title: Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics

text: Vero cells transfected with either neo- or bcl-2-plasmid were infected with SARS-CoV at a high multiplicity of infection. Apoptosis appeared after the onset of CPE and completion of virus replication, and could be prevented by Bcl-2 expression. Apoptosis is likely mediated by the mitochondrial pathway, as demonstrated by its inhibition using Bcl-2, and by the activation of the caspase cascade, resulting in PARP cleavage. Prevention of apoptosis did not affect susceptibility to infection, kinetics and extent of viral replication and release, thus implying that apoptosis is not involved in facilitating release and/or dissemination of SARS-CoV in Vero cells.


title: Borna Disease Virus and its role in Neurobehavioral Diseases Ladanyi M Kathryn M

text: Unknown


Call for improvement in personal protective equipment guidance and research


title: Molecular detection of Pneumocystis in the lungs of cats

text: The genus Pneumocystis comprises potential pathogens that reside normally in the lungs of a wide range of mammals. Although they generally behave as transient or permanent commensals, they can occasionally cause life-threatening pneumonia (Pneumocystis pneumonia; PCP) in immunosuppressed individuals. Several decades ago, the presence of Pneumocystis morphotypes (trophic forms and cysts) was described in the lungs of normal cats and cats with experimentally induced symptomatic PCP (after immunosuppression by corticosteroids); yet to date spontaneous or drug-induced PCP has not been described in the clinical feline literature, despite immunosuppression of cats by long-standing retrovirus infections or after kidney transplantation. In this study, we describe the presence of Pneumocystis DNA in the lungs of normal cats (that died of various unrelated causes; n = 84) using polymerase chain reactions (PCRs) targeting the mitochondrial small and large subunit ribosomal RNA gene (mtSSU rRNA and mtLSU rRNA). The presence of Pneumocystis DNA was confirmed by sequencing in 24/84 (29%) cats, with evidence of two different sequence types (or lineages). Phylogenetically, lineage1 (L1; 19 cats) and lineage 2 (L2; 5 cats) formed separate clades, clustering with Pneumocystis from domestic pigs (L1) and carnivores (L2), respectively. Results of the present study support the notion that cats can be colonized or subclinically infected by Pneumocystis, without histological evidence of damage to the pulmonary parenchyma referable to pneumocystosis. Pneumocystis seems most likely an innocuous pathogen of cats’ lungs, but its possible role in the exacerbation of chronic pulmonary disorders or viral/bacterial coinfections should be considered further in a clinical setting.


Characteristics and Palliative Care Needs of COVID‐19 Patients Receiving Comfort‐Directed Care


title: Intravenous immunoglobulin for infectious diseases: back to the pre-antibiotic and passive prophylaxis era?

text: Abstract The dramatic increase in both the number of novel infectious agents and resistance to antimicrobial drugs has incited the need for adjunct therapies in the war against infectious diseases. Exciting recent studies have demonstrated the use of antibodies in the form of intravenous immunoglobulin (IVIg) against infections. By virtue of the diverse repertoire of immunoglobulins that possess a wide spectrum of antibacterial and antiviral specificities, IVIg provides antimicrobial efficacy independently of pathogen resistance and represents a promising alternative strategy for the treatment of diseases for which a specific therapy is not yet available.


title: Coronavirus-induced ER stress response and its involvement in regulation of coronavirus–host interactions

text: Abstract Coronavirus replication is structurally and functionally associated with the endoplasmic reticulum (ER), a major site of protein synthesis, folding, modification and sorting in the eukaryotic cells. Disturbance of ER homeostasis may occur under various physiological or pathological conditions. In response to the ER stress, signaling pathways of the unfolded protein response (UPR) are activated. UPR is mediated by three ER transmembrane sensors, namely the PKR-like ER protein kinase (PERK), the inositol-requiring protein 1 (IRE1) and the activating transcriptional factor 6 (ATF6). UPR facilitates adaptation to ER stress by reversible translation attenuation, enhancement of ER protein folding capacity and activation of ER-associated degradation (ERAD). In cells under prolonged and irremediable ER stress, UPR can also trigger apoptotic cell death. Accumulating evidence has shown that coronavirus infection causes ER stress and induces UPR in the infected cells. UPR is closely associated with a number of major signaling pathways, including autophagy, apoptosis, the mitogen-activated protein (MAP) kinase pathways, innate immunity and pro-inflammatory response. Therefore, studies on the UPR are pivotal in elucidating the complicated issue of coronavirus-host interaction. In this paper, we present the up-to-date knowledge on coronavirus-induced UPR and discuss its potential involvement in regulation of innate immunity and apoptosis.


title: Persistence of intestinal SARS-CoV-2 infection in patients with COVID-19 leads to re-admission after pneumonia resolved

text: Abstract The current reports of COVID-19 focus on the respiratory system, but intestinal infections caused by SARS-CoV-2 are also worthy of attention. Here we report persistence of intestinal SARS-CoV-2 infection in three cases with COVID-19 leads to re-admission after pneumonia resolved.


Verrast


title: The impact of SARS on hospital performance

text: BACKGROUND: During the SARS epidemic, healthcare utilization and medical services decreased significantly. However, the long-term impact of SARS on hospital performance needs to be further discussed. METHODS: A municipal hospital in Taipei City was shut down for a month due to SARS and then became the designated SARS and infectious disease hospital for the city. This study collected the outpatient, inpatient and emergency service volumes for every year from April to March over four years. Average monthly service amount ± standard deviation were used to compare patient volume for the whole hospital, as well as the outpatient numbers accessing different departments. The ARIMA model of outpatient volume in the pre-SARS year was developed. RESULTS: The average monthly service volume of outpatient visits for the base year 2002 was 52317 ± 4204 visits per month, and number for 2003 and the following two years were 55%, 82% and 84% of the base year respectively. The average emergency service volume was 4382 ± 356 visits per month at the base year and this became 45%, 77% and 87% of the base year for the following three years respectively. Average inpatient service volume was 8520 ± 909 inpatient days per month at the base year becoming 43%, 81% and 87% of the base year for the following three years respectively. Only the emergency service volume had recovered to the level of a non-significant difference at the second year after SARS. In addition, the departments of family medicine, metabolism and nephrology reached the 2002 patient number in 2003. The ARIMA (2,1,0) model was the most suitable for outpatient volume in pre-SARS year. The MAPE of the ARIMA (2,1,0) model for the pre-SARS year was 6.9%, and 43.2%, 10.6%, 6.2% for following 3 years. CONCLUSION: This study demonstrates that if a hospital is completely shut down due to SARS or a similar disease, the impact is longer than previous reported and different departments may experience different recover periods. The findings of this study identify subspecialties that are particularly vulnerable in an infectious disease designated hospital and such hospitals need to consider which subspecialties should be included in their medical structure.


Rhinovirus durant l’enfance : asthme à l’adolescence ? Paradoxe de l’œuf et de la poule ?


title: Follow-up studies in COVID-19 recovered patients - is it mandatory?

text: Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.


title: Characterization of N protein self-association in coronavirus ribonucleoprotein complexes

text: Abstract Mouse hepatitis virus (MHV) nucleocapsid (N) protein binds to the large, single-stranded, positive-sense viral genomic RNA to form a helical nucleocapsid structure in mature virions. In addition N protein binds the intracellular form of the genomic RNA, all of the MHV subgenomic mRNAs, and expressed non-MHV RNA transcripts to form ribonucleoprotein (RNP) complexes in infected cells. Among the intracellular viral RNP complexes, only the genomic RNP complex is packaged into virus particles. The present study demonstrated that N protein in the MHV virion nucleocapsid and in the intracellular genome-length RNP complex that bound to viral envelope M protein was tightly self-associated such that its association was retained even after extensive RNase A-treatment of the RNP complexes. The RNase A-resistant tight N protein association in the virion nucleocapsid was not mediated by an intermolecular disulfide bridge between N proteins. In contrast, N protein association in the majority of the intracellular RNP complexes was susceptible to RNase A-treatment. Because the RNP complexes that specifically interact with the M protein are selectively packaged into MHV particles, the present data suggested that there was a distinct difference between N protein association in viral genomic RNP complexes that undergo packaging into virus particles and the subgenomic RNP complexes that are not packaged into MHV particles.


title: Immunization with Cry1Ac from Bacillus Thuringiensis Increases Intestinal IgG Response and Induces the Expression of FcRn in the Intestinal Epithelium of Adult Mice

text: We have shown that Cry1Ac protoxin from Bacillus thuringiensis is a potent mucosal and systemic immunogen with adjuvant properties. Interestingly, we have observed that Cry1Ac preferentially induces high specific IgG responses in intestinal fluid when it is intraperitoneally administered to mice; therefore, in the present study, we used this protocol, as a model to address the influence of systemic immunization on the induction of the intestinal IgG response. The data shown indicate that upon intraperitoneal immunization with Cry1Ac, significant intestinal specific IgG cell responses were produced in the lamina propria, accompanied by an increased frequency of intestinal IgG+ lymphocytes and epithelial cells containing IgG. Considering that FcRn is the receptor responsible for the transport of IgG in neonatal intestinal epithelia, but it is developmentally downregulated in the rodent intestine, we analysed whether upon intestinal IgG induction, FcRn mRNA expression was induced in intestinal epithelial cells, of adult mice. Whereas in intestinal epithelia of unimmunized adult mice FcRn mRNA was not detected, in Cry1Ac immunized mice it was expressed, although the level was lower in comparison with that found in neonatal epithelia. Then using flow cytometry and immunofluorescence we confirmed that the expression of the protein FcRn was induced in the intestines of adult immunized mice especially in the large intestine. Finally, we found that Cry1Ac also increased FcRn expression in isolated intestinal epithelial cells stimulated in vitro. The outcomes suggest that the expression of FcRn in intestinal epithelium might be reactivated upon immunization, and possibly facilitate IgG transport.


title: Human migration and infectious diseases

text: Emerging infectious diseases (EID) are defined as diseases that have appeared recently or that have recently increased in their frequency, geographical distribution or both. Commercial globalisation, population movements and environmental changes are the main factors favouring the international spread of microorganisms. Transport and communication development constitutes also a remarkable factor in the worldwide dispersion of microorganisms. The mass movement of large numbers of people creates new opportunities for the spread and establishment of common or novel infectious diseases. A surveillance system to detect emergent and re-emergent infections, a rapid responsiveness of healthcare systems and laboratories, vector control, and the provision of healthcare education programmes to inform the population of how to avoid infections are needed in order to stop the spread of infectious diseases.


title: Discovery of Hydrocarbon-Stapled Short α-Helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors

text: [Image: see text] The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide’s native α-helical conformation when taken out of the parent protein structure. Here, we describe that appropriate all-hydrocarbon stapling of the short helical portion-based peptide to reinforce its bioactive secondary structure remarkably improves antiviral potency. The resultant stapled peptide P21S10 could effectively inhibit infection by MERS-CoV pseudovirus and its spike protein-mediated cell–cell fusion; additionally, P21S10 exhibits improved pharmacokinetic properties than HR2P-M2, suggesting strong potential for development as an anti-MERS-CoV therapeutic.


title: Quantitation of canine coronavirus RNA in the faeces of dogs by TaqMan RT-PCR

text: Abstract A TaqMan® fluorogenic reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed for the detection and quantitation of canine coronavirus (CCoV) RNA in the faeces of naturally or experimentally infected dogs. The CCoV fluorogenic RT-PCR assay, which targeted the ORF5 (M gene), was more sensitive than a conventional RT-PCR assay targeting the same gene, showing a detection limit of 10 copies of CCoV standard RNA, and was linear from 10 to 108 copies, allowing quantitation of samples with a wide range of CCoV RNA loads. A total of 78 faecal samples of diarrhoeic dogs were tested simultaneously by conventional and fluorogenic RT-PCR: 29 were negative by both techniques, whereas 27 tested positive by conventional RT-PCR and 48 by the established CCoV fluorogenic assay. One sample, which was positive by conventional RT-PCR, gave no signal in the fluorogenic assay. In addition, by the fluorogenic assay CCoV shedding in the faecal samples of an experimentally infected dog was monitored for 28 days. The high sensitivity, simplicity and reproducibility of the CCoV fluorogenic RT-PCR assay, combined with its wide dynamic range and high throughput, make this method especially suitable for efficacy trials on CCoV vaccines.


title: Influenza B virus infections in Western Saxony, Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features

text: BACKGROUND: The impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine). AIM: The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. METHODS: Partial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts. FINDINGS: During the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza. INTERPRETATION: Phylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar. CONCLUSION: World Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines. FUNDING: This research was partially supported by the Association of Sponsors and Friends of Leipzig University.


Survey of Ophthalmology in the Time of COVID-19


title: RNA recombination in the genome of Barley stripe mosaic virus

text: Abstract Barley stripe mosaic Hordeivirus (BSMV) is a positive-strand RNA virus requiring three single-stranded RNAs (α, β, and γ) for infectivity. A terminal-sequence-dependent cloning strategy was used to clone the entire genome of the CV17 strain. Full-length γ cDNA clones were obtained when oligonucleotides specific for the 5′-terminal sequence of RNA α were used in the cloning procedure, but not when RNA γ-specific oligonucleotides were used. Sequence analysis of six putative γ cDNA clones revealed that nucleotides 1–70 possess 89% homology with the first 70 nucleotides of RNA α. This leader region is separated from the γ-specific coding region by an eight-base intervening sequence common to both CV17 RNAs α and γ. Northern and Southern hybridization with oligonucleotide probes specific for either α or γ leader sequences indicated that CV17 γ cDNA clones are representative of native CV17 γ RNAs. Furthermore, bioassays indicated that in vitro transcripts derived from these γ cDNA clones were infectious when coinoculated with in vitro transcripts of full-length α and β cDNA clones. Thus, the evidence suggests that RNA γ of BSMV strain CV17 is a recombinant molecule which may have arisen as a result of natural recombination between RNAs α and γ.


title: Chapter 13 Host Genetics It Is Not Just the Virus, Stupid

text: Abstract Much of the focus of viral pathogenesis is on viral virulence factors; however, virulence can only be defined in the context of a virus–host combination. Furthermore, there is abundant evidence that highly pathogenic viruses have been selected for specific host genetic variants within the target population. The identification and mechanistic dissection of host genetic polymorphisms therefore has powerful implications for our understanding of viral diseases, including the identification of novel therapeutic targets. In this chapter, we review the classical approaches used to identify host allelic variations that regulate disease susceptibility. We also discuss next-generation molecular technologies and computational approaches that are poised to revolutionize our understanding of the impact of host genetic variation on viral diseases at the population level.


title: T-bet(+) Treg Cells Undergo Abortive Th1 Cell Differentiation due to Impaired Expression of IL-12 Receptor β2

text: Foxp3(+) regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis. Although comprised of several phenotypically and functionally distinct subsets, the differentiation of specialized Treg cell populations within the periphery is poorly characterized. We demonstrate that the development of T-bet(+) Treg cells that potently inhibit T helper (Th)1 cell responses was dependent on the transcription factor STAT1, and occurred directly in response to interferon-γ produced by effector T cells. Additionally, delayed induction of the IL-12Rβ2 receptor component following STAT1 activation helped ensure that Treg cells do not readily complete STAT4-dependent Th1 cell development and lose their ability to suppress effector T cell proliferation. Thus, we define a pathway of abortive Th1 cell development that results in the specialization of peripheral Treg cells, and demonstrate that impaired expression of a single cytokine receptor helps maintain Treg cell suppressive function in the context of inflammatory Th1 cell responses.


title: Review of evidence on using ACEi and ARBs in patients with hypertension and COVID-19

text: COVID-19 has recently become a major pandemic with associated socioeconomic dimensions. Mortality statistics suggest that COVID-19 is more lethal in aged patients with comorbid conditions including hypertension. There is ongoing debate about whether the use of angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are useful or hazardous in patients with COVID-19, with both narratives supported by researchers with different hypotheses. The researchers supporting the use of these medications believe ACE2 functional blockers may block cellular entry of the SARS-CoV-2 virus and thus improve patient outcomes. The counter viewpoint argues that continuous use of these drugs results in hyperexpression of ACE2 receptors on respiratory epithelium allowing easier SARS-CoV-2 intracellular entry, resulting in enhanced viral replication and tissue damage. This short review discusses the available research on the subject with the objective to consolidate data to allow formulation of recommendations on their use or otherwise. Moreover, the authors also suggest areas for future research on the subject.


title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe

text: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient’s sequence clustered with sequences from Germany while the tourist’s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients’ sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.


title: Expression, crystallization and preliminary X-ray diffraction analysis of the N-terminal domain of nsp2 from avian infectious bronchitis virus

text: Avian infectious bronchitis virus (IBV) is a prototype of the group III coronaviruses and encodes 15 nonstructural proteins which make up the transcription/replication machinery. The nsp2 protein from IBV has a unique and novel sequence and has no experimentally confirmed function in replication, whereas it has been proposed to be crucial for early viral infection and may inhibit the early host immune response. The gene that encodes a double-mutant IBV nsp2 N-terminal domain (residues 9–393 of the polyprotein, with mutations Q132L and L270F) was cloned and expressed in Escherichia coli and the protein was subjected to crystallization trials. The crystals diffracted to 2.5 Å resolution and belonged to space group P6(2) or P6(4), with unit-cell parameters a = b = 114.2, c = 61.0 Å, α = β = 90, γ = 120°. Each asymmetric unit contained one molecule.


title: Ligand recognition by antigen-presenting cell C-type lectin receptors

text: It is now appreciated that the range of ligands interacting with C-type lectin type receptors on antigen presenting cells includes endogenous self-molecules as well as pathogens and pathogen-derived ligands. Interestingly, not all interactions between these receptors and pathogenic ligands have beneficial outcomes, and it appears that some pathogens have evolved immunoevasive or immunosuppressive activities through receptors such as DC-SIGN. In addition to this, recent data indicate that the well-characterised macrophage mannose receptor is not essential to host defence against fungal pathogens, as previously thought, but has an important role in regulating endogenous glycoprotein clearance. New studies have also demonstrated that different ligand binding and/or sensing receptors collaborate for full and effective immune responses.


title: Estimating the nationwide transmission risk of measles in US schools and impacts of vaccination and supplemental infection control strategies

text: BACKGROUND: The spread of airborne infectious diseases such as measles is a critical public health concern. The U.S. was certified measles-free in 2000, but the number of measles cases has increased in recent years breaking the record of the nationwide annual number of cases since 1992. Although the characteristics of schools have made them one of the most vulnerable environments during infection outbreaks, the transmission risk of measles among students is not completely understood. We aimed to evaluate how three factors influence measles transmission in schools: personal (vaccination), social (compartmentalizing), and building systems (ventilation, purification, and filtration). METHODS: We used a combination of a newly developed multi-zone transient Wells-Riley approach, a nationwide representative School Building Archetype (SBA) model, and a Monte-Carlo simulation to estimate measles risk among U.S. students. We compared our risk results with the range of reported transmission rates of measles in school outbreaks to validate the risk model. We also investigated the effectiveness of vaccination and ten supplemental infection control scenarios for reducing the risk of measles transmission among students. RESULTS: Our best nationwide estimate of measles transmission risk in U.S. schools were 3.5 and 32% among all (both unvaccinated and immunized) and unvaccinated students, respectively. The results showed the transmission risk of measles among unvaccinated students is > 70 times higher than properly immunized ones. We also demonstrated that the transmission risk of measles in primary schools (assuming teacher self-contained classrooms) is less than secondary schools (assuming departmentalized systems). For building-level interventions, schools with ductless-with-air-filter and ductless-without-air-filter systems have the lowest and highest transmission risks of measles, respectively. Finally, our simulation showed that infection control strategies could cut the average number of infected cases among all students in half when a combination of advanced air filtration, ventilation, and purification was adopted in the modeled schools. CONCLUSIONS: Our results highlight the primary importance of vaccination for reducing the risk of measles transmission among students. Yet, additional and significant risk reduction can be achieved through compartmentalizing students and enhancing building ventilation and filtration systems.


title: Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

text: PURPOSE: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. METHODS: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. RESULTS: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.


title: Society of Cardiovascular Computed Tomography Guidance for Use of Cardiac Computed Tomography Amidst the COVID-19 Pandemic

text: Abstract The world is currently suffering through a pandemic outbreak of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) known as Coronavirus Disease 2019 (COVID-19). The United States (US) Centers for Disease Control and Prevention (CDC) currently advises medical facilities to “reschedule non-urgent outpatient visits as necessary” (1). The European Centre for Disease Prevention and Control, the United Kingdom National Health Service and several other international agencies covering Asia, North America and most regions of the world have recommended similar “social distancing” measures(2, 3). The Society of Cardiovascular Computed Tomography (SCCT) offers guidance for cardiac CT (CCT) practitioners to help implement these international recommendations in order to decrease the risk of COVID-19 transmission in their facilities while deciding on the timing of outpatient and inpatient CCT exams. This document also emphasizes SCCT’s commitment to the health and well-being of CCT technologists, imagers, trainees, and research community, as well as the patients served by CCT.


title: Localization of ribophorin II to the endoplasmic reticulum involves both its transmembrane and cytoplasmic domains

text: Summary Proteins that are concentrated in specific compartments of the endomembrane system in order to exert their organelle-specific function must possess specific localization signals that prevent their transport to distal regions of the exocytic pathway. Some resident proteins of the endoplasmic reticulum (ER) that are known to escape with low efficiency from this organelle to a post ER compartment are recognized by a recycling receptor and brought back to their site of residence. Other ER proteins, however, appear to be retained in the ER by mechanisms that operate in the organelle itself. The mammalian oligosaccharyltransferase (OST) is a protein complex that effects the cotranslational N-glycosylation of newly synthesized polypeptides, and is composed of at least four rough ER-specific membrane proteins: ribophorins I and II (RI and RII), OST48, and Dad1. The mechanism(s) by which the subunits of this complex are retained in the ER are not well understood. In an effort to identify the domains within RII responsible for its ER localization we have studied the fate of chimeric proteins in which one or more RII domains were replaced by the corresponding ones of the Tac antigen, the latter being a well characterized plasma membrane protein that lacks intrinsic ER retention signals and serves to provide a neutral framework for the identification of retention signals in other proteins. We found that the luminal domain of RII by itself does not contain retention information, while the cytoplasmic and transmembrane domains contain independent ER localization signals. We also show that the retention function of the transmembrane domain is strengthened by the presence of a flanking luminal region consisting of 15 amino acids.


title: Formation of stable homodimer via the C-terminal α-helical domain of coronavirus nonstructural protein 9 is critical for its function in viral replication

text: Abstract Coronaviruses devote more than three quarters of their coding capacity to encode two large polyproteins (1a and 1ab polyproteins), which are proteolytically processed into 15–16 mature, nonstructural replicase proteins (nsp1 to 16). These cleavage products are believed to play essential roles in replication of the giant RNA genome of ∼30 kb and transcription of a nested set of 5 to 9 subgenomic RNA species by a unique discontinuous transcription mechanism. In this report, one of these replicase proteins, nsp9 of the coronavirus infectious bronchitis virus (IBV) is systematically studied using both biochemical and reverse genetic approaches. The results showed that substitution mutation of a conserved Gly (G98) residue in the C-terminal α-helix domain with an Asp greatly destabilized the IBV nsp9 homodimer and abolished its RNA-binding activity. Introduction of the same mutation into an infectious IBV clone system showed that the mutation totally abolishes the transcription of subgenomic RNA and no infectious virus could be recovered. Mutation of a semi-conserved Ile (I95) residue in the same region showed moderately destabilizing effect on the IBV nsp9 homodimer but minimal effect on its RNA-binding activity. Introduction of the mutation into the IBV infectious clone system showed recovery of a mutant virus with severe growth defects, supporting that dimerization is critical for the function of this replicase protein. Meanwhile, mutations of some positively charged residues in the β-barrel regions of the IBV nsp9 protein significantly reduced its RNA-binding activity, but with no obvious effect on dimerization of the protein. Introduction of these mutations into the viral genome showed only mild to moderate effects on the growth and infectivity of the rescued mutant viruses.


title: Are health care workers protected? An observational study of selection and removal of personal protective equipment in Canadian acute care hospitals

text: BACKGROUND: The proper use of personal protective equipment (PPE) by health care workers (HCWs) is vital in preventing the spread of infection and has implications for HCW safety. METHODS: An observational study was performed in 11 hospitals participating in the Canadian Nosocomial Infection Surveillance Program between January 7 and March 30, 2011. Using a standardized data collection tool, observers recorded HCWs selecting and removing PPE and performing hand hygiene on entry into the rooms of febrile respiratory illness patients. RESULTS: The majority of HCWs put on gloves (88%, n = 390), gown (83%, n = 368), and mask (88%, n = 386). Only 37% (n = 163) were observed to have put on eye protection. Working in a pediatric unit was significantly associated with not wearing eye protection (7%), gown (70%), gloves (77%), or mask (79%). Half of the observed HCWs (54%, n = 206) removed their PPE in the correct sequence. Twenty-six percent performed hand hygiene after removing their gloves, 46% after removing their gown, and 57% after removing their mask and/or eye protection. CONCLUSION: Overall adherence with appropriate PPE use in health care settings involving febrile respiratory illness patients was modest, particularly on pediatric units. Interventions to improve PPE use should be targeted toward the use of recommended precautions (eg, eye protection), HCWs working in pediatric units, the correct sequence of PPE removal, and performing hand hygiene.


title: Integrating spatial support tools into strategic planning—SEA of the GMS North–South Economic Corridor Strategy and Action Plan

text: Abstract The GMS countries, supported by the Asian Development Bank, have adopted a holistic, multidimensional approach to strengthen infrastructural linkages and facilitate cross border trade through (i) the establishment of a trans-boundary road connecting two economic nodes across marginalised areas, followed by 2) facilitation of environmentally and socially sound investments in these newly connected areas as a means to develop livelihoods. The North–South Economic Corridor is currently in its second phase of development, with investment opportunities to be laid out in the NSEC Strategy and Action Plan (SAP). It targets the ecologically and culturally sensitive border area between PR China's Yunnan Province, Northern Lao PDR, and Thailand. A trans-boundary, cross-sectoral Strategic Environmental Assessment was conducted to support the respective governments in assessing potential environmental and social impacts, developing alternatives and mitigation options, and feeding the findings back into the SAP writing process. Given the spatial dimension of corridor development—both with regard to opportunities and risks—particular emphasis was put in the application of spatial modelling tools to help geographically locate and quantify impacts as a means to guide interventions and set priorities.


Philanthropy and Humanity in the Face of a Pandemic – A letter to the editor on “World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)” (Int J Surg 2020; 76:71-6)


title: The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases

text: The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.


title: Computational and Experimental Studies of ADP-Ribosylation

text: The macrodomains are a multifunctional protein family that function as receptors and enzymes acting on poly(ADP-ribose), ADP-ribosylated proteins, and other metabolites of nicotinamide adenine dinucleotide (NAD(+)). Several new functions for macrodomains, such as nucleic acid binding and protein/protein interaction, have recently been identified in this family. Here, we discuss methods for the identification of new macrodomains in viruses and the prediction of their function. This is followed by the expression and purification of these proteins following overexpression in bacterial cells and confirmation of folding and function using biophysical methods.


title: Education, the science of learning, and the COVID-19 crisis

text: In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.


Feasibility of controlling COVID-19 – Authors' reply


title: Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent

text: PURPOSE: Muscle, bone and tendon regeneration depend on the microperfusion of the corresponding tissue which can be quantified with contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride contrast agent (SonoVue(®)). This study investigated the incidence of adverse events (AEs) in musculoskeletal patients and gives an overview of musculoskeletal CEUS applications. PATIENTS AND METHODS: Based on 13 studies in a standardized monocentric setting, a total of 2268 CEUS examinations in 764 patients were performed and AEs due to the administration of sulfur hexafluoride contrast agent were classified as either mild, moderate or severe. RESULTS: No fatal events occurred. AEs were reported in three cases, of which only one was classified as severe and two as mild. The total rate of all AEs was 0.13% and 0.04% for severe AEs. CONCLUSION: The present analysis confirms the safety of musculoskeletal CEUS using sulfur hexafluoride contrast agent with a lower rate of AEs than that reported for other contrast agents even in elderly patients with concomitant diseases.


title: Competition in Public Procurement in the Czech and Slovak Public Health Care Sectors

text: Sustainability of health financing is a critical issue for all countries, especially now in the COVID-19 period The final level of achievements of critical public health goals is connected not only with the efforts of the people involved, but also with the availability of funding to cover the costs of the actions needed One of the "internal sources" providing more resources to cover public health care costs is effective public procurement in the health care sector According to existing scientific literature, a low rate of competition represents one important factor that has a direct negative impact on the efficiency of public procurement The aim of our article is to examine the degree of competitiveness of public procurement in the Czech and Slovak health care systems and its impact on the final price of a contract The research fully attested the findings of those studies carried out so far - the higher the number of tenderers, the lower the final price, even in the Czech and Slovak health sectors However, the average number of tenderers is only around two and in the Czech Republic for more than half of the tenders only one bid was submitted


title: C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) break out from Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) has been associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature survey in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger’s regression analysis (intercept=0.04, P=0.98, 95%CI=-5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q=252.03, P(heterogeneity)= 0.000, I(2)=93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means= 1.371, P=0.000). CONCLUSIONS: Concentrations of CRP remained increased in patients who died in COVID-19 infection and could be a promising biomarker for accessing disease lethality.


title: Pathogenesis of severe acute respiratory syndrome

text: Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441–700 of the spike protein (S protein) as the major epitope.


title: Spatial associations of dockless shared e-scooter usage

text: In this study, we explore the usage of e-scooter sharing services in Austin, Texas over about a six-month period. The study is based on trip records of all the shared e-scooter operators in Austin and includes trip start and end locations. We use both analysis of trip patterns and spatial regression techniques to examine how the built environment, land use, and demographics affect e-scooter trip generation. Our findings show that people use e-scooters almost exclusively in central Austin. Commuting does not seem to be the main trip purpose, and usage of e-scooters is associated with areas with high employment rates, and in areas with bicycle infrastructure. People use e-scooter sharing regardless of the affluence of the neighborhood, although less affluent areas with high usage rates have large student populations, suggesting that students use this mode of travel. Implications for planners suggest that better bicycle infrastructure will facilitate e-scooter usage, college towns are a ready market for e-scooter sharing services, and e-scooters may be a substitute for some short non-work trips, reducing car usage, and benefiting the environment.


title: Using cellular automata to generate image representation for biological sequences

text: A novel approach to visualize biological sequences is developed based on cellular automata (Wolfram, S. Nature 1984, 311, 419–424), a set of discrete dynamical systems in which space and time are discrete. By transforming the symbolic sequence codes into the digital codes, and using some optimal space-time evolvement rules of cellular automata, a biological sequence can be represented by a unique image, the so-called cellular automata image. Many important features, which are originally hidden in a long and complicated biological sequence, can be clearly revealed thru its cellular automata image. With biological sequences entering into databanks rapidly increasing in the post-genomic era, it is anticipated that the cellular automata image will become a very useful vehicle for investigation into their key features, identification of their function, as well as revelation of their “fingerprint”. It is anticipated that by using the concept of the pseudo amino acid composition (Chou, K.C. Proteins: Structure, Function, and Genetics, 2001, 43, 246–255), the cellular automata image approach can also be used to improve the quality of predicting protein attributes, such as structural class and subcellular location.


A Long Journey Back to Normal Life


Protocol against coronavirus diseases in patients on renal replacement therapy: Dialysis and kidney transplant


Dengue et Covid-19, une association à haut risque


title: Massive use of disinfectants against COVID-19 poses potential risks to urban wildlife

text: • Globally, massive disinfectants are used to contain the rapid spread of COVID-19. • Applying massive disinfectants pose a significant threat to urban environment and wildlife. • Policies are required to minimize the adverse effects on wildlife due to overuse of disinfectants.


title: A numerical study of ventilation strategies for infection risk mitigation in general inpatient wards

text: Aerial dispersion of human exhaled microbial contaminants and subsequent contamination of surfaces is a potential route for infection transmission in hospitals. Most general hospital wards have ventilation systems that drive air and thus contaminants from the patient areas towards the corridors. This study investigates the transport mechanism and deposition patterns of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within a typical six bedded general inpatient ward cubicle through numerical simulation. It demonstrates that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. Moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. Hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient’s bed. To achieve infection prevention and control, high exhaust airflow rate is also suggested. Regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. The outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection.


title: Nucleic acid detection using G-quadruplex amplification methodologies

text: Abstract In the last decade, there has been an explosion in the use of G-quadruplex labels to detect various analytes, including DNA/RNA, proteins, metals and other metabolites. In this review, we focus on strategies for the detection of nucleic acids, using G-quadruplexes as detection labels or as enzyme labels that amplify detection signals. Methods to detect other analytes are briefly mentioned. We highlight various strategies, including split G-quadruplex, hemin–G-quadruplex conjugates, molecular beacon G-quadruplex or inhibited G-quadruplex probes. The tandem use of G-quadruplex labels with various DNA-modifying enzymes, such as polymerases (used for rolling circle amplification), exonucleases and endonucleases, is also discussed. Some of the detection modalities that are discussed in this review include fluorescence, colorimetric, chemiluminescence, and electrochemical methods.


title: SARS-CoV-2 Infection and the Newborn

text: Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) affects people at all ages and it may be encountered in pregnant women and newborns also. The information about its clinical features, laboratory findings and prognosis in children and newborns is scarce. All the reported cases in pregnant women were in the 2nd or 3rd trimester and only 1% of them developed severe disease. Miscarriages are rare. Materno-fetal transmission of the disease is controversial. Definitive diagnosis can be made by a history of contact with a proven case, fever, pneumonia and gastrointestinal disorder and a Polymerase chain reaction (PCR) test of nasopharyngeal swabs. Lymphopenia as well as liver and renal dysfunctions may be seen. Suspected or proven cases of newborns with symptoms should be quarantined in the neonatal intensive care unit for at least 14 days with standart and droplet isolation precautions. Asymptomatic infants may be quaratined at home. Transport of the neonates should be performed in a dedicated transport incubator and ambulance with isolation precautions. There is no specific treatment for the disease, but hemodynamic stabilization of the infant, respiratory management and other daily care are essential. Drugs against cytokine storm syndrome such as corticosteroids or tocilizumab are under investigation. Routine antibiotics are not recommended. No deaths have been reported so far in the neonatal population. Families and healthcare staff should receive pyschological support. Since the infection is quite new and knowledge is constantly accumulating, following developments and continuous updates are crucial.


title: Swine Influenza (H1N1) Pneumonia: Clinical Considerations

text: Influenza is a viral zoonosis of birds and mammals that has probably existed since antiquity. Attack rates of influenza are relatively high but mortality is relatively low. Influenza mortality is highest in the very young, the very old, and the immunosuppressed. Influenza has the potential for rapid spread and may involve large populations. This article examines the swine influenza (H1N1) strain of recent origin, and compares the microbiology, epidemiology, clinical presentation, differential, clinical, and laboratory diagnosis, therapy, complications, and prognosis with previous recorded outbreaks of avian and human seasonal influenza pneumonias.


title: Etiology of Pulmonary Infections in Human Immunodeficiency Virus–infected Inpatients Using Sputum Multiplex Real-time Polymerase Chain Reaction

text: BACKGROUND: There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)–infected patients in resource-limited settings. METHODS: We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples. RESULTS: We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>10(5) copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected. CONCLUSIONS: Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections.


title: Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant

text: The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm(2) at 08:00 hours to 0.07 ± 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.


title: Severe acute respiratory syndrome (SARS) in Hong Kong: patients' experiences

text: Abstract Background This past year there was an outbreak of Severe Acute Respiratory Syndrome (SARS) in Hong Kong. During that time we investigated the clinical features, treatment, and nursing care of 36 patients and reported on 12 of these patients' perceptions of their illness experience. Purpose The purpose of this article is to describe the clinical features, treatment, nursing care and perceptions of the illness experience of patients with SARS in Hong Kong in order to better inform nurses caring for patients with this highly contagious and potentially lethal disease. Method We abstracted data from the medical and nursing records on the clinical features, treatment and nursing care of 36 patients (21 women, 15 men) in whom SARS was diagnosed and who were admitted to the Queen Mary Hospital in Hong Kong between March 15 and April 15, 2003. A review of the hospital's policy and procedures on infection control was also undertaken. Semi-structured interviews were conducted with 12 of the patients to elicit their perceptions of the illness experience. Findings The most common symptoms were cough (83%), dyspnea (80.6%), malaise (69.4%) and fever (61%). Less common symptoms included headache (38.9%), diarrhea (38.9%), dizziness (30.6%), myalgia (25%), chills (19.4%), nausea and vomiting (19.4%) and rigor (the occurrence of a sensation of hot-and-cold and shivering in addition to teeth chattering and bed shaking) (8.3%). All 36 patients received a combination of corticosteroids and ribavirin. The patients were at risk of drug-related adverse reactions and deterioration of respiratory function, and nursing vigilance was required. Conclusion Nursing patients with SARS was challenging as the disease was highly contagious and potentially lethal, and not much was known about this disease. In addition to the use of frontline treatment, infection control and sensitivity to individual responses to sudden and catastrophic illness were required to support these patients. From this outbreak of SARS, we have learned the importance of infection control in containing and controlling the disease. Other lessons included the need to strengthen the surge capacity in our hospitals and support health care workers during the crisis.


COVID-19: TIMING IS IMPORTANT


How and why rheumatologists are relevant to COVID-19?


title: Mitral valve prolapse in adolescent female with hyperthyroidism

text: Mitral valve prolapse is prevalent in about 6% of young healthy females yet two to three times as prevalent in patients with hyperthyroidism [1, 8]. Hyperthyroidism is often missed as an underlying diagnosis when mitral valve prolapse is visualized by echocardiogram. There are many cardiac findings reported in the literature associated with hyperthyroidism. However, hyperthyroidism may be difficult to diagnose in the early stages of the disease process without other classic signs and symptoms. We report a case of an adolescent female who presented to our cardiology clinic with palpitations and chest pain diagnosed with hyperthyroidism after subtle findings of mitral valve prolapse and trivial mitral regurgitation. This case report will review the classic cardiac changes which may be observed on echocardiography in patients with hyperthyroidism.


Javier Padilla Bernáldez. ¿A quién vamos a dejar morir? Sanidad pública, crisis y la importancia de lo político. Madrid: Capitán Swing; 2019. 176 p. ISBN: 9788412064421


title: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study

text: Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.


Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death 1 1 For a glossary of abbreviations and terms used in this chapter see E-Glossary 1-1.


title: Secondary Household Transmission of SARS, Singapore

text: Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588).


Incidence of Anxiety in Parkinson's Disease During the Coronavirus Disease (COVID‐19) Pandemic


title: Rapid molecular diagnosis of infectious viruses in microfluidics using DNA hydrogel formation

text: There has been an urgent need to quickly screen and isolate patients with viral infections from patients with similar symptoms at point-of-care. In this study, we introduce a new microfluidic method for detection of various viruses using rolling circle amplification (RCA) of pathogens on the surface of thousands of microbeads packed in microchannels. When a targeted pathogen meets the corresponding particular template, the DNAs are rapidly amplified into a specific dumbbell shape through the RCA process, forming a DNA hydrogel and blocking the flow path formed between the beads. Due to the significant increase in reaction surface area, the detection time was shortened to less than 15 min and the detection limit of various pathogens has been reached to 0.1 pM. By injecting the stained liquid, the existence of the target pathogens in a sample fluid can be determined with the naked eye. Furthermore, by integrating multi-channel design, simultaneous phenotyping of various infective pathogens (i.e., Ebola, Middle East respiratory syndrome (MERS), and others) in biological specimens can be performed at a point-of-care.


title: Toxic proteins in plants

text: Abstract Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant’s resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed.


title: A framework for identifying and mitigating the equity harms of COVID-19 policy interventions

text: Abstract: Introduction Coronavirus disease 2019 (COVID-19) is a global pandemic. Governments have implemented combinations of ‘lockdown’ measures of various stringencies, including school and workplace closures, cancellations of public events, and restrictions on internal and external movements. These policy interventions are an attempt to shield high risk individuals and to prevent overwhelming countries’ healthcare systems, or, colloquially, ‘flatten the curve’. However, these policy interventions may come with physical and psychological health harms, group and social harms, and opportunity costs. These policies may particularly affect vulnerable populations and not only exacerbate pre-existing inequities, but also generate new ones. Methods We developed a conceptual framework to identify and categorise adverse effects of COVID-19 lockdown measures. We based our framework on Lorenc and Oliver’s framework for the adverse effects of public health interventions and the PROGRESS-Plus equity framework. To test its application we purposively sampled COVID-19 policy examples from around the world and evaluated them for the potential physical, psychological, and social harms, as well as opportunity costs, in each of the PROGRESS-Plus equity domains: Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, and disability). Results We found examples of inequitably distributed adverse effects for each COVID-19 lockdown policy example, stratified by LMIC and HIC, in every PROGRESS-Plus equity domain. We identified known policy interventions intended to mitigate some of these adverse effects. The same harms (anxiety; depression; food insecurity; loneliness; stigma; violence) appear to be repeated across many groups, and are exacerbated by several COVID-19 policy interventions. Conclusion Our conceptual framework highlights the fact that COVID-19 policy interventions can generate or exacerbate interactive and multiplicative equity harms. Applying this framework can help in three ways: (1) identifying areas where a policy intervention may generate inequitable adverse effects; (2) mitigating policy and practice interventions by facilitating the systematic examination of relevant evidence; and (3) planning for lifting COVID-19 lockdowns and policy interventions around the world.


title: Clinical and epidemiological features of COVID-19 family clusters in Beijing, China

text: ABSTRACT Background Since its discovery, SARS-CoV-2 has been spread throughout China before becoming a global pandemic. In Beijing, family clusters are the main mode of human-human transmission accounting for 57.6% of the total confirmed cases. Method We present the epidemiological and clinical features of the clusters of three large and one small families. Result Our results revealed that SARS-CoV-2 is transmitted quickly through contact with index case, and a total of 22/24 infections were observed. Among those infected, 20/22 had mild symptoms and only two had moderate to severe clinical manifestations. Children in the families generally showed milder symptoms. The incubation period varied from 2 to 13 days, and the shedding of virus from the upper respiratory tract lasted from 5 to over 30 days. A prolonged period of virus shedding (>30 days) in upper respiratory tract was observed in 6/24 cases. Conclusion SARS-CoV-2 is transmitted quickly in the form of family clusters. While the infection rate is high within the cluster, the disease manifestations, latent period, and virus shedding period varied greatly. We therefore recommend rigorously testing contacts even during the no-symptom phase and consider whether viral shedding has ceased before stopping isolation measures for an individual.


title: Strategies to control PRRS: A summary of field and research experiences

text: Abstract Various methods for the control of PRRS virus have been published. The technology of nursery depopulation (ND) appears to effectively control the spread of virus between members of endemically infected populations. ND consists of a strategic adjustment in pigflow based on the presence of specific serologic patterns as detected by the indirect fluorescent antibody test. This pattern indicates a low seroprevalence of antibodies detected in the breeding herd and recently weaned piglets (≤ 10%), in contrast to a high (> 50%) seroprevalence in 8 to 10 week old piglets. ND has been carried out on swine farms in the US and results indicate improvements in nursery piglet growth rate and mortality levels. Three examples are provided in the following text. Recently a modified live virus vaccine (RespPRRS, NOBL Laboratories/Boerhinger Ingleheim) has become commercially available. It is currently approved for use in piglets from 3 to 18 weeks of age; however, potential for the use in adult animals is currently under investigation.


title: Genetic polymorphisms and risk of recurrent wheezing in pediatric age

text: BACKGROUND: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes. METHODS: The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument. RESULTS: IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03). CONCLUSIONS: This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.


title: Soluble HLA Class I and Class II Molecule Levels in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

text: Increased concentrations of soluble HLA class I and class II molecules (sHLA-I and sHLA-II) have been observed in infectious, inflammatory, and autoimmune diseases. Because autoimmune mechanisms are considered to play a role in the pathogenesis of multiple sclerosis (MS), we decided to dose sHLA-I and sHLA-II in serum and cerebrospinal fluid (CSF) of MS patients comparing their concentrations with those observed in serum and CSF of patients with other neurologic diseases (OND) without evidence of neuroradiologic involvement of central nervous system (CNS) and in serum of healthy donors. The serum concentrations of sHLA-I were higher in both MS and OND patients than in healthy donors (P < 0.05) whereas sHLA-II serum concentrations were lower in MS patients than in both OND patients and healthy donors (P < 0.01). Detectable amounts of sHLA-II were observed in the CSF of 45% of MS patients and in CSF of only 6% of OND patients (P < 0.001). In MS patients a significant correlation between sHLA-I serum and CSF concentrations was observed (P < 0.01), whereas sHLA-II serum and CSF levels did not correlate. In conclusion, alterations of sHLA-I and sHLA-II serum and CSF concentrations are present in MS patients and could be involved in the induction of enhanced susceptibility to develop MS or in MS pathogenesis.


title: The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection

text: The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections.


title: The Impact of the COVID-19 Pandemic on Bariatric Surgery: Results from a Worldwide Survey

text: BACKGROUND: The ongoing “coronavirus disease 19” (COVID-19) pandemic has had a strong effect on the delivery of surgical care worldwide. Elective surgeries have been canceled or delayed in order to reallocate resources to the treatment of COVID-19 patients. Currently, the impact of the COVID-19 pandemic on bariatric and metabolic surgical practice remains unclear. METHODS: An internet-based online survey was performed among bariatric surgeons worldwide. The survey was sent to bariatric surgeons via the International Bariatric Club Facebook group and by electronic mail via the International Federation for the Surgery of Obesity and metabolic disorders (IFSO) secretariat to members of the associated national IFSO societies. RESULTS: One hundred sixty-nine (n = 169) bariatric surgeons participated in the survey. The majority of the respondents postponed preoperative upper gastrointestinal tract endoscopies, appointments in the outpatient clinic and bariatric operations. Most surgeons performed video calls for follow-up appointments instead of meeting the patients in the outpatient clinics. Laparoscopy was still the preferred treatment for surgical emergencies, but a trend towards conservative treatment of acute appendicitis and acute cholecystitis was shown. Rapid preoperative COVID-19 testing availability was poor; therefore, routine screening of emergency bariatric cases was not widely provided. A wide variance occurred regarding precautions and personal protection equipment among the participants. CONCLUSION: The COVID-19 pandemic showed a strong impact on bariatric surgical practice regarding surgical and outpatient planning as well as personnel management. Coordinated effort from the national bariatric societies should focus on strict implementation of the current recommendations regarding precaution measures and personal protection equipment. Further studies should evaluate how this impact will evolve in the near future.


title: New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets

text: BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.


title: Investing in Our First Line of Defense: Environmental Services Workers

text: Environmental services personnel are a critical first line of defense against the spread of COVID-19. This commentary discusses the importance of environmental cleaning during the pandemic and the essential role of environmental services personnel in patient safety.


title: A new player in a deadly game: influenza viruses and the PI3K/Akt signalling pathway

text: Upon influenza A virus infection of cells, a wide variety of antiviral and virus‐supportive signalling pathways are induced. Phosphatidylinositol‐3‐kinase (PI3K) is a recent addition to the growing list of signalling mediators that are activated by these viruses. Several studies have addressed the role of PI3K and the downstream effector protein kinase Akt in influenza A virus‐infected cells. PI3K/Akt signalling is activated by diverse mechanisms in a biphasic manner and is required for multiple functions during infection. While the kinase supports activation of the interferon regulatory factor‐3 during antiviral interferon induction, it also exhibits virus supportive functions. In fact, PI3K not only regulates a very early step during viral entry but also results in suppression of premature apoptosis at later stages of infection. The latter function is dependent on the expression of the viral non‐structural protein‐1 (A/NS1). It has been shown that PI3K activation occurs by direct interaction of A/NS1 with the p85 regulatory subunit and interaction sites of A/NS1 and p85 have now been mapped in detail. Here, we summarize the current knowledge on influenza virus‐induced PI3K signalling and how this pathway supports viral propagation.


title: COVID‐19 and the heart: An update for clinicians

text: SARS‐CoV‐2, the cause of the COVID‐19 pandemic has significantly impacted cardiovascular healthcare. Patients with pre‐existing cardiovascular disease are at higher risk of morbidity and mortality. The virus may affect the heart directly and indirectly with clinical syndromes of acute myocardial injury, myocarditis, acute coronary syndromes, heart failure, arrhythmias, and venous thromboembolism. Some therapeutics under investigation for COVID‐19 may also have adverse cardiac effects. The involvement of the RAAS system in viral entry makes it pertinent to consider the effects of medications that modulate the system. Comprehensive knowledge of peculiar cardiovascular manifestations of COVID‐19 and the role of RAAS in the prognosis of COVID‐19 disease is needed for optimal patient management.


title: Contact with Domestic Dogs Increases Pathogen Exposure in Endangered African Wild Dogs (Lycaon pictus)

text: BACKGROUND: Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus). Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) “reservoir” hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. METHODOLOGY/PRINCIPAL FINDINGS: We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. CONCLUSIONS/SIGNIFICANCE: These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches – including no intervention – which are most appropriate for each pathogen.


title: Intracellular antibodies for proteomics

text: Abstract The intracellular antibody technology has many applications for proteomics studies. The potential of intracellular antibodies for the systematic study of the proteome has been made possible by the development of new experimental strategies that allow the selection of antibodies under conditions of intracellular expression. The Intracellular Antibody Capture Technology (IACT) is an in vivo two-hybrid-based method originally developed for the selection of antibodies readily folded for ectopic expression. IACT has been used for the rapid and effective identification of novel antigen–antibody pairs in intracellular compartments and for the in vivo identification of epitopes recognized by selected intracellular antibodies. IACT opens the way to the use of intracellular antibody technology for large-scale applications in proteomics. In its present format, its use is however somewhat limited by the need of a preselection of the input phage antibody libraries on protein antigens or by the construction of an antibody library from mice immunized against the target protein(s), to provide an enriched input library to compensate for the suboptimal efficiency of transformation of the yeast cells. These enrichment steps require expressing the corresponding proteins, which represents a severe bottleneck for the scaling up of the technology. We describe here the construction of a single pot library of intracellular antibodies (SPLINT), a naı̈ve library of scFv fragments expressed directly in the yeast cytoplasm in a format such that antigen-specific intrabodies can be isolated directly from gene sequences, with no manipulation whatsoever of the corresponding proteins. We describe also the isolation from SPLINT of a panel of intrabodies against a number of different proteins. The application of SPLINT on a genome-wide scale should help the systematic study of the functional organization of cell proteome.


title: Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19

text: This article reviews the correlation between angiotensin‐converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID‐19) and the possible mechanisms. ACE2 is a crucial component of the renin‐angiotensin system (RAS). The classical RAS ACE‐Ang II‐AT1R regulatory axis and the ACE2‐Ang 1‐7‐MasR counter‐regulatory axis play an essential role in maintaining homeostasis in humans. ACE2 is widely distributed in the heart, kidneys, lungs, and testes. ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. Similar to SARS‐CoV, SARS‐CoV‐2 also uses the ACE2 receptor to invade human alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is a clinical high‐mortality disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of patients with COVID‐19 is related to factors such as sex (male), age (>60 years), underlying diseases (hypertension, diabetes, and cardiovascular disease), secondary ARDS, and other relevant factors. Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein‐based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID‐19 in the future.


title: Identification and characterization of a mouse mammary tumor virus protein uniquely expressed on the surface of BALB/cV mammary tumor cells

text: Abstract A unique subline of BALB/c mice, designated BALB/cV, exhibits an intermediate mammary tumor incidence (47%) and harbors a distinct milk-transmitted mouse mammary tumor virus (MMTV). The BALB/cV subline was used to study the molecular basis of potential virus-host interactions involving cell surface-expressed MMTV proteins. Cell surface iodination identified virus-specific proteins expressed on BALB/cv primary mammary tumor cells grown in culture. In contrast to (C3H)MMTV-producing cell lines which expressed MMTV gp52, BALB/cV tumor cells lacked gp52 and expressed instead a 68K, env-related protein. The 68K env protein was also detected on the surface of metabolically labeled BALB/cV tumor cells by an external immunoprecipitation technique. The expression of 68K env was restricted to mammary tissues of BALB/cV mice that also expressed other MMTV proteins. Biochemical analysis established that 68K env was not modified by N-linked glycosylation. 125I-labeled 68K env was rapidly released into the media of tumor cell cultures and was recovered both in the form of a soluble protein and in a 100,000 g pellet. The biologic function of this cell surface-expressed viral protein remains unknown.


title: COVID-19–We urgently need to start developing an exit strategy

text: Abstract Aim The purpose of this perspective is to review the options countries have to exit the draconian “lock downs” in a carefully staged manner. Methods Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) review evidence and country specific approaches and results of their interventions. Results Three key factors are important: 1. Reintroduction from countries with ongoing community transmission; 2. The need for extensive testing capacity and widespread community testing, and 3. Adequate supply of personal protective equipment, PPE, to protect health care workers. Lifting social distancing is discussed at length. How to open manufacturing, construction and logistics. The opening og higher educational institutions and schools. The use of electronic surveillance is discussed. Conclusion Each country has to decide what is the best path forward. However, we can learn from each other and the approach is in reality very similar.


title: Confirmation of electron microscopy results by direct testing of viruses adhered to grids using nucleic acid amplification techniques

text: Abstract It is possible to visualize rapidly viral particles by electron microscopy (EM) in patient samples and in cell cultures, and characterize the particles on the basis of their size and morphology. In many instances, EM has contributed to the diagnosis of specific infectious agents. Four different types of viruses with different characteristics of particle size, capsid structure, the presence or absence of an envelope, genomic content and stability outside the host were screened and diagnosed by EM at the level of family/genus. The results were confirmed at the species level by elution of the sample material from the grids used for EM examination and nucleic acid amplification. This approach could be valuable in situations where the immediate diagnosis is unclear, or when new infectious agents appear.


title: Viral pathogen discovery

text: Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease.


Enemy at the Gate


title: Biowarfare and Bioterrorism

text: Bioterrorism is not only a reality of the times in which we live but bioweapons have been used for centuries. Critical care physicians play a major role in the recognition of and response to a bioterrorism attack. Critical care clinicians must be familiar with the diagnosis and management of the most likely bioterrorism agents, and also be adequately prepared to manage a mass casualty situation. This article reviews the epidemiology, diagnosis, and treatment of the most likely agents of biowarfare and bioterrorism.


title: Principles of Virus Structural Organization

text: Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of variety of viruses. These studies have significantly furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective.