title: Clinical Features of Pneumonia Caused by 2009 Influenza A(H1N1) Virus in Beijing, China

text: Background Data on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported. Methods During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. Results Of the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%. Conclusions Ground-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).


title: Up-regulation of components of the renin–angiotensin system in liver fibrosis in the rat induced by CCL4

text: Abstract The purpose of this study was to investigate the components of renin–angiotensin system (RAS), liver function and histology in liver fibrogenesis in the rats induced by low-dose chronic carbon tetrachloride (CCL4) administration and evaluate the relationship between biochemical variables and components of RAS. Male Sprague–Dawley (SD) rats were randomly divided into the CCL4 group which received intraperitoneal injection of 40% CCL4 dissolved in olive oil every three days for four consecutive weeks (Initial dose was 5mL/kg, other dose: 3mL/kg) and the control group which received the same dose of olive oil. The micro-structure of the liver was examined by H&E. Hepatic Ang II and Ang(1–7) was detected. Real-time PCR and Western-blot were performed to determine the gene and protein expression of the RAS. The components of RAS were all up-regulated in CCL4 group, and the increased extent of ACE-Ang II-AT1 axis was higher than the ACE2-Ang(1–7)-Mas axis. There was a significant correlation between ACE and ACE2 gene expression, AT1 and MAS gene expression, Ang II and Ang(1–7) in the liver of rats. ACE (or ACE2) gene expression strongly correlated with the index of liver injury significantly. These results suggest hepatic fibrogenesis induced by chronic CCL4 administration may be associated with the relationship of ACE-Ang II-AT1 axis and ACE2-Ang(1–7)-MAS axis.


title: Proceedings of a Consensus Conference: Pathogen Inactivation—Making Decisions About New Technologies

text: Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.


title: Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

text: Abstract A strong cell-mediated immunity (CMI) is thought to be indispensable for protection against infection with feline infectious peritonitis virus (FIPV) in cats. In this study, the role of natural killer (NK) cells and regulatory T cells (Tregs), central players in the innate and adaptive CMI respectively, was examined during natural FIPV infection. When quantified, both NK cells and Tregs were drastically depleted from the peripheral blood, mesenteric lymph node (LN) and spleen in FIP cats. In contrast, mesentery and kidney from FIP cats did not show any difference when compared to healthy non-infected control animals. In addition, other regulatory lymphocytes (CD4+CD25−Foxp3+ and CD3+CD8+Foxp3+) were found to be depleted from blood and LN as well. Phenotypic analysis of blood-derived NK cells in FIP cats revealed an upregulation of activation markers (CD16 and CD25) and migration markers (CD11b and CD62L) while LN-derived NK cells showed upregulation of only CD16 and CD62L. LN-derived NK cells from FIPV-infected cats were also significantly less cytotoxic when compared with healthy cats. This study reveals for the first time that FIPV infection is associated with severe suppression of NK cells and Tregs, which is reflected by cell depletion and lowered cell functionality (only NK cells). This will un-doubtfully lead to a reduced capacity of the innate immune system (NK cells) to battle FIPV infection and a decreased capacity (Tregs) to suppress the immunopathology typical for FIP. However, these results will also open possibilities for new therapies targeting specifically NK cells and Tregs to enhance their numbers and/or functionality during FIPV infection.


title: Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses

text: Abstract Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an in-silico survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.


docid: ovtrbxhl

title: Epidemiologie von SARS-CoV-2-Infektion und COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new β‑Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV‑2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2–14) days. Although most infections are uncomplicated, 5–10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV‑2, leading to rapid reductions in R. Which of the measures have been effective is still unknown.


docid: hzahejqk

title: New Developments in Rapid Diagnostic Testing for Children

text: The advent of new diagnostics assays for Group A Streptococcus, influenza, and respiratory syncytial virus now provide rapid results with increased sensitivity and specificity. Molecular testing is no longer confined to the walls of the laboratory, but moving to the patient in the form of point-of-care tests. In addition, multiplex syndromic panels are allowing broad testing of pathogens associated with a single clinical presentation. This article focuses specifically on rapid diagnostic tests for pathogens most affecting children. Rapid and accurate pathogen detection in children may result in decreased time to optimal antimicrobial treatment and improved patient outcomes.


title: Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin

text: Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response.


title: Measurement of airborne particle exposure during simulated tracheal intubation using various proposed aerosol containment devices during the COVID‐19 pandemic

text: The COVID‐19 pandemic has led to the production of novel devices intended to protect airway managers during the aerosol‐generating procedure of tracheal intubation. Using an in‐situ simulation model, we evaluated laryngoscopist exposure of airborne particles sized 0.3 ‐ 5.0 microns using five aerosol containment devices (aerosol box; sealed box with and without suction; vertical drape; and horizontal drape) compared with no aerosol containment device. Nebulised saline was used as the aerosol‐generating model for 300 seconds, at which point, the devices were removed to assess particle spread. Primary outcome was the quantity and size of airborne particles measured at the level of the laryngoscopist’s head at 30, 60, 120, and 300 seconds, as well as 360 seconds (60 seconds after device removal). Airborne particles sizes of 0.3, 0.5, 1.0, 2.5 and 5.0 microns were quantified using an electronic airborne particle counter. Compared with no device use, the sealed intubation box with suction resulted in a decrease in 0.3, 0.5, 1.0 and 2.5 micron, but not 5.0 micron, particle exposure over all time‐periods (p = 0.003 for all time periods). Compared with no device use, the aerosol box showed an increase in 1.0, 2.5 and 5.0 micron airborne particle exposure at 300 seconds (p = 0.002, 0.008, 0.002, respectively). Compared with no device use, neither horizontal nor vertical drapes showed any difference in any particle size exposure at any time. Finally, when the patient coughed, use of the aerosol box resulted in a marked increase in airborne particle exposure compared with other devices or no device use. In conclusion, novel devices intended to protect the laryngoscopist require objective testing to ensure they are fit for purpose and do not result in increased airborne particle exposure.


Limited restriction in αβTCR usage of T cell clones specific for MBP (a.a. 84–102) and 65kD HSP (a.a. 3–13) peptides within twins and MHC identical individuals


title: Human infections associated with wild birds

text: Summary Introduction Wild birds and especially migratory species can become long-distance vectors for a wide range of microorganisms. The objective of the current paper is to summarize available literature on pathogens causing human disease that have been associated with wild bird species. Methods A systematic literature search was performed to identify specific pathogens known to be associated with wild and migratory birds. The evidence for direct transmission of an avian borne pathogen to a human was assessed. Transmission to humans was classified as direct if there is published evidence for such transmission from the avian species to a person or indirect if the transmission requires a vector other than the avian species. Results Several wild and migratory birds serve as reservoirs and/or mechanical vectors (simply carrying a pathogen or dispersing infected arthropod vectors) for numerous infectious agents. An association with transmission from birds to humans was identified for 10 pathogens. Wild birds including migratory species may play a significant role in the epidemiology of influenza A virus, arboviruses such as West Nile virus and enteric bacterial pathogens. Nevertheless only one case of direct transmission from wild birds to humans was found. Conclusion The available evidence suggests wild birds play a limited role in human infectious diseases. Direct transmission of an infectious agent from wild birds to humans is rarely identified. Potential factors and mechanisms involved in the transmission of infectious agents from birds to humans need further elucidation.


title: Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

text: BACKGROUND: Early during the current COVID-19 pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only the effectiveness of HCQ has remained questionable, and mainly based on pre-clinical, and a few small clinical studies, but also HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. OBJECTIVE: To investigate the arrhythmic effects of HCQ as the heightened risk is especially relevant as COVID-19 patients are at a higher risk of cardiac complications and arrhythmias at baseline. METHODS: Here, we use the optical mapping technique, using voltage-sensitive fluorescent dyes, to illustrate the arrhythmic effects of hydroxychloroquine in ex-vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum doses of HCQ (up to 1000ng/ml). RESULTS: We observe that HCQ markedly increases the action potential dispersion and results in the development of repolarization alternans and initiate polymorphic ventricular tachycardia. CONCLUSIONS: These results further highlight the proarrhythmic effects of HCQ.


title: Heterologous expression of fused genes encoding the glycoprotein 5 from PRRSV: A way for producing functional protein in prokaryotic microorganism

text: Abstract Based on the bioinformatics analysis of the gene encoding glycoprotein 5 (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) isolate HH08, two gene fragments were amplified by polymerase chain reaction (PCR), deleting the signal peptide and transmembrane sequences in GP5 gene. Both gene fragments were designated GP5a and GP5b, respectively. They were ligated with a linker and cloned into prokaryotic expression vector, pET-30a. Expression of the protein of interest was induced by isopropyl β-d-1-thiogalactopyranoside. The purified protein was used as an immunogen to elicit antibody in rabbit. The immunoreactivity of the protein was determined using ELISA and Western blot. Biologically active GP5 and anti-GP5 antibody inhibited cell infection by PRRSV. Moreover, the antibody produced in this study was capable of detecting the cell infection by PRRSV and distinguishing this virus from other viruses.


title: MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease

text: Polyglutamine (polyQ) tract expansion leads to proteotoxic misfolding and drives a family of nine diseases. We study spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder of the neuromuscular system caused by the polyQ androgen receptor (AR). Using a knock-in mouse model of SBMA, AR113Q mice, we show that E3 ubiquitin ligases which are a hallmark of the canonical muscle atrophy machinery are not induced in AR113Q muscle. Similarly, we find no evidence to suggest dysfunction of signaling pathways that trigger muscle hypertrophy or impairment of the muscle stem cell niche. Instead, we find that skeletal muscle atrophy is characterized by diminished function of the transcriptional regulator Myocyte Enhancer Factor 2 (MEF2), a regulator of myofiber homeostasis. Decreased expression of MEF2 target genes is age- and glutamine tract length-dependent, occurs due to polyQ AR proteotoxicity, and is associated with sequestration of MEF2 into intranuclear inclusions in muscle. Skeletal muscle from R6/2 mice, a model of Huntington disease which develops progressive atrophy, also sequesters MEF2 into inclusions and displays age-dependent loss of MEF2 target genes. Similarly, SBMA patient muscle shows loss of MEF2 target gene expression, and restoring MEF2 activity in AR113Q muscle rescues fiber size and MEF2-regulated gene expression. This work establishes MEF2 impairment as a novel mechanism of skeletal muscle atrophy downstream of toxic polyglutamine proteins and as a therapeutic target for muscle atrophy in these disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-020-02156-4) contains supplementary material, which is available to authorized users.


title: Pseudoknot and translational control in the expression of the S15 ribosomal protein

text: Abstract Translational autocontrol of the expression of the ribosomal protein S15 proceeds through the transitory formation of a pseudoknot. A synopsis of the known data is used to propose a molecular model of the mechanism involved and for the role of the pseudoknot. This latter structure is able to recruit 30S ribosomal subunits to initiate translation, but also to bind S15 and to stop translation by trapping the ribosome on its loading site. Information on the S15 protein recognition of the messenger RNA site was deduced from mutational analyses and chemical probinb. A comparison of this messenger site with the S15 ribosomal binding site was conducted by analysing hydroxyl radical footprintings of these two sites. The existence of two subsites in 16S RNA suggests that the ribosomal protein S15 might present either two different binding sites or at least one common subsite. Clues for the presence of a common site between the messenger and 16S RNA are given which cannot rule out that recognition specificity is linked to a few other determinants. Whether these determinants are different or not remains an open question.


title: Spectrum of respiratory viral infections in liver disease patients with cirrhosis admitted in critical care unit

text: BACKGROUND: Clinical significance of respiratory viruses (RVs) as an etiology of pneumonia in liver disease patients with cirrhosis is usually underestimated. Therefore, the aim of this study was to evaluate the spectrum of RVs in cirrhotic patients with pneumonia admitted in critical care units (CCUs) and its impact on the clinical outcome of cirrhotic patients. MATERIAL AND METHOD: A prospective study was conducted in a tertiary care CCU, and consecutive cirrhotic patients with pneumonia were included. Bronchoalveolar lavage or throat swab/nasal swab was collected in viral transport medium for analysis of RVs by multiplex real-time polymerase chain reaction. A total of 135 cirrhotic patients were included, viral and bacterial etiology of pneumonia was identified, and analysis was done with the clinical outcome. RESULTS: Overall, RVs were detected in 30 (22.2%) cirrhotic patients and viral–bacterial coinfection in 16 (11.8%) cirrhotic patients. The most common virus detected was rhinovirus in 9 (30%) patients. Mortality in cirrhotic patients with RV infection was significantly higher in comparison to cirrhotic patients with no RV infection (25 [83.3%] and 11 [12.3%], respectively, P < 0.001). CONCLUSION: Respiratory viruses in cirrhotic patients with pneumonia are associated with poor clinical outcome.


title: Coinfection, coepidemics of COVID‐19, and dengue in dengue‐endemic countries: A serious health concern

text: During the Covid-19 pandemic, dengue cases have been increased in most of the dengue-endemic countries in the world. Therefore, in these countries, both Covid-19 and Dengue are occurring simultaneously. The dengue-endemic countries are at the risk of possible co-infection and co-epidemics in where Covid-19 and dengue disease are co-existing, and the viruses are cocirculating. Thus, co-infection and co-epidemics trigger alert, especially for the health care professionals in the dengue-endemic countries. This article is protected by copyright. All rights reserved.


title: Cell tropism and expression of mouse hepatitis viruses (MHV) in mouse spinal cord cultures

text: Abstract Mouse hepatitis viruses (MHV) are coronaviruses which cause various infections in mice affecting lung, intestine, liver, and other organs as well as the central nervous system. The replication of three different MHV strains was studied in mouse dissociated spinal cord cultures containing differentiated neurons and nonneuronal cells (NN) (including astrocytes). Cell tropism and maturation of each virus strain was analyzed by immunolabeling methods using antisera to the virion or to purified membrane glycoproteins (E1 and E2) and by electron microscopy (EM). Wt-JHM, which causes acute encephalitis in mice, produces acute cytopathic changes in both neurons and NN cells. In neurons, virions mature in smooth ER cisternae closely associated to the Golgi apparatus. As judged by EM, fewer virions are produced by neurons than NN cells and neurons do not fuse or stain for E2 as do NN cells. NN cells contain large inclusions made of nucleocapsid strands. A temperature-sensitive mutant of JHM, Ts8-JHM, which causes demyelination in mice, infects NN cells but not neurons. Infected NN cells synthesize E1 and E2, and contain large inclusions but few mature virions, even at permissive temperatures. These inclusions appear granular and rarely contain nucleocapsid strands in contrast to wt-JHM infection. NN cells infected with this mutant also display numerous membrane whorls. The hepatotropic strain A59 lacks tropism for neurons and primarily infects NN cells, thus resembling ts8-JHM. Infected NN cells become loaded with intracytoplasmic virions which are secreted from the cells. E1 can only be detected in the perinuclear area of these cells while E2 rapidly spreads throughout the cytoplasm. The cytoplasm of A59 infected NN cells frequently contains large tubular structures often in the lumen of the RER. In conclusion, in primary CNS cultures consisting of neurons and NN cells: (1) wt-JHM replicates in both neurons and NN cells but has different effects on these cells; (2) Ts8-JHM exhibits no productive infection of neurons, and in NN cells appears to be defective in assembly and to stimulate membrane synthesis; (3) A59 also shows tropism restricted to NN cells which produce many viruses and display differential distribution of the two virion glycoproteins. Thus, in the absence of the immune system, the MHV strains assayed exhibit differences in viral tropism, cytopathic changes, and viral assembly in CNS cells, and these differences may account for the different disease patterns.


title: Social Frailty Is Independently Associated with Mood, Nutrition, Physical Performance, and Physical Activity: Insights from a Theory-Guided Approach

text: Notwithstanding the increasing body of evidence that links social determinants to health outcomes, social frailty is arguably the least explored among the various dimensions of frailty. Using available items from previous studies to derive a social frailty scale as guided by the Bunt social frailty theoretical framework, we aimed to examine the association of social frailty, independently of physical frailty, with salient outcomes of mood, nutrition, physical performance, physical activity, and life–space mobility. We studied 229 community-dwelling older adults (mean age 67.22 years; 72.6% females) who were non-frail (defined by the FRAIL criteria). Using exploratory factor analysis, the resultant 8-item Social Frailty Scale (SFS-8) yielded a three-factor structure comprising social resources, social activities and financial resource, and social need fulfilment (score range: 0–8 points). Social non-frailty (SNF), social pre-frailty (SPF), and social frailty (SF) were defined based on optimal cutoffs, with corresponding prevalence of 63.8%, 28.8%, and 7.4%, respectively. In logistic regression adjusted for significant covariates and physical frailty (Modified Fried criteria), there is an association of SPF with poor physical performance and low physical activity (odds ratio, OR range: 3.10 to 6.22), and SF with depressive symptoms, malnutrition risk, poor physical performance, and low physical activity (OR range: 3.58 to 13.97) compared to SNF. There was no significant association of SPF or SF with life–space mobility. In summary, through a theory-guided approach, our study demonstrates the independent association of social frailty with a comprehensive range of intermediary health outcomes in more robust older adults. A holistic preventative approach to frailty should include upstream interventions that target social frailty to address social gradient and inequalities.


title: Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19

text: PURPOSE: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. RESULTS: Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two ‘some concerns’ and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. CONCLUSIONS: Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed.


title: Severe obesity is associated with higher in-hospital mortality in a cohort of patients with COVID-19 in the Bronx, New York

text: BACKGROUND & AIMS: New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes independently from age, gender and other comorbidities. METHODS: This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. RESULTS: 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m(2). The median age was 64 years. Hypertension (76%), hyperlipidemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI < 25 kg/m(2): 31.6%, BMI 25–34 kg/m(2): 17.2%, BMI ≥ 35 kg/m(2): 34.8%, p = 0.03). Increasing age (analyzed in quartiles), male sex, BMI ≥ 35 kg/m(2) (reference: BMI 25–34 kg/m(2)), heart failure, CAD, and CKD or ESRD were found to have a significant univariate association with mortality. The multivariate analysis demonstrated that BMI ≥ 35 kg/m(2) (reference: BMI 25–34 kg/m(2), OR: 3.78; 95% CI: 1.45–9.83; p = 0.006), male sex (OR: 2.74; 95% CI: 1.25–5.98; p = 0.011) and increasing age (analyzed in quartiles, OR: 1.73; 95% CI: 1.13–2.63; p = 0.011) were independently associated with higher in-hospital mortality. Similarly, age, male sex, BMI ≥ 35 kg/m(2) and current or prior smoking were significant predictors for increasing oxygenation requirements in the multivariate analysis, while male sex, age and BMI ≥ 35 kg/m(2) were significant predictors in the multivariate analysis for the outcome of intubation. CONCLUSIONS: In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were independently associated with higher in-hospital mortality and in general worse in-hospital outcomes.


title: In vivo and in vitro models of demyelinating disease IX. Progression of JHM virus infection in the central nervous system of the rat during overt and asymptomatic phases

text: Abstract JHM virus, when inoculated into neonatal rats, can cause either a rapidly fatal acute encephalomyelitis or, after longer incubation periods, a paralytic disease. The cerebrospinal fluid (CSF) and serum anti-JHM virus IgG concentrations present in rats prior to onset of clinical symptoms or during the acute and paralytic phases of disease were compared. High CSF/serum ratios, indicative of local antibody production in the CNS, were noted only where disease was demonstrable suggesting that local antibody production accompanied the infection but did not prevent the neurological disease. Among animals in which neurologic symptoms had not become manifest, only those with elevated CSF/serum ratios were found to have histological CNS lesions. Immunofluorescent microscopy indicated that viral antigens were present in both glia and neurons. Antigen-positive cells were frequently present in histologically normal CNS tissue, while regions of necrosis were antigen negative. Testing for the presence of viral RNA with JHM cDNA probes revealed that the virus was rapidly disseminated throughout the CNS, presumably establishing centers of infection prior to the development of recognizable tissue damage. Viral RNA was also detected in the CNS following recovery from paralysis and as late as 5 months postinfection, where no disease occurred. These findings indicate that, although infection by JHM virus can spread rapidly throughout the CNS, formation of lesions during chronic disease is a slower process. The current data and previous observations suggest that JHM virus can remain in a latent state for periods of at least several months in rats without apparent neurologic disease despite the absence of any known provirus phase in the replicative strategy of coronaviruses.


COVID‐19 in pediatric hematopoietic stem cell transplantation: The experience of Spanish Group of Transplant (GETMON/GETH)


title: Dampened STING-Dependent Interferon Activation in Bats

text: Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.


title: The art of partnerships for vaccines

text: Abstract The Developing Countries Vaccine Manufacturers Network (DCVMN) convened vaccine manufacturing experts and leaders from local and global public health organizations for its 19th Annual General Meeting. Lectures and panel discussions centered on international cooperation for better access to vaccines, and partnerships in areas ranging from vaccine research and process development, to clinical studies, regulatory, supply chain and emergency preparedness and response. Global vaccine market trends and changes that will impact vaccine financing and procurement methods were discussed as well as capital sources, including funding, for the development of new or improved vaccines. DCVMN members presented their progress in developing novel Hexavalent, Meningitis, Pneumococcal Conjugate Vaccine, Shigella, Mumps, Rotavirus, Yellow Fever, Polio, Hepatitis E and Dengue vaccines, and a novel monoclonal antibody cocktail for post-bite prophylaxis against rabies infections. Access to and availability of vaccines is enhanced through sharing of best practices for vaccine quality control, reducing redundant testing and promoting development of harmonized common standards. Eligible stakeholders were encouraged to join the WHO-National Control Laboratory Network for Biologicals which serves as a platform for collaboration and technical exchange in this area. Increasing regulatory convergence at the regional and global levels through mechanisms such as joint dossier review and the WHO Collaborative Registration Procedure can help to accelerate vaccine access globally. Additionally, four proposals for streamlining procedures and alignment of dossiers were discussed. Successful partnerships between a broad range of stakeholders, including international organizations, manufacturers, academic research institutes and regulators have provided support for, and in some cases accelerated, vaccine innovation, clinical trials and registration, WHO prequalification, vaccine introduction and access. Strong partnerships, based on experience and trust, help leverage opportunities and are critically important to advancing the shared goal of providing quality vaccines for all people.


title: European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy

text: Spinal muscular atrophy (SMA) used to be one of the most common genetic causes of infant mortality. New disease modifying treatments have changed the disease trajectories and most impressive results are seen if treatment is initiated in the presymptomatic phase of the disease. Very recently, the European Medicine Agency approved Onasemnogene abeparvovec (Zolgensma®) for the treatment of patients with SMA with up to three copies of the SMN2 gene or the clinical presentation of SMA type 1. While this broad indication provides new opportunities, it also triggers discussions on the appropriate selection of patients in the context of limited available evidence. To aid the rational use of Onasemnogene abeparvovec for the treatment of SMA, a group of European neuromuscular experts presents in this paper eleven consensus statements covering qualification, patient selection, safety considerations and long-term monitoring.


title: Chapter 4 Viral Diseases Transmissible by Kissing

text: Abstract Viral infections can be transmitted by various routes. At one extreme, airborne or droplet viral infections (e.g., varicella zoster, ebola) are highly contagious. Most viruses can be spread by touching surfaces contaminated by the virus and then touching the mouth or eyes. Mass gatherings, clinical, and chronic care facilities may be hotspots for virus spread when transmission is via aerosols, droplets, or fomites (contaminated surfaces). Environmental factors which are often important for virus survival may include the ambient humidity, temperature, and pH of the environment they are in, so many viruses survive only a few hours in the environment and are often readily inactivated by common hygiene techniques, such as using soap and water, and some detergents, disinfectants, and antiseptics. Sexually transmitted viral infections, such as herpes simplex, are often transmitted by close mucosal contacts.


docid: bdncqwkp

title: A Methodological Approach for Predicting COVID-19 Epidemic Using EEMD-ANN Hybrid Model

text: Abstract Predicting the Coronavirus epidemic, popularly known as COVID-19, that has been explored more than 200 countries and already declared as a pandemic by the World Health Organization is an invaluable task. This virus was first identified around December 2019, from central China, but later spread in the rest of the world. To ensure better healthcare service management, an accurate prediction of the uncertain gruesomeness is situational demand. In orders with limited information frameworks, demonstrating and predicting COVID-19 turns into a challenging endeavor. The primary objective of this study is to propose a hybrid model that incorporates ensemble empirical mode decomposition (EEMD) and artificial neural network (ANN) for predicting the COVID-19 epidemic. A real-time COVID-19 time series data has been used on the window periods January 22, 2020, to May 18, 2020. The time-series data first decomposed using EEMD to produce sub-signals and make original data denoised, and ANN architecture has built to train the denoised data. Finally, the result of the proposed model has compared with some traditional statistical analysis. The result of this investigation shows our proposed model outperforms compared with traditional statistical analysis. Thus the model might be promising for COVID-19 epidemic prediction. The government and healthcare provider can take preventive action by understanding the upcoming COVID-19 situation for better healthcare management.


title: Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019‐nCoV

text: OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019‐nCoV). METHODS: Based on the susceptible‐exposed‐infected‐removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019‐nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real‐time reports on the number of 2019‐nCoV‐infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019‐nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.


title: An XML-based System for Synthesis of Data from Disparate Databases

text: Diverse data sets have become key building blocks of translational biomedical research. Data types captured and referenced by sophisticated research studies include high throughput genomic and proteomic data, laboratory data, data from imagery, and outcome data. In this paper, the authors present the application of an XML-based data management system to support integration of data from disparate data sources and large data sets. This system facilitates management of XML schemas and on-demand creation and management of XML databases that conform to these schemas. They illustrate the use of this system in an application for genotype–phenotype correlation analyses. This application implements a method of phenotype–genotype correlation based on phylogenetic optimization of large data sets of mouse SNPs and phenotypic data. The application workflow requires the management and integration of genomic information and phenotypic data from external data repositories and from the results of phenotype–genotype correlation analyses. Our implementation supports the process of carrying out a complex workflow that includes large-scale phylogenetic tree optimizations and application of Maddison's concentrated changes test to large phylogenetic tree data sets. The data management system also allows collaborators to share data in a uniform way and supports complex queries that target data sets.


title: Chapter 17 Hong Kong Pathway to the Freest Economy

text: Abstract This chapter gives a summary of the economic development of Hong Kong. Since its early colonial days, Hong Kong has been an open port serving China and the international community. Reexport trade was the traditional advantage until 1949, when China adopted a closed-door policy. Industrialization since the 1950s has brought growth and expansion, taking advantage of the low cost of labor and the British legal system. However, the situation changed after the early 1980s, partly because of low costs in China pulled investment from Hong Kong, and the post-1997 political uncertainty also resulted in short-term investment behavior. Economic overheating in the mid-1990s led to severe recession after the Asian financial crisis. Economic restructuring has been slow since 1997. Economic narrowness with concentration in real estate development and finance, together with an increase in welfare spending, lowered competitiveness. Economic integration with China would best be based on comparative advantage, with “win, win” outcomes.


title: Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds

text: Abstract We here report on the synthesis of new series of polycyclic amines initially designed as ring-rearranged analogs of amantadine and featuring pentacyclo, hexacyclo, and octacyclo rings. A secondary amine, 3-azahexacyclo[7.6.0.01,5.05,12.06,10.011,15]pentadeca-7,13-diene, 3, effectively inhibited A/M2 proton channel function, and, moreover, possessed dual activity against an A/H3N2 virus carrying a wild-type A/M2 proton channel, as well as an amantadine-resistant A/H1N1 virus. Among the polycyclic amines that did not inhibit influenza A/M2 proton channel function, several showed low-micromolar activity against tested A/H1N1 strains (in particular, the A/PR/8/34 strain), but not A/H3N2 influenza viruses. A/PR/8/34 mutants selected for resistance to these compounds possessed mutations in the viral hemagglutinin that markedly increased the hemolysis pH. Our data suggest that A/H1N1 viruses such as the A/PR/8/34 strain are particularly sensitive to a subtle increase in the endosomal pH, as caused by the polycyclic amine compounds.


docid: zhiuggha

title: Electrophoretic RNA genomic profiles of Brazilian Picobirnavirus (PBV) strains and molecular characterization of a PBV isolated from diarrheic calf

text: Abstract Picobirnavirus (PBV) belongs to the family Picobirnaviridae. PBV are a group of emerging non-enveloped viruses, with a bisegmented double-stranded RNA genome that can infect a wide range of hosts. This study reports the occurrence of PBV in fecal samples from five Brazilian dairy cattle herds. From the 289 stool samples of individual calves analyzed by silver-stained polyacrylamide gel electrophoresis (ss-PAGE) the PBV was detected in 8.3 % (24/289), of which 10.2% (18/176) had diarrheic consistency. Of the 24 positive samples in ss-PAGE, 5 (20.8%) of them showed a small electrophoretic profile and 19 (79.2%) samples had large profile. From the 24 positives samples by ss-PAGE, 15 (62.5%) were successfully amplified (201bp) using GI specific primers targeting the RdRp gene of PBV. The analysis of nucleotide identity matrix revealed that the bovine PBV strain identified in this study, showed the highest nucleotide identity (81%) with PBV strain detected in turkey (MD-2010/HM803965). This is the first nucleotide sequence of a bovine PBV strain in the American continent and the first detection of small genome profile of PBV-like strains in bovine hosts.


title: COVID-19 and the crisis of national development

text: The global practice of monetizing ecosystems to further national economic development has laid fertile ground for the COVID-19 pandemic and others like it, writes Cobus van Staden.


title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating

text: Leukocyte migration is controlled by a membrane-based chemosensory pathway on the leading edge pseudopod that guides cell movement up attractant gradients during the innate immune and inflammatory responses. This study employed single cell and population imaging to investigate drug-induced perturbations of leading edge pseudopod morphology in cultured, polarized RAW macrophages. The drugs tested included representative therapeutics (acetylsalicylic acid, diclofenac, ibuprofen, acetaminophen) as well as control drugs (PDGF, Gö6976, wortmannin). Notably, slow addition of any of the four therapeutics to cultured macrophages, mimicking the slowly increasing plasma concentration reported for standard oral dosage in patients, yielded no detectable change in pseudopod morphology. This finding is consistent with the well established clinical safety of these drugs. However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). The novel observation of adaptive exposures leads us to hypothesize that rapid addition of an adaptive drug overwhelms an intrinsic or extrinsic adaptation system yielding temporary collapse followed by adaptive recovery, while slow addition enables gradual adaptation to counteract the drug perturbation in real time. Overall, the results illustrate an approach that may help identify therapeutic drugs that temporarily inhibit the leading edge pseudopod during extreme inflammation events, and toxic drugs that yield long term inhibition of the pseudopod with negative consequences for innate immunity. Future studies are needed to elucidate the mechanisms of drug-induced pseudopod collapse, as well as the mechanisms of adaptation and recovery following some inhibitory drug exposures.


title: Molecular characterization of a novel coronavirus associated with epizootic catarrhal enteritis (ECE) in ferrets

text: Abstract A novel coronavirus, designated as ferret enteric coronavirus (FECV), was identified in feces of domestic ferrets clinically diagnosed with epizootic catarrhal enteritis (ECE). Initially, partial sequences of the polymerase, spike, membrane protein, and nucleocapsid genes were generated using coronavirus consensus PCR assays. Subsequently, the complete sequences of the nucleocapsid gene and the last two open reading frames at the 3′ terminus of the FECV genome were obtained. Phylogenetic analyses based on predicted partial amino acid sequences of the polymerase, spike, and membrane proteins, and full sequence of the nucleocapsid protein showed that FECV is genetically most closely related to group 1 coronaviruses. FECV is more similar to feline coronavirus, porcine transmissible gastroenteritis virus, and canine coronavirus than to porcine epidemic diarrhea virus and human coronavirus 229E. Molecular data presented in this study provide the first genetic evidence for a new coronavirus associated with clinical cases of ECE.


title: Ethics Education for Successful Infectious Disease Control of COVID-19

text: The infection rates of COVID-19 have been exponential in some countries despite the imposition of infectious disease control measures such as lockdowns and physical distancing, which form one of the basic principles of public health and infectious disease control. There have been significant problems with leaders and citizenry deliberately ignoring and not complying with such measures and which have directly resulted in sudden rises in infection numbers. Here, I show the nature and extent of the widespread problem and argue that the problem is in large part due to our modern society characterised by liberal individualism. I apply the philosophy proposed by philosopher Alasdair MacIntrye to show that one key underlying cause of the non-compliant behaviour of citizenry is due to modern liberal individualism that has deprived the modern nation state of the opportunities and authority for it to teach or to dictate what is the common good of the society as a whole to individuals in its community. This is the first time MacIntyre’s philosophy has been applied to public health, and this paper demonstrates the need for ethics education to counter-balance liberal individualism in order to contain and to prevent another pandemic and public health crisis in modern society.


title: 3C protein of feline coronavirus inhibits viral replication independently of the autophagy pathway

text: Abstract Feline coronavirus (FCoV) can cause either asymptomatic enteric infection or fatal peritonitis in cats. Although the mutation of FCoV accessory gene 3c has been suggested to be related to the occurrence of feline infectious peritonitis (FIP), how the 3C protein is involved in this phenomenon remains unknown. To investigate the role of the 3C protein, a full-length 3c gene was transiently expressed and the cytoplasmic distribution of the protein was found to be primarily in the perinuclear region. Using 3c-stable expression cells, the replication of a 3c-defective FCoV strain was titrated and a significant decrease in replication (p < 0.05) was observed. The mechanism underlying the decreased FIPV replication caused by the 3C protein was further investigated; neither the induction nor inhibition of autophagy rescued the viral replication. Taken together, our data suggest that the 3C protein might have a virulence-suppressing effect in FCoV-infected cats. Deletion of the 3c gene could therefore cause more efficient viral replication, which leads to a fatal infection.


title: Oligonucleotide microarray with a minimal number of probes for the detection and identification of thirteen genera of plant viruses

text: Abstract A major challenge facing agriculture at present is the development of techniques that can screen field samples and other plant materials simultaneously for the presence of many viruses. Microarray techniques show promise in this regard, as their high throughput nature can potentially detect a range of viruses using a single test. In this paper we present an array that can detect a wide spectrum of 169 plant virus species from 13 different genera. The array was constructed using an automated probe design protocol which generated a minimal number of probes to detect viruses at the genus level. The designed arrays showed a high specificity and sensitivity when tested with a set of standard virus samples. Field samples collected from a severe disease outbreak of Panax notoginseng farms in Yunnan, China, in 2001 were screened, where a potyvirus infection was identified associated with the disease.


title: Co-infection with respiratory pathogens among COVID-2019 cases

text: Accumulating evidence shows that microbial co-infection increases the risk of disease severity in humans. There have been few studies about SARS-CoV-2 co-infection with other pathogens. In this retrospective study, 257 laboratory-confirmed COVID-19 patients in Jiangsu Province were enrolled from January 22 to February 2, 2020. They were re-confirmed by real-time RT-PCR and tested for 39 respiratory pathogens. In total, 24 respiratory pathogens were found among the patients, and 242 (94.2 %) patients were co-infected with one or more pathogens. Bacterial co-infections were dominant in all COVID-19 patients, Streptococcus pneumoniae was the most common, followed by Klebsiella pneumoniae and Haemophilus influenzae. The highest and lowest rates of co-infections were found in patients aged 15–44 and below 15, respectively. Most co-infections occurred within 1–4 days of onset of COVID-19 disease. In addition, the proportion of viral co-infections, fungal co-infections and bacterial-fungal co-infections were the highest severe COVID-19 cases. These results will provide a helpful reference for diagnosis and clinical treatment of COVID-19 patients.


title: COVID-19: Living through Another Pandemic

text: Novel beta-coronavirus SARS-CoV-2 is the pathogenic agent responsible for coronavirus disease-2019 (COVID-19), a globally pandemic infectious disease. Due to its high virulence and the absence of immunity among the general population, SARS-CoV-2 has quickly spread to all countries. This pandemic highlights the urgent unmet need to expand and focus our research tools on what are considered “neglected infectious diseases” and to prepare for future inevitable pandemics. This global emergency has generated unprecedented momentum and scientific efforts around the globe unifying scientists from academia, government and the pharmaceutical industry to accelerate the discovery of vaccines and treatments. Herein, we shed light on the virus structure and life cycle and the potential therapeutic targets in SARS-CoV-2 and briefly refer to both active and passive immunization modalities, drug repurposing focused on speed to market, and novel agents against specific viral targets as therapeutic interventions for COVID-19.


title: Guidance for clinical neurophysiology examination throughout the COVID-19 pandemic. Latin American chapter of the IFCN task force – COVID-19

text: On 31st December 2019, China notified the World Health Organization of an outbreak of atypical pneumonia from patients at a local seafood market in Wuhan, Hubei, China, responsible for a new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that caused COVID-19 disease, which spread rapidly around the world. WHO declared a state of pandemic (11th March, 2020), which has caused more than 1 million infected and more than 110,000 deaths; it was observed that up to 29% of those infected were health care personnel. The main route of transmission of SARS-CoV2 is through respiratory secretions and direct contact with contaminated surfaces and material. The pandemic induced an international saturation of health care services and a rupture in the supply chain of protective equipment for healthcare personnel, which poses a high occupational risk to all. Based on the different healthcare systems, human resources, infrastructure and medical emergencies that will warrant the conduct of clinical neurophysiology studies and the lack of a guide for the management of the situation, it was decided by an expert task force of the Latin American Chapter of the International Federation of Clinical Neurophysiology to carry out these guidelines for the protection of patient and healthcare professionals conducting clinical neurophysiological studies.


title: ID: 203 Middle East respiratory syndrome coronavirus accessory protein NS4b is a 2H-Phosphoesterase that degrades 2′,5′-oligoadenylate activators of RNase L

text: Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The interferon-inducible 2′,5′-oligoadenylate (2-5A) synthetases (OAS) and ribonuclease L (RNase L) are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein ns2, group A rotavirus (RVA) VP3 carboxy-terminal domain (VP3-CTD), and mammalian AKAP7 are members of 2H phosphoesterase superfamily with 2′-phosphodiesterase (2′-PDE) activity that potently cleaves 2-5A thereby preventing activation of RNase L (Zhao, Jha et al., PMID: 22704621; Zhang, Jha et al., PMID: 23878220 and Gusho, Zhang, Jha et al., PMID: 24987090). Here, we will demonstrate that Middle East respiratory syndrome (MERS)-CoV gene NS4b encodes a homologous and similar PDE that cleaves 2-5A in vitro (km/Kcat=12.1M−1 s−1), inhibits 2-5A accumulation in cell culture and prevents ribosomal (r) RNA degradation in murine bone marrow macrophages (BMM), a hallmark of RNase L antagonism, and rescues an MHV mutant virus with a catalytically inactive NS2a protein unable to antagonize RNase L in vivo. Interestingly, NS4b has a nuclear localization signal however there is a mixed nuclear/cytoplasmic localization when overexpressed in human airway cell line A549 and in BMM when expressed from chimeric MHV. Viral evasion of OAS/RNase L pathway is a critical hepatovirulence determinant for lineage A Betacoronavirus mouse hepatitis virus (MHV). Taken together, our data suggest that RNase L antagonism may be a critical component of MERS-CoV pathogenesis. Additionally, this is the first evidence of RNase L antagonism by a lineage C Betacoronavirus.


title: Fading Russian Influence in the Baltic States

text: Abstract Since the beginning of Vladimir Putin's rule in Russia 20 years ago, Russia has lost much of the leverage that it previously enjoyed in the Baltics. On the one hand, Russia has antagonized Baltic states through its wars in Georgia and Ukraine, on the other hand, deep integration in the EU and NATO has pulled the Baltic states from the Russian zone of influence. This article discusses the gradual decrease of Russia's influence in the Estonia, Latvia and Lithuania while considering the increased NATO presence in the region, Baltic energy security, and Baltic Russian-speaking communities.


Undergraduate Global Health Degrees: The Time is Right


title: Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection

text: Mitochondria are key for cellular metabolism and signalling processes during viral infection. We report a methodology to analyse mitochondrial properties at the single-organelle level during viral infection using a recombinant adenovirus coding for a mitochondrial tracer protein for tagging and detection by multispectral flow cytometry. Resolution at the level of tagged individual mitochondria revealed changes in mitochondrial size, membrane potential and displayed a fragile phenotype during viral infection of cells. Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies.


title: COVID‐19 and spinal cord injuries: The viewpoint from an emergency department resident with quadriplegia

text: Spinal cord injuries (SCIs) present distinct physiological and social considerations for the emergency physician. During the COVID‐19 pandemic, these considerations may generate unique challenges for emergency physicians managing patients with SCIs. Physiological disruptions may alter the way SCI patients present with COVID‐19. The same disruptions can affect management of this vulnerable patient group, perhaps warranting early aggressive treatment. The medical picture will often be complicated by unique social characteristics. The reliance on caregivers for activities of daily living can, as an example, increase the human resource requirement of an ED. Considering the vulnerabilities and complexities of patients with SCI, the community should prioritise prevention of COVID‐19 infections in this group. In the event that they do present to an ED, planning for and understanding their complexities will facilitate optimal management.


docid: xslozete

title: Monomerization of the viral entry inhibitor griffithsin yields insights into the relationship between multivalent binding to high mannose oligosaccharides and antiviral activity

text: Mutations were introduced to the domain-swapped homodimer of the antiviral lectin griffithsin (GRFT). Whereas several single and double mutants remained dimeric, insertion of either two or four amino acids at the dimerization interface resulted in a monomeric form of the protein (mGRFT). Monomeric character of the modified proteins was confirmed by sedimentation equilibrium ultracentrifugation and by their high resolution X-ray crystal structures, whereas their binding to carbohydrates was assessed by isothermal titration calorimetry. Cell-based antiviral activity assays utilizing different variants of mGRFT indicated that the monomeric form of the lectin had greatly reduced activity against HIV-1, suggesting that the antiviral activity of GRFT stems from crosslinking and aggregation of viral particles via multivalent interactions between GRFT and oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal structure of a complex between mGRFT and nonamannoside revealed that a single mGRFT molecule binds to two different nonamannoside molecules through all three carbohydrate-binding sites present on the monomer.


title: Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: Structure–activity relationships

text: Abstract Glycyrrhizic acid (18β-GL or GL) is a herbal drug with a broad spectrum of antiviral activities and pharmacological effects and multiple sites of action. Previously we showed that GL inhibits Epstein-Barr virus (EBV) infection in vitro by interfering with an early step of the EBV replication cycle (possibly attachment/penetration). Here we tested the effects of 15 GL derivatives against EBV infection by scoring the numbers of cell expressing viral antigens and quantifying EBV DNA copy numbers in superinfected Raji cells. The derivatives were made either by transformation of GL on carboxyl and hydroxyl groups or by conjugation of amino acid residues into the carbohydrate part. We identified seven compounds active against EBV and all showed dose-dependent inhibition as determined by both assays. Among these active compounds, the introduction of amino acid residues into the GL carbohydrate part enhanced the antiviral activity in three of the seven active compounds. However, when Glu(OH)-OMe was substituted by Glu(OMe)-OMe, its antiviral activity was completely abolished. Introduction of potassium or ammonium salt to GL reduced the antiviral activity with no significant effect on cytotoxicity. The α-isomer (18α-GL) of 18β-GL was as potent as the β-form, but its sodium salt lost antiviral activity. The metabolic product of GL, 18β-glycyrrhetinic acid (18β-GA or GA), was 7.5-fold more active against EBV than its parental compound GL but, concomitantly, exhibited increased cytotoxicity resulting in a decreased therapeutic index.


Outbreak of Kawasaki Syndrome


title: Reduced activity of the epithelial sodium channel in malaria-induced pulmonary oedema in mice

text: Abstract Lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ARDS). Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (iRBCs), and leukocyte infiltration into the lungs. This new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investigation of mechanisms leading to the lung disease. The activity of the amiloride-sensitive epithelial sodium channel (ENaC) in alveolar epithelial cells is decreased by several respiratory tract pathogens and this is suggested to contribute to pulmonary oedema. We show that PbK, a pathogen that remains in the circulation, also decreased the activity and expression of ENaC, suggesting that infectious agents can have indirect effects on ENaC activity in lung epithelial cells. The reduced ENaC activity may contribute to the pulmonary oedema induced by PbK malaria.


title: Delta inulin-based adjuvants promote the generation of polyfunctional CD4(+) T cell responses and protection against Mycobacterium tuberculosis infection

text: There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4(+) T cells (IFN-γ(+)TNF(+)IL-2(+)). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax(CpG)), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax(CpG) resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4(+) T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/Advax(CpG) is a strong candidate for further preclinical evaluation for progression to human trials.


title: The Evaluation of Sleep Disturbances for Chinese Frontline Medical Workers under the Outbreak of COVID-19

text: OBJECTIVE: To evaluate sleep disturbances of Chinese frontline medical workers (FMW) under the outbreak of coronavirus disease 2019, and make a comparison with non-FMW. METHODS: The medical workers from multiple hospitals in Hubei Province, China, volunteered to participate in this cross-sectional study. An online questionnaire, including Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS) and Visual Analogue Scale (VAS), was used to evaluate sleep disturbances and mental status. Sleep disturbances were defined as PSQI>6 points or/and AIS>6 points. We compared the scores of PSQI, AIS, anxiety and depression VAS, and prevalence of sleep disturbances between FMW and non-FMW. RESULTS: A total of 1306 subjects (801 FMW and 505 non-FMW) were enrolled. Compared to non-FMW, FMW had significantly higher scores of PSQI (9.3±3.8 vs 7.5±3.7; P<0.001; Cohen's d=0.47), AIS (6.9±4.3 vs 5.3±3.8; P<0.001; Cohen's d=0.38), anxiety (4.9±2.7 vs 4.3±2.6; P<0.001; Cohen's d= 0.22) and depression (4.1±2.5 vs 3.6±2.4; P=0.001; Cohen's d=0.21), and higher prevalence of sleep disturbances according to PSQI > 6 points (78.4% vs 61.0%; relative risk [RR]= 1.29; P<0.001) and AIS > 6 points (51.7% vs 35.6%; RR=1.45; P<0.001). CONCLUSION: FMW have higher prevalence of sleep disturbances and worse sleep quality than non-FMW. Further interventions should be administrated for FMW, aiming to maintain their healthy condition and guarantee their professional performance in the battle against COVID-19.


title: Diagnostic performance of a rapid in-clinic test for the detection of Canine Parvovirus under different storage conditions and vaccination status

text: Abstract Canine parvovirus (CPV) is one of the most common causes of acute haemorrhagic enteritis in young dogs, while clinical diagnosis is often indecisive. The aim of our study was to evaluate the diagnostic accuracy of an in-clinic rapid test in the detection of CPV infection in dogs. To this end, we compared the Rapid Diagnostic Kit of Canine Parvovirus, Coronavirus and Rotavirus antigen (Quicking®) to PCR, which is considered as the most reliable diagnostic method. A total of 78 duplicated faecal samples were collected from diarrhoeic dogs. Vaccination history within a month prior to the onset of diarrhoea was reported for 12 of the sampled dogs. The rapid diagnostic test was performed in 23 of the faecal samples directly, while the rest were placed into a sterile cotton tipped swab suitable for collection and transportation of viruses (Sigma Σ-VCM®) and stored at −20°C. The sensitivity of the Quicking rapid diagnostic test compared to PCR in the total number of samples, in samples from non-vaccinated dogs and in samples tested directly after collection were 22.22% (95% CI: 13.27–33.57%), 26.67% (95% CI: 16.08–39.66%) and 76.47% (95% CI: 50.10–93.04%) respectively, while the specificity of the test was 100% in any case. In conclusion, negative results do not exclude parvoenteritis from the differential diagnosis, especially in dogs with early vaccination history, but a positive result almost certainly indicates CPV infection. An improved sensitivity may be expected when the test is performed immediately.


title: Transplant renal artery stenosis in a child with BK nephropathy

text: TRAS and BK nephropathy are known complications of RT, but the association between both has not been reported. A 2‐year‐old girl underwent a deceased donor renal transplant from a 20‐year‐old donor, along with bilateral native nephrectomies. She had a DGF due to a renal artery thrombus and required thrombectomy with re‐anastomosis. Heparin and aspirin were used. Immunosuppressive agents included thymoglobulin, steroid, tacrolimus, and MMF. CMV and EBV DNA PCRs were negative, but she developed BK viremia at 2 months with stable allograft function. Immunosuppression was reduced, and leflunomide was initiated. Blood pressures were well controlled on low‐dose amlodipine. Five months after RT, she presented with hypertensive emergency, following a respiratory infection, and required dialysis for oliguric acute kidney injury. Allograft biopsy showed evidence of BK nephropathy. Immunosuppression was further minimized. Doppler renal US and renal artery duplex studies were both suggestive of TRAS. Angiogram showed severe proximal anastomotic TRAS (>95% occlusion). PTA with stenting was done with immediate improvement in the blood flow and reduction in the pressure gradient. BPs and renal function normalized. Ten months post‐RT, she remains normotensive with stable renal function and resolution of BK viremia. Although ureteral stenosis and nephropathy are known to occur with BK infection, TRAS is an interesting association and possibly suggest the tropism of BK virus to the vascular endothelial cells. Timely recognition and management of both is important to prevent uncontrolled hypertension and allograft dysfunction.


docid: mjqirgqe

title: Determination of anticoagulant rodenticides in faeces of exposed dogs and in a healthy dog population

text: BACKGROUND: Exposure to anticoagulant rodenticides (ARs) in dogs is among the most common causes of poisoning in small animal practice, but information about toxicokinetic of these rodenticides in dogs is lacking. We analysed blood and faeces from five accidentally exposed dogs and 110 healthy dogs by reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry. The aim of the study was to estimate elimination of brodifacoum, bromadiolone and difenacoum after acute exposure, calculate the half-lives of these rodenticides in dogs, estimate faecal elimination in a litter of puppies born, and further to identify the extent of AR exposure in a healthy dog population. RESULTS: Three dogs were included after single ingestions of brodifacoum; two dogs ingested bromadiolone and one dog ingested difenacoum. Maximum concentrations in faeces were found after day 2–3 for all ARs. The distribution half-lives were 1–10 days for brodifacoum, 1–2 days for bromadiolone and 10 days for difenacoum. Brodifacoum and difenacoum had estimated terminal half-lives of 200–330 days and 190 days, respectively. In contrast, bromadiolone had an estimated terminal half-life of 30 days. No clinical signs of poisoning or coagulopathy were observed in terminal elimination period. In blood, the terminal half-life of brodifacoum was estimated to 8 days. Faeces from a litter of puppies born from one of the poisoned dogs were examined, and measurable concentrations of brodifacoum were detected in all samples for at least 28 days after parturition. A cross-sectional study of 110 healthy domestic dogs was performed to estimate ARs exposure in a dog population. Difenacoum was detected in faeces of one dog. Blood and faecal samples from the remaining dogs were negative for all ARs. CONCLUSIONS: Based on the limited pharmacokinetic data from these dogs, our results suggest that ARs have a biphasic elimination in faeces using a two-compartment elimination kinetics model. We have shown that faecal analysis is suitable and reliable for the assessment of ARs exposure in dogs and a tool for estimating the AR half-lives. Half-lives of ARs could be a valuable indicator in the exposed dogs and provides important information for veterinarians monitoring AR exposure and assessment of treatment length in dogs.


title: Tratamiento Hipolipemiante En La Era Covid-19

text: Resumen Antecedentes y objetivos: La pandemia por COVID-19 ha puesto de manifiesto que las enfermedades cardiovasculares conllevan mayor riesgo de mortalidad. Han surgido dudas en cuanto la terapia lipídica en estos pacientes. Nuestro objetivo en esta revisión es analizar la eficacia y seguridad de la terapia hipolipemiante en los pacientes con COVID-19. Material y métodos: Se realizó una revisión de la literatura científica en PubMed, informes CDC, NIH y NCBI SARS-CoV-2 utilizando las palabras claves: COVID-19, statins, ezetimibe, PCSK9 inhibitors, hypercholesterolemia and hypolipidemic drugs. Resultados: Las estatinas se deben seguir utilizando en los pacientes con COVID-19 en base a su eficacia, seguridad, efectos inmunosupresores, antiinflamatorios disponibilidad y accesibilidad. En función de los niveles de riesgo cardiovascular de estos pacientes, puede ser necesario el empleo de estatinas de alta potencia y/o ezetimiba y/o inhibidores de la proproteína convertasa subtilisina (iPCSK9) en pacientes de alto y muy alto riesgo cardiovascular. Los pacientes tratados con iPCSK9 deben seguir con el tratamiento por sus efectos beneficiosos sobre la prevención de la enfermedad cardiovascular. Los pacientes con hipercolesterolemia familiar y COVID-19 son especialmente vulnerables a la enfermedad cardiovascular precoz y deben seguir recibiendo el tratamiento hipolipemiante intensivo. Conclusiones: En los pacientes con COVID-19, la mayoría de las enfermedades cardiovasculares basales son de origen aterosclerótico, con peor pronóstico para los pacientes con alto riesgo y muy alto riesgo de enfermedad cardiovascular. En estos pacientes, el tratamiento intensivo con estatinas y/o combinación fija con ezetimiba y/o iPCSK9 juega un papel fundamental. Abstract Background and objectives: The COVID-19 pandemic has shown that cardiovascular diseases carry a higher risk of mortality. Doubts have been raised regarding lipid therapy in these patients. The objectives are to analyze the efficacy and safety of lipid lowering therapy in patients with COVID-19 Material and Methods: A review of the scientific literature was conducted in PubMed, CDC Reports, NIH, and NCBI SARS-CoV-2 using the keywords: COVID-2; statins; ezetimibe; PCSK9 inhibitors; hypercholesterolemia; and hypolipidemic drugs. Results: The stations should continue to use patients with COVID-19 based on their efficacy, safety, immunosuppressive effects, anti-inflammatory availability and accessibility. Depending on the cardiovascular risk levels of these patients, the use of high potency statins and / or ezetimibe and / or iPCSK9 may be necessary in patients with high and very high cardiovascular risk. Patients treated with iPCSK9 should continue treatment for its beneficial effects in preventing cardiovascular disease. Patients with familial hypercholesterolemia and COVID-19 are especially vulnerable to cardiovascular disease and should continue to receive severe lipid lowering therapy. Conclusions: In patients with COVID-19, the majority of baseline CVDs are of atherosclerotic origin, with the worst prediction for patients with high risk and very high risk of CVD. In these patients, intensive treatment with statins and / or fixed combination with ezetimibe and / or iPCSK9 plays a fundamental role.


title: Effects of wearing N95 and surgical facemasks on heart rate, thermal stress and subjective sensations

text: Aim: The study was aimed at investigating the effects of wearing N95 and surgical facemasks with and without nano-functional treatments on thermophysiological responses and the subjective perception of discomfort. Method: Five healthy male and five healthy female participants performed intermittent exercise on a treadmill while wearing the protective facemasks in a climate chamber controlled at an air temperature of 25°C and a relative humidity of 70%. Four types of facemasks, including N95 (3M 8210) and surgical facemasks, which were treated with nano-functional materials, were used in the study. Results: (1) The subjects had significantly lower average heart rates when wearing nano-treated and untreated surgical facemasks than when wearing nano-treated and untreated N95 facemasks. (2) The outer surface temperature of both surgical facemasks was significantly higher than that of both N95 facemasks. On the other hand, the microclimate and skin temperatures inside the facemask were significantly lower than those in both N95 facemasks. (3) Both surgical facemasks had significantly higher absolute humidity outside the surface than both N95 facemasks. The absolute humidity inside the surgical facemask was significantly lower than that inside both N95 facemasks. (4) Both surgical facemasks were rated significantly lower for perception of humidity, heat, breath resistance and overall discomfort than both N95 facemasks. The ratings for other sensations, including feeling unfit, tight, itchy, fatigued, odorous and salty, that were obtained while the subjects were wearing the surgical facemasks were significantly lower than when the subjects were wearing the N95 facemasks. (5) Subjective preference for the nano-treated surgical facemasks was the highest. There was significant differences in preference between the nano-treated and untreated surgical facemasks and between the surgical and N95 facemasks. Discussion: We discuss how N95 and surgical facemasks induce significantly different temperature and humidity in the microclimates of the facemasks, which have profound influences on heart rate and thermal stress and subjective perception of discomfort.


title: Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4

text: The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.


title: Spontaneous Pneumothorax Following COVID-19 Pneumonia

text: Patient presents with dyspnea after recovering from COVID-19 pneumonia and is found to have pneumothorax. This represents an under-reported sequelae of COVID-19.


title: The influence of job satisfaction, resilience and work engagement on turnover intention among village doctors in China: a cross-sectional study

text: BACKGROUND: As the gatekeepers of rural residents’ health, teams of village doctors play a vital role in improving rural residents’ health. However, the high turnover of village doctors, both individually and collectively, threaten the stability of village medical teams. This research evaluated the influence of job satisfaction, resilience, and work engagement on the village doctors’ turnover intention, and explored the mediating role of work engagement and resilience between job satisfaction and the turnover intention of village doctors in China. METHODS: A quantitative study using a self-administered questionnaire containing mostly structured items was conducted among village doctors with a sample size of 2693 from 1345 rural clinics in Shandong province, China, during May and June 2019. All variables including demographic characteristics, job satisfaction, resilience, work engagement and turnover intention were based on available literature, and measured on a 5- or 6-point Likert scale. Such statistical methods as one-way ANOVA, bivariate correlation, exploratory factor analysis (EFA), and Structural Equation Modelling (SEM) were used. RESULTS: Up to 46.9% of the subjects had a higher turnover intention and more than 26.3% of them had a medium turnover intention. The job satisfaction of village doctors could not only have a direct negative effect on turnover intention (β = − 0.37, p < 0.001), but also have an indirect effect through work engagement (β = − 0.04,=< 0.001). Meanwhile, work engagement also had a direct negative impact on turnover intention (β = − 0.13, p < 0.001), and resilience had an indirect negative impact on turnover intention through work engagement (β = − 0.09, p < 0.001). The above results of this study strongly confirmed that job satisfaction, resilience, and work engagement were early, powerful predicators of village doctors’ turnover intention. CONCLUSION: According to the results, the following should be taken seriously to improve job satisfaction: reasonable and fair income, effective promotion mechanism, fair social old-age security, reasonable workload, and strong psychological coping mechanisms for work stress. The turnover intention of village doctors could be reduced through improving job satisfaction, resilience and work engagement.


title: Aminopeptidase‐N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

text: Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti‐cancer and anti‐inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity. © 2005 Wiley Periodicals, Inc. Med Res Rev


title: Detection and Molecular Characterization of Porcine Enteric Calicivirus in Korea, Genetically Related to Sapoviruses

text: Porcine enteric calicivirus (PECV) shares morphological and genetical similarities with Sapoviruses (SVs), which are the leading cause of epidemic, non‐bacterial gastroenteritis in children worldwide. The aim of this study was to identify the prevalence of PECV infection in pig farms in Korea, and to compare the evolutionary inter‐relationships between Korean PECVs and other caliciviruses. Among 102 diarrhoeic faecal samples of sucking (n = 50) and weaned (n = 52) piglets from 31 different farms in Korea, five samples (4.9%) were detected positive by reverse‐transcriptase polymerase chain reaction (PCR), but nine (8.8%) by nested‐PCR. Furthermore, we found that Korean PECVs are closely related to SVs.


title: COVID-19, SARS and MERS: are they closely related?

text: Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.


title: Acute exacerbation of COPD

text: The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia‐Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the ‘pathogens’ (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X‐ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease‐specific self‐management, pulmonary rehabilitation, early medical follow‐up, home visits by respiratory health workers, integrated programmes and telehealth‐assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long‐acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long‐term macrolides. Further studies are needed to assess the cost‐effectiveness of these interventions in preventing COPD exacerbations.


title: Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

text: Viral respiratory tract infections in lung transplant recipients may be severe. During three consecutive winter‐spring seasons, 49 symptomatic lung transplant recipients with suspected respiratory viral infection, and 26 asymptomatic patients were investigated for presence of respiratory viruses either in 56 nasopharyngeal aspirate or 72 bronchoalveolar lavage samples taken at different times after transplantation. On the whole, 1 asymptomatic (3.4%) and 28 symptomatic (57.1%) patients were positive for human metapneumovirus (hMPV, 4 patients), influenza virus A (3 patients), and B (2 patients), respiratory syncytial virus (2 patients), human coronavirus (2 patients), human parainfluenza virus (2 patients), rhinovirus (5 patients), while 4 patients were coinfected by 2 respiratory viruses, and 5 were infected sequentially by 2 or more respiratory viruses. In bronchoalveolar lavage samples, hMPV predominated by far over the other viruses, being responsible for 60% of positive specimens, whereas other viruses were present in nasopharyngeal aspirates at a comparable rate. RT‐PCR (detecting 43 positive samples/128 examined) was largely superior to monoclonal antibodies (detecting 17 positive samples only). In addition, HCMV was detected in association with a respiratory virus in 4/18 HCMV‐positive patients, and was found at a high concentration (>10(5) DNA copies/ml) in 3/16 (18.7%) patients with HCMV‐positive bronchoalveolar lavage samples and pneumonia. Coinfections and sequential infections by HCMV and respiratory viruses were significantly more frequent in patients with acute rejection and steroid treatment. In conclusion: (i) about 50% of respiratory tract infections of lung transplant recipients were associated with one or more respiratory viruses; (ii) hMPV largely predominates in bronchoalveolar lavage of symptomatic lung transplant recipients, thus suggesting a causative role in lower respiratory tract infections; (iii) RT‐PCR appears to be the method of choice for detection of respiratory viruses in lung transplant recipients, (iv) a high HCMV load in bronchoalveolar lavage is a risk factor for viral pneumonia, suggesting some measure of intervention for the control of viral infection. J. Med. Virol. 78:408–416, 2006. © 2006 Wiley‐Liss, Inc.


title: Psychoanalysing the 21st Century: Introduction

text: The purpose of this introduction is to sketch out the value of psychoanalysis for the twenty-first century and in particular the ways in which analysis might enable us to move beyond the crisis of the post-Cold War symbolic order.


title: An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections

text: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.


title: Significance of Clostridium spiroforme in the enteritis-complex of commercial rabbits

text: Abstract Commercial rabbits showing clinical signs of enteritis-complex were examined for the presence of Clostridium spiroforme and its iota-like toxin. The bacterium was detected by Gram stain in 52.4% of 149 cecal samples and iota-like toxin in 7.4%. From 29 strains of C. spiroforme tested, 26 were toxigenic, originating from 24 of 29 rabbitries. In 13.4% of the samples, C. spiroforme was present as the only known disease agent. Gross and microscopic lesions were similar to those described in the literature. In the other samples, C. spiroforme was associated with attaching effacing Escherichia coli (29.5%), Bacillus piliformis (10.3%), rotaviruses (25.6%), coronavirus (2.6%), Eimeria spp. (44.9%) and cryptosporidia (6.4%). In 33.3% of C. spiroforme-containing samples, more than one of these agents was present. There was no significant difference between the presence of these organisms in C. spiroforme-positive and negative samples. On the basis of these results as well as that of previous data, we suggest that C. spiroforme-mediated diarrhea is favoured by maldigestion, initiated by infectious agents and/or nutritional factors.