title: Public views of the uk media and government reaction to the 2009 swine flu pandemic

text: BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.


title: Fc Receptors in Immune Responses

text: Abstract Antibodies are major molecular effectors of adaptive immune responses. Most, if not all, biological activities of antibodies, however, depend on the functional properties of cells that express receptors for the Fc portion of antibodies (FcR). Most FcR are activating receptors; some are inhibitory. When engaged by antibodies and antigen, the various FcR expressed by a given cell trigger a mixture of positive and negative signals whose integration determines cellular responses. Responses of cell populations can be either protective or pathogenic. As a consequence, FcR are potential target/tools in a variety of diseases including infection, allergy, autoimmune diseases, and cancer.


IgG subclasses of antibodies reacting with HIV and myelin basic protein in CSF from HIV infected patients


Caspase activation during virus infection: more than just the kiss of death?


title: Encephalitis, Viral

text: Abstract Encephalitis is inflammation and swelling of the brain, often caused by an acute viral infection, or a para- or postinfectious phenomenon known as acute disseminated encephalomyelitis (ADEM). The most common sporadic viral cause is herpes simplex virus, but arthropodborne viruses, such as Japanese encephalitis virus, are a major cause in some settings, and rabies in others. Herpes simplex encephalitis is treated with acyclovir; rabies and Japanese encephalitis are preventable with vaccines. With the reduction in measles through vaccination, the incidence of ADEM, which often follows measles, has also reduced.


title: Using psychoneuroimmunity against COVID-19

text: Abstract The worldwide outbreak of coronavirus disease 2019 (COVID-19) raises concerns of widespread panic and anxiety in individuals subjected to the real or perceived threat of the virus. Compared to general populations, patients who are institutionalized in a closed unit are also very vulnerable to COVID-19 infection and complications. This crisis touched on difficult issues of not only psychiatric care and ethics, but also psychological impacts to psychiatric care givers. In this Viewpoint, we address both physical and biopsychosocial aspects of this infection, as well as the psychoneuroimmunity of preventive strategies of healthy lifestyle, regular exercise, balanced nutrition, quality sleep and a strong connection with people. Social distancing and wearing masks might help us from pathogen exposure, yet such these measures also prevent us from expressing compassion and friendliness. Therefore, all forms of psychological support should be routinely implemented not only to consider psychological resilience but also to enhance psychoneuroimmunity against COVID-19.


title: Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications

text: BACKGROUND: Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans. HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various diagnostic, immunization and pathogenesis studies. Plants are considered as an expression system for producing safe and inexpensive biopharmaceutical proteins. Although invention of transgenic (stable) tobacco plants expressing HCVcp with proper antigenic properties was recently reported, no data for “transient-expression” that is currently the method of choice for rapid, simple and lower-priced protein expression in plants is available for HCVcp. OBJECTIVES: The purpose of this study was to design a highly codon-optimized HCVcp gene for construction of an efficient transient-plant expression system for production of HCVcp with proper antigenic properties in a regional tobacco plant (Iranian Jafarabadi-cultivar) by evaluation of different classes of vectors and suppression of gene-silencing in tobacco. MATERIALS AND METHODS: A codon-optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL peptide in tandem (from N- to C-terminal) was designed and inserted into potato virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions. The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens and vacuum infiltrated into tobacco leaves. The effect of gene silencing suppressor P19 protein derived from tomato bushy stunt virus on the expression yield of HCVcp by each construct was also evaluated by co-infiltration in separate groups. The expressed HCVcp was evaluated by dot and western blotting and ELISA assays. RESULTS: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of “GGTAAG” splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for diagnostic/immunization applications. CONCLUSIONS: By employment of gene optimization strategies, use of viral-based vectors and suppression of plant-derived gene silencing effect, efficient transient expression of HCVcp in tobacco with proper antigenic properties could be possible.


title: Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.


title: Isolation of Rotavirus from Calves in the Federal Republic of Germany

text: SUMMARY: Faeces samples obtained from fourteen calves with acute enteritis were examined in the electron microscope. Two out of fourteen samples contained large numbers of rotavirus particles typically 60 nm. in diameter, lacking the outer layer of capsomeres. Larger particles (70–75 nm.) having an extra capsomere layer were not observed. ZUSAMMENFASSUNG: Isolierung von Rotavirus aus Kälbern in der Bundesrepublik Deutschland In Fäzesproben von 2 Kälbern, die unter akuter Enteritis litten, wurden elektronenmikroskopisch Rotavirus‐Partikel nachgewiesen. Die Partikel hatten einen Durchmesser von 60 nm; die äußere Kapsomerenschicht fehlte.


title: The airborne transmission of infection between flats in high-rise residential buildings: Tracer gas simulation

text: Abstract Airborne transmission of infectious respiratory diseases in indoor environments has drawn our attention for decades, and this issue is revitalized with the outbreak of severe acute respiratory syndrome (SARS). One of the concerns is that there may be multiple transmission routes across households in high-rise residential buildings, one of which is the natural ventilative airflow through open windows between flats, caused by buoyancy effects. Our early on-site measurement using tracer gases confirmed qualitatively and quantitatively that the re-entry of the exhaust-polluted air from the window of the lower floor into the adjacent upper floor is a fact. This study presents the modeling of this cascade effect using computational fluid dynamics (CFD) technique. It is found that the presence of the pollutants generated in the lower floor is generally lower in the immediate upper floor by two orders of magnitude, but the risk of infection calculated by the Wells–Riley equation is only around one order of magnitude lower. It is found that, with single-side open-window conditions, wind blowing perpendicularly to the building may either reinforce or suppress the upward transport, depending on the wind speed. High-speed winds can restrain the convective transfer of heat and mass between flats, functioning like an air curtain. Despite the complexities of the air flow involved, it is clear that this transmission route should be taken into account in infection control.


title: Enhanced Infrared Absorbance of the CMOS Compatible Thermopile by the Subwavelength Rectangular-Hole Arrays

text: The enhanced infrared absorbance (IRA) of the complementary metal-oxide-semiconductor (CMOS) compatible thermopile with the subwavelength rectangular-hole arrays in active area is investigated. The finite-difference time-domain (FDTD) method considered and analyzed the matrix arrangement (MA) and staggered arrangement (SA) of subwavelength rectangular-hole arrays (SRHA). For the better cases of MA-SRHA and SA-SRHA, the geometric parameters are the same and the infrared absorption efficiency (IAE) of the SA type is better than that of the MA type by about 19.4% at target temperature of 60 °C. Three proposed thermopiles with SA-SRHA are manufactured based on the 0.35 μm 2P4M CMOS-MEMS process. The measurement results are similar to the simulation results. The IAE of the best simulation case of SA-SRHA is up to 3.3 times higher than that without structure at the target temperature of 60 °C. Obviously, the staggered rectangular-hole arrays with more appropriate geometric conditions obtained from FDTD simulation can excellently enhance the IRA of the CMOS compatible thermopile.


title: Experience for use of modified full‐face snorkel mask as personal protective equipment during endoscopic procedures in the era of coronavirus disease pandemic

text: The rapid spread of COVID‐19 has led to personal protective equipment (PPE) shortage worldwide(1,2). Recently, the adaptation of commercially available modified full‐faced snorkel masks (mFFSMs) has been proposed as an alternative of PPE shortage. mFFSMs were adapted and used by health care workers during the COVID‐19 crisis(3). An mFFSM is composed of an off‐the‐shelf snorkel mask, a custom adapter (three‐dimensional‐printed with a custom print file that sourced attributes from the designs found at Pneumask and OceanReef.), and a filter cartridge (Figure1‐a).


title: Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study

text: After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013–2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan’s migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan’s migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan’s total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan’s migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3–4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan’s migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions.


COVID‐19 deaths in long term care facilities ‐ a critical piece of the pandemic puzzle


title: Auswirkungen von COVID-19 auf die rheumatologische Versorgung: Eine nationale Umfrage im April 2020

text: BACKGROUND: The preparations of healthcare systems to accommodate the large numbers of severely ill COVID-19 patients in March/April 2020 also had a substantial impact on rheumatological patient care. OBJECTIVE: The aim of this online survey was to assess the changes and current status of rheumatology departments and practices in Germany. MATERIAL AND METHODS: A web-based questionnaire was designed to differentiate the impact of the pandemic on inpatient and outpatient operations. Questions addressed the following issues: characteristics of the department, impact on patient care, application of recommendations, personal protective equipment (PPE), and organizational adaptations to the new framework conditions. The survey was available for 14 days and closed on 3 May 2020. RESULTS: A total of 66 complete answers were recorded and evaluated. In the first 4 weeks of the COVID-19 crisis the proportion of outpatients in the institutions decreased on average by −40.6%. The number of outpatients receiving infusions decreased by −25.6%. Of the inpatient facilities 81% reported an average decrease of hospitalized patients of −54.9% and 52% of the participants complained of a lack of PPE. Organizational adjustments are reported. CONCLUSION: The rheumatological services were significantly reduced 4 weeks after the SARS-CoV‑2 pandemic had reached Germany on a large scale. The study showed that in this phase there were decisive turning points in patient care and implicated substantial organizational and ultimately also economic effects on the healthcare system, both in hospitals and private practices. As the survey cannot adapt to the daily dynamic changes in priorities it serves as a first snapshot, which requires follow-up studies.


docid: rhoyeyzm

title: Unfavorable outcomes in pregnant patients with COVID-19 outside Wuhan, China


title: Viral Phylogenomics Using an Alignment-Free Method: A Three-Step Approach to Determine Optimal Length of k-mer

text: The development of rapid, economical genome sequencing has shed new light on the classification of viruses. As of October 2016, the National Center for Biotechnology Information (NCBI) database contained >2 million viral genome sequences and a reference set of ~4000 viral genome sequences that cover a wide range of known viral families. Whole-genome sequences can be used to improve viral classification and provide insight into the viral “tree of life”. However, due to the lack of evolutionary conservation amongst diverse viruses, it is not feasible to build a viral tree of life using traditional phylogenetic methods based on conserved proteins. In this study, we used an alignment-free method that uses k-mers as genomic features for a large-scale comparison of complete viral genomes available in RefSeq. To determine the optimal feature length, k (an essential step in constructing a meaningful dendrogram), we designed a comprehensive strategy that combines three approaches: (1) cumulative relative entropy, (2) average number of common features among genomes, and (3) the Shannon diversity index. This strategy was used to determine k for all 3,905 complete viral genomes in RefSeq. The resulting dendrogram shows consistency with the viral taxonomy of the ICTV and the Baltimore classification of viruses.


title: Quality evaluation of Lonicerae Japonicae Flos and Lonicerae Flos based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis

text: INTRODUCTION: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) belong to different genera of Caprifoliaceae. They have been historically utilised as herbal medicine to treat various diseases. However, the comprehensive assessment of them still remains a challenge. OBJECTIVE: To develop a comprehensive method of ultra‐fast liquid chromatography‐tandem triple quadrupole mass spectrometry (UFLC‐QTRAP‐MS/MS) coupled with multivariate statistical analysis for the quality evaluation and reveal differential components of LJF and LF. METHODOLOGY: A validated UFLC‐QTRAP‐MS/MS method was established for simultaneous determination of 50 constituents, including 12 organic acids, 12 flavonoids, 6 iridoids, 3 saponins, 13 amino acids and 4 nucleosides. The obtained data were employed to multivariate statistical analysis. Principal component anlysis (PCA) and partial least squares determinant analysis (PLS‐DA) were performed to classify and reveal differential components of samples; grey relational analysis (GRA) was introduced to assess the samples according to the contents of 50 constituents by calculating the relative correlation degree of each sample. RESULTS: Fifty constituents were simultaneously determined of LJF and LF. Based on obtained data, PCA and PLS‐DA were easy to distinguish samples and the classification of the samples was related to 11 chemical constituents. GRA implied the quality of LJF was better, and that the flower buds were superior to the flowers. Moreover, organic acids are the main components of samples. CONCLUSION: This study not only established a method of simultaneous determination of multiple bioactive constituents in LJF and LF, but provided comprehensive information on the quality control of them. The developed method is conducive to distinguish orthologues or paralogues of them, and supply the support for “heterologous effects”.


title: New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and Prevention

text: Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.


title: Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

text: Background Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions. Data sources The data of mouse hepatic models and relevant human liver diseases presented in this review are systematically collected from PubMed, ScienceDirect and the Web of Science databases published in English. Results The hepatotoxic liver injury in mice induced by the metabolites of CCl4, acetaminophen or alcohol represent necrotic cell death with activation of cytochrome pathway, formation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-α induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrated the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The α-GalCer-induced liver injury was mediated by TNF-α. The LPS-induced hepatitis involved TNF-α, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-α signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune cells and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcoholic fatty liver disease and alcoholic liver disease in human were discussed. Conclusions The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.


title: Viral infections in interferon-γ receptor deficiency

text: Abstract Interferon-γ receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-γ receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-γ receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens. (J Pediatr 1999;135:640-3)


title: Increasing Host Cellular Receptor—Angiotensin‐Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019‐nCoV (or SARS‐CoV‐2) Infection

text: The ongoing outbreak of a new coronavirus (2019‐nCoV, or SARS‐CoV‐2) has caused an epidemic of the acute respiratory syndrome known as COVID‐19 in humans. SARS‐CoV‐2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS‐CoV‐1 and SARS‐CoV‐2 may use the same host cellular receptor, angiotensin‐converting enzyme 2 (ACE2), for entering into host cells. The affinity between ACE2 and the SARS‐CoV‐2 S protein is much higher than that of ACE2 binding to the SARS‐CoV S protein, explaining why SARS‐CoV‐2 seems to be more readily transmitted from the human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS‐CoV‐1 and SARS‐CoV‐2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS‐CoV‐2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high‐risk factors for developing COVID‐19, and the infection of other viruses may increase the risk of SARS‐CoV‐2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses. This article is protected by copyright. All rights reserved.


title: Black–White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges

text: Background: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black–White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. Methods: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black–White risk differentials. Results: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01–1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93–1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10–2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36–3.88. Conclusion: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.


title: COVID‐19 pneumonia in lung transplant recipients: report of two cases

text: Coronavirus disease 2019 (COVID‐19) has been declared pandemic since March 2020. In Europe, Italy has been the first nation affected by this infection. In this paper we report anamnestic data, clinical features and therapeutic management of two lung transplant recipients with confirmed COVID‐19 pneumonia. Both patients were in good clinical conditions prior to the infection and were on immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil and corticosteroids. Whilst mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS‐CoV‐2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions and had a fatal outcome. Further insight into SARS‐CoV‐2 infection is eagerly awaited to improve the outcome transplant recipients affected by COVID‐19 pneumonia.


title: Mutations in the genome of porcine reproductive and respiratory syndrome virus responsible for the attenuation phenotype

text: Although live-attenuated vaccines have been used for some time to control clinical symptoms of the porcine reproductive and respiratory syndrome (PRRS), the molecular bases for the attenuated phenotype remain unclear. We had previously determined the genomic sequence of the pathogenic PRRSV 16244B. Limited comparisons of the structural protein coding sequence of an attenuated vaccine strain have shown 98% homology to the pathogenic 16244B. Here we have confirmed the attenuated phenotype and determined the genomic sequence of that attenuated PRRSV vaccine and compared it to its parental VR-2332 and the 16244B strains. The attenuated vaccine sequence was colinear with that of the strain 16244B sequence containing no gaps and 212 substitutions over 15,374 determined nucleotide sequence. We identified nine amino acid changes distributed in Nsp1β, Nsp2, Nsp10, ORF2, ORF3, ORF5 and ORF6. These changes may provide the molecular bases for the observed attenuated phenotype.


docid: zwpqwpry

title: Tocilizumab treatment in COVID‐19: A single center experience

text: Tocilizumab (TCZ), a monoclonal antibody against interleukin‐6 (IL‐6), emerged as an alternative treatment for COVID‐19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID‐19 infected patients. The demographic, treatment, laboratory parameters of C‐reactive protein (CRP) and IL‐6 before and after TCZ therapy and clinical outcome in the 15 COVID‐19 patients were retrospectively assessed. Totally 15 patients with COVID‐19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL‐6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL‐6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID‐19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL‐6, the repeated dose of the TCZ is recommended.


title: Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein

text: The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28γ-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28γ-knockout cells was greater than in PA28γ-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28γ gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced proteolysis of nCoV N compared to that in PA28γ-N151Y cells containing a dominant-negative PA28γ mutation, which reduced this process. These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19.


El síndrome respiratorio agudo severo


AB 3.1.1.1 (or EC 3.1.1.?)


title: Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV–exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedaries—apart from conventional antibodies—have relatively unique, heavy chain–only antibodies (HCAbs). These HCAbs are devoid of light chains and have long complementarity-determining regions with unique epitope binding properties, allowing them to recognize and bind with high affinity to epitopes not recognized by conventional antibodies. Through direct cloning and expression of the variable heavy chains (VHHs) of HCAbs from the bone marrow of MERS-CoV–infected dromedaries, we identified several MERS-CoV–specific VHHs or nanobodies. In vitro, these VHHs efficiently blocked virus entry at picomolar concentrations. The selected VHHs bind with exceptionally high affinity to the receptor binding domain of the viral spike protein. Furthermore, camel/human chimeric HCAbs—composed of the camel VHH linked to a human Fc domain lacking the CH1 exon—had an extended half-life in the serum and protected mice against a lethal MERS-CoV challenge. HCAbs represent a promising alternative strategy to develop novel interventions not only for MERS-CoV but also for other emerging pathogens.


title: A host gene expression approach for identifying triggers of asthma exacerbations

text: RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES: To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. METHODS: Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. RESULTS: Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. CONCLUSIONS: Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.


title: Polyarthrite associée à une leishmaniose chez un jeune chien

text: Résumé Un chien de race Cane corso, mâle, âgé de deux ans, est examiné en consultation pour abattement et dysorexie. Il présente également une boiterie d’appui persistante du membre postérieur gauche depuis plusieurs semaines. À l’examen clinique, le chien est en hyperthermie (39,3°C) ; il a des saignements spontanés des babines, une polyadénomégalie périphérique, notamment des nœuds lymphatiques poplités, ainsi qu’une splénomégalie. Par ailleurs, l’examen orthopédique montre que les tarses sont gonflés et chauds. Cela laisse suspecter une synovite bilatérale. L’examen cytologique des nœuds lymphatiques et du liquide synovial permet de diagnostiquer avec certitude une leishmaniose. En effet, de très nombreuses formes amastigotes sont visualisées dans les macrophages. Une analyse par PCR sur sang, liquide synovial, suc ganglionnaire et ponction de moelle osseuse écarte l’ehrlichiose et la borréliose. Une PCR leishmaniose sur sang est également effectuée pour suivre la réponse au traitement. Malgré une forte infestation, une anémie non régénérative, une leucopénie, des signes de néphropathie et l’apparition d’une épistaxis, le chien est traité avec succès principalement à l’aide d’antimoniate de méglumine, d’allopurinol, de corticostéroïdes, associés à des antibiotiques. Summary A 2-year-old male Cane Corso dog was presented with lameness anorexia and lethargy since several weeks. At presentation, the animal had fever (39.3°C), generalised lymphadenopathy (in particular popliteal lymph nodes), splenomegaly and bilateral swelling of the tarsal joints. Synovial fluid from tarsal joints and fine-needle aspirations of lymph nodes were submitted to cytological examination: Leishmania amastigotes contained in macrophages were observed. Some other causes of polyarthritis (Borrelia and Ehrlichia) were excluded by PCR. The follow-up of the treatment was done with PRC Leishmania on blood. Although the animal had non-regenerative anaemia, nephropathy, leukopenia and epistaxis, it was successfully treated with meglumine antimoniate, allopurinol, corticoids, and antibiotherapy.


title: The new normal

text: [Image: see text] Deputy Editor‐in‐Chief, Prof Aris T Papageorghiou, discusses the latest thinking in women’s health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/june-editorial-2020


title: Molecular Modeling Evaluation of the Binding Effect of Ritonavir, Lopinavir and Darunavir to Severe Acute Respiratory Syndrome Coronavirus 2 Proteases

text: Three anti-HIV drugs, ritonavir, lopinavir and darunavir, might have therapeutic effect on coronavirus disease 2019 (COVID-19). In this study, the structure models of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteases, coronavirus endopeptidase C30 (CEP_C30) and papain like viral protease (PLVP), were built by homology modeling. Ritonavir, lopinavir and darunavir were then docked to the models, respectively, followed by energy minimization of the protease-drug complexes. In the simulations, ritonavir can bind to CEP_C30 most suitably, and induce significant conformation changes of CEP_C30; lopinavir can also bind to CEP_C30 suitably, and induce significant conformation changes of CEP_C30; darunavir can bind to PLVP suitably with slight conformation changes of PLVP. It is suggested that the therapeutic effect of ritonavir and lopinavir on COVID-19 may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.


title: A Leaderless Genome Identified during Persistent Bovine Coronavirus Infection Is Associated with Attenuation of Gene Expression

text: The establishment of persistent viral infection is often associated with the selection of one or more mutant viruses. For example, it has been found that an intraleader open reading frame (ORF) in genomic and subgenomic mRNA (sgmRNA) molecules is selected during bovine coronavirus (BCoV) persistence which leads to translation attenuation of the downstream ORF. Here, we report the unexpected identification of leaderless genomes, in addition to leader-containing genomes, in a cell culture persistently infected with BCoV. The discovery was made by using a head-to-tail ligation method that examines genomic 5′-terminal sequences at different times postinfection. Functional analyses of the leaderless genomic RNA in a BCoV defective interfering (DI) RNA revealed that (1) the leaderless genome was able to serve as a template for the synthesis of negative-strand genome, although it cannot perform replicative positive-strand genomic RNA synthesis, and (2) the leaderless genome retained its function in translation and transcription, although the efficiency of these processes was impaired. Therefore, this previously unidentified leaderless genome is associated with the attenuation of genome expression. Whether the leaderless genome contributes to the establishment of persistent infection remains to be determined.


title: Promises and pitfalls for recombinant oligoclonal antibodies-based therapeutics in cancer and infectious disease

text: Monoclonal antibodies (mAbs) have revolutionized the diagnosis and treatment of many human diseases and the application of combinations of mAbs has demonstrated improved therapeutic activity in both preclinical and clinical testing. Combinations of antibodies have several advantages such as the capacities to target multiple and mutating antigens in complex pathogens and to engage varied epitopes on multiple disease-related antigens (e.g. receptors) to overcome heterogeneity and plasticity. Oligoclonal antibodies are an emerging therapeutic format in which a novel antibody combination is developed as a single drug product. Here, we will provide historical context on the use of oligoclonal antibodies in oncology and infectious diseases and will highlight practical considerations related to their preclinical and clinical development programs.


docid: csqfvinw

title: The COVID exception


title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling

text: Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.


docid: znuqdzdp

title: A Qualitative Study on the Psychological Experience of Caregivers of COVID-19 Patients

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly, bringing pressure and challenges to nursing staff. OBJECTIVE: To explore the psychology of nurses caring for COVID-19 patients. METHOD: Using a phenomenological approach, we enrolled 20 nurses who provided care for COVID-19 patients in the First Affiliated Hospital of Henan University of Science and Technology from 20 January to 10 February 2020. The interviews were conducted face-to-face or by telephone and were analysed by Colaizzi's 7-step method. RESULTS: The psychological experience of nurses caring for COVID-19 patients can be summarized into four themes. Firstly, negative emotions present in early stage consisting of fatigue, discomfort, and helplessness was caused by high-intensity work, fear and anxiety, and concern for patients and family members. Secondly, self-coping styles included psychological and life adjustment, altruistic acts, team support, and rational cognition. Thirdly, we found growth under pressure, which included increased affection and gratefulness, development of professional responsibility, and self-reflection. Finally, we showed that positive emotions occurred simultaneously with negative emotions. CONCLUSIONS: During an epidemic outbreak, positive and negative emotions of the front-line nurses interweaved and coexisted. In the early stage, negative emotions were dominant and positive emotions appeared gradually. Self-coping styles and psychological growth played an important role in maintaining mental health of nurses.


docid: berrojmq

title: Sleeping Sickness at the Crossroads

text: Human African trypanosomiasis (HAT; sleeping sickness) is a disease with truly historic dimensions [...].


title: Chapter 13 National Health Systems

text: Abstract Health care systems ideally include universal access to comprehensive prepaid medical care along with health promotion and disease prevention. National health insurance and national health services of various models have evolved in the developed world and increasingly in developing countries as well. Some models, such as the Bismarckian social security model and the Bereidge National Health Service model, or National Health insurance such as in pioneered in Canada, are used by a number of countries. The common features are based on principles of national responsibility and solidarity for health, social solidarity for providing funding and searching for effective ways of providing care. Various universal systems of health coverage exist in all industrialized countries, except in the United States which has a mix of public and private insurance but with high percentages of uninsured and poorly insured. Health reform is a continuing process as all countries aspire to assure health care for all. Aging populations, increasing costs, advancing and increasing technology all require nations to modify and adapt organization and financing systems of health care, health protection and promotion.


title: Active surveillance documents rates of clinical care seeking due to respiratory illness

text: BACKGROUND: Respiratory viral infections are a leading cause of disease worldwide. However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. METHODS: We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross‐sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. RESULTS: The likelihood of seeking medical attention was virus‐dependent: higher for influenza and metapneumovirus (19%‐20%), lower for coronavirus and RSV (4%), and 71% of individuals with self‐reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. CONCLUSION: Standard, healthcare‐based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare‐based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.


title: Public Health Education in the United States: Then and Now

text: It was against a background of no formal career path for public health officers that, in 1915, the seminal Welch-Rose Report(1) outlined a system of public health education for the United States. The first schools of public health soon followed, but growth was slow, with only 12 schools by 1960. With organization and growing numbers, accreditation became an expectation. As the mission of public health has grown and achieved new urgency, schools have grown in number, depth and breadth. By mid-2011, there were 46 accredited schools of public health, with more in the pipeline. While each has a unique character, they also must possess certain core characteristics to be accredited. Over time, as schools developed, and concepts of public health expanded, so too did curricula and missions as well as types of people who were trained. In this review, we provide a brief summary of US public health education, with primary emphasis on professional public health schools. We also examine public health workforce needs and evaluate how education is evolving in the context of a growing maturity of the public health profession. We have not focused on programs (not schools) that offer public health degrees or on preventive medicine programs in schools of medicine, since schools of public health confer the majority of master’s and doctoral degrees. In the future, there likely will be even more inter-professional education, new disciplinary perspectives and changes in teaching and learning to meet the needs of millennial students.


title: Experience on radiological examinations and infection prevention for COVID-19 in radiology department

text: Abstract In December 2019, a cluster of patients with emerging pneumonia of unknown etiology were discovered in Wuhan city, China. Laboratory examination identified a novel coronavirus which was tentatively named as 2019 novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in January 2020. The WHO has more recently formally named the 2019-nCoV as coronavirus Diseases 2019 (COVID-19). Within one month, the novel coronavirus rapidly spread across the whole of China through droplet transmission and contact transmission, and the reported number of confirmed COVID-19 cases demonstrated a rising trend. Radiological examinations, especially computed tomography CT, were confirmed as effective methods for the screening and diagnosis of infected cases. Reports stated that many radiologists and technologists were being infected when examining patients with COVID-19. In order to clarify the imaging features of COVID-19 and reduce the infection risk of medical personnel in radiology departments, we summarized the experience on radiological examinations and infection prevention for COVID-19, aiming to guide virus prevention, diagnosis and control within radiology departments.


title: Ultrasonography of the Harderian gland in the rabbit, guinea pig, and chinchilla

text: OBJECTIVE: To evaluate the Harderian gland in rabbits, guinea pigs, and chinchillas using B‐mode ultrasound and to determine normal size and changes in size and/or location in normal and diseased eyes and orbits by ultrasonographic measurements. PROCEDURE: Normal Harderian glands were evaluated ultrasonographically in 20 rabbits, 10 guinea pigs, and eight chinchillas. The Harderian gland was measured ultrasonographically in horizontal and vertical planes. Normal Harderian gland sizes were then compared with sizes in 27 rabbits, 13 guinea pigs, and three chinchillas that had exophthalmos. RESULTS: Harderian glands in normal rabbits were 0.69 ± 0.07 cm (mean value ± SD) horizontally and 1.33 ± 0.14 cm vertically. Harderian glands in normal guinea pigs were 0.58 ± 0.05 cm horizontally and 0.61 ± 0.10 vertically. In normal chinchillas, the Harderian glands were 0.53 ± 0.04 cm horizontally and 0.53 ± 0.03 cm vertically. Harderian glands were significantly larger in the vertical plane in rabbits with exophthalmos (P = 0.001) and in the horizontal plane in guinea pigs with exophthalmos (P = 0.018). Harderian glands of rabbits with exophthalmos were significantly larger in both diseased and healthy glands in both planes compared with those of normal rabbits. Guinea pigs and chinchillas with exophthalmos had larger Harderian glands bilaterally in only the vertical plane. CONCLUSIONS: Ultrasonography is a valuable diagnostic imaging technique to evaluate the Harderian gland in the rabbit, guinea pig, and chinchilla. Retrobulbar pathologic processes cause enlargement of the Harderian gland, which may be attributable to inflammation or possible obstruction of the excretory ducts.


title: A multiplex real-time PCR assay for the detection and differentiation of the newly emerged porcine circovirus type 3 and continuously evolving type 2 strains in the United States

text: Abstract A multiplex quantitative real-time polymerase chain reaction (mqPCR) assay was developed and validated for the detection and differentiation of porcine circovirus type 3 (PCV3) and type 2 (PCV2) strains. The assay coverage was 97.9% (184/188) for PCV3 and 99.1% (1889/1907) for PCV2 sequences that were available from the current GenBank database. The PCR amplification efficiencies were 98–99% for plasmids, and 92–96% for diagnostic samples, with correlation coefficients all greater than 0.99. The limit of detection (LOD) determined as plasmid copies per reaction was 17 for PCV3 and 14 for PCV2. The assay specifically detected the targeted viruses without cross reacting to each other or to other common porcine viruses. Among 336 swine clinical samples collected in 2018, 101 (30.1%) were PCV3 positive, 56 (16.7%) were PCV2 positive and 18 (5.4%) were co-positives. Sixty selected PCV3 positives were confirmed by Sanger sequencing, and 53 of the 56 PCV2 positive samples were tested positive by another validated PCR assay.


Regulating inspiratory pressure to individualize tidal volumes in a simulated two-patient, one-ventilator system


title: Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia

text: The incubation period is an important epidemiologic distribution, it is often incorporated in case definitions, used to determine appropriate quarantine periods, and is an input to mathematical modeling studies. Middle East Respiratory Syndrome coronavirus (MERS) is an emerging infectious disease in the Arabian Peninsula. There was a large outbreak of MERS in South Korea in 2015. We examined the incubation period distribution of MERS coronavirus infection for cases in South Korea and in Saudi Arabia. Using parametric and nonparametric methods, we estimated a mean incubation period of 6.9 days (95% credibility interval: 6.3–7.5) for cases in South Korea and 5.0 days (95% credibility interval: 4.0–6.6) among cases in Saudi Arabia. In a log-linear regression model, the mean incubation period was 1.42 times longer (95% credibility interval: 1.18–1.71) among cases in South Korea compared to Saudi Arabia. The variation that we identified in the incubation period distribution between locations could be associated with differences in ascertainment or reporting of exposure dates and illness onset dates, differences in the source or mode of infection, or environmental differences.


docid: iuzfexig

title: Middle East Respiratory Syndrome Coronavirus: Update for Clinicians

text: Although much recent focus has been on the recognition of Ebola virus disease among travelers from West Africa, cases of Middle East respiratory syndrome coronavirus (MERS-CoV), including travel-associated cases, continue to be reported. US clinicians need to be familiar with recommendations regarding when to suspect MERS-CoV, how to make a diagnosis, and what infection control measures need to be instituted when a case is suspected. Infection control is especially critical, given that most cases have been healthcare-associated. Two cases of MERS-CoV were identified in the United States in May 2014; because these cases were detected promptly and appropriate control measures were put in place quickly, no secondary cases occurred. This paper summarizes information that US clinicians need to know to prevent secondary cases of MERS-CoV from occurring in the United States.


title: Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic

text: Abstract It is an ugly fact that a significant amount of the world's population will contract SARS-CoV infection with the current spreading. While specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.


title: Understanding the T cell immune response in SARS coronavirus infection

text: The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.


title: First detection and genome sequencing of SARS‐CoV‐2 in an infected cat in France

text: After its first description in Wuhan (China), SARS‐CoV‐2 the agent of coronavirus disease 2019 (COVID‐19) rapidly spread worldwide. Previous studies suggested that pets could be susceptible to SARS‐CoV‐2. Here, we investigated the putative infection by SARS‐CoV‐2 in 22 cats and 11 dogs from owners previously infected or suspected of being infected by SARS‐CoV‐2. For each animal, rectal, nasopharyngeal swabs and serum were taken. Swabs were submitted to RT‐qPCR assays targeting 2 genes of SARS‐CoV‐2. All dogs were tested SARS‐CoV‐2 negative. One cat was tested positive by RT‐qPCR on rectal swab. Nasopharyngeal swabs from this animal were tested negative. This cat showed mild respiratory and digestive signs. Serological analysis confirms the presence of antibodies against the SARS‐CoV‐2 in the both serum samples taken 10 days apart. Genome sequence analysis revealed that the cat SARS‐CoV‐2 belongs to the phylogenetic clade A2a like most of the French human SARS‐CoV‐2. This study reports for the first time the natural infection of a cat in France (near Paris) probably through their owners. There is currently no evidence that cats can spread COVID‐19 and owners should not abandon their pets or compromise their welfare.


title: In vitro activity of cepharanthine hydrochloride against clinical wild-type and lamivudine-resistant hepatitis B virus isolates

text: Abstract Hepatitis B virus (HBV) infection causes major public health problems worldwide. The clinical limitation of current antiviral drugs for HBV, such as lamivudine, is the emergence of drug-resistant viral strains during prolonged antiviral therapy. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound, has been reported to possess potent activity against various viruses. The present study was performed to evaluate the in vitro activity of CH against clinical wild-type and lamivudine-resistant HBV isolates in transiently transfected cells. HBV DNA was extracted from serum samples collected both before lamivudine therapy and at the time of viral breakthrough and was amplified by polymerase chain reaction (PCR). The amplicons were cloned into a novel expression vector, pHY106, which can initiate the intracellular HBV replication cycle after cell transfection. Following transfection of the cloned amplicon into HepG2 cells, a drug susceptibility assay was performed. The level of viral antigen, HBeAg, was determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (Q-PCR) was used for determining the amount of intracellular HBV DNA. Heat stress cognate 70 (Hsc70), a host protein required for HBV replication, was also analyzed by reverse transcription PCR (RT-PCR) to explore the possible antiviral mechanism of CH. The results showed that CH inhibited replication and HBeAg production by either wild-type or lamivudine-resistant HBV clinical isolates in a dose-dependent manner. The Hsc70 mRNA was also downregulated significantly. In conclusion, CH is active against both wild-type and lamivudine-resistant HBV clinical isolates, and its activity may be associated with its inhibition of host Hsc70.


title: Sustained High Effectiveness of RotaTeq on Hospitalizations Attributable to Rotavirus-Associated Gastroenteritis During 4 Years in Finland

text: KEY POINTS: The effectiveness of pentavalent rotavirus vaccine against rotavirus-associated hospitalization was more than 90% 4 years after introduction into the national immunization program in Finland. A major impact on hospitalization for all-cause gastroenteritis was observed also. BACKGROUND: Rotavirus vaccination with exclusive use of RotaTeq was added to the National Immunization Programme (NIP) of Finland in September 2009. The objective of our study was to estimate the effectiveness and impact of RotaTeq after 4 years of follow-up. METHODS: Between 2009 and 2013, we conducted a prospective surveillance study of children aged <16 years with acute gastroenteritis (AGE) and admitted in 2 hospitals in Finland. Rotavirus and other gastroenteritis viruses were detected in stool samples by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. The effectiveness of RotaTeq was investigated by using a case-control design; wild-type rotavirus-positive children were classified as “cases” and rotavirus-negative children as “controls.” Hospital discharge records were used to estimate the impact of RotaTeq on rotavirus-associated AGE (RV-AGE) and all-cause AGE (AC-AGE) hospitalizations of age-eligible children in the NIP by comparing the prevaccination (2001–2006) and post-NIP seasons (2009–2013). RESULTS: The crude estimate of the effectiveness of RotaTeq to prevent RV-AGE hospitalization in NIP age-eligible children was 94.4% (95% confidence interval, 79.8%–98.4%). No change in prevalent wild-type rotavirus genotypes was observed. Vaccine-derived rotaviruses were detected in 8% of the children with RV-AGE, with a probable causal association in 2 children. Hospital discharge records revealed that RV-AGE and AC-AGE hospitalizations in children aged <16 years decreased in the two post-NIP seasons by 79% and 58%, respectively, compared to those in the prevaccination seasons. CONCLUSIONS: Over 4 years of follow-up, high rotavirus vaccine coverage in the NIP (>95%) has led to a major reduction in RV-AGE and AC-AGE hospitalizations without a resurgence of rotavirus activity. However, rotavirus continues to circulate in older unvaccinated children.


title: Catalytic sterilization of Escherichia coli K 12 on Ag/Al2O3 surface

text: Abstract Bactericidal action of Al2O3, Ag/Al2O3 and AgCl/Al2O3 on pure culture of Escherichia coli K 12 was studied. Ag/Al2O3 and AgCl/Al2O3 demonstrated a stronger bactericidal activity than Al2O3. The colony-forming ability of E. coli was completely lost in 0.5min on both of Ag/Al2O3 and AgCl/Al2O3 at room temperature in air. The configuration of the bacteria on the catalyst surface was observed using scanning electron microscopy (SEM). Reactive oxygen species (ROS) play an important role in the expression of the bactericidal activity on the surface of catalysts by assay with O2/N2 bubbling and scavenger for ROS. Furthermore, the formation of CO2 as an oxidation product could be detected by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and be deduced by total carbon analysis. These results strongly support that the bactericidal process on the surface of Ag/Al2O3 and AgCl/Al2O3 was caused by the catalytic oxidation.


The Corona crisis and climate protection—keeping long-term goals in mind: Cleverly directing economic aid and exploiting synergy potentials for urgently needed investments


title: Conventional Influenza Vaccination Is Not Associated with Complications in Working-Age Patients with Asthma or Chronic Obstructive Pulmonary Disease

text: By using a nested case-control design, the authors studied the effectiveness of the influenza vaccine in reducing severe and fatal complications in 4,241 and 5,966 primary care, working-age patients aged 18–64 years who had asthma or chronic obstructive pulmonary disease during the 1998–1999 and 1999–2000 influenza epidemics in the Netherlands. Patients developing fatal or nonfatal exacerbations of lung disease, pneumonia, congestive heart failure, or myocardial infarction during either epidemic were considered cases. For each case, four age- and sex-matched controls were randomly sampled, and patient records were reviewed. Conditional logistic regression and propensity scores were used to assess vaccine effectiveness after adjustment for confounding factors. In seasons one and two, respectively, 87% (47/54) and 85% (171/202) of the cases and 74% (155/210) and 75% (575/766) of the controls had been vaccinated. After adjustments, vaccination was not associated with reductions in complications (season one: odds ratio = 0.95, 95% confidence interval (CI): 0.26, 3.48; season two: odds ratio = 1.07, 95% CI: 0.59, 1.96; pooled odds ratio = 1.07, 95% CI: 0.63, 1.80). Because influenza vaccination appeared not to be associated with a clinically relevant reduction in severe morbidity, other measures need to be explored.


title: Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge

text: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50–66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.


title: Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 mediated myocarditis

text: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection of host cells occurs predominantly via binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. Hypertension and pre-existing cardiovascular disease are risk factors for morbidity from COVID-19, and it remains uncertain whether the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) impacts infection and disease. Here, we aim to shed light on this question by assessing ACE2 expression in normal and diseased human myocardial samples profiled by bulk and single nucleus RNA-seq.


title: Kelp is on the way

text: Seaweed farming could help clean up the oceans and the atmosphere, reports Michael Marshall


docid: vtohspxq

title: Geostatistical COVID-19 infection risk maps for Portugal

text: The rapid spread of the SARS-CoV-2 epidemic has simultaneous time and space dynamics. This behaviour results from a complex combination of factors, including social ones, which lead to significant differences in the evolution of the spatiotemporal pattern between and within countries. Usually, spatial smoothing techniques are used to map health outcomes, and rarely uncertainty of the spatial predictions are assessed. As an alternative, we propose to apply direct block sequential simulation to model the spatial distribution of the COVID-19 infection risk in mainland Portugal. Given the daily number of infection data provided by the Portuguese Directorate-General for Health, the daily updates of infection rates are calculated by municipality and used as experimental data in the geostatistical simulation. The model considers the uncertainty/error associated with the size of each municipality’s population. The calculation of daily updates of the infection risk maps results from the median model of one ensemble of 100 geostatistical realizations of daily updates of the infection risk. The ensemble of geostatistical realizations is also used to calculate the associated spatial uncertainty of the spatial prediction using the interquartile distance. The risk maps are updated daily and show the regions with greater risks of infection and the critical dynamics related to its development over time.


title: Evidences for the unfolding mechanism of three-dimensional domain swapping

text: The full or partial unfolding of proteins is widely believed to play an essential role in three-dimensional domain swapping. However, there is little research that has rigorously evaluated the association between domain swapping and protein folding/unfolding. Here, we examined a kinetic model in which domain swapping occurred via the denatured state produced by the complete unfolding of proteins. The relationships between swapping kinetics and folding/unfolding thermodynamics were established, which were further adopted as criteria to show that the proposed mechanism dominates in three representative proteins: Cyanovirin-N (CV-N), the C-terminal domain of SARS-CoV main protease (M(pro)-C), and a single mutant of oxidized thioredoxin (Trx_W28A(ox)).


title: AAIM Recommendations for the 2020-2021 Internal Medicine Residency Application Cycle in Response to the COVID-19 Pandemic

text: This statement was released in June 2020 by the Alliance for Academic Internal Medicine to provide guidance for the 2020-2021 residency application cycle in light of the COVID-19 pandemic. While many of the recommendations are specific to this cycle, others, such as the Department Summary Letter of Evaluation, are meant to be an enduring change to the internal medicine residency application process. We realize that some schools may not yet have the tools or resources to implement the template fully this cycle and look towards collaboration within the internal medicine education community to facilitate adoption in the cycles to come. • Limit away rotations • Conduct virtual interviews • Adopt a standardized Department Summary Letter of Evaluation • Adjust requirements for Letters of Recommendation • Reflect challenges related to acquiring fourth-year medical student experiences in program requirements • Utilize data when advising students on number of applications • Consider innovations in addressing application inflation


title: Role of natural interferon-producing cells and T lymphocytes in porcine monocyte-derived dendritic cell maturation

text: Maturation of dendritic cells (DC) is a key immunological process regulating immune responses to pathogens and vaccines, as well as tolerance and autoimmune processes. Consequently, the regulation of DC maturation should reflect these multifaceted immunological processes. In the present study, we have defined the role of particular cytokines, Toll-like receptor (TLR) ligands and T lymphocytes in the porcine monocyte-derived DC (MoDC). Interferon-α (IFN-α) alone was a poor inducer of MoDC maturation, but in association with tumour necrosis factor-α (TNF-α), or TLR ligands such as lipopolysaccharide and polyinosinic-polycytidylic acid I:C, an up-regulation of major histocompatibility complex II and CD80/86 expression was noted, along with reduced endocytic activity. In contrast, TNF-α alone or in combination with the TLR ligands was a poor inducer of DC maturation, but co-operated with T-lymphocytes in the presence of antigen to induce DC maturation. Natural interferon producing cells (NIPC, or plasmacytoid DCs) represent a danger-recognition system of the immune defences, and can respond to viruses not otherwise recognized as posing a danger. Indeed, MoDC did not respond to transmissible gastroenteritis virus (TGEV), whereas NIPC produced high levels of IFN-α and TNF-α after TGEV stimulation. Moreover, supernatants from the stimulated NIPC induced maturation in MoDCs. These matured MoDCs displayed an enhanced ability to present antigen to and thus stimulate T cells. Taken together, the present work demonstrates that maturation of MoDC not only results from TLR signalling, but can require co-operation with various cell types – principally NIPC and activated T cells – which would reflect the particular immunological situation.


Contact Tracing for Native Americans in Rural Arizona On a reservation in eastern Arizona, most of the Native Americans with Covid-19 live with others who are at high risk Identifying patients who


Abstract Since the coronavirus disease 2019 (COVID-19) outbreak was declared a pandemic on 11 March 2020. Several dental care facilities in affected countries have been completely closed or have been only providing minimal treatment for emergency cases. However, several facilities in some affected countries are still providing regular dental treatment. This can in part be a result of the lack of universal protocol or guidelines regulating the dental care provision during such a pandemic. This lack of guidelines can on one hand increase the nosocomial COVID-19 spread through dental health care facilities, and on the other hand deprive patients’ in need of the required urgent dental care. Moreover, ceasing dental care provision during such a period will incense the burden on hospitals emergency departments already struggle with the pandemic. This work aimed to develop guidelines for dental patients’ management during and after the COVID-19 pandemic. Guidelines for dental care provision during the COVID-19 pandemic were developed after considering the nature of COVID-19 pandemic, and were based on grouping the patients according to condition and need, and considering the procedures according to risk and benefit. It is hoped that the guidelines proposed in this work will help in the management of dental care around the world during and after this COVID-19 pandemic.


title: Analysis of synonymous codon usage in 11 Human Bocavirus isolates

text: Abstract Human Bocavirus (HBoV) is a novel virus which can cause respiratory tract disease in infants or children. In this study, the codon usage bias and the base composition variations in the available 11 complete HBoV genome sequences have been investigated. Although, there is a significant variation in codon usage bias among different HBoV genes, codon usage bias in HBoV is a little slight, which is mainly determined by the base compositions on the third codon position and the effective number of codons (ENC) value. The results of correspondence analysis (COA) and Spearman's rank correlation analysis reveals that the G+C compositional constraint is the main factor that determines the codon usage bias in HBoV and the gene's function also contributes to the codon usage in this virus. Moreover, it was found that the hydrophobicity of each protein and the gene length are also critical in affecting these viruses’ codon usage, although they were less important than that of the mutational bias and the genes’ function. At last, the relative synonymous codon usage (RSCU) of 44 genes from these 11 HBoV isolates is analyzed using a hierarchical cluster method. The result suggests that genes with same function yet from different isolates are classified into the same lineage and it does not depend on geographical location. These conclusions not only can offer an insight into the codon usage patterns and gene classification of HBoV, but also may help in increasing the efficiency of gene delivery/expression systems.


title: Asthma risk factors

text: BACKGROUND: Bronchial asthma is one of the most common chronic diseases in childhood, with a current prevalence of 6% to 9%, but a prevalence that is increasing at an alarming rate. Asthma is a complex genetic disorder with strong environmental influence. It imposes a growing burden on our society in terms of morbidity, quality of life, and healthcare costs. Despite large‐scale efforts, only a few asthma genes have been confirmed, suggesting that the genetic underpinning of asthma is highly complex. METHODS: A review of the literature was performed regarding atopic and nonatopic asthma risk factors, including environmental risk factors and genetic studies in adults and children. RESULTS: Several environmental risk factors have been identified to increase the risk of developing asthma such as exposure to air pollution and tobaccos smoke as well as occupational risk factors. In addition atopy, stress, and obesity all can increases the risk for asthma in genetically susceptible persons. CONCLUSION: Asthma represents a dysfunctional interaction with our genes and the environment to which they are exposed, especially in fetal and early infant life. The increasing prevalence of asthma in all age groups indicate that our living environment and immunity are in imbalance with each other reacting with airway inflammation to the environmental exposures and often non‐harmful proteins, such as allergens causing the current “asthma and allergy epidemic.” Because of the close relationship between asthma and chronic rhinosinusitis, it is important that otolaryngologists have a good understanding of asthma, the etiologic factors associated with disease, and its evaluation and management.


title: Peptides with 16R in S2 protein showed broad reactions with sera against different types of infectious bronchitis viruses

text: Abstract Vaccination plays a vital role in controlling diseases caused by chicken infectious bronchitis virus (IBV). The continuously variant antigenicity of IBV limits the application of current vaccine strategies and serological diagnostic systems. S2 protein is an invariant that harbors broad neutralizing epitopes. However, little is known about the key amino acids that contribute to the broad-spectrum S2 epitopes. In this study, we aimed to elucidate the specific amino acids contributing to S2 epitopes. Site mutagenesis and peptide-based enzyme-linked immunosorbent assays (ELISAs) showed that 16R in S2 protein was a key amino acid mediating the antigenicity of S2 protein. S2-derived peptides with 16R, but not those with 16 K, could react with sera against different types of IBVs. Notably, a commercial ELISA kit for detection of antibodies against IBV did not react with sera against all types of IBVs. Taken together, these data demonstrated that S2-derived peptides with 16R could be used as novel marker-based antigens for developing both broad-spectrum vaccines and serological diagnostic kits to control IBV.


title: Pathogen Security-Help or Hindrance?

text: Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.


title: Spread of SARS-CoV-2 in the Icelandic Population

text: BACKGROUND: During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population. METHODS: We targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons. We sequenced SARS-CoV-2 from 643 samples. RESULTS: As of April 4, a total of 1221 of 9199 persons (13.3%) who were recruited for targeted testing had positive results for infection with SARS-CoV-2. Of those tested in the general population, 87 (0.8%) in the open-invitation screening and 13 (0.6%) in the random-population screening tested positive for the virus. In total, 6% of the population was screened. Most persons in the targeted-testing group who received positive tests early in the study had recently traveled internationally, in contrast to those who tested positive later in the study. Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older. Fewer females than males received positive results both in targeted testing (11.0% vs. 16.7%) and in population screening (0.6% vs. 0.9%). The haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time. The percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening. CONCLUSIONS: In a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts. (Funded by deCODE Genetics–Amgen.)


title: Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA

text: BACKGROUND: Infectious cDNA clones are a prerequisite for directed genetic manipulation of RNA viruses. Here, a strategy to facilitate manipulation and rescue of classical swine fever viruses (CSFVs) from full-length cDNAs present within bacterial artificial chromosomes (BACs) is described. This strategy allows manipulation of viral cDNA by targeted recombination-mediated mutagenesis within bacteria. RESULTS: A new CSFV-BAC (pBeloR26) derived from the Riems vaccine strain has been constructed and subsequently modified in the E2 coding sequence, using the targeted recombination strategy to enable rescue of chimeric pestiviruses (vR26_E2gif and vR26_TAV) with potential as new marker vaccine candidates. Sequencing of the BACs revealed a high genetic stability during passages within bacteria. The complete genome sequences of rescued viruses, after extensive passages in mammalian cells showed that modifications in the E2 protein coding sequence were stably maintained. A single amino acid substitution (D3431G) in the RNA dependent RNA polymerase was observed in the rescued viruses vR26_E2gif and vR26, which was reversion to the parental Riems sequence. CONCLUSIONS: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses.


Health Care–Associated Infections (HAIs)


title: Acute hepatic failure in IFN-γ-deficient BALB/c mice after murine coronavirus infection

text: Abstract We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) persists in interferon-γ (IFN-γ)-deficient C57BL/6 (B6-GKO) mice and results in subacute fatal peritonitis, which bears a resemblance to feline infectious peritonitis. To examine the role of other host factors in MHV infection in mice, IFN-γ-deficient mice with a BALB/c background (BALB-GKO) were infected intraperitoneally with MHV and compared with B6-GKO mice. In contrast to B6-GKO mice, BALB-GKO mice died within 1 week due to acute hepatic failure. The viral titer of the liver in BALB-GKO mice was significantly higher than that in B6-GKO mice. All hepatocytes in BALB-GKO mice were necrotic at 5 days post-infection, which was clearly distinct from large but limited lesion in the liver from infected B6-GKO mice. The serum alanine aminotransferase activity of infected BALB-GKO mice were higher than that of B6-GKO mice and was paralleled with the severity of the pathological changes and viral titers in infected mice. Administration of exogenous IFN-γ to BALB-GKO partially inhibited the acute death. These results indicate that BALB-GKO and B6-GKO mice clearly show different diseases following MHV infection, although wild type counterparts of both mice apparently showed the same clinical course after MHV infection.


title: Changing the narrative on fisheries subsidies reform: Enabling transitions to achieve SDG 14.6 and beyond

text: Abstract The World Trade Organization (WTO) is in the final stages of negotiating an agreement to prohibit harmful fisheries subsidies, thereby achieving UN Sustainable Development Goal (SDG) 14.6. An effective agreement should be viewed as an opportunity for nations to proactively transition towards sustainable and equitable fisheries and pave the path for other SDGs. Supporting fishers does not require harmful subsidies, and we provide evidence-based options for reform that highlight equity needs while reducing environmental harm. Subsidy reforms need clear goals, co-design, transparency, and fair implementation. An agreement on SDG 14.6 could be a turning point for the oceans and for the well-being of those that depend on the oceans for livelihoods and nutrition. Responsible seafood production will require international cooperation not only at WTO, but among governments, fisher organizations, civil society, and the wider public.


title: The protean prion protein

text: The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrP(C)) and the scrapie conformation (PrP(Sc)). PrP(C) features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with β-strand propensity has been identified within it. The PrP(Sc) conformation is very rare and has the characteristics of an amyloid. Furthermore, PrP(Sc) is a prion, i.e., it is infectious. This involves 2 steps: (1) PrP(Sc) can template PrP(C) and coerce it to adopt the PrP(Sc) conformation and (2) PrP(Sc) can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrP(Sc) is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology, Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.


title: Human iPSC-Derived Cardiomyocytes , are Susceptible to SARS-CoV-2 Infection

text: Summary Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA-sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.


title: A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin

text: Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.


title: Micro- and nanotechnology for viral detection

text: Since the identification of viruses at the start of the 20th century, detecting their presence has presented great challenges. In the past two decades, there has been significant progress in viral detection methods for clinical diagnosis and environmental monitoring. The earliest advances were in molecular biology and imaging techniques. Advances in microfabrication and nanotechnology have now begun to play an important role in viral detection, and improving the detection limit, operational simplicity, and cost-effectiveness of viral diagnostics. Here we provide an overview of recent advances, focusing especially on advances in simple, device-based approaches for viral detection.


title: Clinical outcomes of patients treated with intravenous zanamivir for severe influenza A(H1N1)pdm09 infection: a case report series

text: BACKGROUND: Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited. CASE PRESENTATION: We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections. CONCLUSIONS: IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.


title: Stress, anxiety, and depression in people aged over 60 in the COVID-19 outbreak in a sample collected in Northern Spain.

text: OBJECTIVE: This study examines the levels of stress, anxiety, and depression in people over 60 years of age at the time of the COVID-19 outbreak. DESIGN: The study used an exploratory-descriptive cross-sectional methodology. The resulting responses were analyzed using SPSS v.25 PARTICIPANTS: Participants (N=210) were aged 60 years and above. SETTING: The study was carried out in the Basque Country (North of Spain) MEASUREMENTS: Stress, anxiety and depression were measured using the Anxiety and Stress Scale - 21 (DASS-21) RESULTS: Most of the participants did not report levels of stress, anxiety, and depression. Among participants age 66 and above and those with chronic illness, a proportion reported experiencing one, two or all three of these symptoms