and mitigation of risk of infectious disease widespread. A prototype developed based on our proposed architecture of the platform was tested in a pilot study, which was conducted in two medical wards of the intensive care unit of one of the largest public general hospitals in Hong Kong. This pilot study demonstrates the feasibility of the implementation of this RFID-enabled platform for practical use in hospital wards. Furthermore, the data collected from the pilot study are used to provide data analytics for hospital ward management.
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CD4(+) T Cells at the Center of Inflammaging
Bharath et al., 2020 report that CD4(+) T lymphocytes from aged individuals exhibit defective mitochondrial autophagy, resulting in altered redox metabolism and upregulation of TH17 cytokines, which in turn may contribute to aging-associated chronic inflammation or “inflammaging.” Of note, the antiaging drug metformin reverses this autophagy defect and rejuvenates CD4(+) T cell function.
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A Diallel of the Mouse Collaborative Cross Founders Reveals Strong Strain-Specific Maternal Effects on Litter Size
Reproductive success in the eight founder strains of the Collaborative Cross (CC) was measured using a diallel-mating scheme. Over a 48-month period we generated 4,448 litters, and provided 24,782 weaned pups for use in 16 different published experiments. We identified factors that affect the average litter size in a cross by estimating the overall contribution of parent-of-origin, heterosis, inbred, and epistatic effects using a Bayesian zero-truncated overdispersed Poisson mixed model. The phenotypic variance of litter size has a substantial contribution (82%) from unexplained and environmental sources, but no detectable effect of seasonality. Most of the explained variance was due to additive effects (9.2%) and parental sex (maternal vs. paternal strain; 5.8%), with epistasis accounting for 3.4%. Within the parental effects, the effect of the dam’s strain explained more than the sire’s strain (13.2% vs. 1.8%), and the dam’s strain effects account for 74.2% of total variation explained. Dams from strains C57BL/6J and NOD/ShiLtJ increased the expected litter size by a mean of 1.66 and 1.79 pups, whereas dams from strains WSB/EiJ, PWK/PhJ, and CAST/EiJ reduced expected litter size by a mean of 1.51, 0.81, and 0.90 pups. Finally, there was no strong evidence for strain-specific effects on sex ratio distortion. Overall, these results demonstrate that strains vary substantially in their reproductive ability depending on their genetic background, and that litter size is largely determined by dam’s strain rather than sire’s strain effects, as expected. This analysis adds to our understanding of factors that influence litter size in mammals, and also helps to explain breeding successes and failures in the extinct lines and surviving CC strains.
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Trypanosoma livingstonei: a new species from African bats supports the bat seeding hypothesis for the Trypanosoma cruzi clade
BACKGROUND: Bat trypanosomes have been implicated in the evolutionary history of the T. cruzi clade, which comprises species from a wide geographic and host range in South America, Africa and Europe, including bat-restricted species and the generalist agents of human American trypanosomosis T. cruzi and T. rangeli. METHODS: Trypanosomes from bats (Rhinolophus landeri and Hipposideros caffer) captured in Mozambique, southeast Africa, were isolated by hemoculture. Barcoding was carried out through the V7V8 region of Small Subunit (SSU) rRNA and Fluorescent Fragment Length barcoding (FFLB). Phylogenetic inferences were based on SSU rRNA, glyceraldehyde phosphate dehydrogenase (gGAPDH) and Spliced Leader (SL) genes. Morphological characterization included light, scanning and transmission electron microscopy. RESULTS: New trypanosomes from bats clustered together forming a clade basal to a larger assemblage called the T. cruzi clade. Barcoding, phylogenetic analyses and genetic distances based on SSU rRNA and gGAPDH supported these trypanosomes as a new species, which we named Trypanosoma livingstonei n. sp. The large and highly polymorphic SL gene repeats of this species showed a copy of the 5S ribosomal RNA into the intergenic region. Unique morphological (large and broad blood trypomastigotes compatible to species of the subgenus Megatrypanum and cultures showing highly pleomorphic epimastigotes and long and slender trypomastigotes) and ultrastructural (cytostome and reservosomes) features and growth behaviour (when co-cultivated with HeLa cells at 37°C differentiated into trypomastigotes resembling the blood forms and do not invaded the cells) complemented the description of this species. CONCLUSION: Phylogenetic inferences supported the hypothesis that Trypanosoma livingstonei n. sp. diverged from a common ancestral bat trypanosome that evolved exclusively in Chiroptera or switched at independent opportunities to mammals of several orders forming the clade T. cruzi, hence, providing further support for the bat seeding hypothesis to explain the origin of T. cruzi and T. rangeli.
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Letter: Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports (Diabetes Metab J 2020;44:349–53)
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73 Stem Cell-based Products in Medicine: FDA Regulatory Considerations
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ACE and ACE2: a tale of two enzymes
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Emerging Role of Online Virtual Teaching Resources for Medical Student Education in Plastic Surgery: COVID-19 Pandemic and Beyond
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Re: Hanbing Song, Bobak Seddighzadeh, Matthew R. Cooperberg, Franklin W. Huang. Expression of ACE2 and TMPRSS2, the SARS-CoV-2 Receptor and Co-Receptor, in Prostate Epithelial Cells. Eur Urol. In press
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Phage Display: A Powerful Technology for the Generation of High-Specificity Affinity Reagents from Alternative Immune Sources
Antibodies are critical reagents in many fundamental biochemical methods such as affinity chromatography, enzyme-linked immunosorbent assays (ELISA), flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry techniques. As our understanding of the proteome becomes more complex, demand is rising for rapidly generated antibodies of higher specificity than ever before. It is therefore surprising that few investigators have moved beyond the classical methods of antibody production in their search for new reagents. Despite their long-standing efficacy, recombinant antibody generation technologies such as phage display are still largely the tools of biotechnology companies or research groups with a direct interest in protein engineering. In this chapter, we discuss the inherent limitations of classical polyclonal and monoclonal antibody generation and highlight an attractive alternative: generating high-specificity, high-affinity recombinant antibodies from alternative immune sources such as chickens, via phage display.
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Ebola virus VP35 has novel NTPase and helicase-like activities
Ebola virus (EBOV) is a non-segmented, negative-sense RNA virus (NNSV) in the family Filoviridae, and is recognized as one of the most lethal pathogens in the planet. For RNA viruses, cellular or virus-encoded RNA helicases play pivotal roles in viral life cycles by remodelling viral RNA structures and/or unwinding viral dsRNA produced during replication. However, no helicase or helicase-like activity has ever been found to associate with any NNSV-encoded proteins, and it is unknown whether the replication of NNSVs requires the participation of any viral or cellular helicase. Here, we show that despite of containing no conserved NTPase/helicase motifs, EBOV VP35 possesses the NTPase and helicase-like activities that can hydrolyse all types of NTPs and unwind RNA helices in an NTP-dependent manner, respectively. Moreover, guanidine hydrochloride, an FDA-approved compound and inhibitor of certain viral helicases, inhibited the NTPase and helicase-like activities of VP35 as well as the replication/transcription of an EBOV minigenome replicon in cells, highlighting the importance of VP35 helicase-like activity during EBOV life cycle. Together, our findings provide the first demonstration of the NTPase/helicase-like activity encoded by EBOV, and would foster our understanding of EBOV and NNSVs.
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Inhibition of Chikungunya virus by an adenosine analog targeting the SAM‐dependent nsP1 methyltransferase
Alphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral nonstructural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S‐adenosyl methionine‐dependent N‐7‐methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)‐based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase inhibition efficiency of a few adenosine analogs and identified 5‐iodotubercidin (5‐IT) as an inhibitor of nsP1. The antiviral potency of 5‐IT was evaluated in vitro using a combination of cell‐based assays, which suggest that 5‐IT is efficacious against CHIKV in cell culture (EC(50): 0.409 µm).
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Spectrum of chest computed tomographic (CT) findings in coronavirus disease-19 (COVID-19) patients in India
PURPOSE: To report the spectrum of chest computed tomographic (CT) imaging findings in coronavirus disease-19 (COVID-19) infected Indian patients. METHODS: This was a prospective descriptive study comprising 147 consecutive reverse transcriptase polymerase chain reaction (RT-PCR) positive patients who underwent CT chest. Prevalence, distribution, extent and type of abnormal lung findings were recorded. RESULTS: Among the total study cohort of 147 patients, 104 (70.7%) were males and 43 (29.3%) were females with mean age of 40.9 ± 17.2 years (range 24-71 years). We observed lung parenchymal abnormalities in 51 (34.7%) cases whereas 96 (65.3%) RT-PCR positive cases had a normal chest CT. Only 12.2% of the patients were dyspneic, 6.1% had desaturation, 7.4% had increased respiratory rate and 10.9% had comorbidities. Among the patients with abnormal CT findings bilateral 39/51 (76.5%), multilobar (88.2%) lung involvement with a predominant peripheral and posterior distribution was commonly observed. With regards to the type of opacity, ground glass opacity (GGO) was the dominant abnormality found in all 51 (100%) cases. Pure GGO was observed in 15 (29.4%), GGO with crazy paving pattern was seen in 15 (29.4%) and GGO mixed with consolidation was noted in 21(41.2%). Peri-lesional or intralesional segmental or subsegmental pulmonary vessel enlargement was observed in 36 (70.6%) cases. CONCLUSION: In this study population predominantly with mild symptoms and few comorbidities, two-thirds of RT-PCR positive patients had a normal chest CT; whereas the remaining patients showed typical findings of predominant GGOs with a bilateral distribution and peripheral predominance.
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Report of the ‘Mechanisms of lung injury and immunomodulator interventions in influenza’ workshop, 21 March 2010, Ventura, California, USA
Please cite this paper as: Howard et al. (2011) Report of the ‘Mechanisms of lung injury and immunomodulator interventions in influenza’ workshop, 21 March 2010, Ventura, California, USA*. Influenza and Other Respiratory Viruses 5(6), 453–e475. The clinical course of influenza and the extent of lung injury are determined by both viral and host factors, as well as sometimes secondary bacterial infections and exacerbations of underlying conditions. The balance between viral replication and the host immune responses is central to disease pathogenesis, and the extent of lung injury in severe influenza infections may be due in part to overly exuberant or dysregulated innate inflammatory responses or sometimes deficient responses. Acute respiratory distress syndrome (ARDS) is the principal cause of respiratory failure associated with severe influenza. ARDS can be triggered by both direct lung insults (e.g. respiratory pathogens) and systemic insults (e.g. sepsis), and the lung damage is exacerbated by the inflammatory response associated with either infectious or non‐infectious insults. This workshop aimed to review the current understanding of lung injury in acute influenza and describe cellular and molecular mechanisms of lung injury that are common to influenza and infections by other respiratory pathogens. In addition, therapeutic agents that target host response proteins and pathways were identified and investigational agents in development reviewed. A logical strategy would be to combine antiviral treatment with drugs that modify excessive host responses or supplement deficient ones. However, a better understanding of common cell signalling pathways associated with acute lung injury caused by influenza and other pathogens is necessary to understand immunopathologic causes of lung injury. This will help determine which immunomodulatory interventions might be useful, and to predict the appropriate timing and consequences of their use.
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Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage
RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant for their use as reagents including for deep sequencing. Here, we report that certain RNA template structures and G-rich sequences, ahead of diverse reverse transcriptases can be strong stimulators for slippage at slippage-prone template motif sequence 3′ of such ‘slippage-stimulatory’ structures. Where slippage is stimulated, the resulting products have one or more additional base(s) compared to the corresponding template motif. Such structures also inhibit slippage-mediated base omission which can be more frequent in the absence of a relevant stem–loop. Slippage directionality, base insertion and omission, is sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5′ adjacent base. The retrotransposon-derived enzyme TGIRT exhibits more slippage in vitro than the retroviral enzymes tested including that from HIV. Structure-mediated slippage may be exhibited by other polymerases and enrich gene expression. A cassette from Drosophila retrotransposon Dme1_chrX_2630566, a candidate for utilizing slippage for its GagPol synthesis, exhibits strong slippage in vitro. Given the widespread occurrence and importance of retrotransposons, systematic studies to reveal the extent of their functional utilization of RT slippage are merited.
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Evidence-Based Process for Prioritizing Positive Behaviors for Promotion: Zika Prevention in Latin America and the Caribbean and Applicability to Future Health Emergency Responses
Since the 2015 Zika outbreak in Latin America and the Caribbean, a plethora of behavior change messages have been promoted to reduce Zika transmission. One year after the United States Agency for International Development (USAID) initiated its Zika response, more than 30 variants of preventive behaviors were being promoted. This situation challenged social and behavior change (SBC) programming efforts that require a coordinated response and agreed upon set of focus behaviors to be effective. To support USAID implementing partners in harmonizing prevention efforts to reduce Zika infection, we developed an evidence-based process to identify behaviors with the highest potential to reduce Zika infection and transmission. We compiled a full list of behaviors and selected the most promising for a full evidence review. The review included systematic keyword searches on Google Scholar, extraction of all relevant published articles on Aedes-borne diseases between 2012 and 2018, review of seminal papers, and review of gray literature. We examined articles to determine each behavior's potential effectiveness in preventing Zika transmission or reducing the Aedes aegypti population. We also developed assessment criteria to delineate the ease with which the target population could adopt each behavior, including: (1) required frequency; (2) feasibility of the behavior; and (3) accessibility and cost of the necessary materials in the setting. These behaviors were refined through a consensus-building process with USAID's Zika implementing partners, considering contextual factors. The resulting 7 evidence-based preventive behaviors have high potential to strengthen SBC programming's impact in USAID's Zika response: (1) apply mosquito repellent, (2) use condoms during pregnancy, (3) remove standing water, (4) cover water storage containers, (5) clean/remove mosquito eggs from water containers, (6) seek antenatal care, and (7) seek family planning counseling. This case study documents a flexible process that can be adapted to inform the prioritization of behaviors when there is limited evidence available, as during many emergency responses.
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Can steroids reverse the severe COVID‐19 induced ‘cytokine storm’?
Severe COVID‐19 is characterized by an excessive pro‐inflammatory cytokine storm, resulting in acute lung injury and development of ARDS. The role of corticosteroids is controversial in severe COVID‐19 pneumonia and associated hyper‐inflammatory syndrome. We reported a case series of six consecutive COVID‐19 patients with severe pneumonia, ARDS and laboratory indices of hyper‐inflammatory syndrome. All patients were treated early with a short course of corticosteroids, and clinical outcomes were compared before and after corticosteroids administration. All patients evaded intubation and intensive care admission, ARDS resolved within 11.8 days (median), viral clearance was achieved in 4 patients within 17.2 days (median), and all patients were discharged from the hospital in 16.8 days (median). Early administration of short course corticosteroids improves clinical outcome of patients with severe COVID‐19 pneumonia and evidence of immune hyper‐reactivity. This article is protected by copyright. All rights reserved.