title: The relevance of psychosocial variables and working conditions in predicting nurses’ coping strategies during the SARS crisis: An online questionnaire survey

text: Abstract Objectives The purpose of this investigation was to examine the relationship between psychosocial variables and working conditions, and nurses’ coping methods and distress in response to the severe acute respiratory syndrome (SARS) crisis in Canada. Participants and procedure The sample consisted of 333 nurses (315 women, 18 men) who completed an Internet-mediated questionnaire that was posted on the Registered Nurses’ Association of Ontario (RNAO) website between March and May 2004. The questionnaire was restricted to respondents who had to authenticate their RNAO membership with a valid username and password before accessing the questionnaire. This served a dual purpose: to ensure that only RNAO nurses completed the questionnaire and thereby safeguarding the generalizability of the findings; and second, to prevent any one nurse from contributing more than once to the overall sample. Results Correlational analysis yielded several significant relationships between psychosocial variables and working conditions, and the traditional correlates of burnout and stress. Three multiple regression analysis revealed that the model we evolved—including higher levels of vigor, organizational support, and trust in equipment/infection control initiative; and lower levels of contact with SARS patients, and time spent in quarantine—predicted to lower levels of avoidance behavior, emotional exhaustion, and state anger. Conclusions By employing models of stress and burnout that combine psychosocial variables and working conditions, researchers can account for significant amounts of variance in outcomes related to burnout. These findings highlight the importance of vigor and perceived organizational support in predicting nurses’ symptoms of burnout. For healthcare administrators, this means that a likely strategy for assuaging the negative outcomes of stress should address nurses’ psychosocial concerns and the working conditions that they face during novel times of crisis.


title: Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus

text: Abstract Background Human coronavirus HKU1 (HCoV-HKU1) is a recently identified coronavirus with a global distribution and known to cause mainly respiratory infections. Objectives To investigate the seroepidemiology of HKU1 infections in our local population. Study design An ELISA-based IgG antibody detection assay using recombinant HCoV-HKU1 nucleocapsid and spike (S) proteins (genotype A) were developed for the diagnosis of CoV-HKU1 infections, Additionally, a neutralization antibody assay using the HCoV-HKU1 pseudotyped virus was developed to detect the presence of neutralizing antibodies in serum with antibody positivity in an S protein-based ELISA. Results Results of the recombinant S protein-based ELISA were validated with Western blot, immunofluorescence analysis and flow cytometry. The coupled results demonstrated good correlation with Spearmen's coefficient of 0.94. Seroepidemiological study in a local hospital-based setting using this newly developed ELISA showed steadily increasing HCoV-HKU1 seroprevalence in childhood and early adulthood, from 0% in the age group of <10 years old to a plateau of 21.6% in the age group of 31–40 years old. Conclusions Our study demonstrated the usefulness of the S-based ELISA which could be applied to future epidemiological studies of HCoV-HKU1 in other localities.


Clearing up the obesity paradox in cardiac surgery


title: Evaluating the virucidal efficacy of hydrogen peroxide vapour

text: Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces.


Filtration Group switches part of German production to face masks


title: Fifty years of the bottleneck model: A bibliometric review and future research directions

text: Abstract The bottleneck model introduced by Vickrey in 1969 has been recognized as a benchmark representation of the peak-period traffic congestion due to its ability to capture the essence of congestion dynamics in a simple and tractable way. This paper aims to provide a 50th anniversary review of the bottleneck model research since its inception. A bibliometric analysis approach is adopted for identifying the distribution of all journal publications, influential papers, top contributing authors, and leading topics in the past half century. The literature is classified according to recurring themes into travel behavior analysis, demand-side strategies, supply-side strategies, and joint strategies of demand and supply sides. For each theme, typical extended models developed to date are surveyed. Some potential directions for further studies are discussed.


docid: ppmsfcqh

title: Bioproduction of Therapeutic Proteins in the 21st Century and the Role of Plants and Plant Cells as Production Platforms

text: abstract: In the last decade, the technique to genetically modify crop plants has gained more and more interest in terms of bioproduction of heterologous proteins. Plants have been discovered as a possible source for large amounts of cost effective recombinant protein. Main application fields are therapeutics for use in animal and human health, diagnostics, and technical enzymes. This review is focused on the recent progress in this field of molecular farming. After a comparison with hitherto established protein production systems, the advantages of plants as an alternative production system are discussed. An overview about the different host plants and possible expression strategies is given and the progress in commercialization of the techniques is highlighted. Finally, the role of plant cell cultures for the production of recombinant proteins is discussed.


title: Molecular detection of CF lung pathogens: Current status and future potential

text: Abstract Molecular diagnostic tests, based on the detection and identification of nucleic acids in human biological samples, are increasingly employed in the diagnosis of infectious diseases and may be of future benefit to CF microbiology services. Our growing understanding of the complex polymicrobial nature of CF airway infection has highlighted current and likely future shortcomings in standard diagnostic practices. Failure to detect fastidious or slow growing microbes and misidentification of newly emerging pathogens could potentially be addressed using culture-independent molecular technologies with high target specificity. This review considers existing molecular diagnostic tests in the context of the key requirements for an envisaged CF microbiology focussed assay. The issues of assay speed, throughput, detection of multiple pathogens, data interpretation and antimicrobial susceptibility testing are discussed.


title: Snapshot PCR Surveillance for SARS-CoV-2 in Hospital Staff in England

text: BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional ‘snapshot’ survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2•0% (23/1152 participants), median cycle threshold value 35•70 (IQR:32•42-37•57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3•46, 95%CI 1•38-8•67; p=0•008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.


docid: vmvgyktq

title: Reported Direct and Indirect Contact with Dromedary Camels among Laboratory-Confirmed MERS-CoV Cases

text: Dromedary camels (Camelus dromedarius) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018. We present any reported dromedary contact: direct, indirect, and type of indirect contact. Of all 1125 laboratory-confirmed MERS-CoV cases reported to WHO during the time period, there were 348 (30.9%) primary cases, 455 (40.4%) non-primary cases, and 322 (28.6%) unclassified cases. Among primary cases, 191 (54.9%) reported contact with dromedaries: 164 (47.1%) reported direct contact, 155 (44.5%) reported indirect contact. Five (1.1%) non-primary cases also reported contact with dromedaries. Overall, unpasteurized milk was the most frequent type of dromedary product consumed. Among cases for whom exposure was systematically collected and reported to WHO, contact with dromedaries or dromedary products has played an important role in zoonotic transmission.


title: Pulmonary Infections Following Lung Transplantation

text: Infectious complications are a major cause of morbidity and mortality in solid organ transplant recipients. Infections with viruses, bacteria, and fungi have all been associated with the development of bronchiolitis obliterans syndrome (chronic allograft rejection) in lung transplant recipients. Lung transplant recipients have a higher risk of infectious complications than recipients of other solid organs because of the intensity of immunosuppression, blunted cough mechanism, and constant exposure to the environment. This review provides a broad overview of the infectious complications encountered in caring for patients who have undergone lung transplantation.


title: Immunity and age: living in the past?

text: Increasing age is associated with a decreasing ability to mediate effective immune responses to newly encountered antigens. It is generally believed that this reflects the age-associated decline in the number, repertoire and function of available naive T cells. Here, we propose that naive T cells become increasingly irrelevant to the immune system, and that responses to newly encountered antigens are progressively dominated by cross-reactive memory T cells as the individual ages. In addition, we propose that the majority, if not all, of the response to newly encountered antigens in the elderly is mediated by cross-reactive memory T cells. This predicts highly stochastic responses to new infections that should vary between individuals, and has important implications for vaccination strategies in the elderly.


title: The infodemics of COVID-19 amongst healthcare professionals in India

text: BACKGROUND: There is a deluge of information and misinformation about COVID-19. The present survey was conducted to explore the sources of information /misinformation for healthcare professionals from India. METHODS: A cross-sectional online survey using snowballing technique was conducted from 24 Mar to 10 Apr 2020. The questionnaire was pretested and developed using standard techniques. It was circulated among medical students and physicians. Data were analysed using the STATA software. RESULTS: Data of 758 participants were analysed. A total of 255 (33.6%) medical students, 335 (44.2%) nonspecialists and 168 (22.1%) specialists participated. The most common source of formal and informal information was official government websites and online news, respectively. A total of 517 (68.2%) participants accepted receiving misinformation. Social media and family and friends were the most common sources of misinformation. Seventy-two percent of participants agreed that spread of information helped to contain COVID-19, but more than that 75% agreed to having received inaccurate information. Seventy-four percent of respondents felt the need for regulation of information during such times; 26% and 33% felt that information about COVID-19 made them feel uncomfortable and distracts routine decision-making, respectively, and 50% felt it was difficult to differentiate correct from incorrect information about COVID-19. CONCLUSION: The study explored the sources of information and misinformation and found a high prevalence of misinformation, especially from social media. We suggest the need to better manage the flow of information so that it can be an effective weapon against SARS-CoV2. There is a need for doctors to adapt to the changing times of infodemics accompanying pandemics.


title: Evaluating MERS-CoV Entry Pathways

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic pathogen with a broad host range. The extent of MERS-CoV in nature can be traced to its adaptable cell entry steps. The virus can bind host-cell carbohydrates as well as proteinaceous receptors. Following receptor interaction, the virus can utilize diverse host proteases for cleavage activation of virus-host cell membrane fusion and subsequent genome delivery. The fusion and genome delivery steps can be completed at variable times and places, either at or near cell surfaces or deep within endosomes. Investigators focusing on the CoVs have developed several methodologies that effectively distinguish these different cell entry pathways. Here we describe these methods, highlighting virus-cell entry factors, entry inhibitors, and viral determinants that specify the cell entry routes. While the specific methods described herein were utilized to reveal MERS-CoV entry pathways, they are equally suited for other CoVs, as well as other protease-dependent viral species.


title: Factors affecting stability and infectivity of SARS-CoV-2

text: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20∼25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.


Reply to: ‘No evidence for an increased liver uptake of SARS-CoV-2 in metabolic associated fatty liver disease’


docid: hcoonxax

title: Fighting COVID-19 Hypoxia with One Hand Tied Behind Our Back: Blanket Prohibition of High Flow Oxygen and Non-Invasive Positive End-Expiratory Pressure in United States Hospitals


title: Characterization of the porcine epidemic diarrhea virus codon usage bias

text: Abstract Porcine epidemic diarrhea virus (PEDV) has been responsible for several recent outbreaks of porcine epidemic diarrhea (PED) and has caused great economic loss in the swine-raising industry. Considering the significance of PEDV, a systemic analysis was performed to study its codon usage patterns. The relative synonymous codon usage value of each codon revealed that codon usage bias exists and that PEDV tends to use codons that end in T. The mean ENC value of 47.91 indicates that the codon usage bias is low. However, we still wanted to identify the cause of this codon usage bias. A correlation analysis between the codon compositions (A3s, T3s, G3s, C3s, and GC3s), the ENC values, and the nucleotide contents (A%, T%, G%, C%, and GC%) indicated that mutational bias plays role in shaping the PEDV codon usage bias. This was further confirmed by a principal component analysis between the codon compositions and the axis values. Using the Gravy, Aroma, and CAI values, a role of natural selection in the PEDV codon usage pattern was also identified. Neutral analysis indicated that natural selection pressure plays a more important role than mutational bias in codon usage bias. Natural selection also plays an increasingly significant role during PEDV evolution. Additionally, gene function and geographic distribution also influence the codon usage bias to a degree.


title: Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis

text: Abstract Crimean Congo hemorrhagic fever virus (CCHFV) causes an acute disease with the potential of a fatal outcome. The virus is prevalent in about 30 countries. Clinical symptoms of infection commonly include fever, myalgia, and hemorrhages. Levels of liver enzymes are raised, and bleeding markers are often increased. A role of inflammatory cytokines in the pathogenesis has been suggested, and CCHFV employs a range of passive and active mechanisms to avoid induction of the antiviral type I interferons. Here, we review the most recent findings on the molecular pathogenesis and the interaction of CCHFV with the type I interferon and cytokine responses and discuss implications for pathogenesis.


title: Codon usage pattern and its influencing factors in different genomes of hepadnaviruses

text: Codon usage bias (CUB) arises from the preference for a codon over codons for the same amino acid. The major factors contributing to CUB are evolutionary forces, compositional properties, gene expression, and protein properties. The present analysis was performed to investigate the compositional properties and the extent of CUB across the genomes of members of the family Hepadnaviridae, as previously no work using bioinformatic tools has been reported. The viral genes were found to be AT rich with low CUB. Analysis of relative synonymous codon usage (RSCU) was used to identify overrepresented and underrepresented codons for each amino acid. Correlation analysis of overall nucleotide composition and its composition at the third codon position suggested that mutation pressure might influence the CUB. A highly significant correlation was observed between GC12 and GC3 (r = 0.910, p < 0.01), indicating that directional mutation affected all three codon positions across the genome. Translational selection (P2) and mutational responsive index (MRI) values of genes suggested that mutation plays a more important role than translational selection in members of the family Hepadnaviridae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04533-6) contains supplementary material, which is available to authorized users.


title: Fatal HBoV-1 infection in adult female cystic fibrosis patient

text: Abstract A clinical case of fatal HBoV infection in an adult cystic-fibrosis patient awaiting lung transplantation is reported. The case is important as the genetic background of the underlying disease is congruent with the background of the sole permissive permanent cell culture CuFi-8 which originates also from a CF patient donor.


title: An experimental vaccine for calf pneumonia caused by Mycoplasma bovis: clinical, cultural, serological and pathological findings

text: A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3–4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24 h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.


title: Home Medical Nutrition during SARS-CoV-2 pandemic – a position paper

text: Summary Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a worldwide rapidly spreading illness, Coronavirus Disease 2019 (COVID-19). Patients fed enterally and parenterally at home are exposed to the same risk of infection as the general population, but more prone to complications than others. Therefore the guidance for care-givers and care-takers of these patients is needed. Methods The literature search identified no relevant systematic reviews or studies on the subject. Therefore a panel of 21 experts from 13 home medical nutrition (HMN) centres in Poland was formed. Twenty-three key issues relevant to the management of SARS-CoV-2 infection or COVID-19 in the HMN settings were identified and discussed. Some statements diverge from the available nutrition, surgical or ICU guidelines, some are based on the best available experience. Each topic was discussed and assessed during two Delphi rounds subsequently. Statements were graded strong or weak based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results the panel issued 23 statements, all of them were graded strong. Two scored 85.71% agreement, eleven 95.23%, and ten 100%. The topics were: infection control, enrolment to HMN, logistics and patient information. Conclusions the position paper present pragmatic statements for HMN to be implemented in places without existing protocols for SARS-CoV-2 pandemic. They represent the state of knowledge available at the moment and may change should new evidence occurs.


title: SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon

text: SARS-CoV is a pathogenic coronavirus that emerged from a zoonotic reservoir, leading to global dissemination of the virus. The association SARS-CoV with aberrant cytokine, chemokine, and Interferon Stimulated Gene (ISG) responses in patients provided evidence that SARS-CoV pathogenesis is at least partially controlled by innate immune signaling. Utilizing models for SARS-CoV infection, key components of innate immune signaling pathways have been identified as protective factors against SARS-CoV disease, including STAT1 and MyD88. Gene transcription signatures unique to SARS-CoV disease states have been identified, but host factors that regulate exacerbated disease phenotypes still remain largely undetermined. SARS-CoV encodes several proteins that modulate innate immune signaling through the antagonism of the induction of Interferon and by avoidance of ISG effector functions.


title: Mosaic Structure of Human Coronavirus NL63, One Thousand Years of Evolution

text: Abstract Before the SARS outbreak only two human coronaviruses (HCoV) were known: HCoV-OC43 and HCoV-229E. With the discovery of SARS-CoV in 2003, a third family member was identified. Soon thereafter, we described the fourth human coronavirus (HCoV-NL63), a virus that has spread worldwide and is associated with croup in children. We report here the complete genome sequence of two HCoV-NL63 clinical isolates, designated Amsterdam 57 and Amsterdam 496. The genomes are 27,538 and 27,550 nucleotides long, respectively, and share the same genome organization. We identified two variable regions, one within the 1a and one within the S gene, whereas the 1b and N genes were most conserved. Phylogenetic analysis revealed that HCoV-NL63 genomes have a mosaic structure with multiple recombination sites. Additionally, employing three different algorithms, we assessed the evolutionary rate for the S gene of group Ib coronaviruses to be ∼3×10−4 substitutions per site per year. Using this evolutionary rate we determined that HCoV-NL63 diverged in the 11th century from its closest relative HCoV-229E.


docid: ajlnhmnt

title: Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

text: Abstract In the last 30 years, since the discovery that vanadium is a cofactor found in certain enzymes of tunicates and possibly in mammals, different vanadium-based drugs have been developed targeting to treat different pathologies. So far, the in vitro studies of the insulin mimetic, antitumor and antiparasitic activity of certain compounds of vanadium have resulted in a great boom of its inorganic and bioinorganic chemistry. Chemical speciation studies of vanadium with amino acids under controlled conditions or, even in blood plasma, are essential for the understanding of the biotransformation of e.g. vanadium antidiabetic complexes at the physiological level, providing clues of their mechanism of action. The present article carries out a bibliographical research emphaticizing the chemical speciation of the vanadium with different amino acids and reviewing also some other important aspects such as its chemistry and therapeutical applications of several vanadium complexes.


Case Report of Leishmaniasis in Four Cats


title: Modulation of immune-associated surface markers and cytokine production by murine retinal glial cells

text: Abstract Murine retinal glia are normally negative for major histocompatibility complex (MHC) Class II antigens and express low levels of MHC Class I and intercellular adhesion molecule-1 (ICAM-1) as detected by avidin-biotin-peroxidase immunohistochemistry. These surface molecules associated with immune function were either induced (Class II) or upregulated (Class I and ICAM-1) on cultured retinal glial cells in a dose- and time-dependent manner following exposure to recombinant Interferonγ (rIFN-γ). MHC Class I and II expression by passaged and primary cells was maximal (> 90% positive) after incubation with 100 U/ml of rlFN-y for 48 h. ICAM-1 expression by primary and passaged cells tripled between 48 and 72 h after exposure to 25 or 50 U/ml of rIFN-γ. By 72 h after exposure to 100 U/ml of rIFN-y, 62% of the retinal glia were positive for ICAM-1, whereas under normal culture conditions these molecules were detected on < 3% of the retinal glia. Bacterial lipopolysaccharide (LPS), a known stimulator of central nervous system (CMS) astrocytes, increased ICAM-1 expression only 3-fold to 9% of cells staining positively, but neither MHC Class I nor Class II expression was altered from baseline levels. Surface expression of ICAM-1, MHC Class I, and MHC Class II was unaffected by exposure to either rTNF-α (1000 U/ml) or rIL-6 (100 U/ml) for 24 h. Under normal culture conditions, intracellular interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected immunohistochemically. Exposure to either rIFN-γ or LPS induced more intense staining which correlated with increased secreted levels of both cytokines in culture supernatants. Levels of secreted TNF-α increased 6-fold after stimulation with LPS for 24 h, while secreted IL-6 increased over 9-fold. These results support the hypothesis that retinal glia may participate in intraretinal immune processes following stimulation during inflammatory and infectious processes via either cell surface- or soluble mediator-dependent mechanisms or a combination of both.


title: Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc

text: Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.


title: Comparison of initial high resolution computed tomography features in viral pneumonia between metapneumovirus infection and severe acute respiratory syndrome

text: Abstract Objective To review and compare initial high resolution computed tomography (HRCT) findings in patients with metapneumovirus pneumonia and severe acute respiratory syndrome (SARS-Coronovirus). Materials and methods 4 cases of metapneumovirus pneumonia (mean age of 52.3years) in an institutional outbreak (Castle Peak Hospital) in 2008 and 38 cases of SARS-coronovirus (mean age of 39.6years) admitted to Tuen Mun hospital during an epidemic outbreak in 2003 were included. HRCT findings of the lungs for all patients were retrospectively reviewed by two independent radiologists. Results In the metapneumovirus group, common HRCT features were ground glass opacities (100%), consolidation (100%), parenchymal band (100%), bronchiectasis (75%). Crazy paving pattern was absent. They were predominantly subpleural and basal in location and bilateral involvement was observed in 50% of patients. In the SARS group, common HRCT features were ground glass opacities (92.1%), interlobular septal thickening (86.8%), crazy paving pattern (73.7%) and consolidation (68%). Bronchiectasis was not seen. Majority of patient demonstrated segmental or lobar in distribution and bilateral involvement was observed in 44.7% of patients. Pleural effusion and lymphadenopathy were of consistent rare features in both groups. Conclusion Ground glass opacities, interlobular septal thickening and consolidations were consistent HRCT manifestations in both metapneumovirus infection and SARS. The presence of bronchiectasis (0% in SARS) may point towards metapneumovirus while crazy paving pattern is more suggestive of SARS.


title: Mechanisms of action of ribavirin against distinct viruses

text: The nucleoside analogue ribavirin has antiviral activity against many distinct viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to explain the antiviral properties of ribavirin. These include both indirect mechanisms (inosine monophosphate dehydrogenase inhibition, immunomodulatory effects) and direct mechanisms (interference with RNA capping, polymerase inhibition, lethal mutagenesis). Recent concerns about bioterrorism have renewed interest in exploring the antiviral activity of ribavirin against unique viruses. In this paper, we review the proposed mechanisms of action with emphasis on recent discoveries, as well as the implications of ribavirin resistance. Evidence exists to support each of the five proposed mechanisms of action, and distinct virus/host combinations may preferentially favour one or more of these mechanisms during antiviral therapy. Copyright © 2005 John Wiley & Sons, Ltd.


title: Global Epidemiology of Bat Coronaviruses

text: Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.


title: Mining association rules with multiple minimum supports: a new mining algorithm and a support tuning mechanism

text: Abstract Mining association rules with multiple minimum supports is an important generalization of the association-rule-mining problem, which was recently proposed by Liu et al. Instead of setting a single minimum support threshold for all items, they allow users to specify multiple minimum supports to reflect the natures of the items, and an Apriori-based algorithm, named MSapriori, is developed to mine all frequent itemsets. In this paper, we study the same problem but with two additional improvements. First, we propose a FP-tree-like structure, MIS-tree, to store the crucial information about frequent patterns. Accordingly, an efficient MIS-tree-based algorithm, called the CFP-growth algorithm, is developed for mining all frequent itemsets. Second, since each item can have its own minimum support, it is very difficult for users to set the appropriate thresholds for all items at a time. In practice, users need to tune items' supports and run the mining algorithm repeatedly until a satisfactory end is reached. To speed up this time-consuming tuning process, an efficient algorithm which can maintain the MIS-tree structure without rescanning database is proposed. Experiments on both synthetic and real-life datasets show that our algorithms are much more efficient and scalable than the previous algorithm.


title: The SARS-CoV-2 outbreak: What we know

text: Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.


title: Phylogenetic analysis of porcine astrovirus in domestic pigs and wild boars in South Korea

text: Porcine astrovirus (PAstV) belongs to genetically divergent lineages within the genus Mamastrovirus. In this study, 25/129 (19.4 %) domestic pig and 1/146 (0.7 %) wild boar fecal samples tested in South Korea were positive for PAstV. Positive samples were mainly from pigs under 6 weeks old. Bayesian inference (BI) tree analysis for RNA-dependent RNA polymerase (RdRp) and capsid (ORF2) gene sequences, including Mamastrovirus and Avastrovirus, revealed a relatively geographically divergent lineage. The PAstVs of Hungary and America belong to lineage PAstV 4; those of Japan belong to PAstV 1; and those of Canada belong to PAstV 1, 2, 3, and 5, but not to 4. This study revealed that the PAstVs of Korea belong predominantly to lineage PAstV 4 and secondarily to PAstV 2. It was also observed that PAstV infections are widespread in South Korea regardless of the disease state in domestic pigs and in wild boars as well.


title: Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

text: Abstract Analysis of virus–host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus–host interactions than previously thought is examined.


title: Prostaglandin E(2) stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis

text: BACKGROUND: Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE(2) stimulated lung cancer cell growth and progression through PGE(2) receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE(2) in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE(2). METHOD: The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE(2). PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE(2) receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. RESULTS: We demonstrated that PGE(2) increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE(2) on normal cell growth. The PGE(2)-induced PDK1 expression was blocked by an antagonist of the PGE(2) receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE(2) was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE(2). In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. CONCLUSION: PGE(2) increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell hyperplasia induced by PGE(2).


title: Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

text: The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1(+)CD57(+) exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4(+) T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.


title: Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice

text: Abstract To analyze the immune responses of DNA vaccine encoded different gene fragments of severe acute respiratory syndrome coronavirus (SARS-Cov), SARS-Cov gene fragments of membrane (M), nucleocapsid (N), spike a (Sa), and spike b (Sb) proteins were cloned into pcDNA3.1 (Invitrogen) vector to form plasmids pcDNAM, pcDNAN, pcDNASa, and pcDNASb, respectively. After mice were immunized intramuscularly with pcDNAM, pcDNAN or pcDNASa–pcDNASb plasmid, blood was collected and serum was separated. Humoral immune response was detected with the enzyme-linked immunosorbent assay, and cellular immune response of SARS-Cov DNA vaccines was detected with lymphoproliferation assay and cytotoxic T lymphocyte assay. Results show that cellular and humoral immune responses can be detected after immunization with pcDNAM, pcDNAN or pcDNASa–pcDNASb plasmids in BALB/c mice. However, pcDNAM stimulated the highest cellular immune response than other plasmids, and pcDNASa–pcDNASb stimulated the highest humoral immune response in week 12. The present results not only suggest that DNA immunization with pcDNAM, pcDNAN or pcDNASa–pcDNASb could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also to illustrate that gene immunization with these SARS DNA vaccines different immune response characters.


Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola


title: Structure, function and metabolism of sialic acids

text: Sialic acids represent a family of sugar molecules with an unusual and highly variable chemical structure that are found mostly in the terminal position of oligosaccharide chains on the surface of cells and molecules. These special features enable them to fulfil several important and even diametrical biological functions. Because of the great importance of sialic acids, it is also worth having a look at their metabolism in order to get an idea of the intimate connection between structure and function of these fascinating molecules and the often serious consequences that result from disturbances in the balance of metabolic reactions. The latter can be due to genetic disorders that result in the absence of certain enzyme activity, leading to severe illness or even to death.


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title: D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19

text: A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å(3) on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easily to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.


title: Coronavirus disease 2019 (COVID-19) pneumonia presentations in chest computed tomography: a pictorial review

text: Despite imaging not being a tool for novel coronavirus disease 2019 (COVID-19) diagnosis, there has been an increased number of chest computed tomography (CT) scans done worldwide. There are no pathognomonic CT features for COVID-19 pneumonia, as findings are also common in other infectious diseases and noninfectious aetiologies. Nonetheless, point-of-care physicians should be familiarized with the most common imaging presentations of the COVID-19. In this pictorial review, we have summarized the most reported imaging features of COVID-19 pneumonia, including possible differential diagnosis according to the CT finding.


title: Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition).

text: Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.


title: Effect of Substance P and Receptor Antagonists on Secretion of Lingual Lipase and Amylase from Rat von Ebner's Gland

text: Field, R. B., S. J. Chirtel and R. S. Redman. Effect of substance P and receptor antagonists on secretion of lingual lipase and amylase from rat von Ebner's gland. Peptides 18(2) 277–285, 1997.— Substance P (SP, 1 μM) when incubated with minced von Ebner's glands for 15, 30, and 60 min, stimulated secretion of lingual lipase (12.14%±0.90) and amylase (8.30%±0.42). Only 10 μM of the SP receptor antagonist CP-96,345 significantly inhibited SP-evoked secretion. d-Pro(2)-d-Phe(7)-d-Trp(9)-SP (Ia), d-Pro(2)-d-Trp(7,9)-SP (Ib), d-Arg(1)-d-Trp(7,9)-d-Leu(11)-SP (Ic), or 1 μM CP-96,345 were not effective, suggesting that the SP receptor of von Ebner's gland might be an isoform. Propranolol and timolol, β(1)/β(2)-adrenergic receptor antagonists were not effective and the cholinergic receptor antagonist, atropine, was effective in only slightly reducing amylase secretion but not lingual lipase. Differential secretion of the two enzymes was observed for basal and stimulated secretion. Thus, exocytosis may not be the only pathway involved in SP-evoked protein secretion.


title: User acceptance of reusable respirators in health care

text: BACKGROUND: Inclusion of reusable respirators, such as elastomeric half-face respirators (EHFRs) and powered air-purifying respirators (PAPRs), in hospital respiratory protection inventories may represent 1 solution to the problem of N95 respirator shortages experienced during pandemics. User acceptance of these devices is 1 potential barrier to implementing such a strategy in respiratory protection programs. METHODS: To assess user attitudes toward various respirators, health care workers enrolled in respiratory protection programs in a medical system using EHFRs, N95s, and PAPRs and completed an online questionnaire that addressed attitudes, beliefs, and respirator preferences under different risk scenarios. Responses were compared between user groups. RESULTS: Of 1,152 participants, 53% currently used N95s, 24% used EHFRs, and 23% used PAPRs. N95 users rated their respirators more favorably compared with EHFR and PAPR users (P < .001) regarding comfort and communication, however, EHFR users rated their respirators much more highly regarding sense of protection (P < .001). For all user groups, reusable respirators were significantly more likely (odds ratios 2.3-7.7) to be preferred over N95 filtering facepiece respirators in higher risk scenarios compared to “usual circumstance” scenarios. CONCLUSIONS: Despite somewhat less favorable ratings on comfort and communication, experienced EHFR and PAPR users still prefer reusable respirators over N95s in certain higher risk scenarios. This suggests that reusable respirators are an acceptable alternative to N95 respirators in health care and offer 1 viable solution to prevent pandemic-generated respirator shortages.


title: The Covid‐19 ‘infodemic’: a new front for information professionals

text: The virus, commonly known as COVID‐19 which emerged in Wuhan, China, in December 2019, has spread in 213 countries, areas or territories around the globe, with nearly 144 683 deaths worldwide on 18 April 2020. In the wake of this pandemic, we have witnessed a massive infodemic with the public being bombarded with vast quantities of information, much of which is not scientifically correct. Fighting fake news is now the new front in the COVID‐19 battle. This regular feature comments on the role of health sciences librarians and information professionals in combating the COVID‐19 infodemic. To support their work, it draws attention to the myth busters, fact‐checkers and credible sources relating to COVID‐19. It also documents the guides that libraries have put together to help the general public, students and faculty recognise fake news.


title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

text: Abstract Twelve aminoarylazocompounds (A–C) and 46 aryltriazene 7 derivatives (D–G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1 > 7 > 8 > 4; YFV: 7 > 5; CVB-2: 25 > 56 > 18; RSV: 14 > 20 > 55 > 38 > 18 > 19; HSV-1: 2. For these compounds the EC50 ranged from 1.6μM (1) to 12μM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values.


title: Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

text: Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.


title: Decentralization and collaborative disaster governance: Evidence from South Korea

text: Decentralized disaster governance has been gaining much attention with the rising global urbanization rate and the complex nature of the disasters occurring in densely urbanized areas today. This paper studies the case of South Korea, a highly urbanized country with relatively recent decentralization reforms, in order to analyze the evolution of its disaster management system and to draw out implications from its experience. Specifically, it traces the national-level institutional changes in its disaster management, and then closely examines a hydrofluoric gas leakage in the industrial city of Gumi. The finding is that South Korea simultaneously carried out both centralization and decentralization of disaster management, which are not contradictory but rather complementary. Nevertheless, while the country successfully set up an integrated and comprehensive national-level management system, from which disaster governance can successfully be decentralized to localities, it still requires much more developed and consolidated multilevel (vertical) and broader (horizontal) collaboration, which are the preconditions for decentralized disaster governance.


title: PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production

text: Infections by coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) result in very little type I interferon (IFN) production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNβ reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase (DUB) activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/cr.2008.294) contains supplementary material, which is available to authorized users.


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title: Evaluation of envelope glycoprotein Erns of an atypical bovine pestivirus as antigen in a microsphere immunoassay for the detection of antibodies against bovine viral diarrhea virus 1 and atypical bovine pestivirus

text: Abstract Atypical bovine pestiviruses are related antigenically and phylogenetically to bovine viral diarrhea viruses (BVDV-1 and BVDV-2), and may cause the same clinical manifestations in animals. Glycoprotein Erns of an atypical bovine pestivirus Th/04_KhonKaen was produced in a baculovirus expression system and was purified by affinity chromatography. The recombinant Erns protein was used as an antigen in a microsphere immunoassay for the detection of antibodies against BVDV-1 and atypical bovine pestivirus. The diagnostic performance of the new method was evaluated by testing a total of 596 serum samples, and the assay was compared with enzyme-linked immunosorbent assay (ELISA). Based on the negative/positive cut-off median fluorescence intensity (MFI) value of 2800, the microsphere immunoassay had a sensitivity of 100% and specificity of 100% compared to ELISA. The immunoassay was able to detect antibodies against both BVDV-1 and the atypical pestivirus. This novel microsphere immunoassay has the potential to be multiplexed for simultaneous detection of antibodies against different bovine pathogens in a high-throughput and economical way.


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title: Old and new faces of the nucleolus. Workshop on the Nucleolus and Disease


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title: Une maladie cardio-vasculaire et un diabète sont des facteurs de mortalité au cours du SRAS J.W.M. Chan C.K.

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title: Support students’ changing needs throughout the pandemic

text: The COVID‐19 pandemic has meant new challenges for Disability Services Offices, and colleges and universities will likely experience the impacts for months, if not years. Members of Disability Compliance for Higher Education’s Advisory Board participated in a conference call to discuss what's been happening at their institutions, how they have addressed the challenges, and what they plan for the future.


title: Toward a collaborative model of pandemic preparedness and response: Taiwan's changing approach to pandemics

text: Abstract Background Over time, as newly emerging infectious diseases have become increasingly common and more easily spread, it has become clear that traditional response mechanisms have proven inadequate to the task of prevention and control. Purpose To explore whether enhanced cooperation with local government and community institutions can effectively supplement traditional state-centric public health epidemic responses. Methods Drawing on Taiwan as a case study, we assess the role of the whole-of-society approach to epidemic response as arises from the collaborative governance literature. The approach calls for enhanced cooperation, trust building, resource sharing and consensus-oriented decision making among multiple levels of government, business, non-profits, and the public in general. Results The Taiwan case illustrates the benefits of the whole-of-society approach. Enhanced cooperation between state, local government and non-state institutions, particularly neighborhood committees, has resulted in a strengthened, holistic epidemic preparedness and response infrastructure. Conclusion The Taiwan case provides evidence that by implementing the whole-of-society approach to pandemic preparedness and response governments can enhance their ability to manage future outbreaks. We recommend that governments beyond Taiwan's borders seriously consider adopting this approach.


title: A Systematic Approach to Novel Virus Discovery in Emerging Infectious Disease Outbreaks

text: The discovery of novel viruses is of great importance to human health—both in the setting of emerging infectious disease outbreaks and in disease syndromes of unknown etiology. Despite the recent proliferation of many efficient virus discovery methods, careful selection of a combination of methods is important to demonstrate a novel virus, its clinical associations, and its relevance in a timely manner. The identification of a patient or an outbreak with distinctive clinical features and negative routine microbiological workup is often the starting point for virus hunting. This review appraises the roles of culture, electron microscopy, and nucleic acid detection–based methods in optimizing virus discovery. Cell culture is generally slow but may yield viable virus. Although the choice of cell line often involves trial and error, it may be guided by the clinical syndrome. Electron microscopy is insensitive but fast, and may provide morphological clues to choice of cell line or consensus primers for nucleic acid detection. Consensus primer PCR can be used to detect viruses that are closely related to known virus families. Random primer amplification and high-throughput sequencing can catch any virus genome but cannot yield an infectious virion for testing Koch postulates. A systematic approach that incorporates carefully chosen combinations of virus detection techniques is required for successful virus discovery.


title: Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala

text: BACKGROUND: The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. RESULTS: For poultry, an overall prevalence of 41 % of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. FOR HUNTING: All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. FOR COOKING: Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. CONCLUSION: According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.


title: Correction to Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil

text: [This corrects the article DOI: 10.1021/acsomega.0c00772.].


title: The Origin and Prevention of Pandemics

text: Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change and communication strategies. Since there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.


title: Informing emergency care for COVID‐19 patients: The COVID‐19 Emergency Department Quality Improvement Project protocol

text: Objectives: There is an urgency to support Australian ED clinicians with real‐time tools as the COVID‐19 pandemic evolves. The COVID‐19 Emergency Department (COVED) Quality Improvement Project has commenced and will provide flexible and responsive clinical tools to determine the predictors of key ED‐relevant clinical outcomes. Methods: The COVED Project includes all adult patients presenting to a participating ED and meeting contemporary testing criteria for COVID‐19. The dataset has been embedded in the electronic medical record and the COVED Registry has been developed. Results: Outcomes measured include being COVID‐19 positive and requiring intensive respiratory support. Regression methodology will be used to generate clinical prediction tools. Conclusion: This project will support EDs during this pandemic.


Treatment options for patients with HR+/HER2− advanced breast cancer during the COVID-19 pandemic: dose reduction of ribociclib does not diminish efficacy


title: The impact of COVID-19 on African American communities in the United States

text: IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.


title: Thrombosis risk associated with COVID-19 infection. A scoping review

text: BACKGROUND: Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging. METHODS: We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services. RESULTS: Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although and increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known. DISCUSSION: A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.


title: Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Causing a COVID-19 Case in Morocco

text: Here, we report a complete genome sequence obtained for a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from a nasopharyngeal swab specimen of a Moroccan patient with coronavirus disease 2019 (COVID-19).


title: Structural and operational redesigning of patient-centered ambulatory care pharmacy services and its effectiveness during the COVID-19 pandemic

text: BACKGROUND: The newly emerged coronavirus pandemic (COVID-19) has collapsed the entire global health care system. Due to these settings, a lot of strategic changes are adopted by healthcare facilities to ensure continuity in patient-centered services. OBJECTIVE: This study aims to evaluate the effectiveness of structural and operational changes made in ambulatory care pharmacy services during the COVID-19 pandemic. METHODS: A retrospective comparative study was conducted to evaluate the impact and effectiveness of patient-centered interventions and consequent access to medication management care within Johns Hopkins Aramco Health Care ambulatory care pharmacy services during the COVID-19 pandemic by comparing patient-centered key performance indicators before and during COVID-19 pandemic for a total of 4 months. RESULTS: As a result of the structural and operational changes made in patient-centered ambulatory care pharmacy services during the COVID-19 pandemic, a 48% prescriptions requests and 90% prescriptions fills are increased through online health portal application. A three-fold increase in the pharmacy call center utilization resulted in around 10% abandoned calls. In the number of physical visits to ambulatory care pharmacies, a 37% reduction was also noted. The decrease in staff schedule efficiency and an increase in average prescription waiting time were also noticed. The prescription collection through remote area pick up locations, and medication home delivery services were successful during COVID-19 pandemic as supported by statistical data. CONCLUSION: The access to ambulatory care pharmacy services during COVID-19 pandemic has been successfully maintained via medication home delivery, remote area pickup locations, pharmacy call-center consultations and refill requests, online health portal application services, and other measures, while reducing the number of physical visits to the JHAH hospital/clinic to ensure compliance with infection control and prevention measures.


docid: kpbpqsxj

title: Synthesizing data and models for the spread of MERS-CoV, 2013: key role of index cases and hospital transmission

text: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April-October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and distinguishes transmission by zoonotic (index) cases and secondary cases. When observation bias is assumed to account for the fact that all reported zoonotic cases are severe, but only ~57% of secondary cases are symptomatic, the average reproduction number of MERS-CoV is estimated to be 0.45 (95%CI:0.29–0.61). Alternatively, if these epidemiological observations are taken at face value, index cases are estimated to transmit substantially more effectively than secondary cases, (R(i) =0.84 (0.58–1.20) vs R(s)=0.36 (0.24–0.51)). In both scenarios the relative contribution of hospital-based transmission is over four times higher than that of community transmission, indicating that disease control should be focused on hospitalized patients. Adjusting previously published estimates for observation bias confirms a strong support for the average R < 1 in the first stage of the outbreak in 2013 and thus, transmissibility of secondary cases of MERS-CoV remained well below the epidemic threshold. More information on the observation process is needed to clarify whether MERS-CoV is intrinsically weakly transmissible between people or whether existing control measures have contributed meaningfully to reducing the transmissibility of secondary cases. Our results could help evaluate the progression of MERS-CoV in recent months in response to changes in disease surveillance, control interventions, or viral adaptation.


title: Molecular chaperones: from proteostasis to pathogenesis

text: Maintaining protein homeostasis (proteostasis) is essential for a functional proteome. A wide range of extrinsic and intrinsic factors perturb proteostasis, causing protein misfolding, misassembly, and aggregation. This compromises cellular integrity and leads to aging and disease, including neurodegeneration and cancer. At the cellular level, protein aggregation is counteracted by powerful mechanisms comprising of a cascade of enzymes and chaperones that operate in a coordinated multistep manner to sense, prevent, and/or dispose of aberrant proteins. Although these processes are well understood for soluble proteins, there is a major gap in our understanding of how cells handle misfolded or aggregated membrane proteins. This article provides an overview of cellular proteostasis with emphasis on membrane protein substrates and suggests host–virus interaction as a tool to clarify outstanding questions in proteostasis.


The Ethical Governance of the Digital During and After the COVID-19 Pandemic


title: Recombinase polymerase amplification: Basics, applications and recent advances

text: Abstract Recombinase polymerase amplification (RPA) is a highly sensitive and selective isothermal amplification technique, operating at 37–42°C, with minimal sample preparation and capable of amplifying as low as 1–10 DNA target copies in less than 20 min. It has been used to amplify diverse targets, including RNA, miRNA, ssDNA and dsDNA from a wide variety of organisms and samples. An ever increasing number of publications detailing the use of RPA are appearing and amplification has been carried out in solution phase, solid phase as well as in a bridge amplification format. Furthermore, RPA has been successfully integrated with different detection strategies, from end-point lateral flow strips to real-time fluorescent detection amongst others. This review focuses on the different methodologies and advances related to RPA technology, as well as highlighting some of the advantages and drawbacks of the technique.


title: Coagulopathy of Coronavirus Disease 2019

text: Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.” STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.


title: Crisis Decision Making on a Global Scale: Transition from Cognition to Collective Action under Threat of COVID‐19

text: This essay examines basic functions of crisis decision-making—cognition, communication, coordination, and control—in response to COVID-19. This crisis decision-making framework is applied to cases from South Korea, Italy, and the United States as public officials grapple with how to recognize, respond, and recover from this deadly, invisible threat. The authors acknowledge the harsh trade-off between the compelling need to limit transmission of the virus to protect public health and the consequent economic losses of halting social interaction. They draw implications from this crisis for better decision-making and investment in a global information infrastructure system to manage large-scale, multidisciplinary threats to the health, economy, and sustainability of the world's community of nations. The essay concludes that collective cognition, amplified by timely, valid communication and supported by sound planning, trained personnel, appropriate technology, and bold leadership, enables coordinated action needed to bring a large-scale global crisis under control. Evidence for Practice_ Invest in information technology to manage systematic data collection, analysis, and modeling. Provide timely, informed updates on community status to constituents. Maintain a knowledge base of resources, vulnerabilities, and plans.


title: Importance of SARS-CoV Spike Protein Trp-rich Region in Viral Infectivity

text: SARS-CoV entry is mediated by spike glycoprotein. During the viral and host cellular membrane fusion, HR1 and HR2 form 6-helix bundle, positioning the fusion peptide closely to the C-terminal region of ectodomain to drive apposition and subsequent membrane fusion. Connecting to the HR2 region is a Trp-rich region which is absolutely conserved in members of coronaviruses. To investigate the importance of Trp-rich region in SARS-CoV entry, we produced different mutated S proteins using Alanine scan strategy. SARS-CoV pseudotyped with mutated S protein was used to measure viral infectivity. To restore the aromaticity of Ala-mutants, we performed rescue experiments using phenylalanine substitutions. Our results show that individually-substituted Ala-mutants substantially decrease infectivity by >90%, global Ala-mutants totally abrogated infectivity. In contrast, Phe-substituted mutants are able to restore 10–25% infectivity comparing to the wild type. The results suggest that the Trp-rich region of S protein is essential for SARS-CoV infectivity.


title: Development of recombinant rabies viruses vectors with Gaussia luciferase reporter based on Chinese vaccine strain CTN181

text: Abstract The recombinant rabies virus (RV) vectors encoding the secreted gene marker Gaussia luciferase (Gluc) were generated based on Chinese vaccine strain CTN181. Vectors included replication competent CTN-Gluc, CTN/GQ333R-Gluc, in which the amino acid in position 333 of glycoprotein was mutated from glutamine (Q) to arginine (R), and replication constrained CTNΔG-Gluc, in which the glycoprotein encoding gene (G) was deleted. The growth of recombinant RVs in transfected cells was confirmed through biochemical assays of Gluc activities. Gluc expression in recombinant CTNΔG-Gluc virus was highest while that in CTN/GQ333R-Gluc virus was lowest. The optimal time to harvest recombinant RVs was determined and the function of pathogenic and nonpathogenic rabies glycoprotein in virus recovery was examined. The addition of glycoprotein was slightly beneficial for virus recovery and the titer of rescued virus was lowered even when the amino acid in G333 position of glycoprotein was mutated from nonpathogenic Gln to pathogenic Arg. Conclusions: Viral vectors based on a human rabies vaccine strain CTN181 were successful. Gluc was useful as an in vitro gene marker for monitoring the growth of recombinant RVs iteratively in cell culture.


docid: xadfvtxj

title: Analysis of Epidemiological and Clinical features in older patients with Corona Virus Disease 2019 (COVID-19) out of Wuhan

text: BACKGROUND: The outbreak of COVID-19 has become a big threat to China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 out of Wuhan. METHODS: A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from Jan 17 to Feb 12, 2020. Epidemiological, clinical and treatment data were analyzed between those older (≥60y) and younger (<60y) patients. RESULTS: Total 788 patients with confirmed COVID-19 were selected, where 136 were older patients with corresponding age of 68.28y±7.314y. There was a significantly higher frequency of women in the older patients compared with the younger patients (57.35% vs 46.47%, P=0.021). The presence of coexisting medical condition was significantly higher in older patients compared with younger patients (55.15% vs 21.93%, P<0.001), including the rate of hypertension, diabetes, heart diseases and COPD. Significantly higher rates of severe (older vs younger groups: 16.18% vs 5.98%, P<0.001)/critical (8.82% vs 0.77%, P<0.001) type, shortness of breath (12.50% vs 3.07%, P<0.001) and high temperature of >39.0℃ (13.97% vs 7.21%, P=0.010) were observed in older patients compared with younger patients. Finally, Higher rates of ICU admission (9.56% vs 1.38%, P<0.001) and methylprednisolone application (28.68% vs 9.36%, P<0.001) were also identified in older patients. CONCLUSIONS: The specific epidemiological and clinical features of older COVID-19 patients included significantly higher female gender, body temperature, co-existing of basic diseases and rate of severe and critical type.


Comment on: “To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out. Characterization of herpetic lesions in hospitalized COVID-19 patients.”


docid: ajcngwrp

title: Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD

text: This consensus statement established under the auspices of the German working group on BM and blood stem cell transplantation (DAG-KBT), the German Society of Hematology and Oncology (DGHO), the Austrian Stem Cell Transplant Working Group, the Swiss Blood Stem Cell Transplantation Group (SBST) and the German-Austrian Pediatric Working Group on SCT (Päd-Ag-KBT) summarizes current evidence for diagnosis, immunosuppressive and supportive therapy to provide practical guidelines for the care and treatment of patients with pulmonary manifestations of chronic GVHD (cGVHD). Pulmonary cGVHD can present with obstructive and/or restrictive changes. Disease severity ranges from subclinical pulmonary function test (PFT) impairment to respiratory insufficiency with bronchiolitis obliterans being the only pulmonary complication currently considered diagnostic of cGVHD. Early diagnosis may improve clinical outcome, and regular post-transplant follow-up PFTs are recommended. Diagnostic work-up includes high-resolution computed tomography, bronchoalveolar lavage and histology. Topical treatment is based on inhalative steroids plus beta-agonists. Early addition of azithromycin is suggested. Systemic first-line treatment consists of corticosteroids plus, if any, continuation of other immunosuppressive therapy. Second-line therapy and beyond includes extracorporeal photopheresis, mammalian target of rapamycin inhibitors, mycophenolate, etanercept, imatinib and TLI, but efficacy is limited. Clinical trials are urgently needed to improve understanding and treatment of this deleterious complication.


title: Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers

text: We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.


title: Direct multiplexed whole genome sequencing of respiratory tract samples reveals full viral genomic information

text: Abstract Background Acute respiratory tract infections (RTI) cause substantial morbidity during childhood, and are responsible for the majority of pediatric infectious diseases. Although most acute RTI are thought to be of viral origin, viral etiology is still unknown in a significant number of cases. Objectives Multiplexed whole genome sequencing (WGS) was used for virome determination directly on clinical samples as proof of principle for the use of deep sequencing techniques in clinical diagnosis of viral infections. Study design WGS was performed with nucleic acids from sputum and nasopharyngeal aspirates from four pediatric patients with known respiratory tract infections (two patients with human rhinovirus, one patient with human metapneumovirus and one patient with respiratory syncytial virus), and from four pediatric patients with PCR-negative RTI, and two control samples. Results Viral infections detected by routine molecular diagnostic methods were confirmed by WGS; in addition, typing information of the different viruses was generated. In three out of four samples from pediatric patients with PCR-negative respiratory tract infections and the two control samples, no causative viral pathogens could be detected. In one sample from a patient with PCR-negative RTI, rhinovirus type-C was detected. Almost complete viral genomes could be assembled and in all cases virus species could be determined. Conclusions Our study shows that, in a single run, viral pathogens can be detected and characterized, providing information for clinical assessment and epidemiological studies. We conclude that WGS is a powerful tool in clinical virology that delivers comprehensive information on the viral content of clinical samples.


title: Protective and pathogenic roles for mast cells during viral infections

text: Mast cells (MCs) are long-lived immune cells. They are armed with preformed mediators within granules that can be instantaneously released in response to an invading pathogen, including certain viruses. At the skin and mucosae, they initiate innate immune responses and promote the development of adaptive immune responses, through cellular recruitment or antigen presentation. However, systemic MC activation may promote immune pathologies through their vasoactive proteases and biogenic amines. Recently, MC products were identified to contribute to pathologies associated with viral hemorrhagic fever, such vascular leakage and thrombocytopenia. Similar associations of MCs with disease severity have been noted for certain respiratory viral pathogens. Here we discuss the specific MC responses to viruses and their influences on functional immune outcomes during infection.


title: Replication kinetics of different porcine circovirus 2 strains in PK-15 cells, fetal cardiomyocytes and macrophages

text: In this in vitro study, the replication kinetics of porcine circovirus type 2 (PCV2) in porcine alveolar macrophages (PAM) and fetal cardiomyocytes (FCM), two target cells in vivo, was compared with that in PK-15 cells. Cultures were inoculated with either the postweaning multisystemic wasting syndrome (PMWS)-associated strain Stoon-1010 or the abortion-associated strain 1121. Viral proteins were visualized and virus production was determined. In PK-15 cells, the capsid protein was expressed between 6 and 12 hours post inoculation (hpi), it relocated to the nucleus between 12 and 24 hpi. At that time, Rep protein was also detected in the nucleus. This sequence of events also occurred in FCM and PAM but nuclear localized antigens appeared later (48 hpi) and in a lower percentage of cells. In PAM, clear differences in susceptibility were seen between pigs. In PAM from two out of five tested pigs, nuclear localized antigens were not detected, whereas in PAM from three other pigs they were seen in up to 20% of the antigen-positive cells. Virus production was observed in PK-15 but not in PAM or FCM cultures. In a second study, the replication kinetics of seven different PCV2 strains were compared in PK-15 cells. It was shown that the two abortion-associated strains had a different replication kinetics in comparison with PMWS or porcine dermatitis and nephropathy syndrome associated strains. With the abortion-associated strains, a higher number of infected cells was observed at 24 hpi and the percentage of infected cells with nuclear localised antigens was lower compared to that of other strains.


title: Retained copper fragments following removal of a copper intrauterine device: Two case reports

text: Abstract Intrauterine devices (IUDs) are safe, cost-effective, and reliable contraceptives, and are gaining popularity worldwide. While complications associated with IUD use are rare, they range from expulsion to uterine perforation. Numerous reports have been published regarding the sequelae of intraperitoneal copper IUDs or retained fragments following the removal of a fractured device. No data exist, however, on the intraperitoneal retention of copper following the removal of an otherwise intact IUD. Here we present two patients in whom copper IUDs were found to have missing fragments of copper wire despite removal of an otherwise intact IUD found in utero. We caution providers to examine all removed devices carefully, to surgically address intraperitoneal copper in order to mitigate adhesion formation, and to counsel patients about this potentially serious complication.