title: An Intact Retroviral Gene Conserved in Spiny-Rayed Fishes for over 100 My

text: We have identified a retroviral envelope gene with a complete, intact open reading frame (ORF) in 20 species of spiny-rayed fishes (Acanthomorpha). The taxonomic distribution of the gene, “percomORF”, indicates insertion into the ancestral lineage >110 Ma, making it the oldest known conserved gene of viral origin in a vertebrate genome. Underscoring its ancient provenence, percomORF exists as an isolated ORF within the intron of a widely conserved host gene, with no discernible proviral sequence nearby. Despite its remarkable age, percomORF retains canonical features of a retroviral glycoprotein, and tests for selection strongly suggest cooption for a host function. Retroviral envelope genes have been coopted for a role in placentogenesis by numerous lineages of mammals, including eutherians and marsupials, representing a variety of placental structures. Therefore percomORF’s presence within the group Percomorpha—unique among spiny-finned fishes in having evolved placentation and live birth—is especially intriguing.


title: Challenging beliefs and ethical concepts: the collateral damage of SARS

text: The recent SARS (severe acute respiratory syndrome) outbreak exploded on an unsuspecting public and functionally paralyzed health care delivery systems in many countries. Cancer treatments were deferred and elective surgeries, clinic visits and diagnostic tests were postponed. Other collateral damage includes the devastating psychological distress suffered by patients who were isolated from their families, those same families who could not visit their ill loved ones, patients awaiting access to various aspects of the health care system, and health care workers. We are all starting to dig out, and this process will take many months at a minimum and we may never completely return to the way we were. This commentary addresses the implications of a modern-day epidemic like SARS, focusing on the intensive care unit setting, with special attention given to the effect on health care workers. We explore some of the ethical challenges posed to relationships, professional integrity and resource allocation.


title: Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia

text: Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection.


title: Renin-angiotensin-aldosterone system and COVID-19 infection

text: Summary With the multiplication of COVID-19 cases due to SARS COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Because SARS COV2 utilizes ACE2 (angiotensin-converting enzyme 2) as a membrane receptor to enter target cells, the fear that ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection emerged. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. Due to different structural structures with ACE1, ACE2 is insensitive to ACEIs. Although ARBs and ACEi have been shown to upregulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Therefore, to date, the exact impact of bot ARBs and ACEis on COVID-19 infection remains unknown and preliminary results are in favor of a protective role of ACEis and ARBs. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as recommended by several medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.


title: Gold nanoparticle‐adjuvanted S protein induces a strong antigen‐specific IgG response against severe acute respiratory syndrome‐related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs

text: The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS‐CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll‐like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet‐inactivated SARS‐CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse‐adapted SARS‐CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP‐adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro‐inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist‐adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia‐associated coronaviruses.


title: Diversion of stress granules and P-bodies during viral infection

text: Abstract RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain many translation initiation factors, and processing bodies (P-bodies, PBs), which are enriched for proteins involved in RNA turnover. Because of the inverse relationship between appearance of RNA granules and persistence of translation, many viruses must subvert RNA granule function for replicative purposes. Here we discuss the viruses and mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Several themes have emerged for manipulation of RNA granules by viruses: (1) disruption of RNA granules at the mid-phase of infection, (2) prevention of RNA granule assembly throughout infection and (3) co-opting of RNA granule proteins for new or parallel roles in viral reproduction. Viruses must employ one or multiple of these routes for a robust and productive infection to occur. The possible role for RNA granules in promoting innate immune responses poses an additional reason why viruses must counteract the effects of RNA granules for efficient replication.


title: Role of oligosaccharides in the structure and function of respiratory syncytial virus glycoproteins

text: Abstract The contribution of oligosaccharides to the structural and functional make-up of respiratory syncytial (RS) virus G and F proteins was investigated by observing the effects of various oligosaccharide-specific enzymes on their molecular size as well as on virus infectivity. The N-linked oligosaccharides of the F protein were completely removed by endoglycosidase F and N-glycanase. Addition of oligosaccharides to F protein during synthesis was completely partially resistant to TM resulting in an 80-kDa form designated GTM. The G protein was estimated to contain approximately 3% N-linked and 55% O-linked carbohydrates, based on migration of G and GTM in polyacrylamide gels. Furthermore, treatment of detergent-extracted G protein with endoglycosidase F and endo-α-N-acetylgalactosaminidase, enzymes that specifically cleave N-linked and O-linked oligosaccharides, respectively, generated a variety of partially unglycosylated species, ranging in molecular weight from approximately 80 to 40 kDa. Virus infectivity was sensitive to limited removal of N-linked or O-linked oligosaccharides by endoglycosidases under conditions which did not greatly alter the molecular weight of the G protein. Thus, G and F protein oligosaccharides readily accessible to enzymatic removal are presumed to play an important role in the infectious process.


title: Supporting adults bereaved through COVID-19: a rapid review of the impact of previous pandemics on grief and bereavement

text: The global COVID-19 pandemic is likely to have a major impact on the experience of death, dying and bereavement. This study aimed to review and synthesise learning from previous literature focused on the impact on grief and bereavement during other infectious disease outbreaks. We conducted a rapid scoping review according to the principles of the Joanna Briggs Institute and analysed qualitative data using thematic synthesis. From the 218 identified papers, 6 were included in the analysis. They were four qualitative studies, one observational study and a systematic review. Studies were conducted in West Africa, Haiti and Singapore. No research studies have focused on outcomes and support for bereaved people during a pandemic. Studies have tended to focus on survivors i.e. those who had the illness and recovered, recognising that some of these individuals will also be bereaved people. Previous pandemics appear to cause multiple losses both directly related to death itself but also in terms of disruption to social norms, rituals and mourning practices. This affects the ability for an individual to connect with the deceased both before and after the death, potentially increasing the risk of complicated grief. In view of the limited research, specific learning from the current COVID-19 crisis and the impact on the bereaved would be pertinent. Current focus should include innovative ways to promote connection and adapt rituals while maintaining respect. Strong leadership and coordination between different bereavement organisations is essential to providing successful post-bereavement support.


title: Viral RNAs: Lessons from the Enemy

text: Viruses are adept at evolving or co-opting genomic elements that allow them to maximize their replication potential in the infected host. This evolutionary plasticity makes viruses an invaluable system to identify new mechanisms used not only by viruses but also by vertebrate cells to modulate gene expression. Here, I discuss the identification and characterization of viral mRNA structures and noncoding RNAs that have led to important insights into the molecular mechanisms of eukaryotic cells.


title: Pandemic preparedness and forecast

text: Geographic mapping of pathogen emergence risk, as recently done for viral haemorrhagic fever in Africa, provides an important tool for targeting interventions. More comprehensive preparedness and prediction systems that increase surveillance and forecast infectious disease outbreak growth and spread in real time are also needed.


title: Seroprevalence Dynamics of European Bat Lyssavirus Type 1 in a Multispecies Bat Colony

text: We report an active surveillance study of the occurrence of specific antibodies to European Bat Lyssavirus Type 1 (EBLV-1) in bat species, scarcely studied hitherto, that share the same refuge. From 2004 to 2012, 406 sera were obtained from nine bat species. Blood samples were subjected to a modified fluorescent antibody virus neutralization test to determine the antibody titer. EBLV-1-neutralizing antibodies were detected in six of the nine species analyzed (Pipistrellus pipistrellus, P. kuhlii, Hypsugo savii, Plecotus austriacus, Eptesicus serotinus and Tadarida teniotis). Among all bats sampled, female seroprevalence (20.21%, 95% CI: 14.78%–26.57%) was not significantly higher than the seroprevalence in males (15.02%, 95% CI: 10.51%–20.54%). The results showed that the inter-annual variation in the number of seropositive bats in T. teniotis and P. austriacus showed a peak in 2007 (>70% of EBLV-1 prevalence). However, significant differences were observed in the temporal patterns of the seroprevalence modeling of T. teniotis and P. austriacus. The behavioral ecology of these species involved could explain the different annual fluctuations in EBLV-1 seroprevalence.


Navigating Nonessential Research Trials During COVID19: The Push We Needed For Using Digital Technology To Increase Access For Rural Participants?


title: Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling

text: Abstract Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity.


title: Innovations in structure-based antigen design and immune monitoring for next generation vaccines

text: The recent explosion of atomic-level structures of glycoproteins that comprise the surface antigens of human enveloped viruses, such as RSV, influenza, hepatitis C and HIV, provide tremendous opportunities for rational, structure-based vaccine design. Several concepts in structure-based vaccine design have been put into practice and are are well along preclinical and clinical implementation. Testing of these designed immunogens will provide key insights into the ability to induce the desired immune responses, namely neutralizing antibodies. Many of these immunogens in human clinical trials represent only the first wave of designs and will likely require continued tweaking and elaboration to achieve the ultimate result of ever increasingly breadth and potency. Considerable effort is now being invested in germline targeting, epitope focusing, and improved immune presentation such as multivalent nanoparticle incorporation. This review highlights some of the recent advances in these areas as we prepare for the next generation of immunogens for subsequent rounds of iterative vaccine development.


title: Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis

text: BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.


docid: ixytcvge

title: Coronaviruses post-SARS: Update on replication and pathogenesis

text: While coronaviruses were first identified nearly 60 years ago, they received notoriety in 2003 when one of their members was identified as the etiological agent of the Severe Acute Respiratory Syndrome (SARS-CoV) 1. Previously these viruses were known to be important agents of respiratory and enteric infections of domestic and companion animals and to cause approximately 15% of all cases of the common cold. This Review focuses on recent advances in our understanding of the mechanisms of coronavirus replication, interactions with the host immune response and disease pathogenesis and highlights the recent identification of numerous novel coronaviruses and the propensity of this virus family to cross species barriers.


title: Assessment of the potential relationship between egg quality and infectious bronchitis virus infection in Australian layer flocks

text: OBJECTIVE: This investigation aimed to determine if there was a relationship between the production of eggs with poor internal quality, as measured by poor Haugh units, by Australian layer flocks and the detection of infectious bronchitis virus (IBV) in the hens. Other risk factors including flock size, flock type, flock age, chicken breed and vaccination frequency were also assessed. METHODS: The study group comprised 17 flocks from 14 farms. Data relating to the factors investigated were requested on a regular basis. The Haugh unit data were used to grade eggs as good or poor based on the age and flock at the time of data collection. Cloacal swabs were collected from 20 chickens in each flock approximately every 6 weeks. RESULTS: IBV was detected from a majority of the flocks and in 68% of cases the IBV strain detected was an A‐vaccine‐related field strain. Three variant strains were detected. Detection of IBV in a flock, the farm type and flock size were identified as potential risk factors for the production of eggs with poor Haugh units. CONCLUSION: IBV is prevalent in Australian layer flocks, but infection was primarily subclinical. The results complement previous reports indicating that there are many potential risk factors for the production of eggs with poor Haugh units.


title: RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations

text: BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.


REPLY to “Self‐reported olfactory loss in COVID‐19: is it really a favorable prognostic factor?”


title: Patients hospitalized with an infective exacerbation of bronchiectasis unrelated to cystic fibrosis: Clinical, physiological and sputum characteristics

text: BACKGROUND AND OBJECTIVE: Bronchiectasis is a growing health burden both globally and in Australasia. Associated with repeated respiratory infections, the disease often results in hospital admission, impaired quality of life, reduced lung function and shortened life expectancy. We describe the local clinical, physiological and sputum characteristics in patients hospitalized with an infective exacerbation of bronchiectasis. METHODS: This study examined the medical records of all 61 adults admitted to a metropolitan Australian hospital with an infective exacerbation of bronchiectasis in a calendar year. RESULTS: Baseline characteristics include: mean (SD) age of participants was 66 (14) years; 56% were women and 42% were current or ex‐smokers. The majority had other coexisting medical conditions, with asthma in 44%, COPD in 59% and both asthma and COPD in 31%. Seventy‐two percent were on regular inhaled medication, 23% on cyclical antibiotics and 26% undertook regular respiratory physiotherapy. Bronchodilator reversibility was present in 17% and small airway reversibility in 41%. Sputum demonstrated normal flora in 17%, Pseudomonas aeruginosa in 32%, Haemophilus influenzae in 15% and both organisms in 17%. Mean numbers of exacerbations per year requiring hospitalization was 2.3. Sixty‐two percent of subjects had an Index of Relative Socio‐Economic Disadvantage in deciles 1–5. Risk factors for exacerbations included a history of asthma or COPD, documented small airway reversibility and presence of P. aeruginosa. CONCLUSION: Patients hospitalized with an infective exacerbation of bronchiectasis are predominantly older with co‐morbidities and of lower socio‐economic status. Presence of P. aeruginosa was a risk factor for repeated exacerbations, as was a history of asthma, COPD or small airway reversibility.


The Blurred Line between the Art and Science of Medicine


title: Maternal Infection and Adverse Fetal and Neonatal Outcomes

text: Adverse pregnancy outcomes can follow direct placental, fetal, or neonatal infection, or preterm birth associated with vaginal, cervical, intrauterine, or even nonpelvic infections. These latter infections appear to be associated with the majority of very early preterm births, and may explain some of the long-term neurologic damage associated with preterm birth. Bacterial vaginosis and its associated intrauterine infections likely contribute far more to the overall burden of adverse pregnancy outcomes than the more classical perinatal infections such as rubella and syphilis.


Standard precautions: what is meant and what is not


title: Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship

text: Abstract We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.


The Isolation Communication Management System. A Telemedicine Platform to Care for Patients in a Biocontainment Unit


title: Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods

text: Abstract Asthma causes enormous suffering and cost for children in the US and around the world [1–3]. Co-morbid gastroesophageal reflux disease (GERD) makes asthma management more difficult due to increased symptoms. Proton pump inhibitor (PPI) drugs are effective at improving to GERD symptoms, however they have demonstrated only modest and variable effects on asthma control in the setting of co-morbid GERD. Importantly, PPI metabolism and efficacy depend on CYP2C19 genotype. The Genotype Tailored Treatment of Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA) study is a randomized, double-blind, placebo-controlled trial to determine if genotype-tailored PPI dosing improves asthma symptoms among children with inadequately controlled asthma and GERD symptoms. This study has an innovative design to both assess the efficacy of genotype-tailored PPI dosing and perform pharmacokinetic modeling of the oral PPI Lansoprazole. Children ages 6–17 years old with clinician-diagnosed asthma and mild GERD symptoms will submit a saliva sample for CYP2C19 genotyping. Participants will undergo a two-step randomization to: (1) genotype-tailored versus conventional dosing of open-label oral lansoprazole for pharmacokinetic modeling, and (2) genotype-tailored lansoprazole daily versus placebo for 24 weeks to determine the effect of genotype-tailored PPI dosing on asthma control. Measures of asthma control, spirometry, and nasal washes during acute illnesses will be collected at 8-week intervals throughout the study. GenARA will better define the effects of CYP2C19 genotype on the dose response of lansoprazole in children and adolescents and assess if a novel dosing regimen improves GERD and asthma control.


title: Prisoners of war — host adaptation and its constraints on virus evolution

text: Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500–6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus–host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution.


The emergency medical services in Singapore


title: Human parechovirus infections in patients admitted to hospital in Northern Italy, 2008–2010

text: Human parechoviruses (HPeVs) infection is associated with a wide range of clinical syndromes such as respiratory, gastrointestinal, neurologic diseases, and neonatal sepsis‐like illness. The main objective of this study was to investigate the epidemiology of HPeVs infection in hospitalized patients in a period of 2 years. Respiratory samples from 3,525 patients with respiratory syndrome, cerebrospinal fluid (CSF) from 340 patients with neurologic syndrome as well as CSF and plasma samples from five neonatal patients with sepsis‐like illness collected from October 2008 to 2010 were tested retrospectively using HPeV‐specific real‐time RT‐PCR. Phylogenetic analysis of VP3/VP1 region was performed on the positive samples. Fourteen out of 3,525 (0.4%) patients with respiratory syndrome and five out of five patients with sepsis‐like illness were positive for HPeV. In 3/5 patients with sepsis‐like illness multiple samples (e.g., stool, plasma, CSF, or respiratory samples) were available, and HPeV was found in all specimens. In contrast, no positive CSF was detected among the 340 patients with neurologic syndromes. Eleven patients (57.9%) were infected with HPeV1 strain, 7 (36.8%) with HPeV3, and 1 (5.3%) with HPeV6 strains. Ten of the 14 HPeV patients with respiratory syndrome were co‐infected with other respiratory viruses (eight with rhinovirus and two with coronavirus OC43). All five patients with sepsis‐like illness were less than 1 month of age and were infected with HPeV3. Although not circulating at high frequency and unlikely to cause respiratory syndrome, HPeV was associated with severe clinical syndromes in a minority of newborns. J. Med. Virol. 84:686–690, 2012. © 2011 Wiley Periodicals, Inc.


Risk factors for facial pressure sore of healthcare workers during the outbreak of COVID‐19


title: Neuromyelitis optica practice and prescribing changes in the setting of Covid19: A survey of neurologists

text: PURPOSE: This study reports and analyzes the findings from the responses of 192 neurologists in the United States and Canada to a new survey instrument distributed in April 2020 to assess NMO practice and prescribing changes during the Covid19 pandemic. PRINCIPAL RESULTS: 92% of responding neurologists considered their NMO patients to be at an elevated risk of acquiring Covid19. They also indicated sharp declines in visits, delays in treatment and related services, and several unmet needs deterring treatment. MAJOR CONCLUSIONS: There is a need for evidence-based, comprehensive guidelines for treating NMO patients amid healthcare crises moving forward.


title: Neuraminidase treatment of avian infectious bronchitis coronavirus reveals a hemagglutinating activity that is dependent on sialic acid-containing receptors on erythrocytes

text: Abstract The interaction of infectious bronchitis virus (IBV) with erythrocytes was analyzed. The binding activity of IBV was not sufficient to agglutinate chicken erythrocytes. However, it acquired hemagglutinating activity after treatment with neuraminidase to remove α2,3-linked N-acetylneuraminic acid from the surface of the virion. Pretreatment of erythrocytes with neuraminidase rendered the cells resistant to agglutination by IBV. Susceptibility to agglutination was restored by resialylation of asialo-erythrocytes to contain α2,3-linked sialic acid. These results indicate that IBV attaches to receptors on erythrocytes, the crucial determinant of which is sialic acid α2,3-linked to galactose. In contrast to other enveloped viruses with such a binding specificity (influenza viruses and paramyxoviruses) IBV lacks a receptor-destroying enzyme.


title: A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy

text: Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.


title: Establishing a standardized FUO emergency department: design and practice in dealing with COVID-19

text: Background: Since the outbreak of COVID-19 in January, 2020, the fever of unknown origin (FUO) emergency department has become the first station for disease prevention and identification in hospitals Establishing a standardized FUO emergency department within a short period of time has become the key to preventing and controlling COVID-19 in densely populated Chinese cities Methods: Based on the lean management model, the research group established a process of less-link visits, which sees reduced contact between patients and physicians during diagnosis and treatment, and zero-contact consultation through lean workflow and value stream analysis Three steps were implemented to improve the operations of the FUO emergency department: the rapid establishment of an isolation zone, the refinement of duty and protection configuration, and the use of Internet and technology to establish a full-process follow-up consultation system Results: (I) Tests related to COVID-19 screening are all completed in the FUO emergency department;(II) 12 new isolated observation rooms have been built;(III) hospital visiting time, waiting time for consultation, and the time from pre-examination to virus screening has been shortened from 18 to 8 hours, from 2 hours to 10 minutes, and from 34 to 3 hours, respectively;(IV) the transfer distance has been shortened from 450 to 20 m, and the observation time has been shortened from 72 to 26 hours The median waiting time for image examination has been reduced from 40 to 3 minutes, and the moving distance has been shortened from 800 to 10 m;(V) the diagnosis and treatment process is facilitated by 5G, achieving zero contact between doctors and patients Conclusions: Through the implantation of information technology, the local transformation of the site, the rational allocation of medical teams and the planned distribution of protective equipment, in a short period of time, individual medical institutions can set up a safe FUO emergency department to provide 24-hour screening and detention services Establishing an FUO emergency department with lean management and realizing the management approach of combining daily operation with prevention and control could help China and other countries to handle the outbreak of fulminant infectious diseases


title: Changes in nonstructural protein 3 are associated with attenuation in avian coronavirus infectious bronchitis virus

text: Full-length genome sequencing of pathogenic and attenuated (for chickens) avian coronavirus infectious bronchitis virus (IBV) strains of the same serotype was conducted to identify genetic differences between the pathotypes. Analysis of the consensus full-length genome for three different IBV serotypes (Ark, GA98, and Mass41) showed that passage in embryonated eggs, to attenuate the viruses for chickens, resulted in 34.75–43.66% of all the amino acid changes occurring in nsp 3 within a virus type, whereas changes in the spike glycoprotein, thought to be the most variable protein in IBV, ranged from 5.8 to 13.4% of all changes. The attenuated viruses did not cause any clinical signs of disease and had lower replication rates than the pathogenic viruses of the same serotype in chickens. However, both attenuated and pathogenic viruses of the same serotype replicated similarly in embryonated eggs, suggesting that mutations in nsp 3, which is involved in replication of the virus, might play an important role in the reduced replication observed in chickens leading to the attenuated phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-011-0668-7) contains supplementary material, which is available to authorized users.


Optimizing Medication Management During the COVID‐19 Pandemic: An Implementation Guide for Post‐Acute and Long‐Term Care


title: Molecular dynamic simulations analysis of ritronavir and lopinavir as SARS-CoV 3CLpro inhibitors

text: Abstract Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CLpro free enzyme (free SARS) and its complexes with lopinavir (SARS–LPV) and ritonavir (SARS–RTV). The results show that flap closing was clearly observed when the inhibitors bind to the active site of SARS-CoV 3CLpro. The binding affinities of LPV and RTV to SARS-CoV 3CLpro do not show any significant difference. In addition, six hydrogen bonds were detected in the SARS–LPV system, while seven hydrogen bonds were found in SARS–RTV complex.


Safe operating room protocols during the COVID‐19 pandemic


title: A probabilistic approach to incorporating domain knowledge for closed-room people monitoring

text: Abstract We propose a novel probabilistic approach to recognizing people entering and leaving a closed room in human work place or living environment. Specifically, people in the view of a monitoring camera are first tracked and represented using low-level color features. Based on a new color similarity measure, optimal recognition of people leaving and entering the room is carried out by probabilistic reasoning under the constraints imposed by the domain knowledge, e.g., a person currently inside a room cannot enter again without first leaving it, and vice versa. The novelty of our work mainly lies in the development of a systematic way to incorporate the correlation and constraint among a sequence of people observations, and the optimality of recognition is achieved by maximizing a joint posterior probability of the observations. Experimental results of real and synthetic data are presented to show the efficacy of the proposed approach.


title: Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study

text: Background The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. Results The median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. Conclusion Our findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.


title: Early versus late onset of hypertensive disorders in twins—The placental perspective

text: Objectives Early and late hypertensive disorders in pregnancy (HDP) are different entities in singleton gestations, with earlier onset associated with higher rates of placental maternal vascular malperfusion lesions (MVMs). It is still not known if this distinction apply for twin gestations as well. Methods Retrospective study of women with DCDA twin gestations and HDP (2001–2015), with a placental pathology evaluation. Placental lesions were classified according to the Amsterdam criteria. Pregnancies with early onset HDP (≤34 weeks) were compared with pregnancies with late onset HDP (>34 weeks). Results Out of 1655 twin deliveries, 161 (9.7%) were complicated by HDP: 77 (47.8%) had preeclampsia, and 84 (52.2%) had gestational hypertension. Forty patients (24.8%) had early onset HDP. Early HDP was associated with a higher rate of 1 MVMs (p=0.01), ≥2 MVMs (p=0.009) and with a lower rate of chronic villitis (p=0.02). In multivariable analysis, using late HDP as reference, early HDP was associated with a higher prevalence of ≥1 MVMs (aOR 1.9, 95% CI 1.1–3.5, p=0.03) and ≥2 MVMs (aOR 2.6, 95% CI 1.05–6.3, p=0.04). Early HDP was also less associated with chronic villitis (aOR 0.2, 95% CI 0.05–0.9), as chronic villitis is usually associated with a more advanced gestational age. Conclusions While the mechanism underlying HDP in singleton and twins’ gestations may be different, similar to singleton pregnancies, early onset (≤34 weeks gestation) of HDP in twins’ gestation is associated with a higher prevalence of MVM's, suggesting of reduced placental perfusion in early onset HDP in twins.


title: A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics

text: The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC’s ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC’s performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.


title: Evaluation of equine coronavirus fecal shedding among hospitalized horses

text: BACKGROUND: Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. OBJECTIVE: We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. ANIMALS: One‐hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. METHODS: Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. RESULTS: Only 1 of 258 fecal samples was PCR‐positive for ECoV. Electron microscopy identified ECoV‐like particles in 9 of 258 samples, parvovirus‐like particles in 4 of 258 samples, and rotavirus‐like particles in 1 of 258 samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR‐positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.


title: The Sustained Value of an Early Pregnancy Assessment Clinic in the Management of Early Pregnancy Complications: A 10-Year Retrospective Study

text: Abstract Objective This study sought to evaluate the sustained value of an early pregnancy assessment clinic (EPAC) in the management of early pregnancy complications and its effect on the incidence emergency room (ER) visits. Methods A 10-year retrospective study (January 2006 to December 2015) was conducted. The number of patients assessed, sources and reasons for referral, and treatments provided were reviewed. The numbers of ER assessments and reassessments for abortion, hemorrhage, and ectopic pregnancy from January 2004 to December 2005 (pre-EPAC) and January 2006 to December 2015 (post-EPAC) were also reviewed. Results There were 11 349 new referrals and 10 764 follow-up visits. The reasons for referral were threatened miscarriage (n = 3568, 31.4%), missed miscarriage (n = 3056, 26.9%), incomplete miscarriage (n = 1064, 9.4%), complete miscarriage (n = 991, 8.7%), ectopic pregnancy (n = 857, 7.6%), hyperemesis gravidarum (n = 139, 1.2%), and others (n = 1674, 14.8%). There has been a significant decreasing trend (tau = −0.60, P = 0.0127) and a significant decrease in the post-EPAC rate of ER reassessments (P = 0.0396) for hemorrhage, with a concomitant decrease in EPAC visits for hemorrhage. In addition, there has been a significant increasing trend (tau = 0.64, P = 0.0081) and a significant increase in the post-EPAC rate of ER assessments (P = 0.00001) for ectopic pregnancies. Conclusion Over the 10-year period, the EPAC has remained a vital service for managing early pregnancy complications for women. However, the clinic has not yet had a sustained impact on ER visits for miscarriage, ectopic pregnancy, and hemorrhage. It is possible that a reduction in ER assessments and reassessments for early pregnancy complications can be achieved through a clinic with daily access.


title: STudy of Alteplase for Respiratory failure in SARS‐Cov2/COVID‐19: Study Design of the Phase IIa STARS Trial

text: BACKGROUND: The COVID‐19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID‐19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow‐up trial using the widely available tissue‐plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. OBJECTIVE: To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID‐19‐induced ARDS. PATIENTS/METHODS: A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard‐of‐care). Inclusion criteria are known/suspected COVID‐19 infection with PaO2/FiO2 ratio<150mmHg for >4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re‐dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. RESULTS: The primary outcome is improvement in PaO2/FiO2 at 48 hours post‐randomization. Other outcomes include: ventilator‐ and ICU‐free‐days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped‐wedge design with four looks at the data. CONCLUSION: Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID‐19‐induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634)


title: Viral antibody dynamics in a chiropteran host

text: 1. Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. 2. In these, and other, systems, there is evidence that seasonal life‐cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. 3. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30‐month period, using a powerful novel antibody quantitation method. 4. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population‐level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. 5. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half‐life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts.


title: Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans

text: BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.


title: Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase

text: Abstract Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a newly found virus, called SARS coronavirus. In this study, the cleavage mechanism of the SARS coronavirus main proteinase (Mpro or 3CLpro) on the octapeptide NH2-AVLQ↓SGFR-COOH was investigated using molecular mechanics and quantum mechanics simulations based on the experimental structure of the proteinase. It has been observed that the catalytic dyad (His-41/Cys-145) site between domains I and II attracts the π electron density from the peptide bond Gln–Ser, increasing the positive charge on C(CO) of Gln and the negative charge on N(NH) of Ser, so as to weaken the Gln–Ser peptide bond. The catalytic functional group is the imidazole group of His-41 and the S in Cys-145. Nδ1 on the imidazole ring plays the acid–base catalytic role. Based on the “distorted key theory” [K.C. Chou, Anal. Biochem. 233 (1996) 1–14], the possibility to convert the octapeptide to a competent inhibitor has been studied. It has been found that the chemical bond between Gln and Ser will become much stronger and no longer cleavable by the SARS enzyme after either changing the carbonyl group CO of Gln to CH2 or CF2 or changing the NH of Ser to CH2 or CF2. The octapeptide thus modified might become an effective inhibitor or a potential drug candidate against SARS.


title: Metallothioneins (I+II) and thyroid–thymus axis efficiency in old mice: role of corticosterone and zinc supply

text: Abstract Thymic atrophy or thymus absence causes depressed thyroid–thymus axis (TTA) efficiency in old, young propyl-thiouracil (PTU) (experimental hypothyroidism) and in young-adult thymectomised (Tx) mice, respectively. Altered zinc turnover may be also involved in depressed TTA efficiency. Zinc turnover is under the control of zinc-bound metallothioneins (Zn-MTs) synthesis. Thyroid hormones, corticosterone and nutritional zinc affect Zn-MT induction. Zn-MT releases zinc in young-adult age during transient oxidative stress for prompt immune response. In constant oxidative stress (ageing and liver regeneration after partial hepatectomy), high liver Zn-MTs, low zinc ion bioavailability and depressed TTA efficiency appear. This last finding suggested that MT might not release zinc during constant oxidative stress leading to impaired TTA efficiency. The aim of this work/study is to clarify the role of Zn-MTs (I+II) in TTA efficiency during development and ageing. The main results are (1) Old and PTU mice display high corticosterone, enhanced liver MTmRNA, low zinc and depressed TTA efficiency restored by zinc supply. Increased survival and no significant increments in basal liver Zn-MTs proteins occur in old and PTU mice after zinc supply. (2) Lot of zinc ions bound with MT in the liver from old mice than young (HPLC). (3) Young-adult Tx mice, evaluated at 15 days from thymectomy, display high MTmRNA and nutritional–endocrine–immune damage restored by zinc supply or by thymus grafts from old zinc-treated mice. (4) Young-adult Tx mice, but evaluated at 40 days from thymectomy, display natural normalisation in MTmRNA and nutritional–endocrine–immune profile with survival similar to normal mice. (5) Stressed (constant dark for 10 days) mice overexpressing MT display low zinc, depressed immunity, reduced thymic cortex, high corticosterone, altered thyroid hormones turnover showing a likeness with old mice. These findings, taken altogether, show that corticosterone is pivotal in MTs induction under stress. MTs bind preferentially zinc ions in constant oxidative stress, but with no release of zinc from MT leading to impaired TTA efficiency. Zinc supply restores the defect because zinc has no interference in affecting pre-existing Zn-MTs protein concentrations in old and PTU mice. Therefore, free zinc ions are available for TTA efficiency after zinc supply. Thymus from old zinc-treated mice induces the same restoring effect when transplanted in Tx recipients. However, Tx mice display natural normalisation in MTmRNA and in nutritional–endocrine–immune profile in the long run. Therefore, Zn-MTs (I+II) are crucial in zinc homeostasis for endocrine–immune efficiency during the entire life assuming a role of potential and novel ‘biological clock of ageing’.


title: What is Ebola?

text: On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid‐September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter‐disciplinary and cross‐disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences.


title: A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

text: Abstract Background Radix Bupleuri (RB) has been widely used in Chinese Traditional Medicine for over 2000 years and is currently marketed in China as Chai-Hu-Shu-Gan tablets and Xiao-Yao-Wan tablets. Saikosaponins (SSs, especially SSa, SSc and SSd), as the major bioactive compounds in RB, represent anti-inflammatory, anti-tumor, anti-oxidant, anti-viral and hepatoprotective effects. Purpose To summarize recent findings regarding to the extraction, detection, biosynthesis, metabolism, pharmacological/toxicological effects of SSs. Methods Online academic databases (including PubMed, Google Scholar, Web of Science and CNKI) were searched using search terms of “Saikosaponin”, “Radix Bupleuri”, “Bupleurum” and combinations to include published studies of SSs primarily from 2003 to 2018. Several critical previous studies beyond this period were also included. Results 354 papers were found and 165 papers were reviewed. SSs have drawn great attention for their anti-inflammation, anti-viral and anti-cancer effects and contradictory roles in the regulation of cell apoptosis, oxidative stress and liver fibrosis. Meanwhile, increased risks of overdose-induced acute or accumulation-related chronic hepatotoxicity of SSs and RB have also been reported. However, underlying mechanisms of SSs bioactivities, the metabolism of SSs and bioactivities of SSs metabolites are largely unknown. Conclusion This comprehensive review of SSs provides novel insights and perspectives on the limitations of current studies and the importance of metabolism study and the dose-pharmacological/toxic relationship of SSs for the future discovery of SSs-based therapeutic strategies and clinical safe practice.


title: Managing Wildlife Faced with Pathogen Risks Involving Multi-Stable Outcomes

text: Most models designed to understand how to manage infected wildlife systems with bioeconomic multi-stability take the initial conditions as given, thereby treating pathogen invasion as unanticipated. We examine how ex ante management is an opportunity to influence the ex post conditions, which in turn affect the ex post optimal outcome. To capture these ex ante management choices, we extend the Poisson “collapse” model of Reed and Heras (Bull Math Biol 54:185–207, 1992) to allow for endogenous initial conditions and ex post multi-stability. We account for two uncertain processes: the introduction and establishment of the pathogen. Introduction is conditional on anthropogenic investments in prevention, and both random processes are conditional on how we manage the native population to provide natural prevention of invasion and natural insurance against establishment placing the system in an undesirable basin of attraction. We find that both multi-stability of the invaded system and these uncertainty processes can create economic non-convexities that yield multiple candidate solutions to the ex ante optimization problem. Additionally, we illustrate how the nature of natural protection against introduction and establishment risks can play an important role in the allocation of anthropogenic investments.


title: Inactivation of airborne bacteria using different UV sources: Performance modeling, energy utilization, and endotoxin degradation

text: Abstract Airborne bacteria-containing bioaerosols have attracted increased research attention on account of their adverse effects on human health. Ultraviolet germicidal irradiation (UVGI) is an effective method to inactivate airborne microorganisms. The present study models and compares the inactivation performance of three UV sources in the UVGI for aerosolized Escherichia coli. Inactivation efficiency of 0.5, 2.2 and 3.1 logarithmic order was obtained at an exposure UV dose of 370 J/m3 under UVA (365 nm), UVC (254 nm) and UVD (185 nm) sources, respectively. A Beer–Lambert law-based model was developed and validated to compare the inactivation performances of the UV sources, and modeling enabled prediction of inactivation efficiency and analysis of the sensitivity of several parameters. Low influent E. coli concentrations and high UV doses resulted in high energy consumption (EC). The change in airborne endotoxin concentration during UV inactivation was analyzed, and UVC and UVA irradiation showed no marked effect on endotoxin degradation. By contrast, both free and bound endotoxins could be removed by UVD treatment, which is attributed to the ozone generated by the UVD source. The results of this study can provide a better understanding of the air disinfection and airborne endotoxin removal processes.


title: The Demand for Hospital Emergency Services: Trends during the First Month of COVID-19 Response

text: INTRODUCTION: Since December 2019, more than 925,000 cases of COVID-19 have been reported worldwide, 8,251 cases in Portugal by the end of March. Previous studies related to the SARS pandemic showed a decrease up to 80% in the emergency care episodes. Hence, the objective of this study is to analyze the use of emergency services during the first pandemic month, compared to historical records. METHODS: Data from emergency episodes in mainland Portugal, from January 2014 to March 2020, were downloaded from the National Health Service (NHS) Transparency Portal and the NHS monitoring website. The evolution of emergency services from March to September 2020 was forecasted based on historical data from January 2014 to February 2020. Information for March 2020 was forecasted globally, by the Regional Health Administration (RHA) and Manchester Triage System (MTS). RESULTS: Compared with forecasted values, there was a 48% reduction in the number of emergency episodes in March 2020. In the analysis by the RHA, Alentejo had the smallest decrease in the number of episodes; interestingly, Alentejo is also the area with fewer COVID-19 cases in mainland Portugal. In the analysis by the MTS, the episodes classified as yellow showed the highest reduction (50%). For episodes classified as urgent, there is a difference of about 144,000 episodes during March 2020. DISCUSSION: The results of this preliminary study are aligned with the evidence produced for previous pandemics. Data about the use of emergency services, demographic and clinical characteristics of the episodes would be relevant to analyze this reduction. CONCLUSION: There was a significant drop in the number of emergency service use in March 2020, and although the causes of this reduction are not determined, the association between the beginning of the pandemic and the reduction of demand is evident. Understanding this phenomenon is crucial to plan interventions to avoid unnecessary morbidities or deaths, caused by a delayed visit to the emergency department.


title: Discussion on Etiology and Pathogenesis of Corona Virus Disease 2019 from “Cold-dampness and Insidious Dryness”

text: Abstract Based on the characteristics of the epidemic situation and the authors’ understanding of the related ancient books and documents, this paper explores the etiology and pathogenesis of Corona Virus Disease 2019 (COVID-19) from 5 aspects: abnormal climate in “warm winter”, unique geographical location, pathogenesis evolution of cold and dampness mixed with insidious dryness, transmission and change of “triple energizer” of toxic pathogens, and game between healthy Qi and toxic pathogens. Combined with the special treatment of traditional Chinese medicine (TCM), the purpose is to make a modest contribution to curbing the epidemic situation with TCM.


title: How hospitals in mainland China responded to the outbreak of COVID-19 using IT-enabled services: an analysis of hospital news webpages

text: OBJECTIVE: Many countries have implemented quarantine rules during the global outbreak of COVID-19. Understanding how hospitals can continue providing services in an effective manner under these circumstances is thus important. In this study, we investigate how information technology (IT) helped hospitals in mainland China better respond to the outbreak of the pandemic. MATERIALS AND METHODS: We conducted a content analysis of pages published on the websites of the Top 50 hospitals in mainland China between January 22, 2020 and February 21, 2020. In total, we analyzed 368 pages that the hospitals published during the initial days of the COVID-19 pandemic. The purpose was to identify common themes related to the utilization of IT by these hospitals in response to the pandemic’s outbreak. RESULTS: We identified five focal themes across the webpages published by the hospitals during our study period including (1) popular medical science education, (2) digitalized hospital processes, (3) knowledge management for medical professionals, (4) telemedicine, and (5) new IT initiatives for healthcare services. Our analysis revealed that Chinese hospitals spent greater effort in promoting popular medical science education in the initial stages of our study period and more on telemedicine in the latter stages. DISCUSSION: We propose a configurational approach for hospitals to design response strategies to pandemic outbreaks based on their available resources. CONCLUSION: Our study provides rich insights for hospitals to better utilize their IT resources and some recommendations for policy makers to better support hospitals in the future.


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title: Two complementary model-based methods for calculating the risk of international spreading of a novel virus from the outbreak epicentre. The case of COVID-19

text: We present two complementary model-based methods for calculating the risk of international spread of the novel coronavirus SARS-CoV-2 from the outbreak epicentre. One model aims to calculate the number of cases that would be exported from an endemic country to disease-free regions by travellers. The second model calculates the probability that an infected traveller will generate at least one secondary autochthonous case in the visited country. Although this paper focuses on the data from China, our methods can be adapted to calculate the risk of importation and subsequent outbreaks. We found an average R(0) = 5.31 (ranging from 4.08 to 7.91) and a risk of spreading of 0.75 latent individuals per 1000 travellers. In addition, one infective traveller would be able to generate at least one secondary autochthonous case in the visited country with a probability of 23%.


title: The Contribution of Ageing to Hospitalisation Days in Hong Kong: A Decomposition Analysis

text: Background: Ageing has become a serious challenge in Hong Kong and globally. It has serious implications for health expenditure, which accounts for nearly 20% of overall government expenditure. Here we assess the contribution of ageing and related factors to hospitalisation days in Hong Kong. We used hospital discharge data from all publicly funded hospitals in Hong Kong between 2001 and 2012. Methods: A decomposition method was used to examine the factors that account for the change of total hospitalisation days during the two periods, 2001-2004 and 2004-2012. The five factors include two demographic factors – population size and age-gender composition – and three service components – hospital discharge rate, number of discharge episodes per patient, and average length of stay (LOS) – which are all measured at age-gender group level. In order to assess the health cost burden in the future, we also project the total hospitalisation days up to 2041, for a range of scenarios. Results: During the decreasing period of hospitalisation days (2001-2004), the reduction of LOS contributed to about 60% of the reduction. For the period of increase (2004-2012), ageing is associated with an increase in total hospitalisation days of 1.03 million, followed by an increase in hospital discharge rates (0.67 million), an increase in the number of discharge episodes per patient (0.62 million), and population growth (0.43 million). The reduction of LOS has greatly offset these increases (-2.19 million days), and has become one of the most significant factors in containing the increasing number of hospitalisation days. Projected increases in total hospitalisation days under different scenarios have highlighted that the contribution of ageing will become even more prominent after 2022. Conclusion: Hong Kong is facing increasing healthcare burden caused by the rapid increase in demand for inpatient services due to ageing. Better management of inpatient services with the aim of increasing efficiency and reducing LOS, avoidable hospitalisation and readmission, without compromising patient satisfaction and quality of service, are crucial for containing the rapid and enormous increases in total hospitalisation days for Hong Kong. The results would be relevant to many rapidly ageing societies in this region.


title: The structural biology of PRRSV

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped, positive-sense single-stranded RNA virus belonging to the Arteriviridae family. Arteriviruses and coronaviruses are grouped together in the order Nidovirales, based on similarities in genome organization and expression strategy. Over the past decade, crystal structures of several viral proteins, electron microscopic studies of the virion, as well as biochemical and in vivo studies on protein–protein interactions have led to a greatly increased understanding of PRRSV structural biology. At this point, crystal structures are available for the viral proteases NSP1α, NSP1β and NSP4 and the nucleocapsid protein, N. The NSP1α and NSP1β structures have revealed additional non-protease domains that may be involved in modulation of host functions. The N protein forms a dimer with a novel fold so far only seen in PRRSV and other nidoviruses. Cryo-electron tomographic studies have shown the three-dimensional organization of the PRRSV virion and suggest that the viral nucleocapsid has an asymmetric, linear arrangement, rather than the isometric core previously described. Together, these studies have revealed a closer structural relationship between arteri- and coronaviruses than previously anticipated.


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title: Impact of Health on Particle Size of Exhaled Respiratory Aerosols: Case‐control Study

text: Individuals with viral infection could possibly emit an infectious aerosol. The distinction between exhaled breaths of infected and healthy individuals should facilitate an understanding of the airborne transmission of infections. In this context, the present study is aimed at distinguishing healthy individuals from symptomatic ones by the study of their exhaled breath. A setup composed of a modified hood connected to an electrical low pressure impactor, which allows for the study of a wide range of particle sizes (from 7 nm to 10 μm), has been developed in order to collect exhaled breaths. This setup has been used with seventy eight volunteers. The results obtained using Principal Component Analysis (PCA) showed that exhaled breaths of individuals without symptoms have statistical similarities and are different from those of individuals with symptoms. This separation was made by the greater proportional emission by individuals with symptoms of particles collected on stages 3 (D (50) = 0.09 μm), 6 (D (50 )= 0.38 μm), 8 (D (50) = 0.95 μm), 10 (D (50 )= 2.40 μm), and 12 (D (50 )= 4.02 μm) of the impactor. There was not a specific size distribution obtained for the individuals with symptoms. As a consequence, further research on the exhaled breath should be undertaken with symptomatic volunteers and would require the analysis of this wide range of particle sizes.


title: The Management of Pre-School Wheeze

text: Summary Wheeze, a common symptom in pre-school children, is a continuous high-pitched sound, with a musical quality, emitting from the chest during expiration. A pragmatic clinical classification is episodic (viral) wheeze and multiple-trigger wheeze. Diagnostic difficulties include other conditions that give rise to noisy breathing which could be misinterpreted as wheeze. Most preschool children with wheeze do not need rigorous investigations. Primary prevention is not possible but avoidance of environmental tobacco smoke exposure should be strongly encouraged. Bronchodilators provide symptomatic relief in acute wheezy episodes but the evidence for using oral steroids is conflicting for children presenting to the Emergency Department [ED]. Parent initiated oral steroid courses cannot be recommended. High dose inhaled corticosteroids [ICS] used intermittently are effective in children with frequent episodes of moderately severe episodic (viral) wheeze or multiple-trigger wheeze, but this associated with short term effects on growth and cannot be recommended as a routine. Maintenance treatment with low to moderate continuous ICS in pure episodic (viral) wheeze is ineffective. Whilst low to moderate dose regular ICS work in multi-trigger wheeze, the medication does not modify the natural history of the condition. Even if there is a successful trial of treatment with ICS, a break in treatment should be given to see if the symptoms have resolved or continuous therapy is still required. Maintenance as well as intermittent Montelukast has a role in both episodic and multi trigger wheeze. Good multidisciplinary support and education is essential in managing this common condition.


title: Identification of a 24-kDa Polypeptide Processed from the Coronavirus Infectious Bronchitis Virus 1a Polyprotein by the 3C-like Proteinase and Determination of Its Cleavage Sites

text: Abstract We report here the identification of a 24-kDa polypeptide in IBV-infected Vero cells by immunoprecipitation with a region-specific antiserum raised in rabbits against the IBV sequence encoded between nucleotides 10928 and 11493. Coexpression, deletion, and mutagenesis studies have demonstrated that this protein is encoded by ORF 1a from nucleotide 10915 to 11544 and is released from the 1a polyprotein by the 3C-like proteinase-mediated proteolysis. A previously predicted Q-S (Q3462S3463) dipeptide bond encoded by the IBV sequence from nucleotide 10912 to 10917 is identified as the N-terminal cleavage site, and a Q-N (Q3672N3673) dipeptide bond encoded by the IBV sequence between nucleotides 11542 and 11547 is identified as the C-terminal cleavage site of the 24-kDa polypeptide.


title: Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes

text: Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication.


title: Introduction to Tropical Medicine

text: Tropical medicine deals with infectious and noninfectious diseases geographically located between the tropics of Cancer and Capricorn. It encompasses diseases that result from poverty, poor sanitation, infrastructure, and inadequate health resources. Lack of availability of clean water and food made with unhygienic practices add to the morbidity of these diseases. The tropics are reeling under the onslaught of climate change, deforestation, and air, water, and soil pollution, which worsens an already fragile health system. This article provides an overview of the definition, classification, geophysical problems, syndromic approach to common tropical infections, diagnostic challenges in the tropics, and access to medicines.


title: Aerobic bacteriological studies on the respiratory tracts of apparently healthy and pneumonic camels (Camelus dromedaries) in selected districts of Afar Region, Ethiopia

text: A cross-sectional study was conducted to isolate and identify bacterial species from the respiratory tract of apparently healthy and pneumonic camels in Asayita and Dubti woredas in the Afar Region, Ethiopia. From a total of 74 lung tissue and 74 tracheal swab samples Staphylococcus aureus, 16.3%, Streptococcus equi subsp. equi, 13.0%, and Pasteurella multocida, 10.9%, were dominant isolates from pneumonic lungs; Escherichia coli, 12.7%, Proteus species, 10.9%, and Klebsiella pneumoniae, 9.1%, were the majority in the normal lungs. The majority of the isolates colonized both anatomical sites investigated. There was a statistically significant association between the health status of the camels as well as the anatomical site studied with the isolation rates of the major respiratory pathogens (p < 0.05). Furthermore, the isolates were susceptible to norfloxacin, streptomycin, and gentamicin but resistant to ampicillin and tetracycline on in vitro test. Further studies on the pathogenicity of the major isolates are recommended.


title: Étude prospective de l’écologie virale hivernale dans un service de réanimation pédiatrique

text: Résumé Le but de cette étude prospective était d’évaluer l’épidémiologie des virus respiratoires chez les enfants hospitalisés dans une unité de réanimation et de soins continus pédiatriques pendant 3 mois d’hiver, en 2012–2013. Ont été inclus tous les enfants admis en réanimation pédiatrique du centre hospitalier universitaire (CHU) de Caen et ayant bénéficié d’une recherche d’infection par un virus respiratoire à partir d’un prélèvement nasal analysé par amplification génique (PCR) multiplex. Sur 105 enfants admis, 84 répondaient aux critères d’inclusion. Trente-sept enfants présentaient un ou plusieurs symptômes respiratoires à l’admission. Cinquante-quatre échantillons étaient positifs (64,3 %) avec 70 virus détectés. Le virus dont la prévalence était la plus élevée était le virus respiratoire syncytial (VRS) (n =28 ; 40,0 %), suivi par le rhinovirus (n =24 ; 34,3 %). Parmi les enfants sans symptômes respiratoires, 42,6 % étaient infectés par un ou plusieurs virus. Aucune différence de durée d’hospitalisation, de durée de ventilation mécanique n’a été mise en évidence en fonction du virus détecté. La principale limite de cette étude est l’analyse par PCR, beaucoup plus sensible que d’autres méthodes de détection, notamment chez des sujets asymptomatiques sur le plan respiratoire. Cette étude révèle cependant un taux élevé d’infections respiratoires causées par des virus chez les enfants qui ne présentent pas de symptômes respiratoires à leur admission en unité de réanimation et soins continus. Elle suggère un intérêt du dépistage de ces infections virales à l’admission des enfants et un bénéfice à l’extension des mesures d’isolement pour tous les enfants en réanimation pédiatrique. Summary Introduction Viral respiratory infections are common in children, most of which are due to a virus. They can lead to serious infections, and these children may require treatment in a pediatric intensive care unit (PICU). This prospective study evaluated the epidemiology of respiratory viruses and associated illnesses among children hospitalized in a PICU during the three winter months of 2012–2013. Methods All the children admitted to the PICU, University Hospital of Caen, France, were included. Nasal swabs were collected and specimens were tested using a single real-time PCR (polymerase chain reaction). Results Of the 105 patients admitted to the PICU during the study period, 84 fulfilled the inclusion criteria. The “respiratory group” included 37 patients with respiratory symptoms at admission while the “nonrespiratory group” included 47 patients with no respiratory symptoms. The 84 nasal swabs collected included 54 that were considered positive (64.3%) and 70 viruses were detected. The most commonly detected virus was RSV (n =28; 40.0% positive samples), followed by HRV (n =24; 34.3%). Viruses were more frequently detected in the respiratory (86.5%) than in the nonrespiratory (42.6%) group (P <0.001). Statistical analysis by subgroups revealed that RSV infections were significantly more frequent in the respiratory group (54.1%) than in the nonrespiratory group (6.4%) (P <0.001). There was no difference for HRV (32.4% and 27.7%) or for the other viruses. No difference in duration of hospitalization or duration of mechanical ventilation was demonstrated depending on the virus detected. Discussion The use of the very sensitive multiplex PCR technique increased virus detection rates in both symptomatic and asymptomatic subjects. Conclusion We have confirmed the frequency of RSV infections in a PICU and found that many patients without respiratory symptoms have respiratory infections caused by viruses. The impact of these infections on patient outcome should now be analyzed in order to demonstrate the role played by respiratory viruses.


docid: gzivtsho

title: De novo transcriptome reconstruction and annotation of the Egyptian rousette bat

text: BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2124-x) contains supplementary material, which is available to authorized users.


title: Single amino acid substitution (G42E) in the receptor binding domain of mouse mammary tumour virus envelope protein facilitates infection of non-murine cells in a transferrin receptor 1-independent manner

text: BACKGROUND: Mouse mammary tumour virus (MMTV) is a betaretrovirus that infects rodent cells and uses mouse tranferrin receptor 1 (TfR1) for cell entry. Several MMTV strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. Furthermore, there have been reports that the continued passage of MMTV in heterologous cell lines gives rise to novel variants that are able to infect naive non-murine cells with higher efficiency than the parental virus. RESULTS: We show that MMTV(C3H), like other MMTV strains, that had undergone a number of replication cycles in non-murine cells displayed an increased replication kinetic, as compared to parental virus, when applied on naive human cells. Sequence analysis of several replication kinetic variants and the parental virus, together with calculation of the ratio of non-synonymous to synonymous mutations at individual codons, revealed that several regions within the viral genome were under strong positive selection pressure during viral replication in human cells. The mutation responsible, at least in part, for the phenotypic change was subsequently mapped to the segment of env encoding the receptor binding site (F(40)HGFR(44)). Introduction of the identified mutation, leading to single amino acid substitution (G42E), into egfp-containing recombinant MMTV virions enhanced their ability to bind to and infect human cells. Interestingly, neither the replication kinetic mutant nor the parental virus required human TfR1 for infection. Knock-out of TFR1 gene from the human genome did not decrease the susceptibility of Hs578T cells to virus infection. Furthermore, the expression of human TfR1, in contrast to mouse TfR1, did not enhance the susceptibility of MMTV-resistant Chinese hamster ovary cells. Thus, human TfR1 is dispensable for infection and another cell surface molecule mediates the MMTV entry into human cells. CONCLUSION: Taken together, our data explain the mechanism enabling MMTV to form ‘host-range variants’ in non-murine cells that has been known for a long time, the basis of which remained obscure. Our findings may expand our understanding of how viruses gain capability to cross species-specific barriers to infect new hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0168-2) contains supplementary material, which is available to authorized users.


title: COVID 19 and Ethnicity: Spot light on the global rheumatology issues in developing and developed countries

text: A key issue in the response to the coronavirus disease 2019 (COVID‐19) pandemic is the internationally recognised observation that COVID‐19 disproportionally affects the Black and Minority Ethnic Population (BAME) (1). We focus predominantly on the countries of the UK, USA, and India COVID‐19 rheumatology challenges and examples. This unprecedented public health crisis started in China in Dec 2019, following an infection caused by a novel coronavirus strain, named as SARS‐CoV2 (2). The World Health Organisation in March 2020 declared this public health emergency as a pandemic (2). COVID‐19 pandemic has moved from country to country peaking at different times despite implementation of strict preventive measures, including complete lock down periods with varied success. Case fatality and mortality rates have been highly variable across nations as well as different ethnic groups (3).


title: Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study

text: Abstract Background There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. Objectives In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Study design Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Results Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. Conclusions The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers.


Evaluation of endodontic competency in the COVID‐19 era: Problem, solution and results


docid: pnixdzec

title: Impact of Personal Protective Equipment on Surgical Performance During the COVID-19 Pandemic

text: BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has exposed surgeons to hazardous working conditions, imposing the need for personal protective equipment (PPE) use during surgery. The use of such equipment may affect their non-technical skills, augment fatigue, and affect performance. This study aimed to assess the surgeons’ perceptions of the impact of wearing PPE during emergency surgery throughout the pandemic. METHODS: An international cooperation group conducted an anonymous online survey among surgeons from over 30 countries, to assess perceptions about the impact of PPE use on non-technical skills, overall comfort, decision making, and surgical performance during emergency surgery on COVID-19 patients. RESULTS: Responses to the survey (134) were received from surgeons based on 26 countries. The vast majority (72%) were males. More than half of the respondents (54%) felt that their surgical performance was hampered with PPE. Visual impairment was reported by 63%, whereas 54% had communication impediments. Less than half (48%) felt protected with the use of PPE, and the same proportion perceived that the use of such equipment influenced their decision making. Decreased overall comfort was cited by 66%, and 82% experienced increased surgical fatigue. CONCLUSIONS: Surgeons perceived impediment for both visibility and communication, and other non-technical skills while using PPE on emergency surgery in COVID-19 patients. Their perceived lack of protection and comfort and increased fatigue may have inhibited their optimal surgical performance. More attention should be placed in the design of more user-friendly equipment, given the possibility of a second wave of the pandemic.