docid: azzgygzk

title: Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus

text: Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins.


title: “I feel like death on legs”: COVID-19 isolation and mental health

text: Abstract This study investigates the personal and collective responses to COVID-19, as it is described in personal stories and newspaper reports and examines the social and economic impact of the pandemic on different societies. Although some studies have been done on the impact of COVID-19, these studies focus on epidemiology, the importance of language diversity and reflections on the pandemic. None of the studies so far have focused specifically on the impact the coronavirus has had on different societies because of the global lockdown and restrictions on people’s movements. This study attempts to address this gap in the literature by focusing on how the language used in personal stories and newspaper reports reveal the impact of COVID-19 on different societies by investigating how self-isolation and lockdown measures is leading to mental health breakdown in individuals and affecting wider social and economic collapse. Prior literature (Gortner and Pennebaker, 2003) suggests that the media generally parallel society’s psychological response to traumatic events making newspapers an important collective resource similar to personal stories. The scale of the pandemic is such that it has been likened to a situation of war. In this climate, where the response to the pandemic is analogous to fighting a war, it was interesting to see what effect the enforced lockdown has on people’s mental health well-being and what priorities the media focus on. Smith, Anderson-Hanley, Langrock, and Compas (2005) have shown that language use in descriptions of traumatic experiences can shed insight into successful and unsuccessful coping strategies. I have therefore chosen to look at two different countries, Sri Lanka and Britain in order to investigate the following research questions: (1) Is self-isolation due to COVID-19 having an effect on mental health in Britain? And (2) What are the priorities of different countries during the crisis as evident in newspaper reports? To answer these two research questions, I have collected a small corpus of personal stories from Britain and two small corpora of newspaper reports from Britain and Sri Lanka over a span of one month. The data was analysed using corpus linguistics methodology such as keyword analysis of the two newspaper reports using AntConc (Anthony, 2019) and the personal stories were analysed using Linguistic Inquiry and Word Count (LIWC) (Pennebaker, 2015). The findings from LIWC shows that the enforced self-isolation is leading to mental health breakdown but that there are also positive emotions of the desire to help and solidarity with others. The analysis of the news reports show that Britain’s priorities are centered on the government’s handling of the crisis and the economy whereas Sri Lankan newspapers focus on educating people about the dangers of COVID-19.


title: Identification of aromatic amino acid residues in conserved region VI of the large polymerase of vesicular stomatitis virus is essential for both guanine-N-7 and ribose 2'-O methyltransferases

text: Abstract Non-segmented negative-sense RNA viruses possess a unique mechanism for mRNA cap methylation. For vesicular stomatitis virus, conserved region VI in the large (L) polymerase protein catalyzes both guanine-N-7 (G-N-7) and ribose 2'-O (2'-O) methyltransferases, and the two methylases share a binding site for the methyl donor S-adenosyl-l-methionine. Unlike conventional mRNA cap methylation, the 2'-O methylation of VSV precedes subsequent G-N-7 methylation. In this study, we found that individual alanine substitutions in two conserved aromatic residues (Y1650 and F1691) in region VI of L protein abolished both G-N-7 and 2'-O methylation. However, replacement of one aromatic residue with another aromatic residue did not significantly affect the methyltransferase activities. Our studies provide genetic and biochemical evidence that conserved aromatic residues in region VI of L protein essential for both G-N-7 and 2'-O methylations. In combination with the structural prediction, our results suggest that these aromatic residues may participate in RNA recognition.


title: Validity of inner canthus temperature recorded by infrared thermography as a non-invasive surrogate measure for core temperature at rest, during exercise and recovery

text: Abstract Research into obtaining a fast, valid, reliable and non-invasive measure of core temperature is of interest in many disciplinary fields. Occupational and sports medicine research has attempted to determine a non-invasive proxy for core temperature particularly when access to participants is limited and thermal safety is of a concern due to protective encapsulating clothing, hot ambient environments and/or high endogenous heat production during athletic competition. This investigation aimed to determine the validity of inner canthus of the eye temperature (T EC) as an alternate non-invasive measure of intestinal core temperature (T C) during rest, exercise and post-exercise conditions. Twelve physically active males rested for 30min prior to exercise, performed 60min of aerobic exercise at 60% V̇O2max and passively recovered a further 60min post-exercise. T EC and T C were measured at 5min intervals during each condition. Mean differences between T EC and T C were 0.61°C during pre-exercise, −1.78°C during exercise and −1.00°C during post-exercise. The reliability between the methods was low in the pre-exercise (ICC=0.49 [−0.09 to 0.82]), exercise (ICC=−0.14 [−0.65 to 0.44]) and post-exercise (ICC=−0.25 [−0.70 to 0.35]) conditions. In conclusion, poor agreement was observed between the T EC values measured through IRT and T C measured through a gastrointestinal telemetry pill. Therefore, T EC is not a valid substitute measurement to gastrointestinal telemetry pill in sports and exercise science settings.


Pooled Prevalence of Diarrhea among COVID-19 Patients


docid: rqywhjtx

title: The Middle East Respiratory Syndrome Coronavirus – A Continuing Risk to Global Health Security

text: Two new zoonotic coronaviruses causing disease in humans (Zumla et al. 2015a; Hui and Zumla 2015; Peiris et al. 2003; Yu et al. 2014) have been the focus of international attention for the past 14 years due to their epidemic potential; (1) The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) (Peiris et al. 2003) first discovered in China in 2001 caused a major global epidemic of the Severe Acute Respiratory Syndrome (SARS). (2) The Middle East respiratory syndrome coronavirus (MERS-CoV) is a new corona virus isolated for the first time in a patients who died of severe lower respiratory tract infection in Jeddah (Saudi Arabia) in June 2012 (Zaki et al. 2012). The disease has been named Middle East Respiratory Syndrome (MERS) and it has remained on the radar of global public health authorities because of recurrent nosocomial and community outbreaks, and its association with severe disease and high mortality rates (Assiri et al. 2013a; Al-Abdallat et al. 2014; Memish et al. 2013a; Oboho et al. 2015; The WHO MERS-CoV Research Group 2013; Cotten et al. 2013a; Assiri et al. 2013b; Memish et al. 2013b; Azhar et al. 2014; Kim et al. 2015; Wang et al. 2015; Hui et al. 2015a). Cases of MERS have been reported from all continents and have been linked with travel to the Middle East (Hui et al. 2015a; WHO 2015c). The World Health Organization (WHO) have held nine meetings of the Emergency Committee (EC) convened by the Director-General under the International Health Regulations (IHR 2005) regarding MERS-CoV (WHO 2015c). There is wishful anticipation in the political and scientific communities that MERS-CoV like SARS-CoV will disappear with time. However it’s been nearly 4 years since the first discovery of MERS-CoV, and MERS cases continue to be reported throughout the year from the Middle East (WHO 2015c). There is a large MERS-CoV camel reservoir, and there is no specific treatment or vaccine (Zumla et al. 2015a). With 10 million people visiting Saudi Arabia every year for Umrah and/or Hajj, the potential risk of global spread is ever present (Memish et al. 2014a; McCloskey et al. 2014; Al-Tawfiq et al. 2014a).


COVID-19 Resuscitation guidelines: a blanket rule for everyone?


title: Controlling the SARS-CoV-2 Spike Glycoprotein Conformation

text: The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. We found that despite overall similarity in domain organization, different β-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs ‘down’ position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs ‘up’ configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications.


title: The application of self-assembled nanostructures in peptide-based subunit vaccine development

text: Abstract Peptide based-vaccines are becoming one of the most widely investigated prophylactic and therapeutic health care interventions against a variety of diseases, including cancer. However, the lack of a safe and highly efficient adjuvant (immune stimulant) is regarded as the biggest obstacle to vaccine development. The incorporation of a peptide antigen in a nanostructure-based delivery system was recently shown to overcome this obstacle. Nanostructures are often formed from antigens conjugated to molecules such as polymers, lipids, and peptide, with the help of self-assembly phenomenon. This review describes the application of self-assembly process for the production of peptide-based vaccine candidates and the ability of these nanostructures to stimulate humoral and cellular immune responses.


title: Expanding the genetic code: selection of efficient suppressors of four-base codons and identification of “shifty” four-base codons with a library approach in Escherichia coli 1 1 Edited by M. Gottesman

text: Abstract Naturally occurring tRNA mutants are known that suppress +1 frameshift mutations by means of an extended anticodon loop, and a few have been used in protein mutagenesis. In an effort to expand the number of possible ways to uniquely and efficiently encode unnatural amino acids, we have devised a general strategy to select tRNAs with the ability to suppress four-base codons from a library of tRNAs with randomized 8 or 9 nt anticodon loops. Our selectants included both known and novel suppressible four-base codons and resulted in a set of very efficient, non-cross-reactive tRNA/four-base codon pairs for AGGA, UAGA, CCCU and CUAG. The most efficient four-base codon suppressors had Watson-Crick complementary anticodons, and the sequences of the anticodon loops outside of the anticodons varied with the anticodon. Additionally, four-base codon reporter libraries were used to identify “shifty” sites at which +1 frameshifting is most favorable in the absence of suppressor tRNAs in Escherichia coli. We intend to use these tRNAs to explore the limits of unnatural polypeptide biosynthesis, both in vitro and eventually in vivo. In addition, this selection strategy is being extended to identify novel five- and six-base codon suppressors.


title: Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins

text: Abstract IFN-inducible IFITM proteins (IFITM1, 2, and 3) inhibit the replication of various viruses including HIV-1 through poorly understood mechanisms. Here, we further analyzed characteristics of these newly identified HIV-1 restriction factors. Firstly, in contrast to other anti-HIV-1 proteins, such as tetherin and APOBEC3G, IFITMs were resistant to a down-regulation of surface expression or degradation by HIV-1 proteins. Secondly, the enforced expression of IFITMs reduced the production of HIV-1 viruses from cells transfected with proviral plasmids containing whole viral sequences. Although their inhibitory activities were modest when compared to that of tetherin, IFITMs, but not tetherin, directly reduced the expression of HIV-1 proteins including Gag, Vif and Nef. Of importance, however, IFITMs had no inhibitory effect when these viral proteins were expressed by codon-optimized cDNAs that bypassed the viral-specific expression machinery. Indeed, our results supported the idea that IFITMs interfere with viral protein expression mediated by double-stranded viral RNAs, such as RRE and TAR. Finally, the S-palmitoylation of IFITMs, which is crucial for their anti-influenza virus activity, was not required for their anti-HIV-1 activity, indicating that IFITMs restrict these viruses at different steps. These characteristics lead to a better understanding of the mechanism by which IFITMs restrict HIV-1 and other viruses.


title: Electrical Storm in COVID-19

text: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.


Seizure‐Like Episodes in 3 Cats with Intermittent High‐Grade Atrioventricular Dysfunction


docid: ogsazued

title: The hepatitis E virus ORF1 ‘X-domain’ residues form a putative macrodomain protein/Appr-1″-pase catalytic-site, critical for viral RNA replication

text: Abstract The hepatitis E virus (HEV) ORF1 gene encodes the non-structural polyprotein wherein the ‘X-domain’ still remains poorly defined. Cellular X-domain associated macrodomain protein/ADP-ribose-1″-monophosphatase (Appr-1″-pase) activities are also reported in coronaviruses (CoV), including identification of its homologs in alpha and rubella viruses. The present study investigated the role(s) of X-domain residues in HEV replication cycle. In silico analysis showed a high degree of evolutionary conservation of X-domain (a.a. 785–942) a.a. positions wherein the N-terminus residues ‘Asn806, Asn809, His812, Gly815, Gly816, and Gly817’ formed a potential catalytic-site homolog of CoVAppr-1″-pase. To experimentally test this prediction, X-domain ‘active-site’ residues were subjected to mutational analysis using the HEV-SAR55 replicon (pSK-GFP). FACS analysis of mutant RNA transfected S10-3 cells showed that Gly816Ala and Gly817Ala constructs completely abrogated HEV replication, similar to their Gly816Val and Gly817Val counterparts. However, ‘Gly815Ala’ mutant replicated very poorly in contrast to ‘Gly815Val’ that completely abolished GFP synthesis. Furthermore, while ‘Asn806Ala’ mutant retained RNA replication, the ‘Asn809Ala’ and His812Leu mutants showed non-viability. Notably, in a sequential-nucleotide mutation analysis, the dispensability of X-domain in HEV replication at transcriptional level has already been demonstrated (Parvez, 2013b). Taken together, the present data strongly argue for an essential role of X-domain residues (Asn809, His812, Gly816 and Gly817) at post-translational level, indicating its involvement in viral replication. In conclusion, the speculated regulatory role of ORF1 X-domain in HEV replication cycle critically depends on the ‘Asn, Asn, His, Gly, Gly, Gly’ segment/secondary structure. Nevertheless, further biochemical or biophysical characterizations of HEV X-domain associated Appr-1″-pase activity would only confirm its biological significance in virus or host-pathogenesis.


docid: xoowaowx

title: Preparation and characterization of chitosan microsphere loading bovine serum albumin

text: To optimize the preparation process of chitosan microspheres and study its loading capacity, chitosan microsphere was prepared by crosslinking with glutaraldehyde, and bovine serum albumin (BSA) was absorbed onto chitosan microsphere. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FITR), TA instruments and zeta potentiometer analyzer were used to characterize the parameters with respect to size, thermal characters, morphology, and zeta potential of the microspheres. The loading capability and in vitro release tests were carried out. The results showed that chitosan microsphere with particle size less than 10 μm and positively charged (+25.97±0.56 mV) can be obtained under the aldehyde group to amino group ratio at 1:1. A loading capacity of BSA at 28.63±0.15 g/100 g with corresponding loading efficiency at 72.01±1.44% was obtained for chitosan microsphere. In vitro test revealed a burst release followed by sustained-release profile.


title: Spinal motoneurone distress during experimental allergic encephalomyelitis

text: The main pathophysiological feature characterizing multiple sclerosis (MS) is demyelination. However, the possibility of neural damage has recently been proposed as a mechanism in chronic disease. Experimental allergic encephalomyelitis (EAE) is the most widely used experimental model for MS. We investigated occurrences of microglial activation and astrocytosis in the spinal cord, choline acetyl‐transferase (ChAT) and calcitonin gene‐related peptide (CGRP) mRNA regulation in spinal motoneurones during EAE. EAE was induced in female Lewis rats by injecting guinea pig spinal cord tissue in complete Freund's adjuvant (CFA) to which heat‐inactivated Mycobacterium had been added. Rats injected with CFA and uninjected rats were used as controls. ChAT and CGRP mRNAs were studied by in situ hybridization in the lumbar spinal cord and a computerized grain counting procedure was used for quantification. No differences in ChAT mRNA level were found between control and CFA‐injected rats. ChAT mRNA level was strongly reduced in EAE 14 days after immunization and then recovered (29 days after immunization). CGRP mRNA increased 14 days after immunization, and then recovered to control level. Extensive long‐lasting gliosis developed in the spinal cord and around motoneurones and a transient expression of p75(LNGFR) in motoneurones was also found. These data suggest that during EAE, gliosis induces distress in spinal cord neurones involving the synthesis enzyme for the main transmitter.


title: Vaccines against diseases transmitted from animals to humans: A one health paradigm

text: This review focuses on the immunization of animals as a means of preventing human diseases (zoonoses). Three frameworks for the use of vaccines in this context are described, and examples are provided of successes and failures. Framework I vaccines are used for protection of humans and economically valuable animals, where neither plays a role in the transmission cycle. The benefit of collaborations between animal health and human health industries and regulators in developing such products is discussed, and one example (West Nile vaccine) of a single product developed for use in animals and humans is described. Framework II vaccines are indicated for domesticated animals as a means of preventing disease in both animals and humans. The agents of concern are transmitted directly or indirectly (e.g. via arthropod vectors) from animals to humans. A number of examples of the use of Framework II vaccines are provided, e.g. against brucellosis, Escherischia coli O157, rabies, Rift Valley fever, Venezuelan equine encephalitis, and Hendra virus. Framework III vaccines are used to immunize wild animals as a means of preventing transmission of disease agents to humans and domesticated animals. Examples are reservoir-targeted, oral bait rabies, Mycobacterium bovis and Lyme disease vaccines. Given the speed and lost cost of veterinary vaccine development, some interventions based on the immunization of animals could lead to rapid and relatively inexpensive advances in public health. Opportunities for vaccine-based approaches to preventing zoonotic and emerging diseases that integrate veterinary and human medicine (the One Health paradigm) are emphasized.


title: Manipulation of cell surface macromolecules by flaviviruses

text: Cell surface macromolecules play a crucial role in the biology and pathobiology of flaviviruses, both as receptors for virus entry and as signaling molecules for cell–cell interactions in the processes of vascular permeability and inflammation. This review examines the cell tropism and pathogenesis of flaviviruses from the standpoint of cell surface molecules, which have been implicated as receptors in both virus–cell as well as cell–cell interactions. The emerging picture is one that encompasses extensive regulation and interplay among the invading virus, viral immune complexes, Fc receptors, major histocompatibility complex antigens, and adhesion molecules.


CHIRURGIE GYNECOLOGIQUE EN PERIODE COVID +Recommandations de sortie de crise


title: Viral infections and susceptibility to recurrent sinusitis

text: Viral respiratory infection is thought to be the major contributing factor in the pathogenesis of bacterial sinusitis. It is still not clear why some patients suffer from recurrent sinusitis episodes, as information on the exact pathomechanism of how bacterial sinusitis develops as a complication of viral colds is still scarce. In this review, different mechanisms of how a viral infection may predispose some patients to recurrent bacterial sinusitis episodes are presented. Awareness of the fact that different mechanisms may exist behind this single diagnosis of recurrent sinusitis may be of help when diagnostic measures and treatments are planned for these patients.


Aortic Disease in the Time of COVID: Repercussions on Patient Care at an Academic Aortic Center


title: Predictors of mortality in hospitalized COVID‐19 patients: A systematic review and meta‐analysis

text: Mortality rates of coronavirus disease 2019 (COVID‐19) continue to rise across the world. Information regarding the predictors of mortality in COVID‐19 patients remains scarce. Herein, we performed a systematic review of published articles, from January 1 to April 24, 2020, to evaluate the risk factors associated with mortality in COVID‐19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (OR 2.5; 95% CI 2.1‐3.1; P<0.00001), coronary heart disease (OR 3.8; 95% CI 2.1‐6.9; P<0.00001) and diabetes (OR 2.0; 95% CI 1.7‐2.3; P<0.00001) were associated with significantly higher risk of death amongst COVID‐19 patients. Those who died, compared to those who survived, differed on multiple biomarker levels on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI 19.0‐69.4; P=0.0006); C‐reactive protein (+66.3 µg/mL, 95% CI 46.7‐85.9; P<0.00001); interleukin‐6 (+4.6 ng/mL, 95% CI 3.6‐5.6; P<0.00001); D‐dimer (+4.6 µg/mL, 95% CI 2.8‐6.4; P<0.00001); creatinine (+15.3 µmol/L, 95% CI 6.2‐24.3; P=0.001) and alanine transaminase (+5.7 U/L, 95% CI 2.6‐8.8; P=0.0003); as well as decreased levels of albumin (‐3.7 g/L, 95% CI ‐5.3 to ‐2.1; P<0.00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end‐organ damage are at higher risk of mortality due to COVID‐19 infection and should be managed with greater intensity. This article is protected by copyright. All rights reserved.


title: Genomic Signatures of Emerging Viruses: A New Era of Systems Epidemiology

text: Compared to classical epidemiologic methods, genomics can be used to precisely monitor virus evolution and transmission in real time across large, diverse populations. Integration of pathogen genomics with data about host genetics and global transcriptional responses to infection allows for comprehensive studies of population-level responses to infection and provides novel methods for predicting clinical outcomes. As genomic technologies become more accessible, these methods will redefine how emerging viruses are studied and outbreaks are contained. Here we review the existing and emerging genomic technologies that are enabling systems epidemiology and systems virology and making it possible to respond rapidly to emerging viruses such as Zika.


Managing a tertiary‐level NICU in the time of COVID‐19: Lessons learned from a high‐risk zone


Man and Microbe: Fraternizing with the frenemy


title: Enantioselective synthesis and antiviral activity of purine and pyrimidine cyclopentenyl C-nucleosides

text: Abstract The enantiomerically pure carbocyclic purine and pyrimidine C-nucleosides 1–4 were synthesized via the key intermediate, 2,3-(isopropylidenedioxy)-4-(trityloxymethyl)-4-cyclopenten-1-ol (5), which was prepared from d-ribose in eight steps. Synthesized compounds were evaluated as potential antiviral agents against HIV, SARSCoV, Punta Toro, West Nile, and Cowpox viruses. However, only 9-deazaneplanocin A (1) exhibited moderate anti-HIV activity.


title: Fostering Collaborative Research for Customer Experience – Connecting Academic and Practitioner Worlds

text: Abstract This editorial calls for greater use of academic-practitioner workshops to co-create value for academics, practitioners and wider network actors through promotion of research relevance and sharing of problems, ideas and data. It describes how one such workshop, the 2nd Academic-Practitioner Research with Impact Workshop focusing on the design and decision making for customer experience, co-hosted in Manchester on 18th and 19th of June 2018 by Alliance Manchester Business School and Loughborough University’s Centre for Service Management (CSM), was delivered. The key processes for success and issues to consider for future such events are discussed. The workshop resulted in 8 papers (six theoretical and two empirical). This Special Issue advances current understanding of CE through the research considering the role of technology (AI and big data) in CE research, atypical CE (vulnerability, deviance behaviours and service failure and recovery) and focusing on important organizational and B2B issues (business model innovation, and CEM in business markets).


docid: juxbcbxc

title: A case series describing the epidemiology and clinical characteristics of COVID-19 infection in Jilin Province

text: Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23–79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.


title: A capsid gene-based real-time reverse transcription polymerase chain reaction assay for the detection of marine vesiviruses in the Caliciviridae

text: Abstract A real-time reverse transcription polymerase chain reaction (rtRT-PCR) assay was developed for the identification of marine vesiviruses. The primers were designed to target a 176-nucleotide fragment within a highly conserved region of the San Miguel sea lion viruses (SMSVs) capsid gene. The assay detected viral RNA from nine marine vesivirus serotypes described previously, including two serotypes (SMSV-8 and -12) not identified with presently available molecular assays, a highly related bovine vesivirus strain (Bos-1), a mink vesivirus strain (MCV), and two novel genotypes isolated recently from Steller sea lions (SSL V810 and V1415). The real-time assay did not amplify sequences from the corresponding genomic regions of feline calicivirus (also in the genus Vesivirus) and representative members of the genus Norovirus. The rtRT-PCR assay described below may prove useful as a diagnostic tool for the detection of currently circulating, emerging and previously described marine vesiviruses in clinical samples, especially when large numbers are screened in surveillance studies of these restricted viruses.


title: Why estimating population-based case fatality rates during epidemics may be misleading

text: Different ways of calculating mortality ratios during epidemics can yield widely different results, particularly during the COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the length of time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of infected cases to date. Using available data on the recent SARS-CoV-2 outbreaks and simple assumptions, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose a more systematic method to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and errors in the data.


title: Coinfections and their molecular consequences in the porcine respiratory tract

text: Understudied, coinfections are more frequent in pig farms than single infections. In pigs, the term “Porcine Respiratory Disease Complex” (PRDC) is often used to describe coinfections involving viruses such as swine Influenza A Virus (swIAV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine CircoVirus type 2 (PCV2) as well as bacteria like Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae and Bordetella bronchiseptica. The clinical outcome of the various coinfection or superinfection situations is usually assessed in the studies while in most of cases there is no clear elucidation of the fine mechanisms shaping the complex interactions occurring between microorganisms. In this comprehensive review, we aimed at identifying the studies dealing with coinfections or superinfections in the pig respiratory tract and at presenting the interactions between pathogens and, when possible, the mechanisms controlling them. Coinfections and superinfections involving viruses and bacteria were considered while research articles including protozoan and fungi were excluded. We discuss the main limitations complicating the interpretation of coinfection/superinfection studies, and the high potential perspectives in this fascinating research field, which is expecting to gain more and more interest in the next years for the obvious benefit of animal health.


title: Maturation of Japanese encephalitis virus glycoproteins produced by infected mammalian and mosquito cells

text: Abstract The Japanese encephalitis virus (JE) structural glycoprotein (E) and two nonstructural glycoproteins (NS1 and NS1′) were processed differently by JE-infected vertebrate and invertebrate cell lines. All three proteins were released slowly (t 1 2 > 6 hr) from JE-infected monkey cells (Vero cells). Mosquito cell lines released E at a similar rate (t 1 2 > 8 hr), while NS1 and NS1′ were retained in an undegraded form in the cell layer. The proteolytic processing of the three proteins appeared identical in both cell types, but some differences in Winked glycosylation were observed. E, NS1, and NS1′ found within the infected cells of both types contained high-mannose oligosaccharide groups for more than 8 hr after synthesis. Additional sugar residues were added to the single E protein oligosaccharide group prior to release from Vero cells, while sugar residues were trimmed from the E protein oligosaccharide group prior to release from mosquito cells. The forms of NS1 and NS1′ found in the culture fluid of infected Vero cells contained one complex and one high-mannose oligosaccharide. All three glycoproteins released from JE-infected Vero cells were associated with extracellular particles, the virion in the case of E and a low density particle in the case of NS1′ and NSV. Furthermore, E, NS1′ and NS1′ exhibited amphipathic properties in Triton X-114 extraction experiments. Taken together, these results suggest that both the structural (E) and nonstructural NS1′ and NSV) glycoproteins were accumulated within the secretory pathway of the infected Vero cells, assembled into particles, and then released into the extracellular fluid.


Unravelling synergistic immune interactions between respiratory virus infections and allergic airway inflammation


title: Estimating instant case fatality rate of COVID-19 in China

text: Abstract Objective The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate instant case fatality rate and cure rate of COVID-19 in China. Methods We collected 82735 confirmed cases released officially by Chinese authorities from Dec 8, 2019 to April 18, 2020. The estimated diagnosis dates of deaths and cured cases were calculated based on median cure time or median death time of individual cases. Afterward, instant fatality rate was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. Results In China, the instant case fatality rate of COVID-19 was 3.8-14.6% from Jan 1 to Jan 17, and then gradually declined and stabilized at 5.7% in April. The average case fatality rate in China was 6.1%±2.9%. While, the case fatality rate was 1.0±0.4% in China except Hubei. The cure rates of COVID-19 were 93.9%±2.9% in China, and stabilized at 94.3%, while it was 99.0%±0.4% in China except Hubei. Conclusion The instant case fatality rate of COVID-19 in China was much higher than that in China except Hubei. The case fatality rate of COVID-19 in China was underestimated.


title: The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience

text: BACKGROUND: There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths. METHODS: A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included "trend," a continuous variable representing the effect of yearly changes, and two binary variables, "month" and "county," controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates. RESULTS: With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals. CONCLUSION: An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.


title: Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community

text: Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48–96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi‐quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT‐value and disease severity was found in all RSV cases (ρ = −0.52, P = 0.003) and in cases with RSV as the primary pathogen (ρ = −0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection. J. Med. Virol. 82: 1266–1271, 2010. © 2010 Wiley‐Liss, Inc.


Dermatological findings in COVID‐19 patients: Mexican experience


title: Socioeconomic disparities in subway use and COVID-19 outcomes in New York City

text: Background: The United States CDC has reported that racial and ethnic disparities in the COVID-19 pandemic may in part be due to socioeconomic disadvantages that require individuals to continue to work outside their home and a lack of paid sick leave. However, data-driven analyses of the socioeconomic determinants of COVID-19 burden are still needed. Using data from New York City (NYC), we aimed to determine how socioeconomic factors impact human mobility and COVID-19 burden. Methods/Summary: New York City has a large amount of heterogeneity in socioeconomic status (SES) and demographics among neighborhoods. We used this heterogeneity to conduct a cross-sectional spatial analysis of the associations between human mobility (i.e., subway ridership), sociodemographic factors, and COVID-19 incidence as of April 26, 2020. We also conducted a secondary analysis of NYC boroughs (which are equivalent to counties in the city) to assess the relationship between the decline in subway use and the time it took for each borough to end the exponential growth period of COVID-19 cases. Findings: Areas with the lower median income, a greater percentage of individuals who identify as non-white and/or Hispanic/Latino, a greater percentage of essential workers, and a greater percentage of healthcare workers had more subway use during the pandemic. The positive associations between subway use and median income, and between subway use and percent non-white and/or Hispanic/Latino do not remain when adjusted for the percent of essential workers. This suggests essential work is what drives subway use in lower SES zip codes and communities of color. Increased subway use was associated with a higher rate of COVID-19 cases per 100,000 population when adjusted for testing effort (aRR=1.11; 95% CI: 1.03 - 1.19), but this association was weaker once we adjusted for median income (aRR=1.06; 95% CI: 1.00 - 1.12). All sociodemographic variables were significantly associated with the rate of positive cases per 100,000 population when adjusting for testing effort (except percent uninsured) and adjusting for both income and testing effort. The risk factor with the strongest association with COVID-19 was the percent of individuals in essential work (aRR = 1.59, 95% CI: 1.36 - 1.86). We found that subway use declined prior to any executive order, and there was an estimated 28-day lag between the onset of reduced subway use and the end of the exponential growth period of SARS-CoV-2 within New York City boroughs. Interpretation: Our results suggest that the ability to stay home during the pandemic has been constrained by SES and work circumstances. Poorer neighborhoods are not afforded the same reductions in mobility as their richer counterparts. Furthermore, lower SES neighborhoods have higher disease burdens, which may be due to inequities in ability to shelter-in-place, and/or due to the plethora of other existing health disparities that increase vulnerability to COVID-19. Furthermore, the extended lag time between the dramatic fall in subway ridership and the end of the exponential growth phase for COVID-19 cases is important for future policy, because it demonstrates that if there is a resurgence, and stay-at-home orders are re-issued, then cities can expect to wait a month before reported cases will plateau.


title: Intake and growth in transported Holstein calves classified as diarrheic or healthy within the first 21 days after arrival in a retrospective observational study

text: ABSTRACT Strategies that can improve health and maximize growth in the preweaning period should improve the subsequent production and longevity of replacement animals. Few data are available that quantify feed and water consumption, as well as growth, in healthy versus non-healthy calves—the objective of this study. A database of Holstein calves (<1 wk of age; n = 313) was developed to compare calves that developed diarrhea in the first 21 d after arrival from commercial farms to the research facility versus calves that remained healthy. Individual calf data from 4 experiments included daily intake of milk replacer, free water, electrolyte solution, and starter grain, as well as weekly body weight (BW) and frame measures for 21 d after arrival. Calves with a fecal score of >2 for ≥3 consecutive days over the first 21 d of each experiment were retrospectively classified as diarrheic (DIA; n = 96); the remainder were classified as healthy (HEA; n = 217). Other health issues were minimal. The likelihood of elevated fecal score occurrence and the cumulative number of days with an elevated score were greater for DIA calves than for HEA calves. The initial total protein concentration in blood did not differ between classifications. Cumulative milk replacer dry matter intake (DMI) and water consumed from milk replacer were significantly less for DIA calves than for HEA calves, because DIA calves were more likely to refuse milk replacer. Cumulative starter DMI was decreased for DIA versus HEA calves. As a result, cumulative total DMI was significantly less for DIA calves than for HEA calves. Cumulative free water intake did not differ between classifications. The DIA calves were more likely to receive electrolyte solution and have more days given electrolyte solution than HEA calves. As a result, total cumulative intake of electrolyte solution was greater in DIA calves than in HEA calves. Cumulative total water intake did not differ between classifications. Initial BW did not differ between classifications; however, a classification × time interaction for BW indicated that HEA calves were heavier than DIA calves and had greater ADG. Significant classification × time interactions for hip height and heart girth revealed that HEA calves had a larger frame size. Gain–feed ratios for both milk replacer intake and total DMI differed between classifications: DIA calves were less feed-efficient than HEA calves. In conclusion, diarrhea in young calves decreases DMI, BW gain, and feed efficiency relative to HEA calves within 21 d of arrival.


Author's reply to “To the editor - Is it really COVID-19 infection?”


title: Assessing the anxiety level of Iranian general population during COVID-19 outbreak

text: Abstract This study is aimed to assess the anxiety level of Iranian general population during COVID-19 outbreak. The online questionnaire surveyed 10,754 individuals from the general population of 31 provinces of Iran who completed the questionnaire on social networks from March 1 to March 9, 2020. The inferential statistics suggests that the level of anxiety was higher among women (95 % CI [0.1, 81.36], p < 0.001), people who more followed corona-related news (p < 0.001) and the age group of 21–40 years (p < 0.001). Ultimately, the level of anxiety was significantly higher among people who had at least one family member, relative, or friend who contracted COVID-19 disease (95 % CI [1.2, 35.03], p < 0.001). The health care system should adopt a package of psychosocial interventions to reduce the anxiety of high risk groups.


title: Strategies for enhancing the analytical performance of nanomaterial-based sensors

text: Abstract We provide a state-of-the-art review of the main strategies for the enhancement of analytical performance of sensors using nanomaterials, particularly nanowires and carbon-based materials. We emphasize the way to overcome the problem of device-to-device variation. We discuss the study of the influence of nanomaterial characteristics, sensor dimensions and operational conditions on sensing performance, and the application of appropriate calibration models.


title: Statewide Real-Time Tracking of Beds and Ventilators During Coronavirus Disease 2019 and Beyond

text: This brief report describes the rapid deployment of a real-time electronic tracking board for all hospitals in the state of Oregon. In preparation for the coronavirus disease 2019 surge on hospital resources, and in collaboration across health systems, with health authorities and an industry partner, we combined existing infrastructures to create the first automated tracking board for our entire state, including bed types by health system and geographic area, and with granularity to the individual unit level for each participating hospital. At the time of submission, we have a live snapshot of 87% of beds in the state, including real-time ventilator data across eight health systems. The tracking board allows for rapid assessment of available bed and ventilator resources and pulls electronic health record data that is created through normal care processes rather than relying upon manual entry. It is updated every 5 minutes and is drillable from state to unit level. Together these factors make the data actionable, which is essential in a crisis. The new tracking system integrates seamlessly with our preexisting statewide, manually updated tracking board via bidirectional data sharing to ensure existing processes across the state can continue. This new tool allows any health system in our state to visualize occupancy by type and location in real time. Amid pandemic uncertainty, having a reliable tool for tracking critical hospital resources will enhance our statewide ability to maintain healthcare functionality in a world with coronavirus disease 2019.


title: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics

text: The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.


Acute pulmonary embolism: An unseen villain in COVID-19


title: A Blueprint to Evaluate One Health

text: One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the “Network for Evaluation of One Health,” an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy.


title: Fast, selective and quantitative protein profiling of adenovirus-vector based vaccines by ultra-performance liquid chromatography

text: Abstract A method for the quantitative determination of the protein composition of adenovirus-vector based vaccines was developed. The final method used RP-UPLC with UV absorbance detection, a C4 column (300 Å, 1.7 μm, 2.1 × 150 mm), and a water- acetonitrile (ACN) gradient containing trifluoroacetic acid (TFA) as ion-pairing agent. The chromatographic resolution between the various adenovirus proteins was optimized by studying the effect of the TFA concentration and the column temperature, applying a full factorial design of experiments. A reproducible baseline separation of all relevant adenovirus proteins could be achieved within 17 min run time. Samples containing adenovirus particles could be directly injected into the UPLC system without sample pretreatment. The viruses reproducibly dissociate into proteins in the UPLC system upon contact with the mobile phase containing ACN. The new RP-UPLC method was successfully validated for protein profiling and relative quantification of proteins in vaccine products based on adenovirus vector types 26 and 35. The intermediate precision of the relative peak areas of all proteins was between 1% and 14% RSD, except for the peak assigned to protein V (26% RSD). The method proved to be stability indicating with respect to thermal and oxidation stress of the adenovirus-vector based vaccine and was successfully implemented for the characterization of adenovirus-based products.


title: Perinatal Considerations in the Hospital Disaster Management Process

text: ABSTRACT Nurses play a vital role in providing care to mothers and infants during a disaster, yet few are fully prepared for the challenges they will encounter under extreme conditions. The ability to provide the best possible care for families begins with understanding the perinatal issues in relation to each phase of the disaster management process. This article reviews the hospital and perinatal nursing role in the mitigation, preparedness, response, and recovery phases of disaster management.


title: Émergences et barrières d’espèces

text: Résumé Les infections virales émergentes sont définies ici comme celles dont l’incidence a augmenté les 20 dernières années. Ces infections concernent l’homme, mais aussi les viroses animales, touchant les animaux domestiques ou sauvages. Pour l’homme, les émergences virales sont d’origine zoonotique, et sont souvent le fait d’un franchissement de barrière d’espèces. Ce passage interespèces est favorisé par de nombreuses circonstances : variations environnementales, climatiques, bioterrorisme, potentiel évolutif du virus... La recherche du réservoir animal est capitale pour la prévention des réémergences, et pour l’éradication potentielle de la maladie. La réussite émergentielle de certains virus a eu des conséquences graves en santé publique humaine : pandémies grippales, pandémie de sida, fièvres hémorragiques, et plus récemment syndrome de détresse respiratoire aigu (SRAS). Abstract Emergent viral infections are defined as those the incidence of which has increased over the last 20 years. These infections concern human but also animal viruses affecting wild or tame animals. In human, emergent viruses are of zoonotic origin and often due to crossing of species barrier. This inter-species crossing is promoted by various circumstances: environmental and climatic variations, bioterrorism, evolutive potential of the virus, etc. Screening for the animal reservoir is extremely important to prevent re-emergence and to eradicate the disease. The emergential success of some viruses has had serious consequences on human public health: flu pandemics, AIDS pandemic, hemorrhagic fever, and more recently SARS.


title: Middle East Respiratory Syndrome Virus Pathogenesis

text: Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. Infections caused by human coronaviruses (hCoVs) are mostly associated with the respiratory, enteric, and nervous systems. The hCoVs only occasionally induce lower respiratory tract disease, including bronchitis, bronchiolitis, and pneumonia. In 2002 to 2003, a global outbreak of severe acute respiratory syndrome (SARS) was the seminal detection of a novel CoV (SARS-CoV). A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. Although bats might serve as a reservoir of MERS-CoV, it is unlikely that they are the direct source for most human cases. Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. The emergence of MERS-CoV has triggered serious concerns about the potential for a widespread outbreak. All MERS cases were linked directly or indirectly to the Middle East region including Saudi Arabia, Jordan, Qatar, Oman, Kuwait, and UAE. MERS cases have also been reported in the later phases in the United Kingdom, France, Germany, Italy, Spain, and Tunisia. Most of these MERS cases were linked with the Middle East. The high mortality rates in family-based and hospital-based outbreaks were reported among patients with comorbidities such as diabetes and renal failure. MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). The combination regimen of type 1 interferon + lopinavir/ritonavir is considered as the first-line therapy for MERS. Antiviral treatment is generally recommended for 10 to 14 days in patients with MERS-CoV infection. Convalescent plasma therapy has shown some efficacy among patients refractory to antiviral drugs if administered within 2 weeks of the onset of the disease.


title: Expanding our understanding of the role polyprotein conformation plays in the coronavirus life cycle

text: Coronavirus are the causative agents in many globally concerning respiratory disease outbreaks such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease-2019 (COVID-19). It is therefore important that we improve our understanding of how the molecular components of the virus facilitate the viral life cycle. These details will allow for the design of effective interventions. Krichel and coauthors in their article in the Biochemical Journal provide molecular details of how the viral polyprotein (nsp7–10) produced from the positive single stranded RNA genome, is cleaved to form proteins that are part of the replication/transcription complex. The authors highlight the impact the polyprotein conformation has on the cleavage efficiency of the main protease (M(pro)) and hence the order of release of non-structural proteins 7–10 (nsp7–10) of the SARS-CoV. Cleavage order is important in controlling viral processes and seems to have relevance in terms of the protein–protein complexes formed. The authors made use of mass spectrometry to advance our understanding of the mechanism by which coronaviruses control nsp 7, 8, 9 and 10 production in the virus life cycle.


title: Open Sharing During COVID-19: CRISPR-Based Detection Tools

text: Addgene is facilitating the availability and open sharing of plasmids and resources for COVID-19 research and detection of SARS-CoV-2 RNA


docid: epqbljzn

title: Molecular cloning, expression, and purification of SARS-CoV nsp13

text: Abstract The SARS-nsp13 protein was identified as an mRNA cap1 methyltransferase. In this study, the nsp13 gene was cloned from the SARS-CoV PUMC02 strain viral RNA by RT-PCR, and inserted into the expression plasmid pET30a(+). The recombinant plasmid pET30a(+)-nsp13 was confirmed by restriction enzymes and sequencing analysis, and transformed into Escherichia coli BL21(DE3). The His-tag-fused protein was expressed by induction of 0.5mM IPTG and purified by a single Ni2+ affinity chromatography. The protein was validated by western blot and MS analysis. A large quantity of the nsp13 protein obtained with this method may be useful for further study of its structure and function.


docid: glexsajf

title: Virus respiratoire syncytial et virus para-influenza humains : clinique

text: Résumé Le virus respiratoire syncytial (VRS) est responsable de 50 à 90 % des bronchiolites du nourrisson. Des facteurs liés au terrain (prématurité, pathologie associée, prédisposition), au virus (VRS A) ou environnementaux (pollution, tabagisme, …) sont déterminants dans la genèse et la gravité des bronchiolites. La mortalité de la bronchiolite va de 0,005 % à 0,2 % selon le terrain. La physiopathologie de la bronchiolite à VRS n’est pas connue. Le rôle direct du virus sur l‘épithélium, de l’immaturité du nourrisson, et, plus récemment souligné, celui de la réaction inflammatoire sont des facteurs importants. Des mécanismes immunopathologiques (anticorps IgE, réponse CD4+ Th2, …) jouent certainement un rôle dans les bronchiolites de certains enfants ou dans les formes graves. L’immunité anti-VRS n’est jamais vraiment complète, et les réinfections sont fréquentes chez les jeunes enfants et les personnes âgées où l’infection à VRS représente environ 5 % des atteintes respiratoires basses. Les infections à VPI 3 se traduisent essentiellement par des bronchiolites et à VPI 1 et 2 par des laryngotrachéites. L’expression clinique des infections à VPI 4 est peu connue. Le HMPV est responsable de bronchiolites en tous points comparables à celles dues au VRS. Abstract The respiratory syncytial virus (RSV) causes 50% to 90% of all bronchiolitis cases in infants. The occurrence and severity of bronchiolitis are dependent on patient-related factors (preterm birth, comorbidities, individual susceptibility), virus-related factors (RSV A), and environmental factors (pollution, environmental tobacco smoke, and others). Mortality rates in infants with bronchiolitis range from 0.005% to 0.2% according to patient-related factors. The pathophysiology of RSV bronchiolitis is unknown but clearly involves direct effects of the virus on the airway epithelium, airway immaturity, and recently identified effects of the inflammatory response. Immunopathologic mechanisms (e.g., IgE antibodies and CD4+ Th2 cells) play a role in some infants or in severe forms. Complete immunity to the virus is never achieved, and repeat infections are common in the young and the elderly, in whom the RSV causes about 5% of all lower respiratory tract infections. VPI3 infections usually cause bronchiolitis, whereas VPI1 and VPI2 infections manifest chiefly as laryngotracheitis. Little is known about the clinical expression of VPI4 infection. Bronchiolitis due to hMPV is indistinguishable from RSV bronchiolitis.


Introduction to the Symposium on Antimicrobial Therapy


title: Literature in the time of COVID-19: The “phase two”

text: The sudden onset of the COVID-19 pandemic has put a strain on the whole scientific world. We assisted to a tremendous effort by researchers with the final goal of achieving a better management of COVID-19 patients. The world of otorhinolaryngology, likewise, has not been exempt from this commitment to research. In this commentary we perform a bibliometric review of the available academic literature about COVID-19 in the top 20-ranked ENT journal, with the goal of providing an overview of what has been published to date and encouraging a shift towards quantitative research.


title: Parent Perceptions of Caregiver-Mediated Telemedicine Tools for Assessing Autism Risk in Toddlers

text: Telemedicine tools have potential for increasing access to diagnostic services for children with autism spectrum disorder (ASD). Past work has utilized tele-assessment procedures in which remote psychologists observe administration of interactive screening instruments by trained, on-site providers. Although promising, this approach relies on two clinicians, limiting its efficiency and scalability. The present study examined the use, acceptability, and parents’ perceptions of two caregiver-mediated tools for assessing ASD risk in toddlers, in which remote clinicians guided parents to complete interactive screening activities with their children. Most parents found tele-assessment to be comfortable, and many reported liking the parent-led nature of these tools. Parents also offered constructive feedback, which was used to modify the tele-assessment process for future study.


title: Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19

text: Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe COVID-19 might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.


title: Integrated Urban Mobility Policies in Metropolitan Areas: A System Dynamics Approach for the Rhine-Ruhr metropolitan region in Germany

text: In today’s world, urban systems play an important role in sustainable economic development. In particular, urbanisation trends and the increasing demands of urban mobility place additional pressure on existing transportation infrastructure, and this creates new challenges for urban planners in terms of developing integrated and sustainable urban mobility policies. Here, we take a novel and holistic approach to analysing transformative pathways towards sustainable urban mobility, considering the complex dynamics in metropolitan regions. To achieve this, we develop a toolset to assess the impact of potential measures to be taken by decision makers. Our innovative approach is based on the introduction of a new system framework to link the interrelated sector parameters of mobility systems by considering the effects of innovative mixed methods (both qualitative and quantitative) on scenario development and evaluation on the basis of global trends at the macro scale and their specific influences on the mobility sector at the local scale. To this end, we used a participatory modelling approach to develop scenarios and evaluate them as integrated simulation runs via a comprehensive and holistic system dynamics (SD) model. Thus, we estimated dynamic interdependencies between all of the factors relating to the mobility sector and then assigned business decision-making criteria to the urban systems. Furthermore, we introduced a sustainable net present value framework to estimate the sustainability outcomes of government investment in urban mobility infrastructure. A case study relating to the Rhine-Rhine-Ruhr metropolitan region in Germany was applied in order to simulate four scenarios co-created with stakeholders involved in our study, namely, Smart City, Sustainable/Healthy City, Deurbanisation and Business-as-Usual (BaU), which served as a solid basis from which to quantify path dependencies in terms of policy implementation. At the same time, recommendations were derived for sustainable mobility transformation within metropolitan regions.


docid: oimkgers

title: Inactivation of porcine epidemic diarrhea virus using heated water

text: Abstract Porcine epidemic diarrhea virus (PEDV) is a very contagious swine pathogen that spreads easily via the fecal-oral route, notably from contaminated fomites. The present study investigated heated water as a method for rapid thermal inactivation of PEDV. Cell-culture adapted PEDV was treated with water at varying temperatures and viral titers were measured at multiple time points post-treatment. Viable PEDV was not recovered after a ten second or longer treatment with water heated to ≥76°C; however, PEDV nucleic acid was detected in all samples regardless of treatment. Hot water decontamination could be considered in settings where chemical disinfection is impractical.


title: Development of a PCR-and hybridization-based assay (PCR Adenovirus Consensus®) for the detection and the species identification of adenoviruses in respiratory specimens

text: Abstract Background: Antigen detection assays and viral isolation techniques are routinely used to detect adenoviruses (Ad) associated with respiratory infections, and the value of the polymerase chain reaction (PCR) has recently been assessed. Objectives: This paper describes a PCR-hybridization-immunoenzymatic assay (PCR Adenovirus consensus®) used to detect Ad and identify Ad species in respiratory specimens. Results: On seven representative serotypes Ad 12, Ad 3, Ad 7, Ad 11, Ad 1, Ad 8, Ad 4, the mean genome equivalents per ml and the mean 50% infectious doses per ml were 106.3and 104, respectively. Using 362 nasal aspirates from children, Ad were detected by immunofluorescence (IF) and culture in 97 cases (27%), by the PCR-Ad hexon method in 107 cases (29.5%) and by the PCR Adenovirus Consensus® method in 113 cases (31.2%); 13 samples were found positive by both PCR and negative by the IF and culture methods; five samples were only positive according to the PCR Adenovirus Consensus® method. The sensitivity, specificity, predictive positive value and predictive negative value of the PCR Adenovirus Consensus® method were 97.9%, 93.2%, 84%, 99.1%, respectively. The method identified the species (sp) from 91 positive amplicons: 1 Ad sp A, 44 Ad sp B, 42 Ad sp C, 3 Ad sp E, and 1 Ad sp F; 85 isolates were identified by IF or the neutralisation in culture, and 86 by a PCR-RE digestion method. The PCR Adenovirus Consensus® detected six positive samples that were negative according to the IF and culture methods, and it identified the precise species of nine IF-positive and culture-negative nasal aspirates. Conclusion: The PCR Adenovirus Consensus® technique is more efficient than the classical IF or culture techniques for the detection of Ad in respiratory samples. An internal control is included to validate the screening results, and specific probes are used to identify the Ad species.


title: FDG PET/CT in a Patient With Mantle Cell Lymphoma and COVID-19: Typical Findings

text: A 52-year-old woman with no medical history was admitted on March 18, 2020, presenting since 3 days asthenia, abdominal pain, and dry cough but no fever. Adenomegalies, splenomegaly, leukocytosis, and elevated LDH suggested mature lymphoproliferation. Considering the current health context, an RT-PCR testing for COVID-19 (coronavirus disease 2019) was performed and found to be positive. Early chest CT showed no sign of pulmonary infection but multiple adenomegalies. An (18)F-FDG PET/CT performed 5 days later to assess the extent of the hemopathy revealed the apparition of FDG-avid bilateral ground glass and subpleural curvilinear opacities suggesting COVID-19–associated pneumopathy.


title: Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence

text: The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4(+) T cells. The low frequency of naïve CD4(+) T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4(+) T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.


Management Concern for Non-COVID Children During the COVID-19 Pandemic


title: Analysis of household data on influenza epidemic with Bayesian hierarchical model

text: Abstract Data used for modelling the household transmission of infectious diseases, such as influenza, have inherent multilevel structures and correlated property, which make the widely used conventional infectious disease transmission models (including the Greenwood model and the Reed–Frost model) not directly applicable within the context of a household (due to the crowded domestic condition or socioeconomic status of the household). Thus, at the household level, the effects resulting from individual-level factors, such as vaccination, may be confounded or modified in some way. We proposed the Bayesian hierarchical random-effects (random intercepts and random slopes) model under the context of generalised linear model to capture heterogeneity and variation on the individual, generation, and household levels. It was applied to empirical surveillance data on the influenza epidemic in Taiwan. The parameters of interest were estimated by using the Markov chain Monte Carlo method in conjunction with the Bayesian directed acyclic graphical models. Comparisons between models were made using the deviance information criterion. Based on the result of the random-slope Bayesian hierarchical method under the context of the Reed–Frost transmission model, the regression coefficient regarding the protective effect of vaccination varied statistically significantly from household to household. The result of such a heterogeneity was robust to the use of different prior distributions (including non-informative, sceptical, and enthusiastic ones). By integrating out the uncertainty of the parameters of the posterior distribution, the predictive distribution was computed to forecast the number of influenza cases allowing for random-household effect.


title: SARS-coronavirus replication in human peripheral monocytes/macrophages

text: Abstract A novel coronavirus (CoV) has been described in association with cases of severe acute respiratory syndrome (SARS). The virus, SARS-CoV, differs from the previously described human coronaviruses, 229E and OC43. 229E was previously shown to productively infect human monocytes/macrophages, whereas OC43 poorly infected the cells. In this study, we examined whether SARS-CoV could productively infect purified monocytes/macrophages (PM) derived from human donor cells. Unlike 229E-infected cells, which produced viral titers of 103.5 to 106 TCID50/ml, SARS-CoV replicated poorly in PM, producing titers of 101.75 to 102 TCID50/ml. This finding was similar to results reported for OC43-infected cells, with titers ranging from 101.2 to 102.7 TCID50/ml. Of interest, SARS-CoV proteins were detected only in PM that did not produce significant amounts of interferon (IFN)-α, and in one such case, preliminary electron microscope studies demonstrated that SARS-CoV-like particles could enter the cells, possibly via phagocytosis. These results suggest that SARS-CoV, like human CoV OC43, poorly infects human PM, and production of IFN-α by these cells further limits the infection. Given the importance of monocytes/macrophages to the immune response, it is possible that their infection by SARS-CoV and alteration of this infection by IFN-α may be important to the course of the infection in humans.


title: Hemophagocytic lymphohistiocytosis in a patient with glioblastoma: a case report

text: Adult onset hemophagocytic lymphohistiocytosis (HLH) is a rare condition, usually secondary to either a precipitating infective or hematologic malignancy. We present a case of Epstein–Barr virus associated HLH in a 55-year-old female receiving treatment for a glioblastoma (GBM). It is possible that HLH is under recognized, as patients with GBM often have features of a nonspecific systemic inflammatory response syndrome, multiorgan failure and cognitive decline. A high index of suspicion and increased awareness can help improve timeliness of diagnosis. Therapeutically, Epstein–Barr virus associated HLH in patients with solid organ malignancy poses significant challenges. An individualized, multidisciplinary approach is essential when managing adult-onset HLH and providers will need to be mindful of the high mortality rate despite treatment.


title: In vitro and Animal Models for SARS-CoV-2 research

text: Abstract Basic research on SARS-CoV-2 is essential to understand its detailed pathophysiology and identify best drug targets. Models that can faithfully reproduce the viral life cycle and reproduce the pathology of COVID-19 are required. Here, we briefly review the cell lines, organoids, and animal models that are currently being used in COVID-19 research.


title: Psychological symptoms of ordinary Chinese citizens based on SCL-90 during the level I emergency response to COVID-19

text: Abstract The World Health Organization (WHO) has declared that the Corona Virus (COVID-19) has become a global pandemic. This study aimed to investigate the psychological symptoms of ordinary Chinese citizens during the Level I Emergency Response throughout China. From January 31 to February 2 2020, an online questionnaire, Symptom Checklist 90 (SCL-90) was designed, and differences in GSI T-scores among subgroups were examined by ANOVA. Based on a cut-off point of the GSI T-scores of 63, the overall sample was divided into high and low-risk groups. of the 1,060 participants investigated in China, more than 70% of them have moderate and higher level of psychological symptoms specifically elevated scores for obsessive compulsion, interpersonal sensitivity, phobic anxiety, and psychoticism. There were no significant differences between males and females. Those who were of over 50 years old, had an undergraduate education and below, were divorced or widowed, and agricultural workers had significantly more symptoms. However, significantly more minors and medical staff were in the high-risk group. These results show that COVID-19 has a significant adverse socio-psychological influence on ordinary citizens. Therefore, governments should equip psychological health departments and pay attention to the people who are in high-risk groups, providing psychological interventions and assistance.


docid: udokbcki

title: Inspiratory effort and breathing pattern change in response to varying the assist level: a physiological study

text: AIM: To describe the response of breathing pattern and inspiratory effort upon changes in assist level and to assesss if changes in respiratory rate may indicate changes in respiratory muscle effort. METHODS: Prospective study of 82 patients ventilated on proportional assist ventilation (PAV+). At three levels of assist (20%-50%-80%), patients’ inspiratory effort and breathing pattern were evaluated using a validated prototype monitor. RESULTS: Independent of the assist level, a wide range of respiratory rates (16-35br/min) was observed when patients’ effort was within the accepted range. Changing the assist level resulted in paired changes in inspiratory effort and rate of the same tendency (increase or decrease) in all but four patients. Increasing the level in assist resulted in a 31% (8-44%) decrease in inspiratory effort and a 10% (0-18%) decrease in respiratory rate. The change in respiratory rate upon the change in assist correlated modestly with the change in the effort (R = 0.5). CONCLUSION: Changing assist level results in changes in both respiratory rate and effort in the same direction, with change in effort being greater than that of respiratory rate. Yet, neither the magnitude of respiratory rate change nor the resulting absolute value may reliably predict the level of effort after a change in assist.


title: Predictions for the binding domain and potential new drug targets of 2019-nCoV

text: An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.


title: ADLD: A Novel Graphical Representation of Protein Sequences and Its Application

text: To facilitate the intuitional analysis of protein sequences, a novel graphical representation of protein sequences called ADLD (Alignment Diagonal Line Diagram) is introduced in this paper first, and then a new ADLD based method is proposed and utilized to analyze the similarity/dissimilarity of protein sequences. Comparing with existing methods, our ADLD based method is proved to be effective in the similarity/dissimilarity analysis of protein sequences and have the merits of good intuition, visuality, and simplicity. The examinations of the similarities/dissimilarities for both the 16 different ND5 proteins and the 29 different spike proteins illustrate the utility of our ADLD based approach.


title: Seasonality of respiratory viruses and bacterial pathogens

text: BACKGROUND: Seasonal variation has been observed for various bacterial and viral infections. We aimed to further study seasonality of respiratory viruses and bacterial pathogens in relation to antibiotic use, as well as meteorological parameters. METHODS: An ecologic study of antibiotic exposure, meteorological parameters, detection of respiratory viruses and clinical isolates of Clostridioides difficile, Methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and Escherichia coli and Klebsiella pneumoniae (grouped together as gram-negative bacteria; GNB) in Rhode Island from 2012 to 2016. RESULTS: Peak detection of C. difficile occurred 3 months after the peak in antibiotic prescriptions filled (OR = 1.24, 95% CI, 1.07–1.43; P = 0.006). Peak MRSA detection was noted 7 months after the peak in antibiotic prescriptions filled (OR = 1.69, 95% CI, 1.21–2.35; P = 0.003) and 10 months after the peak in respiratory virus detection (OR = 1.04, 95% CI, 1.01–1.06; P = 0.003). Peak GNB detection was noted 2 months after the peak mean monthly ambient temperature (OR = 1.69, 95% C.I., 1.20–2.39; P = 0.004). Peak detection of S. pneumoniae was noted at the same time as the peak in detection of respiratory viruses (OR = 1.01, 95% C.I., 1.00–1.01; P = 0.015). CONCLUSIONS: We identified distinct seasonal variation in detection of respiratory viruses and bacterial pathogens. C. difficile seasonality may, in part, be related to antibiotic prescriptions filled; GNB seasonality may be related to ambient temperature and S. pneumoniae may be related to concurrent respiratory viral infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13756-019-0574-7) contains supplementary material, which is available to authorized users.


title: Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses

text: The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently identified a single IFIT (chIFIT5) gene. The profound transcriptional level of this effector of innate immunity was mapped within its unique cis-acting elements. This highly virus- and IFN-responsive chIFIT5 protein interacted with negative sense viral RNA structures that carried a triphosphate group on its 5′ terminus (ppp-RNA). This interaction reduced the replication of RNA viruses in lentivirus-mediated IFIT5-stable chicken fibroblasts whereas CRISPR/Cas9-edited chIFIT5 gene knockout fibroblasts supported the replication of RNA viruses. Finally, we generated mosaic transgenic chicken embryos stably expressing chIFIT5 protein or knocked-down for endogenous chIFIT5 gene. Replication kinetics of RNA viruses in these transgenic chicken embryos demonstrated the antiviral potential of chIFIT5 in ovo. Taken together, these findings propose that IFIT5 specifically antagonize RNA viruses by sequestering viral nucleic acids in chickens, which are unique in innate immune sensing and responses to viruses of both poultry and human health significance.


title: Consideration of the Aerosol Transmission for COVID‐19 and Public Health

text: This article analyzes the available evidence to address airborne, aerosol transmission of the SARS‐CoV‐2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS‐CoV‐2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection.


How to cite this article: Xiao-Bo H, Poonyathawon S, Semedi BP, Xiao-Yi Z, Wei F, Da-Wei W, et al. International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community. Indian J Crit Care Med 2020;24(4):283–284.


title: Lessons from the past, policies for the future: resilience and sustainability in past crises

text: This article surveys some examples of the ways past societies have responded to environmental stressors such as famine, war, and pandemic. We show that people in the past did think about system recovery, but only on a sectoral scale. They did perceive challenges and respond appropriately, but within cultural constraints and resource limitations. Risk mitigation was generally limited in scope, localized, and again determined by cultural logic that may not necessarily have been aware of more than symptoms, rather than actual causes. We also show that risk-managing and risk-mitigating arrangements often favored the vested interests of elites rather than the population more widely, an issue policy makers today still face.


title: Genetic characterization of commensal Escherichia coli isolated from laboratory rodents

text: BACKGROUND: Escherichia coli, a commensal in the intestines of vertebrates, is capable of colonizing many different hosts and the environment. Commensal E. coli strains are believed to be the precursor of pathogenic strains by means of acquisition of antimicrobial resistant and virulence genes. Laboratory rodents are inherently susceptible to numerous known infectious agents, which could transfer virulence determinants to commensal E. coli. Hence, in this study, the genetic structure of commensal E. coli found in laboratory rodents and their antimicrobial resistance profiles were investigated. RESULTS: E. coli strains belonging to phylogroup A were the predominant strain obtained from the animals used in the study. Four novel sequence types (ST746, ST747, ST748 and ST749) were discovered using the multi locus sequence typing, together with one common ST357 in the gastrointestinal tract, liver and, the trachea and lung. Serotyping demonstrated that these commensal E. coli strains were non-Shiga toxin-producers. Phenotypic and genotypic analyses of extended spectrum beta lactamases were also negative. CONCLUSIONS: These findings implied that the E. coli strains recovered from the laboratory rodents were truly commensal in nature. Further study is required to investigate the possible influence of gender on the susceptibility of hosts to E. coli colonization in laboratory rodents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2745-9) contains supplementary material, which is available to authorized users.


title: Direct structural evidence for formation of a stem-loop structure involved in ribosomal frameshifting in human immunodeficiency virus type 1 1 Kumho Life and Environmental Science Laboratory Publication No. 8. 1

text: Abstract Programmed ribosomal frameshifting in viral messenger RNA occurs in response to neighboring sequence elements consisting of: a frameshift site, a spacer, and a downstream enhancer sequence. In human immunodeficiency virus type 1 (HIV-1) mRNA, this sequence element has a potential to form either a stem-loop or a pseudoknot structure. Based on many mutational studies, the stem-loop structure has been proposed for the downstream enhancer region of the HIV-1 mRNA. This stimulatory stem-loop structure is separated from the shift site by a spacer of seven nucleotides. In contrast, a recent report has proposed an alternative model in which the bases in the spacer sequence form a pseudoknot structure as the downstream enhancer sequence [Du et al., Biochemistry 35 (1996) 4187–4198.]. Using UV melting and enzymatic mapping analyses, we have investigated the conformation of the sequence region involved in ribosomal frameshifting in HIV-1. Our S1, V1, and T1 endonuclease mappings, together with UV melting analysis, clearly indicate that this sequence element of the HIV-1 mRNA frameshift site forms a stem-loop structure, not a pseudoknot structure. This finding further supports the stem-loop structure proposed by many mutational studies for the downstream enhancer sequence of the HIV-1 mRNA.


title: COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System.

text: Coronavirus disease 19 (COVID-19) is an infectious disease caused by SARS-Cov-2, resulting in severe acute respiratory syndrome, with high potential of spreading and infecting humans worldwide. Since January 2020, when the virus was identified in humans, the literature on COVID-19 has grown exponentially, and extra respiratory symptoms including neurological symptoms are increasingly highlighted. These neurological disorders are grouped into several categories, ranging from non-specific and moderate symptoms such as headache, myalgia and hyposmia to severe symptoms including cerebrovascular disease and intracranial infections. Severe neurological symptoms such as acute cerebrovascular disease occur only in a minority of patients with usual risk factor, and are associated with poor outcome. However, most COVID-19 patients exhibit only minor or mild neurological symptoms. Given the high and increasing number of publications reporting neurological involvements of SARS-Cov-2, we think providing an update for neurological complications of COVID-19 could be useful for physician and especially young trainees in neurology and neurosurgery. Indeed, in this review we discuss several neurological aspects reported in the literature to date, including the evidence and pathways of the neuro-invasion in COVID-19, and the main neurological disorders reported in the literature to date, as well as the future perspectives and the potential long term consequence of current neuro-infection in COVID-19 patients.


title: A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition

text: Summary There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.


title: COVID‐19: The residuals

text: The Random House Dictionary of the English Language defines residual as “that which remains.”


title: Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis

text: BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243).