title: COVID-19: immunopathology and its implications for therapy

text: Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management.


title: Saturation Mutagenesis reveals that GLU54 of Norovirus 3C-like Protease is not Essential for the Proteolytic Activity

text: The norovirus 3C-like protease is a member of the chymotrypsin-like serine protease superfamily. Previous characterization of its crystal structure has implicated the Glu54–His30–Cys139 triad in the catalysis. In the present study, the Glu54 residue of the protease was subjected to site-saturation mutagenesis, with the result that nearly half of the mutants retained the significant proteolytic activity. It was suggested that a carboxylate at position 54 was not essential for the activity. The in vitro assays of the proteolysis revealed that most of Glu54 mutants retained relatively high proteolytic activity. When the Glu54 mutation was combined with the Ser mutation of the Cys139 residue, a nucleophile, only the Asp54 and Gln54 mutations showed proteolytic activity comparable to that of the Ser139 single mutant, suggesting that a hydrogen bond between Glu54 and His30 was critical in the Ser139 background. These results suggested that the mechanism of the proteolysis by the wild-type norovirus 3C-like protease was different from that of typical chymotrypsin-like serine proteases.


title: Covid-19

text: Besmetting met het coronavirus kan leiden tot de ziekte covid-19. In dit artikel een overzicht van symptomen, behandeling en verpleegkundige aandachtspunten.(*) De toets bij dit artikel levert 2 accreditatiepunten op.


title: Respiratory Tract Samples, Viral Load, and Genome Fraction Yield in Patients With Middle East Respiratory Syndrome

text: Background. Analysis of clinical samples from patients with new viral infections is critical to confirm the diagnosis, to specify the viral load, and to sequence data necessary for characterizing the viral kinetics, transmission, and evolution. We analyzed samples from 112 patients infected with the recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV). Methods. Respiratory tract samples from cases of MERS-CoV infection confirmed by polymerase chain reaction (PCR) were investigated to determine the MERS-CoV load and fraction of the MERS-CoV genome. These values were analyzed to determine associations with clinical sample type. Results. Samples from 112 individuals in which MERS-CoV was detected by PCR were analyzed, of which 13 were sputum samples, 64 were nasopharyngeal swab specimens, 30 were tracheal aspirates, and 3 were bronchoalveolar lavage specimens; 2 samples were of unknown origin. Tracheal aspirates yielded significantly higher MERS-CoV loads, compared with nasopharyngeal swab specimens (P = .005) and sputum specimens (P = .0001). Tracheal aspirates had viral loads similar to those in bronchoalveolar lavage samples (P = .3079). Bronchoalveolar lavage samples and tracheal aspirates had significantly higher genome fraction than nasopharyngeal swab specimens (P = .0095 and P = .0002, respectively) and sputum samples (P = .0009 and P = .0001, respectively). The genome yield from tracheal aspirates and bronchoalveolar lavage samples were similar (P = .1174). Conclusions. Lower respiratory tract samples yield significantly higher MERS-CoV loads and genome fractions than upper respiratory tract samples.


title: Chapter 9 Pregnancy and Neonatal Care of SCNT Animals

text: Since the birth of the first somatic cell nuclear transfer (SCNT) animal in 1996, SCNT has been successfully applied to produce live animals in many species, but its successful application in animal production has been hampered by heavy fetal and postnatal losses and widespread public concern. So far, cattle remain the species with the largest number of cloned animals born. Success in animal cloning relies not only on the skill of the micromanipulator, but also on integrated knowledge and expertise in the pathophysiology and biotechnology of reproduction, cell and molecular biology, biochemistry, embryology, neonatology and obstetrics, image diagnostics, internal medicine, and surgical procedures, among other complementary disciplines and areas of knowledge. This chapter addresses the care of SCNT individuals and their recipients. The health and care in cattle will be described first, as most information is available in this species. Recommendations regarding pigs and other species will follow.


Ode à nos Vieux en temps de Covid-19


title: Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV-2 RNA-Dependent RNA Polymerase

text: [Image: see text] Starting from late 2019, the coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures, and supporting apparatuses. Recently, because of its positive results in clinical trials, remdesivir was approved by the Food and Drug Administration to treat COVID-19 through Emergency Use Authorization. Here, we used molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). We first constructed the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identity of 95.8%). We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template. The putative binding structure was further optimized with molecular dynamics simulations. The resulting stable preinsertion state of remdesivir appeared to form hydrogen bonds with the RNA template when aligned with the newly solved cryo-EM structure of SARS-CoV-2 RdRp. The relative binding free energy between remdesivir and ATP was calculated to be −2.80 ± 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP. The ∼100-fold improvement in the K(d) from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site. Key residues D618, S549, and R555 are found to be the contributors to the binding affinity of remdesivir. These findings suggest that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA replication, with key residues also identified for future lead optimization and/or drug resistance studies.


title: The pervasive issue of racism and its impact on infertility patients: what can we do as reproductive endocrinologists?

text: Following the horrific events surrounding the death of George Floyd, we aim to shed some light on our perceptions of the pervasive issue of racism in America and how it impacts the work we do as reproductive endocrinologists. This issue is deeply rooted, and tackling it will involve a multifaceted approach. Ultimately, we are interested in starting this conversation and hope that our colleagues will not only acknowledge that there is a problem that requires immediate attention but will join us in providing sustainable solutions to it.


title: Emerging viral diseases of livestock in the developing world

text: Emerging and reemerging viral diseases of livestock and human beings are in sharp rise in recent years. Importantly, many of these viruses, including influenza, Hendra, Nipah and corona are of zoonotic importance. Several viral diseases of livestock such as bluetongue, peste des petits ruminants, camel pox, equine infectious anaemia, chicken anaemia and sheep-associated malignant catarrhal fever are crossing their traditional boundaries. Emergence of new serotypes and variant forms of viruses as in the case of blue tongue virus, avian infectious bronchitis virus, Newcastle disease virus adds additional level of complexity. The increased incidence of emerging and reemerging viral diseases could be attributed to several factors including deforestation and surge in direct contact of livestock and humans with wild animals and birds. This special issue of “Indian Journal of Virology” is focused on diverse aspects of above diseases: isolation and characterization of viruses, epidemiology, pathogenesis, diagnosis, prevention measures and vaccine development.


title: COVID-19 presenting as stroke

text: Abstract Objective Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 present with constitutional and respiratory symptoms, some patients present with atypical symptoms including gastrointestinal, cardiovascular, or neurological symptoms. Here we present a series of four COVID-19 patients with acute stroke as a presenting symptom. Methods We searched the hospital databases for patients presenting with acute strokes and suspected COVID-19 features. All patients that had imaging confirmed strokes and PCR confirmed COVID-19 were included in the study. Patients admitted to the hospital with PCR confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained. Results We identified four patients presenting with imaging confirmed acute strokes and PCR confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course. Conclusions Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed for a comprehensive understanding of the neurological pathology of COVID-19 and its effects on the nervous system.


title: Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus ‐2 (SARS‐CoV‐2)

text: Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement by SARS‐CoV‐2. This article is protected by copyright. All rights reserved.


title: Etiology of Community-Acquired Pneumonia: Increased Microbiological Yield with New Diagnostic Methods

text: BACKGROUND: The microbial etiology of community-acquired pneumonia (CAP) is still not well characterized. During the past few years, polymerase chain reaction (PCR)-based methods have been developed for many pathogens causing respiratory tract infections. The aim of this study was to determine the etiology of CAP among adults—especially the occurrence of mixed infections among patients with CAP—by implementing a new diagnostic PCR platform combined with conventional methods. METHODS: Adults admitted to Karolinska University Hospital were studied prospectively during a 12-month period. Microbiological testing methods included culture from blood, sputum, and nasopharyngeal secretion samples; sputum samples analyzed by real-time quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed by use of PCR; serological testing for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and viruses common in the respiratory tract; and urine antigen assays for detection of pneumococcal and Legionella pneumophila antigens. RESULTS: A microbial etiology could be identified for 67% of the patients (n = 124). For patients with complete sampling, a microbiological agent was identified for 89% of the cases. The most frequently detected pathogens were S. pneumoniae (70 patients [38]) and respiratory virus (53 patients [29]). Two or more pathogens were present in 43 (35%) of 124 cases with a determined etiology. CONCLUSIONS: By supplementing traditional diagnostic methods with new PCR-based methods, a high microbial yield was achieved. This was especially evident for patients with complete sampling. Mixed infections were frequent (most commonly S. pneumoniae together with a respiratory virus).


title: Characterization of Rv0888, a Novel Extracellular Nuclease from Mycobacterium tuberculosis

text: Bacterial extracellular nucleases play important roles in virulence, biofilm formation, utilization of extracellular DNA as a nutrient, and degradation of neutrophil DNA extracellular traps. However, there is no current data available for extracellular nucleases derived from M. tuberculosis. Herein, we have identified and characterized Rv0888, an extracellular nuclease in M. tuberculosis. The protein was overexpressed in E. coli, and the purified Rv0888 protein was found to require divalent cations for activity, with an optimal temperature and pH of 41 °C and 6.5, respectively. Further results demonstrated that Rv0888 nuclease activity could be inhibited by four Chinese medicine monomers. Based on sequence analysis, Rv0888 nuclease exhibited no homology with any known extracellular nucleases, indicating that Rv0888 is a novel nuclease. Site-directed mutagenesis studies revealed that the H353, D387, and D438 residues play catalytic roles in Rv0888. In vivo infection studies confirmed that Rv0888 is required for infection and is related to pathogenicity, as the persistent ability of recombinant Mycobacterium smegmatis (rMS) Rv0888NS/MS and Rv0888S/MS is significantly higher than pMV262/MS in the lung tissue, and the Rv0888NS/MS and Rv0888S/MS could produce pathological changes in the mice lung. These results show that Rv0888 is relevant to pathogenicity of M. tuberculosis.


title: Validation of a SARS-CoV-2 spike protein ELISA for use in contact investigations and sero-surveillance

text: Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed to have had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population.


title: A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C

text: BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating “enediynyl amino acid” (Eda) moiety. “Eda” was inserted between P1 and P1′ residues of hfurin(98–112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) ∼40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) ∼193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases.


title: Roles of the antioxidant properties of icariin and its phosphorylated derivative in the protection against duck virus hepatitis

text: BACKGROUND: Duck viral hepatitis (DVH) is an acute disease of young ducklings with few convenient and effective veterinary drugs to treat. In pathology, present study mainly focused on the immune mechanism, but very few studies have concerned with the role of oxidative stress in the pathogenesis of DVH. To study the antioxidative and hepatoprotective effects of icariin and its phosphorylated derivative against DVH, we prepared phosphorylated icariin (p-icariin) using the sodium trimetaphosphate–sodium tripolyphosphate method. Ducklings were drunk with icariin and p-icariin after being challenged with duck hepatitis virus 1 (DHV-1). We recorded the number of dead ducklings, gross pathological changes in the liver, and changes in indices of oxidative stress and liver injury. The correlations between these indices were also analyzed. RESULTS: Exposure to DHV-1 induced significant oxidative damage in ducklings. Administration of icariin or p-icariin attenuated liver pathological injury and significantly increased the survival rate, with better outcomes in ducklings treated with p-icariin than in those treated with icariin. Icariin and p-icariin also attenuated the changes in oxidative stress and liver injury. We found positive correlations among indices of oxidative stress (malondialdehyde and inducible nitric oxide synthase) and liver injury (alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), suggesting that DHV-1 causes significant oxidative damage, which is related to the extent of hepatic injury. CONCLUSIONS: Icariin and p-icariin improved the survival and attenuated oxidative stress and liver dysfunction induced by DHV-1. These outcomes were better in ducklings treated with p-icariin than in those treated by icariin. The clinical effects of both components were related to their antioxidant activities.


title: Urban disaster preparedness of Hong Kong residents: A territory-wide survey

text: Abstract Objective To assess the state of community disaster preparedness of Hong Kong residents and to identify factors associated with adequate preparedness behaviors. Design A cross-sectional survey using random Global Positioning System (GPS) spatial sampling conducted from the 8 August 2015 to 6 September 2015. Participants Hong Kong residents aged 18 years or more. Method A 19-item questionnaire was developed to assess respondents’ preparedness information acquisition, communication plan, evacuation strategies, first-aid and disaster knowledge, financial resilience, and preparedness behaviors. In total, 1023 residents were interviewed at 516 GPS locations. Multiple logistic regression was used to identify factors associated with preparedness behaviors, defined as having an evacuation kit in our study. Results Television remains the key information source, both before and during disaster, with young respondents also favoring social media and the internet and elder residents preferring television and radio. Many respondents did not have adequate first-aid knowledge and few showed correct responses to a typhoon warning signal. Only 39.4% had an evacuation kit. In logistic regression, correct responses to first aid questions and a typhoon warning signal were significantly associated with kit preparation (OR 2.023, 95% CI 1.233−3.318, p=0.005). Residents with elderly household member(s) were significantly less likely to do so (OR 0.554, 95% CI 0.333−0.922, p=0.023). Conclusions Community resilience-building programs should tailor information provision to different age groups with a focus on the family caregivers of elderly residents. There is a need to promulgate first-aid training and disaster education in the community.


title: Telemedicine for parkinsonism: A two-step model based on the COVID-19 experience in Milan, Italy

text: • Lifting lockdown restrictions (‘Phase Two’) may be more dangerous than ‘Phase One’ of COVID-19 for patients with parkinsonism traveling to in-person care sites. • During the crisis, a telemedicine program for patients with parkinsonism was boosted in Milan, Italy. • We propose a two-step model integrating a telenursing forward triage followed by a video-consultation by experienced neurologists.


title: Immunosuppressive agents for dermatological indications in the ongoing COVID 19 pandemic: rationalizing use and clinical applicability

text: The ongoing COVID 19 epidemic has brought to the fore many concerns related to use of immunosuppressive agents (ISAs) in dermatology. While it is unclear whether the patients on ISAs for skin conditions are more prone to develop COVID 19, and what impact the ISA may have on the clinical outcome if a patient does get infected, rationalizations based on the specific immune effects of each drug, and existing literature on incidence of various infections with each, are possible. In this review, we provide the readers with practically useful insights into these aspects, related to the conventional ISAs, and briefly mention the clinical outcome data available on related scenarios from other patient groups so far. In the end, we have attempted to provide some clinically useful points regarding practical use of each dermatologically relevant conventional ISA in the current scenario. This article is protected by copyright. All rights reserved.


title: The role of children in the transmission of mild SARS‐CoV‐2 infection

text: We thank dr. Ludvigsson (1) on his effort to improve knowledge on SARS-CoV-2 infection in children. In trying to understand the spread of the disease, one of the most notable features is that only a small number of severe SARS-CoV-2 infections have involved children. The huge age disparity in disease severity might be one of the most stringent fundamental knowledge gaps.


Clinical implications of the COVID‐19 pandemic on dental education


title: Serum protein electrophoretic profile in diarrheic neonatal calves

text: The electrophoretic profile of clinically healthy newborn calves and calves with neonatal diarrhea was compared. Blood samples were collected at 3 and 10 days of age from 11 calves that remained clinically healthy throughout the study period and 14 calves with diarrhea. A significant reduction in the gamma globulins was observed in the diarrheic calves that can be attributed to the transfer of serum immunoglobulins, to the intestinal lumen to counteract the infection. Moreover, a significant increase in the albumin was observed in this group between the sampling days that is mainly attributed to the relative reduction of the gamma globulin fraction.


title: Religious Nationalism and the Coronavirus Pandemic: Soul-Sucking Evangelicals and Branch Covidians Make America Sick Again

text: This article investigates the response to the coronavirus crisis by Evangelical Christian nationalists in the USA. The article outlines the curious mediaverse of religious nationalism—its post-truth and fake news aspects in particular—links religious nationalism to American exceptionalism, and analyzes conflicts between secular and religious authorities. Drawing upon some lessons from the past, the article addresses the wider implications of Christian nationalism on American politics, and capitalist ideology, as it has been played out virally in the corporate media. The article shows that the ideological underpinnings of evangelical Christianity prevent its proponents from understanding the virus in an historical and materialist manner and points toward more epistemically sound approaches to relationships between science and religion. It concludes that privatization, austerity capitalism, and ‘gig economy’ need to be replaced by socialist alternatives and seeks inspiration in theory and practice of Marxism and South American liberation theology.


title: Biophysical Reviews—Quantitative analysis of biological phenomenon

text: This Editorial first describes the articles constituting the current Issue (Volume 12 Issue 3). It then goes on to outline the formal invitation procedure for those interested in submitting a review article to the journal. The Editorial concludes by describing the nomination process for the 2021 Michèle Auger Award for Young Scientists’ Independent Research.


The risk of transmission of a viral haemorrhagic fever infection in a United Kingdom laboratory


title: Inter‐country Distancing, Globalization and the Coronavirus Pandemic

text: Originating in China, the Coronavirus has reached the world at different speeds and levels of strength. This paper provides an initial understanding of some driving factors and their consequences. Since transmission requires people, the human factor behind globalization is essential. Globalization, a major force behind global wellbeing and equality, is highly associated with this factor. The analysis investigates the impact globalization has on the speed of initial transmission to a country and on the scale of initial infections in the context of other driving factors. Our cross‐country analysis finds that measures of globalization are positively related to the spread of the virus, both in speed and scale. However, the study also finds that globalized countries are better equipped to keep fatality rates low. The conclusion is not to reduce globalization to avoid pandemics, but to better monitor the human factor at the outbreak and mobilize collaboration forces to curtail diseases.


title: Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource

text: The Poxvirus Bioinformatics Resource Center (PBRC) has been established to provide informational and analytical resources to the scientific community to aid research directed at providing a better understanding of the Poxviridae family of viruses. The PBRC was specifically established as the result of the concern that variola virus, the causative agent of smallpox, as well as related viruses, might be utilized as biological weapons. In addition, the PBRC supports research on poxviruses that might be considered new and emerging infectious agents such as monkeypox virus. The PBRC consists of a relational database and web application that supports the data storage, annotation, analysis and information exchange goals of the project. The current release consists of over 35 complete genomic sequences of various genera, species and strains of viruses from the Poxviridae family. Sequence and annotation information for these viruses has been obtained from sequences publicly available from GenBank as well as sequences not yet deposited in GenBank that have been obtained from ongoing sequencing projects. In addition to sequence data, the PBRC provides comprehensive annotation and curation of virus genes; analytical tools to aid in the understanding of the available sequence data, including tools for the comparative analysis of different virus isolates; and visualization tools to help better display the results of various analyses. The PBRC represents the initial development of what will become a more comprehensive Viral Bioinformatics Resource Center for Biodefense that will be one of the National Institute of Allergy and Infectious Diseases' ‘Bioinformatics Resource Centers for Biodefense and Emerging or Re-Emerging Infectious Diseases’. The PBRC website is available at http://www.poxvirus.org.


title: Excess Out-Of-Hospital Mortality and Declining Oxygen Saturation: The Sentinel Role of EMS Data in the COVID-19 Crisis in Tijuana, Mexico

text: OBJECTIVE: Emergency medical services (EMS) may serve as a key source of real-time data about the evolving health of COVID-19 affected populations, especially in low-and-middle-income countries (LMICs) with less rapid and reliable vital statistic registration systems. Although official COVID-19 statistics in Mexico report almost exclusively in-hospital mortality events, excess out-of-hospital mortality has been identified in other settings, including one EMS study in Italy that showed a 58% increase. EMS and hospital reports from several countries have suggested that silent hypoxemia—low oxygen saturation (SpO2) in the absence of dyspnea—is associated with COVID-19 outbreaks. It is unclear, however, how these phenomena can be generalized to LMICs. We assess how EMS data can be used in a sentinel capacity in Tijuana, a city on the Mexico-United States border with earlier exposure to COVID-19 than many LMIC settings. METHODS: We calculated numbers of weekly out-of-hospital deaths and respiratory cases seen by EMS in Tijuana, and estimate the difference between peak-epidemic rates (during April 14(th)-May 11(th)) and forecasted 2014–2019 trends. Results were compared with official COVID-19 statistics, stratified by neighborhood socioeconomic status (SES), and examined for changing demographic or clinical features, including mean (SpO2). RESULTS: An estimated 194.7 (95%CI: 135.5–253.9) excess out-of-hospital deaths events occurred, representing an increase of 145% (70%−338%) compared to forecasted trends. During the same window, only 8 COVID-19-positive, out-of-hospital deaths were reported in official statistics. This corresponded with a rise in respiratory cases of 274% (119%−1142%), and a drop in mean SpO2 to 77.7%, from 90.2% at baseline. The highest out-of-hospital death rates were observed in low-SES areas, although respiratory cases were more concentrated in high-SES areas. CONCLUSIONS: EMS systems may play an important sentinel role in monitoring excess out-of-hospital mortality and other trends during the COVID-19 crisis in LMICs. Using EMS data, we observed increases in out-of-hospital deaths in Tijuana that were nearly threefold greater magnitude than increases reported using EMS data in Italy. Increased testing in out-of-hospital settings may be required to determine if excess mortality is being driven by COVID-19 infection, health system saturation, or patient avoidance of healthcare. We also found evidence of worsening rates of hypoxemia among respiratory patients seen by EMS, suggesting a rise in silent hypoxemia, which should be met with increased detection and clinical management efforts. Finally, we observed that social disparities in out-of-hospital death that warrant monitoring and amelioration.


title: Knowledge mapping of tourism demand forecasting research

text: Utilizing a scientometric review of global trends and structure from 388 bibliographic records over two decades (1999–2018), this study seeks to advance the building of comprehensive knowledge maps that draw upon global travel demand studies. The study, using the techniques of co-citation analysis, collaboration network and emerging trends analysis, identified major disciplines that provide knowledge and theories for tourism demand forecasting, many trending research topics, the most critical countries, institutions, publications, and articles, and the most influential researchers. The increasing interest and output for big data and machine learning techniques in the field were visualized via comprehensive knowledge maps. This research provides meaningful guidance for researchers, operators and decision makers who wish to improve the accuracy of tourism demand forecasting.


title: Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century

text: Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM(2.5)) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM(2.5) concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM(2.5). In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future.


title: Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology

text: We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos. The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses.


title: Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus

text: Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). We report on the distribution and viral load of SARS-CoV in multiple organ samples from patients who died of SARS during the Toronto outbreak. SARS-CoV was detected in lung (100%), bowel (73%), liver (41%), and kidney (38%) in 19 patients who died of SARS, with the highest viral loads observed in lung (1.0 × 10(10) copies/g) and bowel (2.7 × 10(9) copies/g). Fatal SARS was associated with multiorgan viral dissemination in a distribution that has implications for disease manifestation, viral shedding, and transmission.


title: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019–2020

text: Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019–2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.


title: Arterial hypertension and the risk of severity and mortality of COVID-19

text: We have read with great interest the recently published study from Guan et al. [1] entitled Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. To the best of our knowledge this is the first large scale study that focuses on independent clinical risk factors associated with a composite outcome (death, use of ventilator or ICU requirement), using a Cox regression model.


COVID-19: What are the challenges for NHS surgery?


title: Infection par le SARS-CoV-2 chez les femmes enceintes. État des connaissances et proposition de prise en charge. CNGOF

text: Résumé Un nouveau coronavirus (SARS-CoV-2) mis en évidence en fin d’année 2019 en Chine se diffuse à travers tous les continents. Le plus souvent à l’origine d’un syndrome infectieux sans gravité, associant à différents degrés des symptômes bénins (fièvre, toux, myalgies, céphalées et éventuels troubles digestifs) le SARS-Covid-2 peut être à l’origine de pathologies pulmonaires graves et parfois de décès. Les données sur les conséquences pendant la grossesse sont limitées. Les premières données chinoises publiées semblent montrer que les symptômes chez la femme enceinte sont les mêmes que ceux de la population générale. mais il y a un risque qu'il y ai plus de formes graves. Il n’y a pas de cas de transmission maternofœtale intra utérine mais des cas de nouveau-nés infectés précocement font penser qu’il pourrait y avoir transmission verticale per-partum ou néonatale. Une prématurité induite et des cas de détresses respiratoires chez les nouveau-nés de mères infectées ont été décrits. La grossesse est connue comme une période plus à risque pour les conséquences des infections respiratoires, comme pour la grippe, il parait donc important de dépister le Covid-19 en présence de symptômes et de surveiller de façon rapprochée les femmes enceintes infectées. Dans ce contexte d’épidémie de SARS-Covid-2, les sociétés savantes de gynécologie-obstétrique, d’infectiologie et de néonatalogie ont proposé un protocole français de prise en charge des cas possibles et avérés de SARS-Covid-2 chez la femme enceinte. Ces propositions peuvent évoluer de façon quotidienne avec l’avancée de l’épidémie et des connaissances chez la femme enceinte. Abstract A new coronavirus (SARS-CoV-2) highlighted at the end of 2019 in China is spreading across all continents. Most often at the origin of a mild infectious syndrome, associating mild symptoms (fever, cough, myalgia, headache and possible digestive disorders) to different degrees, SARS-Covid-2 can cause serious pulmonary pathologies and sometimes death. Data on the consequences during pregnancy are limited. The first Chinese data published seem to show that the symptoms in pregnant women are the same as those of the general population. There are no cases of intrauterine maternal-fetal transmission, but cases of newborns infected early suggest that there could be vertical perpartum or neonatal transmission. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. Pregnancy is known as a period at higher risk for the consequences of respiratory infections, as for influenza, so it seems important to screen for Covid-19 in the presence of symptoms and to monitor closely pregnant women. In this context of the SARS-Covid-2 epidemic, the societies of gynecology-obstetrics, infectious diseases and neonatalogy have proposed a French protocol for the management of possible and proven cases of SARS-Covid-2 in pregnant women. These proposals may evolve on a daily basis with the advancement of the epidemic and knowledge in pregnant women. Subsequently, an in-depth analysis of cases in pregnant women will be necessary in order to improve knowledge on the subject.


title: Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement

text: The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8-cineole, against certain respiratory infection-causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry. A micro-well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 μg/ml, while the values of the two constituents were between 130 and 200 μg/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 μg/mouse) and grandisol (135 μg/mouse) significantly reduced the number of viable bacterial cells in the lungs (P<0.01). However, intake of 100 μg/mouse of essential oil or grandisol 135 μg/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly inhibit the growth of different bacterial strains.


title: COVID-19: POSTMORTEM DIAGNOSTIC AND BIOSAFETY CONSIDERATIONS

text: As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (e.g. cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with—but not of—COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there are a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for ME/C offices encountering COVID-19 at autopsy.


title: Chapter 101 Middle Ear and Eustachian Tube Mucosal Immunology

text: Abstract Mucosal immune responses within the middle ear and eustachian tube generally provide an effective and efficient response to the presence of microbial pathogens, with approximately 80% of clinically recognizable middle ear infections resolved within 7days. Particularly for young children aged less than 3years of age, the proximity and direct connection of the middle ear, via the eustachian tube, to the nasopharynx provide increased risk of commensal bacteria and upper respiratory tract viruses infecting the middle ear. Mucosal immunological defense in the middle ear and eustachian tube utilizes a number of mechanisms, including physicochemical barriers of mucus and the mucosal epithelial cells and innate immune responses such as inflammation, cellular infiltration, effusion, and antimicrobial protein secretions, in addition to adaptive host immune responses. Recent advances in otopathogen recognition via microbial pattern recognition receptors and elucidation of complex signaling cascades have improved understanding of the coordination and regulation of the middle ear mucosal response. These advances support vaccine development aiming to reduce the risk of otitis media in children.


title: Chest CT imaging signature of COVID-19 infection: in pursuit of the scientific evidence

text: Abstract Background Chest computed tomography (CT) may be used for the diagnosis of Corona virus disease 2019 (COVID-19), but clear scientific evidence is lacking. Therefore, we systematically reviewed and meta-analyzed the chest CT imaging signature of COVID-19. Methods A systematic literature search was performed for original studies on chest CT findings in patients with COVID-19. Methodological quality of studies was evaluated. Pooled prevalences of chest CT findings were calculated using a random effects model in case of between-study heterogeneity (predefined as I2≥50), otherwise a fixed effects model was used. Results Twenty-eight studies were included. Median number of COVID-19 patients per study was 124 (range 50-476), comprising a total of 3,466 patients. Median prevalence of symptomatic patients was 99% (range >76.3%-100%). 27/28 (96%) of studies had a retrospective design. Methodological quality concerns were present with either risk of or actual referral bias (13 studies), patient spectrum bias (8 studies), disease progression bias (26 studies), observer variability bias (27 studies), and test review bias (14 studies). Pooled prevalence was 10.6% for normal chest CT findings. Pooled prevalences were 90.0% for posterior predilection, 81.0% for ground-glass opacity, 75.8% for bilateral abnormalities, 73.1% for left lower lobe involvement, 72.9% for vascular thickening, and 72.2% for right lower lobe involvement. Pooled prevalences were 5.2% for pleural effusion, 5.1% for lymphadenopathy, 4.1% for airway secretions/tree-in-bud sign, 3.6% for central lesion distribution, 2.7% for pericardial effusion, and 0.7% for cavitation/cystic changes. Pooled prevalences of other CT findings ranged between 10.5%-63.2%. Conclusion Studies on chest CT findings in COVID-19 suffer from methodological quality concerns. More high-quality research is necessary to establish diagnostic CT criteria for COVID-19. Based on the available evidence that requires cautious interpretation, several chest CT findings appear to be suggestive of COVID-19, but normal chest CT findings do not exclude COVID-19, even not in symptomatic patients.


title: Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans

text: RNA viruses are proficient at switching to novel host species due to their fast mutation rates. Implicit in this assumption is the need to evolve adaptations in the new host species to exploit their cells efficiently. However, SARS-CoV-2 has required no significant adaptation to humans since the pandemic began, with no observed selective sweeps to date. Here we contrast the role of positive selection and recombination in the Sarbecoviruses in horseshoe bats to SARS-CoV-2 evolution in humans. While methods can detect some evidence for positive selection in SARS-CoV-2, we demonstrate these are mostly due to recombination and sequencing artefacts. Purifying selection is also substantially weaker in SARS-CoV-2 than in the related bat Sarbecoviruses. In comparison, our results show evidence for positive, specifically episodic selection, acting on the bat virus lineage SARS-CoV-2 emerged from. This signature of selection can also be observed among synonymous substitutions, for example, linked to ancestral CpG depletion on this bat lineage. We show the bat virus RmYN02 has recombinant CpG content in Spike pointing to coinfection and evolution in bats without involvement of other species. Our results suggest the non-human progenitor of SARS-CoV-2 was capable of human-human transmission as a consequence of its natural evolution in bats.


title: Regulation of cell volume and water transport – An old fundamental role of the renin angiotensin aldosterone system components at the cellular level

text: The expression and the role of renin angiotensin aldosterone system (RAAS) components on regulation of cell volume and water transport on vertebrates and invertebrates were reviewed. The presence of these components even in simple organisms like leeches and their relevance for the control of cellular volume and water transport supports the view that the expression of these components, at cellular level, is an acquisition which was preserved throughout evolution.


title: Public Attitudes, Behaviors, and Beliefs Related to COVID-19, Stay-at-Home Orders, Nonessential Business Closures, and Public Health Guidance — United States, New York City, and Los Angeles, May 5–12, 2020

text: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to be transmitted mainly by person-to-person contact (1). Implementation of nationwide public health orders to limit person-to-person interaction and of guidance on personal protective practices can slow transmission (2,3). Such strategies can include stay-at-home orders, business closures, prohibitions against mass gatherings, use of cloth face coverings, and maintenance of a physical distance between persons (2,3). To assess and understand public attitudes, behaviors, and beliefs related to this guidance and COVID-19, representative panel surveys were conducted among adults aged ≥18 years in New York City (NYC) and Los Angeles, and broadly across the United States during May 5-12, 2020. Most respondents in the three cohorts supported stay-at-home orders and nonessential business closures* (United States, 79.5%; New York City, 86.7%; and Los Angeles, 81.5%), reported always or often wearing cloth face coverings in public areas (United States, 74.1%, New York City, 89.6%; and Los Angeles 89.8%), and believed that their state's restrictions were the right balance or not restrictive enough (United States, 84.3%; New York City, 89.7%; and Los Angeles, 79.7%). Periodic assessments of public attitudes, behaviors, and beliefs can guide evidence-based public health decision-making and related prevention messaging about mitigation strategies needed as the COVID-19 pandemic evolves.


title: SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway

text: SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.


title: T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves

text: The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA(+)CD62L(+)), central memory (CM, CD45RA(−)CD62L(+)), effector memory (EM, CD45RA(−)CD62L(−)), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA(+)CD62L(−)) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3(+)CD8(+) in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA(+)CD62L(−)CD3(+)CD8(+) and CD3(+)CD4(+) was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA(+)CD62L(−)CD3(+)CD8(+) cells (p = 0.006). Also the relative number of CD3(+)CD4(+) cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.


COVID-19 and surgical activities


What’s Important: What Is Our Role in the COVID-19 Pandemic?


title: “Cell Phone Acne” Epidemic during COVID‐19 Pandemic

text: As the world plunges into the longest and the biggest lockdown in world’s history, most of us are turning towards an increased use of mobile phones as the most convenient way to stay connected. However, this convenience is also taking a toll on the overall skin health, particularly in the patients of acne.


title: Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020

text: A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9–32%).


title: The Effects of an Online Mind-Body Training Program on Stress, Coping Strategies, Emotional Intelligence, Resilience and Psychological State

text: The goal of this study was to evaluate the effects of an online mind-body training (MBT) program on participants’ stress, anger, coping strategies, emotional intelligence, resilience, and positive and negative affect. Forty-two healthy women participated in an online MBT program for approximately 8–10 minutes a day for 8 weeks; a control group of 45 healthy women did not participate in the program. Self-report psychological questionnaires were administered before the beginning of the program and at 4 and 8 weeks following its onset. Data from the MBT group and the control group were compared using repeated measures ANOVA and Student’s t-tests. Significant time x group interaction effects were found with respect to stress, coping strategies, anger, emotional intelligence, negative affect and resilience. These results demonstrate beneficial effects of the online MBT program and significant improvements in the psychological capabilities of participants compared with the control group. The effects of online MBT program were similar with those of the previous offline MBT in psychological aspects, suggesting further studies for neuroscientific evidence related stress and emotion of online MBT effects.


title: Pharmacists Roles and Responsibilities During Epidemics and Pandemics in Saudi Arabia: An Opinion Paper from the Saudi Society of Clinical Pharmacy

text: Abstract On the 2nd of March 2020, Kingdom of Saudi Arabia confirmed its first case of the coronavirus's newly emerging strain, causing coronavirus disease 2019 (COVID-19). Soon after, the number of confirmed cases started to increase nationally. In light of the emerging outbreak, all healthcare professionals, including pharmacists, began to function with maximum capacity and efforts. The Saudi Society of Clinical Pharmacy (SSCP) acknowledges the substantial impact pharmacists can play during outbreaks. Based on the existing scientific knowledge during this outbreak, the SSCP established an expert writing task force to conceptualize and draft the proposed recommendations that highlights the roles and responsibilities of pharmacists during epidemics and pandemics. The SSCP writing task force issued 28 recommendations. In addition to the national and institutional guidelines, these recommendations could serve as guidance for the impacted entities.


title: Pathophysiology of diarrhoea induced by a combined infection with transmissible gastroenteritis virus and enterotoxigenic Escherichia coli in newly-weaned piglets and the effect of flurbiprofen treatment

text: In newly-weaned 3–4 week old piglets (n=29) diarrhoea (100%) and vomiting (65%) were induced by inoculation with transmissible gastroenteritis virus and enterotoxigenic E. coli strains (0(149):K(91):K(88ac); LT, STa and STb enterotoxin positive). This combined infection resulted in pronounced mortality within 7 days. During this period the piglets had decreases in body weight, arterial pressure and leucocyte count and increases in heart rate and in total plasma protein concentration. The plasma pH and lactic acid concentration decreased, whereas the values for pO(2), pCO(2) and frequency of respiration did not change significantly. No significant changes in the serum concentrations of potassium, chloride or calcium were observed, whereas sodium concentration revealed a transient increase. In shocked and dying piglets an increase in haematocrit was observed, whereas base excess and bicarbonate concentration decreased. Flurbiprofen, a potent non-steroidal anti-inflammatory drug, administered intramuscularly on 3 successive days following the combined infection at a dosage of 1 mg/kg/12 h was without beneficial effect on diarrhoea or mortality.


title: The characteristics and outcomes of 681 severe cases with COVID-19 in China

text: PURPOSE: To clarify the epidemiological, clinical, and therapeutic features of patients with severe COVID-19. METHODS: In this study, we enrolled 681 patients with confirmed cases of severe COVID-19. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected. RESULTS: The median age of the study participants was 65 years, 53.2% were male, and 104 (15.3%) died. Age, Neutrophil-To-Lymphocyte Ratio (NLR), acute myocardial injury, and levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD3 T cells counts were independently and negatively associated with death, while arbidol and ribavirin were protective from death. The combination of NLR and acute myocardial injury on admission (AUC = 0.914) predicted mortality better than NLR, CRP, LDH, and acute myocardial injury. There were 312 (45.8%) patients with cardiovascular disease, of whom 23.4% died. β-blockers, ACEI/ARB, arbidol, and ribavirin might have a beneficial effect for severe COVID-19 patients with cardiovascular disease. CONCLUSION: The combination of NLR and acute myocardial injury on admission was highly predictive of mortality and survival. Clinicians should adopt more aggressive strategies for patients with a high NLR (>6.66) combined with myocardial injury. β-blockers and ACEI/ARB, as well as arbidol and ribavirin, were effective in COVID-19 patients with cardiovascular disease.


title: Response to the challenges of pandemic H1N1 in a small island state: the Barbadian experience

text: BACKGROUND: Having been overwhelmed by the complexity of the response needed for the severe acute respiratory syndrome (SARS) epidemic, public health professionals in the small island state of Barbados put various measures in place to improve its response in the event of a pandemic METHODS: Data for this study was collected using Barbados’ National Influenza Surveillance System, which was revitalized in 2007. It is comprised of ten sentinel sites which send weekly notifications of acute respiratory illness (ARI) and severe acute respiratory illness (SARI) to the Office of the National Epidemiologist. During the 2009 H1N1 pandemic, meetings of the National Pandemic Planning Committee and the Technical Command Committee were convened. The pharmaceutical and non-pharmaceutical interventions (NPIs) implemented as a result of these meetings form the basis of the results presented in this paper. RESULTS: On June 3, 2009, Barbados reported its first case of 2009 H1N1. From June until October 2009, there were 155 laboratory confirmed cases of 2009 H1N1, with one additional case occurring in January 2010. For the outbreak period (June-October 2009), the surveillance team received reports of 2,483 ARI cases, compared to 412 cases for the same period in 2008. The total hospitalization rate due to SARIs for the year 2009 was 90.1 per 100,000 people, as compared to 7.3 per 100,000 people for 2008. Barbados’ pandemic response was characterized by a strong surveillance system combining active and passive surveillance, good risk communication strategy, a strengthened public and private sector partnership, and effective regional and international collaborations. Community restriction strategies such as school and workplace closures and cancellation of group events were not utilized as public health measures to delay the spread of the virus. Some health care facilities struggled with providing adequate isolation facilities. CONCLUSIONS: The number of confirmed cases was small but the significant surge in ARI and SARI cases indicate that the impact of the virus on the island was moderate. As a result of 2009 H1N1, virological surveillance has improved significantly and local, regional and international partnerships have been strengthened.


title: The City Under COVID‐19: Podcasting As Digital Methodology

text: This critical commentary reflects on a rapidly mobilised international podcast project, in which 25 urban scholars from around the world provided audio recordings about their cities during COVID‐19. New digital tools are increasing the speeds, formats and breadth of the research and communication mediums available to researchers. Voice recorders on mobile phones and digital audio editing on laptops allows researchers to collaborate in new ways, and this podcast project pushed at the boundaries of what a research method and community might be. Many of those who provided short audio 'reports from the field' recorded on their mobile phones were struggling to make sense of their experience in their city during COVID‐19. The substantive sections of this commentary discuss the digital methodology opportunities that podcasting affords geographical scholarship. In this case the methodology includes the curated production of the podcast and critical reflection on the podcast process through collaborative writing. Then putting this methodology into action some limited reflections on cities under COVID‐19 lockdown and social distancing initiatives around the world are provided to demonstrate the utility and limitations of this method.


title: Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs

text: Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC(50)s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.


title: Severe Pertussis Infections in the United States, 2011–2015

text: BACKGROUND: The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. METHODS: Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. RESULTS: Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2–11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%–66% reduced risk of hospitalization. Among adolescents aged 12–20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. CONCLUSIONS: Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options.


Admission fasting blood glucose predicts 30‐day poor outcome in patients hospitalized for COVID‐19 pneumonia


title: Recommendations for surgical management of recurrent nasopharyngeal carcinoma during COVID‐19 pandemic

text: Nasopharyngeal carcinoma is endemic in southern parts of China including Hong Kong. Primary treatment entails radiotherapy ± chemotherapy depending on disease stage at presentation. Surgery is offered as a means of salvage for persistent and recurrent disease. Comprehensive preoperative work‐up, careful patient selection, attention to details perioperation and multidisciplinary approach is essential in ensuring optimal outcomes after salvage surgery for recurrent nasopharyngeal carcinoma patients. Since the COVID‐19 outbreak, we are faced with unprecedented challenges with priorities of care and resources being shifted to combat the virus. These include patient selection and timing of treatment, while preventing disease transmission to heath care providers. Practices and recommendations made in this document are intended to support safe clinical practice and efficient use of resources during this challenging time.


title: On the Alert for Cytokine Storm: Immunopathology in COVID‐19

text: Poor outcomes in COVID‐19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID‐19.


title: Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats

text: Bats have been identified as a natural reservoir of a variety of coronaviruses (CoVs). Several of them have caused diseases in humans and domestic animals by interspecies transmission. Considering the diversity of bat coronaviruses, bat species and populations, we expect to discover more bat CoVs through virus surveillance. In this study, we described a new member of alphaCoV (BtCoV/Rh/YN2012) in bats with unique genome features. Unique accessory genes, ORF4a and ORF4b were found between the spike gene and the envelope gene, while ORF8 gene was found downstream of the nucleocapsid gene. All the putative genes were further confirmed by reverse-transcription analyses. One unique gene at the 3’ end of the BtCoV/Rh/YN2012 genome, ORF9, exhibits ~30% amino acid identity to ORF7a of the SARS-related coronavirus. Functional analysis showed ORF4a protein can activate IFN-β production, whereas ORF3a can regulate NF-κB production. We also screened the spike-mediated virus entry using the spike-pseudotyped retroviruses system, although failed to find any fully permissive cells. Our results expand the knowledge on the genetic diversity of bat coronaviruses. Continuous screening of bat viruses will help us further understand the important role played by bats in coronavirus evolution and transmission.


Low-Dose Abiraterone, a Rare European Commodity


title: AID in Antibody Diversification: There and Back again

text: Abstract Activation-Induced cytidine Deaminase (AID) initiates affinity maturation and isotype switching by deaminating deoxycytidines within immunoglobulin genes, leading to somatic hypermutation and class switch recombination. AID thus potentiates the humoral response to clear pathogens. Marking the 20th anniversary of the discovery of AID, we synthesize the current understanding of AID function. We discuss AID biochemistry and how error-free forms of DNA repair are co-opted to prioritize mutagenesis over accuracy during antibody diversification. We discuss the regulation of DNA double-strand break repair pathway during class switch recombination. We describe genomic targeting of AID as a multilayered process involving chromatin architecture, cis and trans-acting factors, and determining mutagenesis -- distinct from AID occupancy at loci that are spared from mutation.


title: Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies

text: BACKGROUND: During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. FINDINGS: We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. CONCLUSIONS: Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.


title: Parallel pathogens in the upper and lower respiratory tracts in children with a respiratory tract infection, as revealed by the Filmarray assay

text: Abstract Background Respiratory tract infection (RTI) is a common disease among children of all ages that causes high hospitalization and mortality rates. Infection with more than one pathogen has been reported in RTI; however, the association of the pathogen spectrum in upper and lower respiratory tract infections remains unclear. Methods A prospective study was conducted during February to October 2016. Fifty-five nasopharyngeal swabs (NPS) and 30 bronchoalveolar lavage fluid (BALF) samples from 55 hospitalized children aged less than 14years (mean age 40months) and diagnosed with an RTI were collected. All samples were detected for 18 respiratory pathogens using the Filmarray assay, real-time PCR, or nested PCR methods. Detection results and clinical characteristics of all cases were analyzed using chi-square and t tests. Results Forty-one of 55 (74.5%) NPS obtained from children were positive for at least one pathogen by the Filmarray assay. Of these cases, 53.7% (22/41) were co-infected. The most commonly detected pathogen was rhinovirus (RV), followed by Mycoplasma pneumoniae (MP) and respiratory syncytial virus (RSV). Infection by both RV and MP was the most frequently observed pattern of co-infection. Similar results were observed using real-time PCR. The pathogens in the NPS from 76.6% of cases detected by Filmarray and 80.0% of cases by real-time PCR included all the pathogens detected in the BALF sample from the same individual. The Filmarray assay showed an 80% concordance rate with real-time PCR and had a turnaround time of less than 1.2h. No significant differences were observed between the association of single-infection and co-infection with clinical characteristics, neither by Filmarray nor real-time PCR. Conclusion The spectrum of pathogens is mostly concordant in the upper and lower respiratory tract. Collecting NPS for detection can be a non-invasive and more convenient option compared with BALF. Although co-infection is common in children with an RTI, the clinical significance of co-infection remains unclear and warrants further analysis.


title: From the American Epicenter: Coronavirus Disease 2019 in Patients with Inflammatory Bowel Disease in the New York City Metropolitan Area

text: BACKGROUND: We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). METHODS: We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. RESULTS: We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn’s disease or older men with comorbidities, and 1 patient expired. DISCUSSION: In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.


title: Impact of the COVID-19 Pandemic on Mental Health and Social Support among Adult Egyptians

text: The psychological impact of outbreaks on individuals includes an intense and wide range of psychiatric morbidities. People are likely to experience feelings as; worry about being infected or getting sick, increased self-blame, and helplessness. This study aimed to assess the impact of COVID-19 on mental health and social support among Egyptian adults during the period of the pandemic. This is a cross-sectional observational study using an anonymous online questionnaire. The survey was conducted through a link shared on social networking sites. It was conducted from 2 May 2020 to 9 May 2020. The general populations of the Egyptian adults were included by using convenience and snowball sampling technique (510 adults). Impact Event scale mean 34.3 ± 15. About 211 (41.4%) suffered a severe impact. There was an increase in stress from work in 174 (34.1%), financial stress in 284 (55.7%), and stress from home in 320 (62.7%). Half of them felt horrified and helpless in 275 (53.9%), and 265 (52%) respectively, while 338 (66.3%) felt apprehensive. only 24.2% reported increased support from friends, while increased support from family members in 207 (40.6%). 46.5% shared their feelings with family members, while 176 (34.5%) shared with others. Caring for family members’ feelings increased in 330 (64.7%). Age and rural residency were negative predictors for the impact of event score, while female gender or presence of chronic condition was a positive predictor for the impact of event score. Covid-19 pandemic has a great psychological impact on adult Egyptians and affected social support.


Potential role of IL‐17 blocking agents in the treatment of severe COVID‐19?


title: SARS-related Virus Predating SARS Outbreak, Hong Kong

text: Using immunofluorescence and neutralization assays, we detected antibodies to human severe acute respiratory syndrome–associated coronavirus (SARS-CoV) and/or animal SARS-CoV–like virus in 17 (1.8%) of 938 adults recruited in 2001. This finding suggests that a small proportion of healthy persons in Hong Kong had been exposed to SARS-related viruses at least 2 years before the recent SARS outbreak.


title: The Diagnosis of Pandemic Coronavirus Pneumonia: A Review of Radiology Examination and Laboratory Test

text: Abstract Since the outbreak of novel coronavirus disease 2019 (COVID-19), epidemic prevention strategies have been implemented worldwide. For the sake of controlling the infectious coronavirus pneumonia, early diagnosis and quarantine play an imperative role. Currently, the mainstream diagnostic methods are imaging and laboratory diagnosis, which differ in their efficacy of diagnosis. To compare the detection rate, we reviewed numerous literature on pneumonia caused by coronaviruses (SARS, MERS, and SARS-CoV-2) and analyzed two different ways of diagnosis. The results showed that the detection rate of computed tomography (CT) diagnosis was significantly higher than that of real-time quantitative polymerase chain reaction (qPCR) (P = 0.00697). Still, clinicians should combine radiology and laboratory methods to achieve a higher detection rate, so that instant isolation and treatment could be effectively conducted to curb the rampant spread of the epidemic.


title: Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis

text: The 2014 Ebola outbreak in West Africa triggered a global crisis. Nine countries have reported more than 20 000 infection cases in total and nearly 8000 lives have been lost. The actual death toll is likely much higher than this figure; the death rate is as high as 70%, considering confirmed cases. The Ebola virus launches its destruction by shutting down the host’s innate and adaptive immune systems. The virus then replicates itself out of control and causes a cytokine storm in the host. Consequently, the host’s overdriven immune system attacks its own endothelial cells and this leads to multiple organ hemorrhagic damage, the host dies of septic shock finally. Under current circumstances where no specific interventions have shown effectiveness against the virus, our opinions are justified in applying a non-specific anti-viral approach during the incubation period of virus infection as an essential protection to put the host’s immune system into an alert state and henceforth to slow down the viral replication. When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host’s immune system to recover.


title: Natural protection of ocular surface from viral infections – a hypothesis

text: A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. One of the interesting aspects of the clinical manifestation of the infection is an accompanying ocular surface viral infection, viral conjunctivitis. Although occasional reports of viral conjunctivitis caused by this and the related SARS-CoV virus (causing the SARS outbreak in the early 2000s) are available, the prevalence of this complication among infected people appears low (∼1%). This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue. The discrepancy between the theoretically expected high rate of concurrence of viral ocular surface inflammation and the observed relatively low occurrence can be explained by several factors. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections.


title: A Hospital Partnership with a Nursing Home Experiencing a COVID‐19 Outbreak: Description of a Multi‐Phase Emergency Response in Toronto, Canada

text: Nursing homes have become “ground zero” for the coronavirus disease 2019 (COVID‐19) epidemic in North America, with homes experiencing widespread outbreaks resulting in severe morbidity and mortality among its residents. This manuscript describes a 371‐bed acute care hospital's emergency response to a 126‐bed nursing home experiencing a COVID‐19 outbreak in Toronto, Canada. Like other health care system responses to COVID‐19 outbreaks in nursing homes, this hospital‐nursing home partnership can be characterized in several phases: 1) engagement, relationship and trust‐building; 2) environmental scan, team‐building and immediate response; 3) early phase response; and 4) stabilization and transition period. This article is protected by copyright. All rights reserved.


title: Comparative efficacy of the front-line anti-HBV drugs in nucleos(t)ide analogue-naive chronic hepatitis B: A protocol for systematic review and network meta-analysis

text: BACKGROUND: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. RESULTS: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. CONCLUSION: Provide stronger evidence to solve the problem, should we wear masks or not right now.


title: The response of the mental health network of the Salamanca area to the COVID-19 pandemic: The role of the telemedicine.

text: The COVID-19 pandemic reached world-wide causing a great impact on healthcare services. The aim of this work is to describe the response of the Mental Health Network of the Salamanca´ Area (Spain) to this crisis and the reorganization of its resources within the first 8 weeks after the state of alarm was declared. The Psychiatry Service applied a contingency plan which included the reorganization of the human resources, the closure of some of the units and the implementation of telemedicine programs along with two specific programs, namely a mental health assistance program in the context of the infection by coronavirus, and another program for homeless people. 9.038 phone interviews were carried out in the outpatients and community mental health programs. The activity in subacute and acute wards, as well as that of the day hospital programs was decreased to 50%. Based on that this real-world response provided we concluded that the usage of telemedicine is promising in patients with any kind of disorder. Its implementation in daily practice will be considered in the future. Research must continue on COVID-19′s impact on patients with mental disorders and Psychiatry's necessary adaptations and new approaches to them.


title: Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis

text: Abstract Background & Aims Infection with SARS-CoV-2 causes COVID-19, which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool, and also summarized data from a cohort of patients with COVID-19 in Hong Kong. Methods We collected data from the cohort of patients with COVID-19 in Hong Kong (n=59; diagnosis from February 2 through Feb 29, 2020), and searched PubMed, Embase, Cochrane and three Chinese databases through March 11, 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. Results Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P=.02). The median fecal viral load was 5.1 log10cpm in patients with diarrhea vs 3.9 log10cpm in patients without diarrhea (P=.06). In a meta-analysis of 60 studies, comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% CI, 12.3%–24.5%); 11.8% of patients with non-severe COVID-19 had gastrointestinal symptoms (95% CI, 4.1%–29.1%) and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9%–36.7%). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3%–57.9%); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6%–85.1%). Conclusions In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients—even in stool collected after respiratory samples tested negative. Healthcare workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19—even during patient recovery.


title: Ribonuclease L and metal-ion–independent endoribonuclease cleavage sites in host and viral RNAs

text: Ribonuclease L (RNase L) is a metal-ion–independent endoribonuclease associated with antiviral and antibacterial defense, cancer and lifespan. Despite the biological significance of RNase L, the RNAs cleaved by this enzyme are poorly defined. In this study, we used deep sequencing methods to reveal the frequency and location of RNase L cleavage sites within host and viral RNAs. To make cDNA libraries, we exploited the 2′, 3′-cyclic phosphate at the end of RNA fragments produced by RNase L and other metal-ion–independent endoribonucleases. We optimized and validated 2′, 3′-cyclic phosphate cDNA synthesis and Illumina sequencing methods using viral RNAs cleaved with purified RNase L, viral RNAs cleaved with purified RNase A and RNA from uninfected and poliovirus-infected HeLa cells. Using these methods, we identified (i) discrete regions of hepatitis C virus and poliovirus RNA genomes that were profoundly susceptible to RNase L and other single-strand specific endoribonucleases, (ii) RNase L-dependent and RNase L-independent cleavage sites within ribosomal RNAs (rRNAs) and (iii) 2′, 3′-cyclic phosphates at the ends of 5S rRNA and U6 snRNA. Monitoring the frequency and location of metal-ion–independent endoribonuclease cleavage sites within host and viral RNAs reveals, in part, how these enzymes contribute to health and disease.


COVID‐19 During the Opioid Epidemic – Exacerbation of Stigma and Vulnerabilities


title: Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis

text: BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.


title: Novel viral translation strategies

text: Viral genomes are compact and encode a limited number of proteins. Because they do not encode components of the translational machinery, viruses exhibit an absolute dependence on the host ribosome and factors for viral messenger RNA (mRNA) translation. In order to recruit the host ribosome, viruses have evolved unique strategies to either outcompete cellular transcripts that are efficiently translated by the canonical translation pathway or to reroute translation factors and ribosomes to the viral genome. Furthermore, viruses must evade host antiviral responses and escape immune surveillance. This review focuses on some recent major findings that have revealed unconventional strategies that viruses utilize, which include usurping the host translational machinery, modulating canonical translation initiation factors to specifically enhance or repress overall translation for the purpose of viral production, and increasing viral coding capacity. The discovery of these diverse viral strategies has provided insights into additional translational control mechanisms and into the viral host interactions that ensure viral protein synthesis and replication. WIREs RNA 2014, 5:779–801. doi: 10.1002/wrna.1246 1.. Translation > Translation Mechanisms; 2.. Translation > Translation Regulation.


title: Respiratory protection for health care workers: A 2020 COVID‐19 perspective

text: As the US health care system began to respond to the coronavirus disease‐2019 pandemic, demand for respiratory personal protective equipment (PPE) increased precipitously, as did the number of users. This commentary discusses ensuing deviations from accepted respiratory PPE program practices, which potentially increased risk to health care workers. Such lapses included omitting user training and fit testing, provision of unapproved devices, and application of devices in settings and ways for which they were not intended. The temporary compromise of professionally accepted standards due to exigencies must not become the new normal. Rather, the current attention to PPE should be leveraged to enhance practice, motivate vital research, and strengthen professional, governmental, and institutional capabilities to control health care worker exposures to infectious hazards.


title: Model-based PEEP titration versus standard practice in mechanical ventilation: a randomised controlled trial

text: BACKGROUND: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS. METHODS AND DESIGN: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6–8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO(2))/FiO(2) during MV, number of desaturation events (SpO(2) < 88%), changes in respiratory mechanics and chest x-ray index scores, rescue therapies (prone positioning, nitric oxide use, extracorporeal membrane oxygenation) and hospital and 90-day mortality. DISCUSSION: The CURE RCT is the first trial comparing significant clinical outcomes in patients with ARDS in whom PEEP is selected at minimum elastance using an objective model-based method able to quantify and consider both inter-patient and intra-patient variability. CURE aims to demonstrate the hypothesized benefit of patient-specific PEEP and attest to the significance of real-time monitoring and decision-support for MV in the critical care environment. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12614001069640. Registered on 22 September 2014. (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366838&isReview=true) The CURE RCT clinical protocol and data usage has been granted by the New Zealand South Regional Ethics Committee (Reference number: 14/STH/132).


title: The impact of oil and gold price fluctuations on the South African equity market: Volatility spillovers and financial policy implications

text: Abstract This paper assesses the impact of gold and oil price fluctuations on the volatility of the South African stock market and its component indices or sectors – namely, the financial, industrial and resource sectors – to infer the link between the commodity and stock markets in South Africa. Use is made of the vector autoregressive asymmetric dynamic conditional correlation generalised autoregressive conditional heteroskedasticity (VAR-ADCC-GARCH) model to this end. Moreover, the paper assesses the magnitude of the optimal portfolio weight, hedge ratio and hedge effectiveness for portfolios constituted of a pair of assets, namely oil-stock and gold-stock pairs. The findings of the study show that there is significant volatility spillover between the gold and stock markets, and the oil and stock markets. This finding suggests the importance of the link between the commodity and stock markets, which is essential for portfolio management. With reference to portfolio optimization and the possibility of hedging when using the pairs of assets under study, the findings suggest the importance of combining gold and stocks as the best strategy to hedge against stocks risk, especially during financial crises.


title: Propagation of the Kakegawa strain of bovine coronavirus in suckling mice, rats and hamsters

text: The Kakegawa strain of bovine coronavirus was easily propagated in suckling mice. Infected animals died with nervous symptoms, and serial passage was readily accomplished by intracerebral inoculation with brain emulsions. The 3rd passage viral material from infected mice evoked the same disease in suckling mice, rats and hamsters inoculated by the intracerebral or by the subcutaneous route. Viruses recovered from mice, rats and hamsters could be clearly differentiated from mouse hepatitis virus strain 2 by the neutralization test.