title: Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells

text: Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis.


title: Comment on the intervention of Traditional Chinese Medicine on survival rates of patients living with human immunodeficiency virus and acquired immune deficiency syndrome

text: Abstract Despite many differences between Traditional Chinese Medicine (TCM) and conventional medicine, the use of TCM in the treatment of human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is increasingly recognized and accepted by patients. Recent research findings on the benefits of Chinese herbal medicine on long-term survival in patients with HIV/AIDS are encouraging and hopeful, but inconclusive. More research is needed.


title: Detection of human bocavirus in hospitalised children

text: Aim: The objectives of this study are to assess the frequency of human bocavirus (HBoV) infection in hospitalised children and to study the clinical symptoms associated with the detection of HBoV. Methods: Two groups of hospitalised children were included in this study: group 1 consisted of 1946 children hospitalised from 1st September 2004 to 30th May 2005, and group 2 consisted of 448 children hospitalised from 1st November 2003 to 30th March 2004. The respiratory specimens were tested by polymerase chain reaction. Results: In the first group, HBoV was detected by polymerise chain reaction in 11/828 (1.3%) of nasal specimens that tested negative for other respiratory viruses. One child tested positive for HBoV in both a nasal aspirate and stool sample. In the second group, nasal specimens were tested for all respiratory viruses, including HBoV. The presence of HBoV infection was detected in seven children (1.6%). Detection of a mixed viral population was observed in four of these children. The main symptoms in children infected with HBoV were rhinitis (50%), cough (45%), dyspnoea (28%), wheezing (28%), fever (23%) and diarrhoea (22%). The final clinical diagnoses were bronchiolitis (seven children), rhinopharyngitis (five children), the exacerbation of asthma (two children) and pneumonia (one child). Moreover, four children have associated gastroenteritis. Conclusion: These results contribute to the interest in the HBoV detection in children. HBoV detection in hospitalised children with or without any other respiratory virus detection was essentially associated with lower respiratory tract infection and in a lower score with upper respiratory tract infection and gastroenteritis.


Living with Authoritarianism: Ho Chi Minh City during COVID‐19 Lockdown


TELE-ICU in the Age of COVID-19: Built for this Challenge


Proposed Resumption of Surgery Algorithm Following the Corona Virus SARS-CoV-2 Pandemic


Mayo Clinic Strategies for COVID-19 Role of the Administrative Partner and the Physician-Administrator Partnership


title: Psychological status of medical workforce during the COVID-19 pandemic: a cross-sectional study

text: Abstract The pandemic of 2019 coronavirus disease (COVID-19) has burdened an unprecedented psychological stress on people around the world, especially the medical workforce. The study focuses on assess the psychological status of them. The authors conducted a single-center, cross-sectional survey via online questionnaires. Occurrence of fear, anxiety and depression were measured by the numeric rating scale (NRS) on fear, Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD), respectively. A total of 2299 eligible participants were enrolled from the authors’ institution, including 2042 medical staff and 257 administrative staff. The severity of fear, anxiety and depression were significantly different between two groups. Furthermore, as compared to the non-clinical staff, front line medical staff with close contact with infected patients, including working in the departments of respiratory, emergency, infectious disease, and ICU, showed higher scores on fear scale, HAMA and HAMD, and they were 1.4 times more likely to feel fear, twice more likely to suffer anxiety and depression. The medical staff especially working in above-mentioned departments made them more susceptible to psychological disorders. Effective strategies toward to improving the mental health should be provided to these individuals.


title: Potential risk of viral transmission from flying foxes to domestic animals and humans on the southern coast of West Java, Indonesia

text: Flying foxes have been considered to be involved in the transmission of serious infectious diseases to humans. Using questionnaires, we aimed to determine the direct and/or indirect contacts of flying foxes in an Indonesian nature conservation area with domestic animals and humans living in the surrounding area. We surveyed 150 residents of 10 villages in West Java. Villages were classified into 3 groups: inside and/or within 1 km from the outer border of the conservation area and 1–5 km or 5–10 km away from the reserve’s outer border. Data were collected by direct interview using a structured questionnaire consisting of the respondent characteristics (age, sex and occupation); histories of contacts between flying foxes and humans, dogs and other domestic animals; and knowledge about infectious diseases, mainly rabies, in flying foxes. We found that flying foxes from the nature conservation area often enter residential areas at night to look for food, especially during the fruit season. In these residential areas, flying foxes had direct contacts with humans and a few contacts with domestic animals, especially dogs. People who encounter flying foxes seldom used personal protective equipment, such as leather gloves, goggles and caps. The residents living around the conservation area mostly had poor knowledge about flying foxes and disease transmission. This situation shows that the population in this region is at a quite high risk for contracting infectious diseases from flying foxes.


title: Angiotensin-converting enzyme 2 in lung diseases

text: The renin-angiotensin system (RAS) plays a key role in maintaining blood pressure homeostasis, as well as fluid and salt balance. Angiotensin II, a key effector peptide of the system, causes vasoconstriction and exerts multiple biological functions. Angiotensin-converting enzyme (ACE) plays a central role in generating angiotensin II from angiotensin I, and capillary blood vessels in the lung are one of the major sites of ACE expression and angiotensin II production in the human body. The RAS has been implicated in the pathogenesis of pulmonary hypertension and pulmonary fibrosis, both commonly seen in chronic lung diseases such as chronic obstructive lung disease. Recent studies indicate that the RAS also plays a critical role in acute lung diseases, especially acute respiratory distress syndrome (ARDS). ACE2, a close homologue of ACE, functions as a negative regulator of the angiotensin system and was identified as a key receptor for SARS (severe acute respiratory syndrome) coronavirus infections. In the lung, ACE2 protects against acute lung injury in several animal models of ARDS. Thus, the RAS appears to play a critical role in the pathogenesis of acute lung injury. Indeed, increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases.


Global Health Is Local Health: A Multidisciplinary Perspective of COVID-19


Improving epidemic surveillance and response: big data is dead, long live big data


title: drVM: a new tool for efficient genome assembly of known eukaryotic viruses from metagenomes

text: Background: Virus discovery using high-throughput next-generation sequencing has become more commonplace. However, although analysis of deep next-generation sequencing data allows us to identity potential pathogens, the entire analytical procedure requires competency in the bioinformatics domain, which includes implementing proper software packages and preparing prerequisite databases. Simple and user-friendly bioinformatics pipelines are urgently required to obtain complete viral genome sequences from metagenomic data. Results: This manuscript presents a pipeline, drVM (detect and reconstruct known viral genomes from metagenomes), for rapid viral read identification, genus-level read partition, read normalization, de novo assembly, sequence annotation, and coverage profiling. The first two procedures and sequence annotation rely on known viral genomes as a reference database. drVM was validated via the analysis of over 300 sequencing runs generated by Illumina and Ion Torrent platforms to provide complete viral genome assemblies for a variety of virus types including DNA viruses, RNA viruses, and retroviruses. drVM is available for free download at: https://sourceforge.net/projects/sb2nhri/files/drVM/ and is also assembled as a Docker container, an Amazon machine image, and a virtual machine to facilitate seamless deployment. Conclusions: drVM was compared with other viral detection tools to demonstrate its merits in terms of viral genome completeness and reduced computation time. This substantiates the platform's potential to produce prompt and accurate viral genome sequences from clinical samples.


title: Middle East Respiratory Syndrome Coronavirus Transmission

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.


title: Emerging epidemic viral encephalitides with a special focus on henipaviruses

text: In the last few decades, there is an increasing emergence and re-emergence of viruses, such as West Nile virus, Enterovirus 71 and henipaviruses that cause epidemic viral encephalitis and other central nervous system (CNS) manifestations. The mortality and morbidity associated with these outbreaks are significant and frequently severe. While aspects of epidemiology, basic virology, etc., may be known, the pathology and pathogenesis are often less so, partly due to a lack of interest among pathologists or because many of these infections are considered “third world” diseases. In the study of epidemic viral encephalitis, the pathologist’s role in unravelling the pathology and pathogenesis is critical. The novel henipavirus infection is a good example. The newly created genus Henipavirus within the family Paramyxoviridae consists of two viruses, viz., Hendra virus and Nipah virus. These two viruses emerged in Australia and Asia, respectively, to cause severe encephalitides in humans and animals. Studies show that the pathological features of the acute encephalitis caused by henipaviruses are similar and a unique dual pathogenetic mechanism of vasculitis-induced microinfarction and parenchymal cell infection in the CNS (mainly neurons) and other organs causes severe tissue damage. Both viruses can cause relapsing encephalitis months and years after the acute infection due to a true recurrent infection as evidenced by the presence of virus in infected cells. Future emerging viral encephalitides will no doubt continue to pose considerable challenges to the neuropathologist, and as the West Nile virus outbreak demonstrates, even economically advanced nations are not spared.


title: Diarrhées aiguës infectieuses

text: Key points Acute infectious diarrhea has various causes: bacterial diarrhea with invasive or toxigenic mechanisms, especially frequent in hot regions and in travelers; viral diarrheas, frequent and cosmopolitan in children but also adults; and parasitic diarrhea, less frequent, and generally in subtropical areas. The major concerns involve the risk of complications, essentially dehydration and malnutrition, especially in vulnerable patients: young children, the elderly, and patients with immunosuppression, for whom rehydration is urgent. Diagnosis of diarrhea requires clinical assessment and history: underlying illnesses, severity of symptoms, presence and extent of dehydration and other clinical symptoms, travel history, known outbreaks, and pathogenic mechanism (invasive or toxigenic). Initial therapy should always include oral or parenteral rehydration; antimotility agents are generally not indicated; specific antibiotic treatment is not systematically indicated, except for invasive or dysenteric diarrhea and in immunosuppressed patients. Points essentiels Les diarrhées aiguës infectieuses ont de multiples causes: bactériennes avec un mécanisme invasif ou toxinique, particulièrement fréquentes dans les régions chaudes, chez les voyageurs; virales, fréquentes et cosmopolites, chez l'enfant, mais également chez l'adulte; parasitaires, plus rarement, et généralement dans les zones intertropicales. Le problème majeur est celui du risque de déshydratation et de dénutrition, en particulier sur les terrains fragilisés: jeunes enfants, vieillards, immunodéprimés, qui feront l'objet d'une prise en charge spécifique pour assurer rapidement la réhydratation. L'évaluation diagnostique repose sur l'analyse épidémiologique et clinique des patients: terrain pathologique, zone géographique d'exposition, signes de gravité et de déshydratation, mécanisme invasif ou toxinique, ce qui conditionne l'approche thérapeutique. Le traitement est d'abord symptomatique, reposant essentiellement sur la réhydratation orale ou parentérale; les ralentisseurs du transit ne sont généralement pas indiqués; l'antibiothérapie spécifique n'est pas systématique, indiquée en cas de diarrhée invasive, de syndrome dysentérique, et sur des terrains fragilisés (immunodéprimés).


title: Q fever in the Netherlands: public perceptions and behavioral responses in three different epidemiological regions: a follow-up study

text: BACKGROUND: Over the past years, Q fever has become a major public health problem in the Netherlands, with a peak of 2,357 human cases in 2009. In the first instance, Q fever was mainly a local problem of one province with a high density of large dairy goat farms, but in 2009 an alarming increase of Q fever cases was observed in adjacent provinces. The aim of this study was to identify trends over time and regional differences in public perceptions and behaviors, as well as predictors of preventive behavior regarding Q fever. METHODS: One cross-sectional survey (2009) and two follow-up surveys (2010, 2012) were performed. Adults, aged ≥18 years, that participated in a representative internet panel were invited (survey 1, n = 1347; survey 2, n = 1249; survey 3, n = 1030). RESULTS: Overall, public perceptions and behaviors regarding Q fever were consistent with the trends over time in the numbers of new human Q fever cases in different epidemiological regions and the amount of media attention focused on Q fever in the Netherlands. However, there were remarkably low levels of perceived vulnerability and perceived anxiety, particularly in the region of highest incidence, where three-quarters of the total cases occurred in 2009. Predictors of preventive behavior were being female, older aged, having Q fever themselves or someone in their household, more knowledge, and higher levels of perceived severity, anxiety and (self-) efficacy. CONCLUSIONS: During future outbreaks of (zoonotic) infectious diseases, it will be important to instil a realistic sense of vulnerability by providing the public with accurate information on the risk of becoming infected. This should be given in addition to information about the severity of the disease, the efficacy of measures, and instructions for minimising infection risk with appropriate, feasible preventative measures. Furthermore, public information should be adapted to regional circumstances.


Reply: Thymopoiesis, Inflamm-aging, and COVID-19 Phenotype


title: Chapter 14 Metabolomics and Lipidomics Yet More Ways Your Health Is Influenced by Fat

text: Abstract Metabolism refers to the chemical reactions that occur in living cells, and the reactants and products of these reactions compose the metabolome. The lipidome is comprised by hydrophobic metabolites and includes several broad classes of structurally diverse molecules. Lipids supplied by the host cell are required for many viral processes, and many if not all viruses have evolved mechanisms to perturb host metabolism to promote viral replication. This chapter provides background and a framework for examining the role of lipid metabolites in viral processes and rational attempts to target host metabolism as an antiviral strategy.


title: Prevalencia de la Infección por SARS-CoV-2 en médicos y enfermeras de Atención Primaria y Residencias de Ancianos del Área de Salud de León y Factores asociados

text: ABSTRACT Objective: To evaluate the prevalence and associated factors with SARS-CoV-2 infection in general practitioners and nurses of primary care centers and nursing homes in the health area of León (Spain). Materials and methods: Cross-sectional study in a convenience sample of professionals from 30 health centers and 30 nursing homes from the primary care management division of the Healthcare Area of Leon. The work center, type of profession, COVID-19 infection, level of exposure, compliance with preventive measures, isolation (if required) and diagnostic tests carried out were collected. The determination of infection was made by differentiated rapid diagnostic test (dRDT), using a finger-stick whole-blood sample. The association of variables with infection was assessed by multivariable non-conditional logistic regression. The true prevalence of SARS-CoV-2 infection was calculated according to two scenarios for RDT (Sensitivity=0.6 and Specificity=0.985; Sensitivity=0.8 and Specificity=1). Results: The true prevalence of SARS-CoV-2 infection was between 4.9% - 11.0%. The observed prevalence was 5.9%, being higher in nursing home compared to primary care centers (9.5% vs. 5.5%). No statistically significant differences were observed by sex, type of professional, level of exposure or compliance with preventive measures. Conclusions: The prevalence of SARS-CoV-2 infection in this group is low. A high number of professionals remain susceptible to SARS-CoV-2 infection and therefore protective measures should be taken, especially in nursing home professionals. RESUMEN Objetivo: Evaluar la prevalencia y los factores asociados a la infección por SARS-CoV-2 en médicos y enfermeras de centros de atención primaria y residencias de ancianos del área de salud de León (España). Material y métodos: Estudio observacional realizado en una muestra de conveniencia de profesionales de 30 centros de salud y 30 residencias de ancianos, de la Gerencia de Atención Primaria del área de salud de León. Se recogió información del centro de trabajo, tipo de profesión, infección por COVID-19, nivel de exposición, cumplimiento de medidas preventivas, aislamiento (si fue requerido) y test diagnósticos realizados. La determinación de infección fue llevada a cabo mediante prueba de diagnóstico rápido diferenciado (PDRd), usando muestra de sangre capilar. La asociación de las variables con la infección se evaluó mediante regresión logística multivariable no condicional. La prevalencia real de infección por SARS-CoV-2 fue calculada de acuerdo a dos escenarios para el PDRd (Sensibilidad=0,6 y Especificidad=0,985; Sensibilidad=0,8 y Especificidad=1). Resultados: La prevalencia real de infección por SARS-CoV-2 se encontró entre 4,9%-11,0%. La prevalencia observada fue de 5,9%, siendo mayor en trabajadores de residencias de ancianos que de centros de salud de atención primaria (9,5% vs 5,5%). No hubo diferencias estadísticamente significativas por sexo, tipo de profesional, nivel de exposición o cumplimiento de medidas preventivas. Conclusiones: La prevalencia de la infección por el SARS-CoV-2 en este grupo es baja. Un gran número de profesionales siguen siendo susceptibles a la infección por el SARS-CoV-2 y, por lo tanto, medidas de protección deben ser adoptadas, especialmente en los profesionales de las residencias de ancianos.


title: The true worth of a nurse..time to act!

text: The COVID‐19 outbreak has shown the world the true value of the nursing profession to the healthcare system and to humanity. Indeed, without nurses (and midwives) there would be no health care!(.) The timing of this "freak" (although not unpredictable) viral pandemic with the World Health Assembly declaration that 2020 is the International Year of the Nurse and Midwife is a poignant coincidence. For almost 200 years we have witnessed the progressive growth of professionalisation, capacity and capability of the nursing profession globally. In most countries in the world that survey the public trust and confidence in professional groups, most select nursing in the top group, often ahead of doctors and other noble professions.


Viruses and Bats


K.03 HPV vaccines: New opportunities for global cervical cancer prevention


title: Auricular chondritis in a cat

text: A four‐year‐old male neutered domestic shorthaired cat developed bilateral thickening of the pinnae, with slight curling, intense erythema and pain. No ear canal disease was present. The cat was negative for feline immunodeficiency virus, feline leukaemia virus and feline coronavirus. Biopsy of the ear lesion revealed auricular chondritis. In humans, histologically similar lesions may involve the pinnae, nose, trachea, joints, eyes and heart, and the disease is termed relapsing polychondritis. The cat reported had a history of corneal damage, resulting in corneal vascularisation and opacity, eyelid distortion, necessitating an entropion operation, and radiological evidence of mild cardiac enlargement. The ear disease responded rapidly to treatment with prednisolone and, apart from slight thickening and curling of the pinnae, the cat remained normal and pain‐free. After two years, the prednisolone was withdrawn, and there was no recurrence of the condition in a follow‐up period of 14 months.


title: Quantitative mapping of scientific research—The case of electrical conducting polymer nanocomposite

text: Abstract This study aims to understand knowledge structure both quantitatively and visually by integrating keyword analysis and social network analysis of scientific papers. The methodology proposed in this study is capable of creating a three-dimensional “Research focus parallelship network” and a “Keyword Co-occurrence Network”, together with a two-dimensional knowledge map. The network and knowledge map can be depicted differently by choosing different information for the network actor, i.e. country, institute, paper and keyword, to reflect knowledge structures from macro, to meso, to micro-levels. A total of 223 highly cited papers published by 142 institutes and 26 countries are analyzed in this study. China and the US are the two countries located at the core of knowledge structure and China is ranked no. 1. This quantitative exploration provides a way to unveil important or emerging components in scientific development and also to visualize knowledge; thus an objective evaluation of scientific research is possible for quantitative technology management.


title: Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis

text: Abstract Background IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. Methods To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4+CD25+ regulatory T cells were also measured. Results rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4+CD25+ regulatory T cells. Conclusions This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4+CD25+ regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis.


RNA internal control, a new tool for the rapid development of detection tools by real time PCR in outbreak situation. Application to the detection of Middle East Respiratory Syndrome human coronavirus


title: Viral lncRNA: A regulatory molecule for controlling virus life cycle

text: Long non-coding RNAs (lncRNAs) are found not only in mammals but also in other organisms, including viruses. Recent findings suggest that lncRNAs play various regulatory roles in multiple major biological and pathological processes. During viral life cycles, lncRNAs are involved in a series of steps, including enhancing viral gene expression, promoting viral replication and genome packaging, boosting virion release, maintaining viral latency and assisting viral transformation; additionally, lncRNAs antagonize host antiviral innate immune responses. In contrast to proteins that function in viral infection, lncRNAs are expected to be novel targets for the modulation of all types of biochemical processes due to their broad characteristics and profound influence. This review highlights our current understanding of the regulatory roles of lncRNAs during viral infection processes with an emphasis on the potential usefulness of lncRNAs as a target for viral intervention strategies, which could have therapeutic implications for the application of a clinical approach for the treatment of viral diseases.


title: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review

text: Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C–25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.


title: An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues

text: The initial cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS‐CoV‐2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS‐CoV‐2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 strains. The key residues of the receptor‐binding domain (RBD) and O‐linked glycan were compared. SARS‐CoV‐2 strains were clustered with RaTG13 (97.41% identity), Pangolin‐CoV (92.22% identity) and Bat‐SL‐CoV (80.36% identity), forms a new clade‐2 in lineage B of beta‐CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS‐CoV‐2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin‐CoV. SARS‐CoV‐2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O‐linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV.


title: HTCC: Broad Range Inhibitor of Coronavirus Entry

text: To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.


Risks of COVID‐19 for surgical cancer patients: The importance of the informed consent process


title: Family mastery enhances work engagement in Chinese nurses: A cross-lagged analysis

text: Abstract Based on Greenhaus and Powell's (2006) theory of work–family enrichment and the job demands-resources (JD-R) model of work engagement (Bakker & Demerouti, 2008), this study focused on the family-to-work enrichment process by investigating the effect of family mastery on work engagement in a Chinese context. A sample of 279 Chinese female nurses completed questionnaires in a two-wave longitudinal survey. With a cross–lagged analysis, the results indicated that family mastery at Time 1 had a significant positive effect on work engagement at Time 2. Furthermore, the relationship between family mastery and work engagement was stronger in a context of high (vs. low) job demand. These findings suggested that resource generated in family could directly help people stay engaged in the workplace, particularly under stressful working conditions. Our findings have expanded the JD-R model of work engagement and bridged it with theory of work–family enrichment. Implications for theory and practices are discussed.


title: Interactions among SARS-CoV accessory proteins revealed by bimolecular fluorescence complementation assay

text: The accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b, 9b and ORF14), predicted unknown proteins (PUPs) encoded by the genes, are considered to be unique to the severe acute respiratory syndrome coronavirus (SARS-CoV) genome. These proteins play important roles in various biological processes mediated by interactions with their partners. However, very little is known about the interactions among these accessory proteins. Here, a EYFP (enhanced yellow fluorescent protein) bimolecular fluorescence complementation (BiFC) assay was used to detect the interactions among accessory proteins. 33 out of 81 interactions were identified by BiFC, much more than that identified by the yeast two-hybrid (Y2H) system. This is the first report describing direct visualization of interactions among accessory proteins of SARS-CoV. These findings attest to the general applicability of the BiFC system for the verification of protein-protein interactions.


title: Inhibition of porcine epidemic diarrhea virus (PEDV) replication by A77 1726 through targeting JAK and Src tyrosine kinases

text: Porcine epidemic diarrhea (PED) virus (PEDV) is a coronavirus that primarily infects porcine intestinal epithelial cells and causes severe diarrhea and high fatality in piglets. A77 1726 is the active metabolite of leflunomide, a clinically approved anti-rheumatoid arthritis (RA) drug. A77 1726 inhibits the activity of protein tyrosine kinases (PTKs), p70 S6 kinase (S6K1), and dihydroorotate dehydrogenase (DHO-DHase). Whether A77 1726 can control coronavirus infections has not been investigated. Here we report that A77 1726 effectively restricted PEDV replication by inhibiting Janus kinases (JAKs) and Src kinase activities but not by inhibiting DHO-DHase and S6K1 activities. Overexpression of Src, JAK2 or its substrate STAT3 enhanced PEDV replication and attenuated the antiviral activity of A77 1726. Our study demonstrates for the first time the ability of A77 1726 to control coronavirus replication by inhibiting PTK activities. Leflunomide has potential therapeutic value for the control of PEDV and other coronavirus infections.


title: From SARS-CoV to Wuhan 2019-nCoV Outbreak: Similarity of Early Epidemic and Prediction of Future Trends

text: This manuscript has been withdrawn as it was submitted without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.


title: Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial

text: Objective To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. Study design Eligible infants aged ≤4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. Results A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. Conclusions A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. Trial registration Clinicaltrials.gov: NCT01435486.


title: Perinatal-Neonatal Management of COVID-19 Infection — Guidelines of the Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum of India (NNF), and Indian Academy of Pediatrics (IAP)

text: JUSTIFICATION: During the current rapidly evolving pandemic of COVID-19 infection, pregnant women with suspected or confirmed COVID-19 and their newborn infants form a special vulnerable group that needs immediate attention. Unlike other elective medical and surgical problems for which care can be deferred during the pandemic, pregnancies and childbirths continue. Perinatal period poses unique challenges and care of the mother-baby dyads requires special resources for prevention of transmission, diagnosis of infection and providing clinical care during labor, resuscitation and postnatal period. PROCESS: The GRADE approach recommended by the World Health Organization was used to develop the guideline. A Guideline Development Group (GDG) comprising of obstetricians, neonatologists and pediatricians was constituted. The GDG drafted a list of questions which are likely to be faced by clinicians involved in obstetric and neonatal care. An e-survey was carried out amongst a wider group of clinicians to invite more questions and prioritize. Literature search was carried out in PubMed and websites of relevant international and national professional organizations. Existing guidelines, systematic reviews, clinical trials, narrative reviews and other descriptive reports were reviewed. For the practice questions, the evidence was extracted into evidence profiles. The context, resources required, values and preferences were considered for developing the recommendations. OBJECTIVES: To provide recommendations for prevention of transmission, diagnosis of infection and providing clinical care during labor, resuscitation and postnatal period. RECOMMENDATIONS: A set of twenty recommendations are provided under the following broad headings: 1) pregnant women with travel history, clinical suspicion or confirmed COVID-19 infection; 2) neonatal care; 3) prevention and infection control; 4) diagnosis; 5) general questions.


title: Smart home technology for telemedicine and emergency management

text: With the ageing population, mobility is an important issue and it deters the elderlies to visit health clinics on a regular basis. Individuals with disabilities also face the same obstacles for their out-of-home medical visits. In addition, people living in remote areas often do not get the needed health care attention unless they are willing to spend the time, effort and cost to travel. Advances in information and telecommunication technologies have made telemedicine possible. Using the latest sensor technologies, a person’s vital data can be collected in a smart home environment. The bio-information can then be transferred wirelessly or via the Internet to medical databases and the healthcare professionals. Using the appropriate sensing apparatus at a smart home setting, patients, elderlies and people with disabilities can have their health signals and information examined on a real-time and archival basis. Recovery process can be charted on a regular basis. Remote emergency alerts can be intercepted and responded quickly. Health deterioration can be monitored closely enabling corrective actions. Medical practitioners can therefore provide the necessary health-related services to more people. This paper surveys and compiles the state-of-the-art smart home technologies and telemedicine systems.


Evaluation of point of care testing platform (ePLEX) for respiratory viral diagnosis


title: Viral and Cellular Proteins Involved in Coronavirus Replication

text: As the largest RNA virus, coronavirus replication employs complex mechanisms and involves various viral and cellular proteins. The first open reading frame of the coronavirus genome encodes a large polyprotein, which is processed into a number of viral proteins required for viral replication directly or indirectly. These proteins include the RNA-dependent RNA polymerase (RdRp), RNA helicase, proteases, metal-binding proteins, and a number of other proteins of unknown function. Genetic studies suggest that most of these proteins are involved in viral RNA replication. In addition to viral proteins, several cellular proteins, such as heterogeneous nuclear ribonucleoprotein (hnRNP) A1, polypyrimidine-tract-binding (PTB) protein, poly(A)-binding protein (PABP), and mitochondrial aconitase (m-aconitase), have been identified to interact with the critical cis-acting elements of coronavirus replication. Like many other RNA viruses, coronavirus may subvert these cellular proteins from cellular RNA processing or translation machineries to play a role in viral replication.


title: A COVID‐19 outbreak's lesson: best use of the pediatric emergency department

text: After finding the first cases in Italy, the Government declared a state of emergency. In The Lancet, Stefano Spina and colleagues (1) reported the strategy of the Emergency Medical System (EMS) of the metropolitan area of Milan to contrast the recent COVID‐19 outbreak in Italy. The EMS instituted a team that manages the patients and their flow to local hospitals. This response is critical, given the public health problem and the need to avoid the Emergency Department overcrowding.


From PREDICT to prevention, one pandemic later


title: Mini-transposons in microbial ecology and environmental biotechnology

text: Abstract Mini-transposon is the generic name given to the members of a collection of genetic assets derived from transposons Tn10 and Tn5, in which the naturally occurring functional segments of DNA have been rearranged artificially to originate shorter mobile elements. In the most widespread design (that known as the pUT system), any heterologous DNA segment can be conveniently cloned within the boundaries of a mini-Tn5 vector and finally inserted into the chromosome of target Gram-negative bacteria after a few simple genetic manipulations. The large variety of antibiotic, non-antibiotic and excisable selection markers available has been combined at ease with DNA fragments encoding one or more phenotypes of interest for ecological or biotechnological applications. These include the tagging of specific strains in a community with selectable and/or optical marker genes, the production of stable gene fusions for monitoring transcriptional regulation in single cells, the metabolic engineering of strains destined for bioremediation, the non-disruptive monitoring of gene transfer and the assembly of gene containment and strain containment circuits for genetically manipulated microorganisms.


CORONAVIRUS (COVID‐19) PANDEMIC: PERSONAL VIEW TO A NEW MODEL OF PAEDIATRIC PRACTICE


title: A Massachusetts prototype like coronavirus isolated from wild peafowls is pathogenic to chickens

text: Abstract Coronavirus infection was investigated in apparently healthy wild peafowls in Guangdong province of China in 2003, while severe acute respiratory syndrome (SARS) broke out there. No SARS-like coronavirus had been isolated but a novel avian coronavirus strain, Peafowl/GD/KQ6/2003 (KQ6), was identified. Sequence analysis revealed that KQ6 was an avian coronavirus infectious bronchitis virus (IBV), a member of coronavirus in group 3. The genome sequence of KQ6 had extremely high degree of identity with that of a Massachusetts prototype IBV M41. KQ6 was pathogenic to chickens but non-pathogenic to peafowls under experimental conditions. Seventeen out of fifty-four (31.48%) peafowl serum samples were tested positive for specific antibodies against IBV. Present results indicate that the peafowl isolate KQ6 is a Massachusetts prototype like coronavirus strain which undergoes few genetic changes and peafowl might have acted as a natural reservoir of IBV for very long time.


title: Coronavirus disease 2019 in pregnancy: early lessons

text: The worldwide incidence of coronavirus disease 2019 (COVID-19) infection is rapidly increasing, but there exists limited information on coronavirus disease 2019 in pregnancy. Here, we present our experience with 7 confirmed cases of coronavirus disease 2019 in pregnancy presenting to a single large New York City tertiary care hospital. Of the 7 patients, 5 presented with symptoms of coronavirus disease 2019, including cough, myalgias, fevers, chest pain, and headache. Of the 7 patients, 4 were admitted to the hospital, including 2 who required supportive care with intravenous hydration. Of note, the other 2 admitted patients who were asymptomatic on admission to the hospital, presenting instead for obstetrically indicated labor inductions, became symptomatic after delivery, each requiring intensive care unit admission.


title: A Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat Function

text: Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 –associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV–pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti–HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti–HIV-1 derivatives to complement cART.


title: Molecular evolution and multilocus sequence typing of 145 strains of SARS-CoV

text: Abstract In this study, we have identified 876 polymorphism sites in 145 complete or partial genomes of SARS-CoV available in the NCBI GenBank. One hundred and seventy-four of these sites existed in two or more SARS-CoV genome sequences. According to the sequence polymorphism, all SARS-CoVs can be divided into three groups: (I) group 1, animal-origin viruses (such as SARS-CoV SZ1, SZ3, SZ13 and SZ16); (II) group 2, all viruses with clinical origin during first epidemic; and (III) group 3, SARS-CoV GD03T0013. According to 10 special loci, group 2 again can be divided into genotypes C and T, which can be further divided into sub-genotypes C1–C4 and T1–T4. Positive Darwinian selections were identified between any pair of these three groups. Genotype C gives neutral selection. Genotype T, however, shows negative selection. By comparing the death rates of SARS patients in the different regions, it was found that the death rate caused by the viruses of the genotype C was lower than that of the genotype T. SARS-CoVs might originate from an unknown ancestor.


title: Infertility influencers: an analysis of information and influence in the fertility webspace

text: PURPOSE: To examine fertility-related social media accounts and influencers on two social media platforms. METHODS: The search function of Twitter (TW) and Instagram (IG) was used to generate a list of accounts with the terms: fertility, infertility, ttc, egg freezing, ivf, endometriosis, and reproductive. Accounts not in English, in private, with no posts in > 1 year, or with content unrelated to search terms were excluded. Accounts were assessed for author type; REI board certification (REI-BC); influencer (INF) status (> 10 K followers on IG; verified check mark on TW); account demographics; and content in last 5 posts. Statistical analysis included unpaired t tests, a classification and regression tree (CART) analysis, and stepwise multiple logistic regression. RESULTS: Seven hundred ten accounts were identified and 537 (278 TW, 259 IG) were included. Account types included societies, clinics, physicians, patients, groups, and “other.” Instagram content (1290 posts reviewed) was primarily personal stories (31.7%) or inspiration/support (23.7%). Twitter content (1390 posts reviewed) was mostly promotion (28.2%) and research/education (20.2%). Thirty-nine accounts (12.5%) were influencers. Fertility influencers were most often awareness/support accounts (59.8% TW, 25.0% IG), patients (12.8% TW, 25% IG), or other (17.9% TW, 21.0% IG). Only 7.7% TW and 7.1% IG INFs were board-certified REI physicians. The best predictor for classification as an influencer was high activity (> 50 posts/month TW, > 10 posts/month IG). CONCLUSION: As patients increasingly utilize social media to obtain and engage with health information, it is critical to understand the fertility-related SM landscape. This understanding may help to successfully enhance relationships with patients and ensure dissemination of accurate information.


title: Simulating the SARS outbreak in Beijing with limited data

text: Abstract We propose a mathematical model to simulate the SARS outbreak in Beijing. The model consists of six subpopulations, namely susceptible, exposed, quarantined, suspect, probable and removed, as China started to report SARS cases as suspect and probable separately from April 27 and cases transferred from suspect class to probable class from May 2. By simplifying the model to a two-compartment suspect-probable model and a single-compartment probable model and using limited data, we are able to simulate the SARS outbreak in Beijing. We estimate that the reproduction number varies from 1.0698 to 3.2524 and obtain certain important epidemiological parameters.


title: Droplet and Particle Generation on Centrifugal Microfluidic Platforms: A Review

text: The use of multiphase flows in microfluidics to carry dispersed phase material (droplets, particles, bubbles, or fibers) has many applications. In this review paper, we focus on such flows on centrifugal microfluidic platforms and present different methods of dispersed phase material generation. These methods are classified into three specific categories, i.e., step emulsification, crossflow, and dispenser nozzle. Previous works on these topics are discussed and related parameters and specifications, including the size, material, production rate, and rotational speed are explicitly mentioned. In addition, the associated theories and important dimensionless numbers are presented. Finally, we discuss the commercialization of these devices and show a comparison to unveil the pros and cons of the different methods so that researchers can select the centrifugal droplet/particle generation method which better suits their needs.


title: Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Atherosclerotic Plaque

text: Atherosclerosis (AS) leading to myocardial infarction and stroke remains worldwide the main cause for mortality. Vulnerable atherosclerotic plaques are responsible for these life-threatening clinical endpoints. Atherosclerosis is a chronic, complex, inflammatory disease with interactions between metabolic dysfunction, dyslipidemia, disturbed microbiome, infectious triggers, vascular, and immune cells. Undoubtedly, the immune response is a most important piece of the pathological puzzle in AS. Although macrophages and T cells have been the focus of research in recent years, B cells producing antibodies and regulating T and natural killer (NKT) cell activation are more important than formerly thought. New results show that the B cells exert a prominent role with atherogenic and protective facets mediated by distinct B cell subsets and different immunoglobulin effects. These new insights come, amongst others, from observations of the effects of innovative B cell targeted therapies in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These diseases associate with AS, and the beneficial side effects of B cell subset depleting (modifying) therapies on atherosclerotic concomitant disease, have been observed. Moreover, the CANTOS study (NCT01327846) showed impressive results of immune-mediated inflammation as a new promising target of action for the fight against atherosclerotic endpoints. This review will reflect the putative role of B cells in AS in an attempt to connect observations from animal models with the small spectrum of the thus far available human data. We will also discuss the clinical therapeutic potency of B cell modulations on the process of AS.


Public Understanding of Pandemic Influenza, United Kingdom


title: Hopf bifurcation analysis of a delayed SEIR epidemic model with infectious force in latent and infected period

text: In this paper, we analyze a delayed SEIR epidemic model in which the latent and infected states are infective. The model has a globally asymptotically stable disease-free equilibrium whenever a certain epidemiological threshold, known as the basic reproduction number [Formula: see text] , is less than or equal to unity. We investigate the effect of the time delay on the stability of endemic equilibrium when [Formula: see text] . We give criteria that ensure that endemic equilibrium is asymptotically stable for all time delays and a Hopf bifurcation occurs as time delay exceeds the critical value. We give formulae for the direction of Hopf bifurcations and the stability of bifurcated periodic solutions by applying the normal form theory and the center manifold reduction for functional differential equations. Numerical simulations are presented to illustrate the analytical results.


title: Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus

text: The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.


title: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

text: BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.)


title: Mind your Language: Discursive Practices Produce Unequal Power and Control Over Infectious Disease: A Critical Discourse Analysis

text: BACKGROUND: Power, socioeconomic inequalities, and poverty are recognized as some of the fundamental determinants of differences in vulnerability of societies to infectious disease threats. The economic south is carrying a higher burden than those in the economic north. This raises questions about whether social preventions and biomedical preventions for infectious disease are given equal consideration, and about social institutions and structures that frame the debate about infectious disease. This article examines how institutionalized ways of talking about infectious disease reinforces, creates, and sustains health inequalities. METHODS: Critical discourse analysis was considered to be epistemologically and ontologically consistent with the aims and context of this study. RESULTS: The study examined three types of infectious disease: • Emerging infectious diseases/pathogens • Neglected tropical diseases • Vector-borne infections. Examination revealed that poverty is the most common determinant of all three. CONCLUSIONS: A sustainable reduction in infectious disease in the southern countries is most likely to be achieved through tackling socioeconomic determinants. There is a need for a change in the discourse on infectious disease, and adopt a discourse that promotes self-determination, rather than one that reinforces the hero-victim scenario and power inequalities.


title: Gender and Fear of COVID-19 in a Cuban Population Sample

text: The COVID-19 pandemic is a global health emergency that could potentially have a serious impact on public health. Fear has been one of the most frequent psychological reaction in the population during the current pandemic. The aim of this study was to compare fear of COVID-19 between genders and to examine whether the differences between genders may be predictors of fear of COVID-19 scores. A cross-sectional web-based survey design was adopted. The sample comprised 772 Cuban participants. The Fear of COVID-19 Scale was used to explore fear reactions in the sample. An independent-samples t test was conducted to compare the fear of COVID-19 scores between genders, and multinomial logistic regression was modeling to identify variables independently associated with fear of coronavirus. In our sample, on average, female participants experienced significantly greater fear of COVID-19 than men. The gender of participants significantly predicted the level of fear of COVID-19. Being female was a predictor of medium and high levels of fear of COVID-19. The odds of a female with middle fear levels compared to low fear was 3.13 times more than for a male, and the odds of a female with high fear levels compared to low fear was 3.45 times more than for a male. Our results corroborate international research that indicate a greater psychological vulnerability in women during the COVID-19 pandemic. This result points to the need to design interventions that reduce the negative impact of the current outbreak on women’s mental health.


title: Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures

text: The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights.


title: Bat–man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations

text: Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans.


title: Plasmablasts as Migratory IgG-Producing Cells in the Pathogenesis of Neuromyelitis Optica

text: Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4. Here, we demonstrate that CD138(+)HLA-DR(+) plasmablasts, a subset of IgG-producing cells, are increased in the peripheral blood and are enriched among the cerebrospinal fluid (CSF) lymphocytes during the relapse of neuromyelitis optica. Notably, these CD138(+)HLA-DR(+) plasmablasts overexpress CXCR3, whose ligands are present in the cerebrospinal fluid during the relapse of neuromyelitis optica. These results led us to speculate that plasmablasts producing anti-aquaporin 4 autoantibodies might traffic toward the central nervous system (CNS). Furthermore, we performed single-cell sorting of plasmablasts from peripheral blood and CSF samples from NMO and sequenced the complementarity-determining regions (CDRs) of the IgG heavy chain expressed by the sorted plasmablast clones. There were high frequencies of mutations in the CDRs compared with framework regions, indicating that these plasmablast clones would represent a post-germinal center B-cell lineage. Consistent with the preceding results, the plasmablast clones from the peripheral blood shared the same CDR sequences with the clones from the CSF. These results indicate that IgG-producing plasmablasts, which are guided by helper T-cells, may migrate from the peripheral blood preferentially to the CSF. Since migratory plasmablasts could be involved in the inflammatory pathology of NMO, the B-cell subset and their migration might be an attractive therapeutic target.


Hemodialysis and COVID-19: An Achilles’ Heel in the Pandemic Healthcare Response in the United States


title: Development of a one-run real-time PCR detection system for pathogens associated with porcine respiratory diseases

text: The etiology of Porcine respiratory disease complex is complicated by infections with multiple pathogens, and multiple infections increase the difficulty in identifying the causal pathogen. In this present study, we developed a detection system of microbes from porcine respiratory by using TaqMan real-time PCR (referred to as Dempo-PCR) to screen a broad range of pathogens associated with porcine respiratory diseases in a single run. We selected 17 porcine respiratory pathogens (Actinobacillus pleuropneumoniae, Boldetella bronchiseptica, Haemophilus parasuis, Pasteurella multocida, Pasteurella multocida toxin, Streptococcus suis, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma hyosynovie, porcine circovirus 2, pseudorabies virus, porcine cytomegalovirus, swine influenza A virus, porcine reproductive and respiratory virus US strain, EU strain, porcine respiratory coronavirus and porcine hemagglutinating encephalomyelitis virus) as detection targets and designed novel specific primer-probe sets for seven of them. In sensitivity test by using standard curves from synthesized DNA, all primer-probe sets showed high sensitivity. However, porcine reproductive and respiratory virus is known to have a high frequency of genetic mutations, and the primer and probe sequences will need to be checked at a considerable frequency when performing Dempo-PCR from field samples. A total of 30 lung samples from swine showing respiratory symptoms on six farms were tested by the Dempo-PCR to validate the assay’s clinical performance. As the results, 12 pathogens (5 virus and 7 bacteria) were detected and porcine reproductive and respiratory virus US strain, Mycoplasma hyorhinis, Haemophilus parasuis, and porcine cytomegalovirus were detected at high frequency. These results suggest that Dempo-PCR assay can be applied as a screening system with wide detection targets.


title: Prise en charge des tumeurs primitives et métastatiques du péritoine en période de pandémie CoViD-19 Pistes de réflexion et de priorisation du groupe RENAPE et BIG-RENAPE

text: Résumé La pandémie due au COVID-19 modifie profondément l’organisation et l’accès aux soins, en particulier pour les pathologies néoplasiques péritonéales, dont la prise en charge curative mobilise des moyens importants en personnel, bloc opératoire et réanimation. Les groupes BIG-RENAPE et RENAPE proposent des pistes de réflexion et de priorisation pour leur prise en charge. Un renforcement des critères habituels de sélection est nécessaire pour une prise en charge à visée curative : patients jeunes, avec peu de co-morbidités et une extension péritonéale limitée. Il est souhaitable de prioriser les pathologies pour lesquelles la chirurgie de cytoréduction associée ou non à une chimiohyperthermie intrapéritonéale (CHIP) est le traitement de référence et celles pour lesquelles la chimiothérapie systémique ne peut être une alternative temporaire ou prolongée : pseudomyxomes péritonéaux; mésothéliomes péritonéaux malins résécables ; métastases péritonéales d’origine colorectale si résécables, non répondeuses à la chimiothérapie systémique et/ou après 12 cures, carcinoses ovariennes en 1ère intention si résécables et limitées ou en situation intervallaire après un maximum de 6 cycles de chimiothérapie systémique. L’adjonction d’une CHIP devra être discutée au cas par cas, en centre expert. La priorisation des indications devra prendre en considération les conditions locales et la phase de la période épidémique pour permettre une prise en charge péri-opératoire optimale. Abstract The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.


title: Chapter 8 Digestive System

text: This chapter provides an overview of species differences in the anatomy and physiology of the gastrointestinal system among rodents, dogs and primates, emphasizing that the dog is a good model for functional aspects of the human gastrointestinal tract. It describes and discusses the human relevance of drug-induced changes in the mouth, oropharynx, teeth and salivary glands of laboratory animals. It describes the pathology that can be seen in the esophagus. It discusses changes that can be seen in the rodent forestomach and their usual but incomplete lack of relevance for humans. Spontaneous and drug-induced inflammatory and proliferative disorders found in the stomach, small and large intestines are described in detail particularly those that result from treatment with non-steroidal anti-inflammatory drugs and anticancer therapies. It also discusses the relevance of gastrointestinal neoplasms that may be found in rodents following treatment with therapeutic agents. Keywords mouth, oropharynx, salivary glands, esophagus, forestomach, glandular stomach, small intestine, large intestine, drug safety, comparative pathology, neoplasia


title: Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study

text: Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009–2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact.


title: Coronavirus 229E susceptibility in man-mouse hybrids is located on human chromosome 15

text: Human coronavirus 229E, an enveloped, RNA-containing virus, causes respiratory illness in man and is serologically related to murine coronavirus JHM, which causes acute and chronic demyelination in rodents. 229E displays a species-specific host range restriction whose genetic basis was studied in human-mouse hybrids. 229E replicated in human WI-38 cells but not in three mouse cell lines tested (RAG, LM/TK(−), and A9). Human coronavirus sensitivity (HCVS) was expressed as a dominant phenotype in hybrids, indicating that mouse cells do not actively suppress 229E replication. HCVS segregated concordantly with the human chromosome 15 enzyme markers mannose phosphate isomerase (MPI) and the muscle form of pyruvate kinase (PKM2), and analysis of hybrids containing an X/15 translocation [t(X;15)(p11;q11)] localized HCVS to the q11 → qter region of chromosome 15. HCVS might code for a specific surface receptor, allowing 229E to be absorbed to and received within the host cell.


title: Age-related pattern of KI and WU polyomavirus infection

text: Abstract Background The role of two recently identified polyomaviruses, KI and WU, in the causation of respiratory disease has not been established. Objectives To determine the prevalence of KI and WU viruses (KIV and WUV) in 371 respiratory samples and evaluate their contribution to respiratory disease. Study Design Specimens were screened for KIV and WUV using single, multiplex or real time PCR; co-infection with other respiratory viruses was evaluated. Results Of the 371 samples analysed, 10 (2.70%) were positive for KIV and 4 (1.08%) were positive for WUV yielding an overall case prevalence of KIV and WUV infection of 3.77%. KIV and WUV were identified in patients aged <15 years (11 patients) with upper or lower respiratory tract infection and >45 years (3 patients) with upper respiratory tract infection. Co-infections were found in 5 (50%) and 3 (75%) of the KIV and WUV positive samples, respectively. Conclusions This study supports previous conclusions that KIV and WUV detection in the respiratory tract may be coincidental and reflect reactivation of latent or persistent infection with these viruses. The age distribution of KIV and WUV infection in this study mirrors that found for the other human polyomaviruses, BK and JC.


title: A randomized trial to examine the mechanisms of cognitive, behavioral and mindfulness-based psychosocial treatments for chronic pain: Study protocol

text: Abstract This randomized trial will evaluate the mechanisms of three chronic pain treatments: cognitive therapy (CT), mindfulness meditation (MM), and activation skills (AS). We will determine the extent to which late-treatment improvement in primary outcome (pain interference) is predicted by early-treatment changes in cognitive content, cognitive process, and/or activity level. The shared versus specific role of these mechanisms across the three treatments will be evaluated during treatment (Primary Aim), and immediately post-treatment to examine relapse mechanisms (Secondary Aim). We will enroll 300 individuals with chronic pain (with low back pain as a primary or secondary condition), with 240 projected to complete the study. Participants will be randomly assigned to eight, 1.5 h telehealth group sessions of CT, MM, or AS. Mechanisms and outcomes will be assessed twice daily during 2-week baseline, 4-week treatment period, and 4-week post-treatment epoch via random cue-elicited ecological momentary assessment (EMA); activity level will be monitored during these time epochs via daily monitoring with ActiGraph technology. The primary outcome will be measured by the PROMIS 5-item Pain Interference scale. Structural equation modeling (SEM) will be used to test the primary aims. This study is pre-registered on clinicaltrials.gov (Identifier: NCT03687762). This study will determine the temporal sequence of lagged mediation effects to evaluate rates of change in outcome as a function of change in mediators. The findings will provide an empirical basis for enhancing and streamlining psychosocial chronic pain interventions. Further, results will guide future efforts towards optimizing maintenance of gains to effectively reduce relapse risk.


title: COVID-19 and digital disruption in UK universities: afflictions and affordances of emergency online migration

text: COVID-19 has caused the closure of university campuses around the world and migration of all learning, teaching, and assessment into online domains. The impacts of this on the academic community as frontline providers of higher education are profound. In this article, we report the findings from a survey of n = 1148 academics working in universities in the United Kingdom (UK) and representing all the major disciplines and career hierarchy. Respondents report an abundance of what we call ‘afflictions’ exacted upon their role as educators and in far fewer yet no less visible ways ‘affordances’ derived from their rapid transition to online provision and early ‘entry-level’ use of digital pedagogies. Overall, they suggest that online migration is engendering significant dysfunctionality and disturbance to their pedagogical roles and their personal lives. They also signpost online migration as a major challenge for student recruitment, market sustainability, an academic labour-market, and local economies.


title: Two types of transmembrane homomeric interactions in the integrin receptor family are evolutionarily conserved

text: Integrins are heterodimers, but recent in vitro and in vivo experiments suggest that they are also able to associate through their transmembrane domains to form homomeric interactions. Two fundamental questions are the biological relevance of these aggregates and their form of interaction in the membrane domain. Although in vitro experiments have shown the involvement of a GxxxG‐like motif, several crosslinking in vivo data are consistent with an almost opposite form of interaction between the transmembrane α‐helices. In the present work, we have explored these two questions using molecular dynamics simulations for all available integrin types. We have tested the hypothesis that homomeric interactions are evolutionary conserved, and essential for the cell, using conservative substitutions to filter out nonnative interactions. Our results show that two models, one involving a GxxxG‐like motif (model I) and an almost opposite form of interaction (model II) are conserved across all α and β integrin types, both in homodimers and homotrimers, with different specificities. No conserved interaction was found for homotetramers. Our results are completely independent from experimental data, both during molecular dynamics simulations and in the selection of the correct models. We rationalize previous seemingly conflicting findings regarding the nature of integrin interhelical homomeric interactions. Proteins 2006. © 2006 Wiley‐Liss, Inc.


title: Evans syndrome in a patient with COVID‐19

text: Evans syndrome (ES) is a rare condition characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia (ITP). While the precise pathophysiology is not entirely understood, it is believed that dysregulation of the immune system is a primary contributor to the condition. ES has been observed in viral infections including hepatitis C, cytomegalovirus, varicella‐zoster, and Epstein‐Barr viruses (1‐4). Initial cases of coronavirus disease 2019 (COVID‐19) were first described in early December 2019 and has now spread to a global pandemic. While knowledge about COVID‐19 continues to evolve, clinicians have reported hematologic complications associated with the virus.


title: SARS to novel coronavirus – old lessons and new lessons

text: The response to the novel coronavirus outbreak in China suggests that many of the lessons from the 2003 SARS epidemic have been implemented and the response improved as a consequence. Nevertheless some questions remain and not all lessons have been successful. The national and international response demonstrates the complex link between public health, science and politics when an outbreak threatens to impact on global economies and reputations. The unprecedented measures implemented in China are a bold attempt to control the outbreak – we need to understand their effectiveness to balance costs and benefits for similar events in the future.


title: Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

text: Abstract Ethnopharmacological relevance Licorice (Glycyrrhiza uralensis Fisch., Leguminosae) has been used in herbal medicine and food supplement worldwide for centuries. Licorice is a common ingredient of several prescriptions of traditional Chinese medicine which have been proved to inhibit infection of human respiratory syncytial virus (HRSV). There are two preparations of licorice, Radix Glycyrrhizae and Radix Glycyrrhizae Preparata. However, it is unknown whether licorice or which preparation of licorice is effective against HRSV, nor is its active constituent. Aim of the study We tested the hypothesis that Radix Glycyrrhizae can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines. We also tried to find out the active constituent. Materials and methods Anti-HRSV activities of hot water extracts of preparations of licorice, glycyrrhizin and 18β-glycyrrhetinic acid (18β-GA), the active constituents of licorice, were examined by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Abilities of crude licorice to inhibit viral replication and to stimulate IFN-β were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results Radix Glycyrrhizae and Radix Glycyrrhizae Preparata dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). The effect of Radix Glycyrrhizae was better than that of Radix Glycyrrhizae Preparata on HEp-2 cells. However, there was no difference of their anti-HRSV effects on A549 cells. Besides, glycyrrhizin was ineffective at all. Nevertheless, 18β-GA showed a potent anti-HRSV activity. Radix Glycyrrhizae was more effective when given before viral inoculation (p<0.0001) which may be due to its inhibition of viral attachment on (p<0.0001) and penetration (p<0.0001) into the host cells. The anti-HRSV activity of Radix Glycyrrhizae was further confirmed by RT-PCR and qRT-PCR. 300μg/ml Radix Glycyrrhizae markedly decreased the viral amounts within the cells and in the suspension. Radix Glycyrrhizae might further stimulate mucosal cells to secrete IFN-β to counteract viral infection. Conclusions Both Radix Glycyrrhizae and Radix Glycyrrhizae Preparata are effective against HRSV infection on airway epithelial cells. Radix Glycyrrhizae inhibited HRSV mainly by preventing viral attachment, internalization, and by stimulating IFN secretion. 18β-GA may be one of its active constituents.


title: Avian preparedness: simulations of bird diseases and reverse scenarios of extinction in Hong Kong, Taiwan, and Singapore

text: This article describes relations between humans, animals, artefacts, and pathogens in simulations of disasters, taking bird diseases in three Chinese sentinel posts as ethnographic cases. Drawing on distinctions between simulation, ritual, and play, it shows that the engagement of actors in the imaginary of simulations, which they describe as ‘realism’, reflectively reverses the oppositions between humans and nonhumans, active and passive, fiction and reality that shape ordinary life. Borrowing from the anthropology of hunting societies, it argues that simulations of bird diseases, considered as signs of future species extinction, rely on cynegetic techniques of power, in which humans and animals symmetrically shift perspectives, and not only on pastoralist techniques, in which humans are above the population they monitor and sometimes sacrifice.


title: Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

text: BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.


title: The Effect of Viral Infection on Exhaled Nitric Oxide in Children with Acute Asthma Exacerbations

text: Background Fraction of exhaled nitric oxide (Feno) level is used as an aid in the diagnosis and management of chronic asthma. Its role in acute asthma remains to be studied. Objective To determine whether Feno levels are elevated in children with asthma exacerbations compared with baseline, and whether there is a difference in Feno levels based on PCR positive (+) (respiratory virus isolated by PCR analysis) versus PCR negative (−) (respiratory virus not isolated by PCR analysis) status. Methods Children with a previous Feno level measurement while stable and who presented to an urgent care facility with an asthma exacerbation were enrolled. Feno levels, spirometry, and nasal swabs for viral PCR were obtained at the time of the exacerbation and following a course of prednisone. Data were available on 66 children. Linear mixed models were used to regress the outcomes of interest (FEV1, FEV1/forced vital capacity, forced expiratory flow at 25% to 75% of forced vital capacity, and natural log Feno) on detected virus (yes/no), visit (baseline, exacerbation, follow-up), and the interaction between the detected virus and visit. Results Compared with baseline, higher Feno values and lower lung function were found at the time of an exacerbation. A respiratory virus was detected in 59% of the exacerbations. The interaction between PCR (+) and PCR (−) groups and visit on log Feno was marginally significant (P = .07). There was no difference in log Feno between the PCR (+) and PCR (−) groups at baseline, while higher log Feno was found in the PCR (−) group at the time of exacerbation and following prednisone (P = .05 and .001, respectively). Conclusions Higher Feno concentration in PCR (−) exacerbations suggests an eosinophilic predominance in nonviral compared with viral exacerbations.


Kawasaki disease patients homozygous for the rs12252-C variant of interferon-induced transmembrane protein-3 are significantly more likely to develop coronary artery lesions


title: ADAMs and ADAMTSs

text: Proteolysis has emerged as a key post-translational regulator of the function of molecules on the cell surface and in the extracellular milieu. In principle, proteolysis can activate or inactivate a substrate, or can change its functional properties. ADAMs (a disintegrin and metalloprotease) and ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin type 1 repeats) proteases are related members of a superfamily of metallo-endopeptidases that also includes MMPs and astacins. ADAMs are integral membrane proteins that typically cleave other membrane anchored proteins, whereas ADAMTS proteases lack a membrane anchor, and process both cell-surface and secreted molecules, the latter mostly extracellular matrix (ECM) components. ADAMs are implicated in fertilization, neurogenesis, in regulating the function of ligands for the EGF-receptor, and in the release of proteins such as the pro-inflammatory cytokine TNFα from the plasma membrane. ADAMTS proteases have key roles in embryonic development, including lung development, the molecular maturation of von Willebrand factor and procollagen as well as organization of fibrillin microfibrils in ECM, and are implicated in the pathogenesis of diverse lung and airway disorders. Here, we provide a general overview of the biochemical properties and physiological functions of ADAMs and ADAMTS proteases and describe their relevance to lung and airway disorders.


title: COVID-19 and the academy: It is time for going digital

text: In many countries, the lock-down due to the COVID-19 pandemic triggered discussions on the use of digital interaction formats for academic exchange. The pace with which researchers adopted digital formats for conferences, lectures, and meetings revealed that currently available tools can substitute many of the physical interactions in the workplace. It also showed that academics are willing to use digital tools for scientific exchange. This article sheds light on scholars' experiences with digital formats and tools during the pandemic. We argue that digital interaction formats increase the inclusivity of knowledge exchange, reduce time and costs of organizing academic interactions, and enable more diverse workspaces with geographical and temporal flexibility. However, we also observe that digital interaction formats struggle to reproduce social interactions such as informal discussions, raise new concerns on data security, and can induce higher stress levels due to the blurring of the boundaries between work and private spaces. We argue that digital formats are not meant to substitute physical interactions entirely, but rather reshape how research communities operate and how academics socialize. We expect hybrid formats to emerge, which combine digital and physical interaction formats, and an increase in digital interactions between geographically distant working groups. We conclude that the time has come for digital interaction formats to be part of a new regime in the field of academic exchange.


title: Micro-Foundations of Diverging Economic Policies: Keynesian, Behavioural, Neoclassic

text: Germany’s austerity-oriented economic policy is the wrong approach. Markets need demand stimulation to achieve full use of resources, argues Krugman, a Keynesian economist. Neoclassical economists have been warning that expansionary macroeconomic policies are not only useless but can even be harmful (e.g. Phelps). These stark differences in the evaluation of economic policy proposals are deeply rooted in their underlying microeconomic reasoning, in the theories of the motivation and behaviour of economic agents as investors, workers, consumers and speculators as well as their interactions. The claim of missing micro-foundations in Keynes’s theory is false. In contrast, recent findings of behavioural economics have strongly confirmed Keynes’s micro-foundations that lead to his macroeconomic conclusions.


title: COVID-19: a case for inhibiting IL-17?

text: IL-17 and IL-17 receptor inhibitors boast an impressive safety history and are widely available. Here, we argue that targeting IL-17 is immunologically plausible as a strategy to prevent acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) and discuss why we think that a clinical trial of a drug in this class could be a logical addition to the effort to find effective therapies.


title: A SARS-CoV-2 serological assay to determine the presence of blocking antibodies that compete for human ACE2 binding

text: As SARS-CoV-2 continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Convalescent serum is being used for treatment and for isolation of patient-derived antibodies. However, currently there is not a simple means to estimate serum bulk neutralizing capability. Here we present an efficient competitive serological assay that can simultaneously determine an individual’s seropositivity against the SARS-CoV-2 Spike protein and estimate the neutralizing capacity of anti-Spike antibodies to block interaction with the human angiotensin converting enzyme 2 (ACE2) required for viral entry. In this ELISA-based assay, we present natively-folded viral Spike protein receptor binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then supplemented with soluble ACE2-Fc to compete for RBD-binding serum antibodies, and antibody binding quantified. Comparison of signal from untreated serum and ACE2-Fc-treated serum reveals the presence of antibodies that compete with ACE2 for RBD binding, as evidenced by loss of signal with ACE2-Fc treatment. In our test cohort of nine convalescent SARS-CoV-2 patients, we found all patients had developed anti-RBD antibodies targeting the epitope responsible for ACE2 engagement. This assay provides a simple and high-throughput method to screen patient sera for potentially neutralizing anti-Spike antibodies to enable identification of candidate sera for therapeutic use.