title: Use of linked electronic health records to assess mortality and length of stay associated with pandemic influenza A(H1N1)pdm09 at a UK teaching hospital

text: Effective use of data linkage is becoming an increasingly important focus in the new healthcare system in England. We linked data from the results of a multiplex PCR assay for respiratory viruses for a population of 230 inpatients at a UK teaching hospital with their patient administrative system records in order to compare the mortality and length of stay of patients who tested positive for influenza A(H1N1)pdm09 with those positive for another influenza A virus. The results indicated a reduced risk of death among influenza A(H1N1)pdm09 patients compared to other influenza A strains, with an adjusted risk ratio of 0·25 (95% confidence interval 0·08–0·75, P = 0·01), while no significant differences were found between the lengths of stay in the hospital for these two groups. Further development of such methods to link hospital data in a routine fashion could provide a rapid means of gaining epidemiological insights into emerging infectious diseases.


title: Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia

text: BACKGROUND: There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change of LDH in COVID-19 pneumonia has not been well investigated. METHODS: Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (− 1 ~ + 1 day). RESULTS: At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression. CONCLUSIONS: Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.


title: Progressive Politics and Humanistic Psychology in the Trump/Coronavirus Era

text: In this article, the author discusses the relationship of progressive politics to humanistic psychology in the Trump/Coronavirus era. The harsh realities of personal fears and severe challenges to our mental health evoked by both the United States presidency of Donald Trump and the coronavirus pandemic are described initially. Then, a number of self-care practices that are consistent with the basic values of humanistic psychology and that we can undertake to help us meet these harsh realities are illustrated. Next, the author describes his own personal engagement and self-care in the world of progressive politics and humanistic psychology in the context of the Resisting Trump movement. The article concludes with the author suggesting that perhaps it may be worthwhile for politically like-minded others to also consider finding ways of merging their progressive politics with humanistic psychology in order to enhance their self-care through these turbulent times in the Trump/Coronavirus era.


title: Infectious Disease and Primary Care Research—What English General Practitioners Say They Need

text: Background: Infections are one of the most common reasons for patients attending primary care. Antimicrobial resistance (AMR) is perhaps one of the biggest threats to modern medicine; data show that 81% of antibiotics in the UK are prescribed in primary care. Aim: To identify where the perceived gaps in knowledge, skills, guidance and research around infections and antibiotic use lie from the general practitioner (GP) viewpoint. Design and Setting: An online questionnaire survey. Method: The survey, based on questions asked of Royal College of General Practitioners (RCGP) members in 1999, and covering letter were electronically sent to GPs between May and August 2017 via various primary care dissemination routes. Results: Four hundred and twenty-eight GPs responded. Suspected Infection in the elderly, recurrent urinary tract infection (UTI), surveillance of AMR in the community, leg ulcers, persistent cough and cellulitis all fell into the top six conditions ranked in order of importance that require further research, evidence and guidance. Acute sore throat, otitis media and sinusitis were of lower importance than in 1999. Conclusion: This survey will help the NHS, the UK National Institute for Health and Care Excellence (NICE) and researchers to prioritise for the development of guidance and research for chronic conditions highlighted for which there is little evidence base for diagnostic and management guidelines in primary care. In contrast, 20 years of investment into research, guidance and resources for acute respiratory infections have successfully reduced these as priority areas for GPs.


title: Dynamics of a model with quarantine-adjusted incidence and quarantine of susceptible individuals

text: Abstract A new deterministic model for the spread of a communicable disease that is controllable using mass quarantine is designed. Unlike in the case of the vast majority of prior quarantine models in the literature, the new model includes a quarantine-adjusted incidence function for the infection rate and the quarantine of susceptible individuals suspected of being exposed to the disease (thereby making it more realistic epidemiologically). The earlier quarantine models tend to only explicitly consider individuals who are already infected, but show no clinical symptoms of the disease (i.e., those latently-infected), in the quarantine class (while ignoring the quarantine of susceptible individuals). In reality, however, the vast majority of people in quarantine (during a disease outbreak) are susceptible. Rigorous analysis of the model shows that the assumed imperfect nature of quarantine (in preventing the infection of quarantined susceptible individuals) induces the phenomenon of backward bifurcation when the associated reproduction threshold is less than unity (thereby making effective disease control difficult). For the case when the efficacy of quarantine to prevent infection during quarantine is perfect, the disease-free equilibrium is globally-asymptotically stable when the reproduction threshold is less than unity. Furthermore, the model has a unique endemic equilibrium when the reproduction threshold exceeds unity (and the disease persists in the population in this case).


Structure and Dynamics of Sars Coronavirus Main Proteinase (M(PRO))


title: In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria

text: The objective of this present study is to focus on the in silico study to screen for an alternative drug that can block the activity of the angiotensin converting enzyme 2 (ACE2) as a receptor for SARS-CoV-2, potential therapeutic target of the COVID-19 virus using natural compounds (Isothymol, Thymol, Limonene, P-cymene and γ-terpinene) derived from the essential oil of the antiviral and antimicrobial plant Ammoides verticillata (Desf.) Briq. which is located in the occidental Algeria areas. This study reveals that Isothymol, a major component of this plant, gives the best docking scores, compared to, the co-crystallized inhibitor β-D-mannose of the enzyme ACE2, to Captropil drug as good ACE2 inhibitor and to Chloroquine antiviral drug also involved in other mechanisms as inhibition of ACE2 cellular receptor. In silico (ADME), drug-likeness, PASS & P450 site of metabolism prediction, pharmacophore Mapper showed that the compound Isothymol has given a good tests results compared to the β-D-mannose co-crystallized inhibitor, to Captopril and Chloroquine drugs. Also the other natural compounds gave good results. The Molecular Dynamics Simulation study showed good result for the Isotymol- ACE2 docked complex. This study revealed for the first time that Isothymol is a functional inhibitor of angiotensin converting enzyme 2 activity and the components of essential oils Ammoides verticillata can be used as potential inhibitors to the ACE2 receptor of SARS-CoV-2. Communicated by Ramaswamy H. Sarma


title: Spatial and Temporal Epidemiology of Lumpy Skin Disease in the Middle East, 2012–2015

text: Lumpy skin disease virus (LSDV) is an infectious disease of cattle that can have severe economic implications. New LSD outbreaks are currently circulating in the Middle East (ME). Since 2012, severe outbreaks were reported in cattle across the region. Characterizing the spatial and temporal dynamics of LSDV in cattle populations is prerequisite for guiding successful surveillance and control efforts at a regional level in the ME. Here, we aim to model the ecological niche of LSDV and identify epidemic progression patterns over the course of the epidemic. We analyzed publically available outbreak data from the ME for the period 2012–2015 using presence-only maximum entropy ecological niche modeling and the time-dependent method for the estimation of the effective reproductive number (R-TD). High-risk areas (probability >0.60) for LSDV identified by ecological niche modeling included parts of many northeastern ME countries, though Israel and Turkey were estimated to be the most suitable locations for occurrence of LSDV outbreaks. The most important environmental predictors that contributed to the ecological niche of LSDV included annual precipitation, land cover, mean diurnal range, type of livestock production system, and global livestock densities. Average monthly effective R-TD was equal to 2.2 (95% CI: 1.2, 3.5), whereas the largest R-TD was estimated in Israel (R-TD = 22.2, 95 CI: 15.2, 31.5) in September 2013, which indicated that the demographic and environmental conditions during this period were suitable to LSDV super-spreading events. The sharp drop of Isreal’s inferred R-TD in the following month reflected the success of their 2013 vaccination campaign in controlling the disease. Our results identified areas in which underreporting of LSDV outbreaks may have occurred. More epidemiological information related to cattle populations are needed to further improve the inferred spatial and temporal characteristics of currently circulating LSDV. However, the methodology presented here may be useful in guiding the design of risk-based surveillance and control programs in the region as well as aid in the formulation of epidemic preparedness plans in neighboring LSDV-free countries.


docid: wforwxes

title: Expert recommendations for the management of autoimmune bullous diseases during the COVID‐19 pandemic

text: Autoimmune bullous diseases (AIBDs) are potentially life‐threatening disorders comprising intra‐epidermal/epithelial (pemphigus) and sub‐epidermal/epithelial blistering diseases (pemphigoid and dermatitis herpetiformis). Corticosteroids and non‐steroid immunomodulatory agents are the mainstays of treatment. Treatment can be challenging particularly in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita which may require more intense immunosuppressive approaches


title: Potential Role of Nrf2 Activators with Dual Antiviral and Anti-Inflammatory Properties in the Management of Viral Pneumonia

text: The outbreak of coronavirus disease 2019 (COVID-19) pandemic has already caused a huge burden to the global healthcare system, with the death toll reached tens of thousands. Although some antiviral agents were identified and used to inhibit viral replication, the management of cytokine storm is also a critical issue. In this article, we reviewed the literature on drug candidates for severe acute respiratory syndrome (SARS-CoV-1) and provided a brief overview of a class of drugs that exert antiviral and anti-inflammatory effects. These molecules mitigated inflammatory cytokine cascades induced by viral infections via Nrf2 activating capacity and might have additional anti-fibrotic and anti-remodeling properties. Besides, their effects on the regulation of scavenger receptors expression by macrophages may offer some benefits to the pulmonary antibacterial defense system after viral infection. The potential roles of these agents assessed on the basis of the pathophysiology of viral pneumonia and acute respiratory distress syndrome were also discussed. Further research is needed to ascertain whether Nrf2 activators are useful in the management of viral pneumonia.


title: Prophylaxis against pulmonary viral and fungal infections in solid organ transplant recipients

text: Pulmonary viral and fungal infections in solid organ transplant recipients are one of the most common and potentially life-threatening infections. Understanding the strategies used for prophylaxis and prevention of these infections is critical for the health and well-being of transplant recipients. Prophylactic measures range from simple patient education to complex chemoprophylactic interventions; however, a multifaceted approach is most often required. This article focuses on strategies to prevent pulmonary viral and fungal infections in transplant recipients, with an emphasis on recent evidence that may influence practice guidelines.


docid: oaceknrb

title: Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action of Huo-Xiang-Zheng-Qi Formula for the Treatment of Gastrointestinal Diseases

text: Multi-components Traditional Chinese Medicine (TCM) treats various complex diseases (multi-etiologies and multi-symptoms) via herbs interactions to exert curative efficacy with less adverse effects. However, the ancient Chinese compatibility theory of herbs formula still remains ambiguous. Presently, this combination principle is dissected through a systems pharmacology study on the mechanism of action of a representative TCM formula, Huo-xiang-zheng-qi (HXZQ) prescription, on the treatment of functional dyspepsia (FD), a chronic or recurrent clinical disorder of digestive system, as typical gastrointestinal (GI) diseases which burden human physical and mental health heavily and widely. In approach, a systems pharmacology platform which incorporates the pharmacokinetic and pharmaco-dynamics evaluation, target fishing and network pharmacological analyses is employed. As a result, 132 chemicals and 48 proteins are identified as active compounds and FD-related targets, and the mechanism of HXZQ formula for the treatment of GI diseases is based on its three function modules of anti-inflammation, immune protection and gastrointestinal motility regulation mainly through four, i.e., PIK-AKT, JAK-STAT, Toll-like as well as Calcium signaling pathways. In addition, HXZQ formula conforms to the ancient compatibility rule of “Jun-Chen-Zuo-Shi” due to the different, while cooperative roles that herbs possess, specifically, the direct FD curative effects of GHX (serving as Jun drug), the anti-bacterial efficacy and major accompanying symptoms-reliving bioactivities of ZS and BZ (as Chen), the detoxication and ADME regulation capacities of GC (as Shi), as well as the minor symptoms-treating efficacy of the rest 7 herbs (as Zuo). This work not only provides an insight of the therapeutic mechanism of TCMs on treating GI diseases from a multi-scale perspective, but also may offer an efficient way for drug discovery and development from herbal medicine as complementary drugs.


title: Identification of cellular proteome using two-dimensional difference gel electrophoresis in ST cells infected with transmissible gastroenteritis coronavirus

text: BACKGROUND: Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs, which is correlated with high morbidity and mortality in suckling piglets. Information remains limited about the comparative protein expression of host cells in response to TGEV infection. In this study, cellular protein response to TGEV infection in swine testes (ST) cells was analyzed, using the proteomic method of two-dimensional difference gel electrophoresis (2D DIGE) coupled with MALDI-TOF-TOF/MS identification. RESULTS: 33 differentially expressed protein spots, of which 23 were up-regulated and 10 were down-regulated were identified. All the protein spots were successfully identified. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and the mitochondrial pathway. Western blot analysis was used to validate the changes of alpha tubulin, keratin 19, and prohibitin during TGEV infection. CONCLUSIONS: To our knowledge, we have performed the first analysis of the proteomic changes in host cell during TGEV infection. 17 altered cellular proteins that differentially expressed in TGEV infection were identified. The present study provides protein-related information that should be useful for understanding the host cell response to TGEV infection and the underlying mechanism of TGEV replication and pathogenicity.


title: SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production

text: BACKGROUND: Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. RESULTS: SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. CONCLUSIONS: The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly.


title: Developing a risk assessment score for cancer patients during COVID-19 pandemic

text: The novel coronavirus (CoV) pandemic is a serious threat for cancer patients, who have an immunocompromised status, and are considered at high risk for infections. Data on the novel CoV respiratory disease (COVID-19) in cancer patients are still limited. Unlike other common viruses, CoV have not shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In cancer patients treated with immunotherapy (e.g. immune-checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk for COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in cancer patients.


title: Severe infantile Bordetella pertussis pneumonia in monozygotic twins with a congenital C3 deficiency

text: Bordetella pertussis or whooping cough is a vaccine-preventable disease that still remains a serious infection in neonates and young infants. We describe two young infants, monozygotic twins, with a severe B. pertussis pneumonia of whom one needed extracorporeal membrane oxygenation. Diagnostic work-up of unexplained hematuria and proteinuria during the illness revealed low serum complement component 3 (C3) levels. During follow-up, C3 levels remained low (400–600 mg/L). Extensive analysis of the persistent low C3 levels revealed an unknown heterozygous mutation in the C3 gene in both siblings and their mother. This C3 mutation in combination with the specific virulence mechanisms of B. pertussis probably contributed to the severe disease course in these cases. Conclusion: We propose that genetically caused complement disorders should be considered when confronted with severe cases of B. pertussis infection.


docid: xyamsqop

title: Evidence is Lacking for the NHS England Interim Guidance for Managing Metastatic Non-small Cell Lung Cancer in the COVID-19 Pandemic


title: Antilipidemic Drug Therapy Today and in the Future

text: The armamentarium for the treatment of dyslipidemia today comprises six different modes of action with overall around 24 different drugs. The treatment of lipid disorders was revolutionized with the introduction of statins which have become the most important therapeutic option available today to reduce and prevent atherosclerosis and its detrimental consequences like cardiovascular diseases and stroke. With and optimized reduction of elevated LDL levels with statins, the risk for cardiovascular diseases (CVD) can be reduced by 30%, indicating a residual remaining risk of 70% for the development and progression of CVD notifying still a high medical need for more effective antilipidemic drugs. Consequently, the search for novel lipid-modifying drugs is still one of the most active areas in research and development in the pharmaceutical industry. Major focus lies on approaches to LDL-lowering drugs superior to statins with regard to efficacy, safety, and patient compliance and on approaches modifying plasma levels and functionality of HDL particles based on the clinically validated inverse relationship between high-plasma HDL levels and the risk for CVD. The available drugs today for the treatment of dyslipidemia are small organic molecules or nonabsorbable polymers for binding of bile acids to be applied orally. Besides small molecules for novel targets, biological drugs such as monoclonal antibodies, antisense or gene-silencing oligonucleotides, peptidomimetics, reconstituted synthetic HDL particles and therapeutic proteins are novel approaches in clinical development are which have to be applied by injection or infusion. The promising clinical results of several novel drug candidates, particularly for LDL cholesterol lowering with monoclonal antibodies raised against PCSK9, may indicate more than a decade after the statins, the entrance of new breakthrough therapies to treat lipid disorders.


title: Severe Acute Respiratory Syndrome, Beijing, 2003

text: The largest outbreak of severe acute respiratory syndrome (SARS) struck Beijing in spring 2003. Multiple importations of SARS to Beijing initiated transmission in several healthcare facilities. Beijing’s outbreak began March 5; by late April, daily hospital admissions for SARS exceeded 100 for several days; 2,521 cases of probable SARS occurred. Attack rates were highest in those 20–39 years of age; 1% of cases occurred in children <10 years. The case-fatality rate was highest among patients >65 years (27.7% vs. 4.8% for those 20–64 years, p < 0.001). Healthcare workers accounted for 16% of probable cases. The proportion of case-patients without known contact to a SARS patient increased significantly in May. Implementation of early detection, isolation, contact tracing, quarantine, triage of case-patients to designated SARS hospitals, and community mobilization ended the outbreak.


title: Lipidomic study of intracellular Singapore grouper iridovirus

text: Abstract Singapore grouper iridoviruses (SGIV) infected grouper cells release few enveloped extracellular viruses by budding and many unenveloped intracellular viruses following cell lysis. The lipid composition and function of such unenveloped intracellular viruses remain unknown. Detergent treatment of the intracellular viruses triggered the loss of viral lipids, capsid proteins and infectivity. Enzymatic digestion of the viral lipids with phospholipases and sphingomyelinase retained the viral capsid proteins but reduced infectivity. Over 220 lipid species were identified and quantified from the viruses and its producer cells by electrospray ionization mass spectrometry. Ten caspid proteins that dissociated from the viruses following the detergent treatments were identified by MALDI-TOF/TOF-MS/MS. Five of them were demonstrated to be lipid-binding proteins. This is the first research detailing the lipidome and lipid–protein interactions of an unenveloped virus. The identified lipid species and lipid-binding proteins will facilitate further studies of the viral assembly, egress and entry.


SARS-CoV-2 RNA from droplets to faeces: a new focus for proctologists. Correspondence


title: Chameleon sequences in neurodegenerative diseases

text: Abstract Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.


title: Re-positive Cases of Nucleic Acid Tests in Discharged Patients With COVID-19: A Follow-Up Study

text: Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 ± 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 ± 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients.


title: G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

text: G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.


title: Risk factors for death in 1859 subjects with COVID-19

text: We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.04; 95% Confidence Interval [CI], 1.03, 1.06 per year increase; P < 0.001); (2) smoking (HR = 1.84 [1.17, 2.92]; P = 0.009); (3) admission temperature per °C increase (HR = 1.32 [1.07, 1.64]; P = 0.009); (4) Log(10) neutrophil-to-lymphocyte ratio (NLR; HR = 3.30 [2.10, 5.19]; P < 0.001); (5) platelets per 10 E + 9/L decrease (HR = 0.996 [0.994, 0.998]; P = 0.001); (6) activated partial thromboplastin (aPTT) per second increase (HR = 1.04 [1.02, 1.05]; P < 0.001); (7) Log(10) D-dimer per mg/l increase (HR = 3.00 [2.17, 4.16]; P < 0.001); and (8) Log(10) serum creatinine per μmol/L increase (HR = 4.55 [2.72, 7.62]; P < 0.001). In piecewise linear regression analyses Log(10)NLR the interval from ≥0.4 to ≤1.0 was significantly associated with an increased risk of death. Our data identify covariates associated with risk of in hospital death in persons with COVID-19.


title: Miniaturized detection technology in molecular diagnostics

text: Miniaturization of genetic tests represents the convergence of molecular biology and engineering and is leading to a new class of small analyzers and test systems for genetic testing with improved analytical characteristics. Miniaturization initially focused on devices that contained micrometer-sized features designed for a particular analytical purpose (e.g., filters for cell isolation and chips for capillary electrophoresis). Now, the focus is shifting to analytical applications based on nano-sized objects such as nanotubes, nanochannels, nanoparticles, nanopores and nanocapacitors. These nanofabricated objects provide new tools for sequencing of nucleic acids and rapid, multiplexed, nucleic acid detection.


title: The risk of QTc-interval prolongation in COVID-19 patients treated with chloroquine

text: BACKGROUND: Chloroquine, a quinolone antimalarial drug, is known to potentially inhibit pH-dependent viral replication of the SARS-CoV‑2 infection. Therefore, chloroquine is considered as a treatment option for coronavirus disease 2019 (COVID-19). Chloroquine is known for prolonging the QT interval, but limited data are available on the extent of this QT-prolonging effect. OBJECTIVE: To assess the QTc-prolonging potential of chloroquine in COVID-19 patients and to evaluate whether this prolongation increases with the cumulative dose of chloroquine and is associated with the peak plasma concentration of chloroquine. Furthermore, the number of patients who prematurely discontinued treatment or had an adjustment in dose due to QTc-interval prolongation was established. METHODS: A retrospective, observational study was performed in patients aged over 18 years, hospitalised for a suspected or proven infection with COVID-19, and therefore treated with chloroquine, with a baseline electrocardiogram (ECG) performed prior to the start of treatment and at least one ECG after starting the treatment. RESULTS: In total, 397 patients were included. The mean increase in QTc interval throughout the treatment with chloroquine was 33 ms. Nineteen out of 344 patients unnecessarily had their treatment prematurely discontinued or adjusted due to a prolonged QTc interval based on the computerised interpretation of the ECG. CONCLUSION: Chloroquine treatment in COVID-19 patients gradually increased the QTc interval. Due to a significant number of overestimated QTc intervals by computer analysis, it is advisable to measure the QTc interval manually before adjusting the dose or withdrawing this potentially beneficial medication.


title: Amyloïdose féline à expression hépatique chez 2 chats

text: Résumé L’amyloïdose hépatique est une maladie très rare et fatale, touchant le Sharpeï dans l’espèce canine et principalement les races Siamois, Abyssin et Orientaux dans l’espèce féline. Un phénomène inflammatoire chronique est le plus souvent à l’origine d’un dépôt de substance amyloïde au sein des organes, en particulier les reins et le foie ; l’infiltration d’amyloïde peut être majeure et conduire à des signes cliniques d’insuffisance rénale et/ou hépatique. Ces symptômes sont peu spécifiques, le diagnostic est souvent tardif et le pronostic sombre. Les traitements sont peu efficaces à ce jour. Summary Hepatic amyloidosis is a very rare and fatal disease, affecting Sharpeï in canine species and mainly the races Siamese, Abyssinian and oriental in the feline species. Most frequently, an inflammatory chronic phenomenon is at the origin of the warehouse of amyloid substance in organs, in particular in liver and kidney, until the complete invasion of the organ, causing then clinical signs of hepatic and/or renal insufficiency. The clinical signs are little specific and when the disease is discovered, the life expectancy is very limited. Treatments are poorly effective at this day.


title: Chemistry and pharmacology of Bidens pilosa: an overview

text: Bidens pilosa L. is an edible herb and has been traditionally used for a wide range of ailments in many countries. The aim of this review is to present comprehensive information of the chemical constituents, nutraceutical and ethnomedical uses as well as the biological and pharmacological effects and toxicity of this plant based on 218 literary sources reported over 40 years. Major chemical constituents (including 301 compounds) belonging to polyacetylenes, polyacetylene glycosides, flavonoids, flavone glycosides, aurones, chalcones, okanin glycosides, phenolic acids, terpenes, pheophytins, fatty acids and phytosterols have been identified or isolated from the different parts of this plant. Many of them have been considered as the bioactive compounds which are potentially responsible for the pharmacological actions. Various types of preparations, extracts and individual compounds derived from this plant have been found to possess biological and pharmacological activities such as anti-malarial, anti-allergy, anti-hypertensive and smooth muscle relaxant, anti-cancerogenic, anti-diabetic, anti-inflammatory, anti-microbial, antioxidant. The results of data analysis on the chemicals, pharmacological and toxicological characteristics of B. pilosa validate the view of its folk worldwide-medicinal uses. This herb has a great beneficial therapeutic property and is possibly used for complement or alternative to pharmaceutical drugs in some specific cases. However, this herb is known as hyperaccumulator and as-excluder; therefore, harvesting the herb for medicinal uses should be judiciously cautioned.


title: Enhancing epilepsy self-management and quality of life for adults with epilepsy with varying social and educational backgrounds using PAUSE to Learn Your Epilepsy

text: PURPOSE: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. METHODS: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8–12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. RESULTS: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. CONCLUSION: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.


title: The DEAD-box RNA helicase 5 positively regulates the replication of porcine reproductive and respiratory syndrome virus by interacting with viral Nsp9 in vitro

text: Abstract The nonstructural protein 9 (Nsp9) of porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to play important roles in viral replication. The present study first screened that the DEAD-box RNA helicase 5 (DDX5) was a cellular protein interacting with the Nsp9 of PRRSV by a yeast two-hybrid method in a pulmonary alveolar macrophages (PAMs) cDNA library. Next, DDX5 was shown to interact with viral Nsp9 in the co-transfected HEK293 cells with the DDX5- and Nsp9-expressing plasmids, and the interaction between endogenous DDX5 and Nsp9 was also confirmed in MARC-145 cells infected with the Nsp9-expressing lentiviruses. Then, the interacting domains between DDX5 and Nsp9 were determined to be the DEXDc and HELICc domains in DDX5 and the RdRp domain in Nsp9, respectively. Moreover, in the HEK293 cells, MARC-145 cells and PAM cell lines co-transfected with the DDX5- and Nsp9-expressing plasmids, Nsp9 was shown to co-localize with DDX5 in the cytoplasm with a perinuclear pattern, and meanwhile in PRRSV-infected MARC-145 cells and PAMs, endogenous DDX5 was also found to co-localize with Nsp9. Finally, silencing the DDX5 gene in MARC-145 cells significantly impacted the replication of PRRSV, and while the over-expression of DDX5 could slightly enhance viral replication. These findings indicate that DDX5 positively regulates the replication of PRRSV via its interaction with viral Nsp9 in vitro.


title: COVID‐19 and the clinical hematology laboratory

text: The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory’s role in the diagnosis of COVID‐19 infection 3) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID‐19 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.


title: SARS‐CoV‐2 pandemic and Vitamin D deficiency—A double trouble

text: The current SARS-CoV-2 pandemic has mandated significant isolation measures. Streets in affected countries are mostly empty, and many individuals spend several consecutive days at home to reduce the risk of infection. While determinant for pandemic control, home reclusion may have a significant toll on the health of individuals.


title: 4 Setting up the fieldwork

text: The underlying methodological principle of this study was to follow the actors in the fieldwork. The field research has been conducted at a university in Bosnia, providing rich data to explore the impact of nationalism and cosmopolitanism on information sharing in academic communities. This chapter describes preparations for the fieldwork, data collection methods employed and Latour’s circulatory system of scientific facts that has been used as a guide to follow the actors at the field.


title: Global epidemiology of non-influenza RNA respiratory viruses: data gaps and a growing need for surveillance

text: Summary Together with influenza, the non-influenza RNA respiratory viruses (NIRVs), which include respiratory syncytial virus, parainfluenza viruses, coronavirus, rhinovirus, and human metapneumovirus, represent a considerable global health burden, as recognised by WHO's Battle against Respiratory Viruses initiative. By contrast with influenza viruses, little is known about the contemporaneous global diversity of these viruses, and the relevance of such for development of pharmaceutical interventions. Although far less advanced than for influenza, antiviral drugs and vaccines are in different stages of development for several of these viruses, but no interventions have been licensed. This scarcity of global genetic data represents a substantial knowledge gap and impediment to the eventual licensing of new antiviral drugs and vaccines for NIRVs. Enhanced genetic surveillance will assist and boost research and development into new antiviral drugs and vaccines for these viruses. Additionally, understanding the global diversity of respiratory viruses is also part of emerging disease preparedness, because non-human coronaviruses and paramyxoviruses have been listed as priority concerns in a recent WHO research and development blueprint initiative for emerging infectious diseases. In this Personal View, we explain further the rationale for expanding the genetic database of NIRVs and emphasise the need for greater investment in this area of research.


title: Reduction of influenza virus-induced lung inflammation and mortality in animals treated with a phosophodisestrase-4 inhibitor and a selective serotonin reuptake inhibitor

text: Inflammatory responses contribute to the morbidity and mortality of severe influenza. Current antiviral therapy offers limited success in treating severe influenza infection with both H1N1 and H5N1 viruses. We evaluated the effect of a neuraminidase inhibitor in combination with immunomodulatory drugs in vitro and in a mouse model of influenza A H1N1 infection by determining survival rate, lung inflammation markers and histopathology. Sertraline and rolipram significantly improved survival in mice infected with a lethal dose of influenza A H1N1 virus. Prophylactic treatment resulted in survival rates of 40% (rolipram), 30% (oseltamivir), 0% (sertraline), 100% (rolipram/oseltamivir) and 70% (sertraline/oseltamivir). Treatment in a therapeutic setting (24 h post-infection) resulted in 80% (rolipram/oseltamivir) and 40% (sertraline/oseltamivir) survival. Sertraline and rolipram had no effect on virus replication in vitro and in vivo, but significantly reduced lung inflammation. A significant reduction in cellular infiltration (10-fold) along with inflammatory cytokines monocyte chemotactic protein-1 (10-fold), interleukin-6 (5-fold) and regulated on activation normal T cell expressed and secreted (5-fold) was observed in the animals treated with the combination compared to oseltamivir alone. Lung histopathology of mice treated with combinations revealed significantly reduced consolidation, infiltration and alveolitis compared to oseltamivir alone. Rolipram and sertraline reduced H1N1 virus-induced lung inflammation and mortality. These data support further development of immunomodulatory agents for severe influenza.


title: IL-17A inhibitions of indole alkaloids from traditional Chinese medicine Qing Dai

text: Abstract Ethnopharmacological relevance Qing Dai, a famous traditional Chinese medicine (TCM), is prepared by a traditional fermentation process with the aerial part of Strobilanthes cusia. Currently, this TCM could treat various clinical inflammatory diseases, such as ulcerative colitis and psoriasis, however, the bioactive components of Qing Dai are unknown clearly. Aim of the study To isolate and identify the anti-IL-17A components of Qing Dai. Materials and methods Silica, RP-18 gels, and size exclusion resin were used for column chromatography to isolate the pure compounds. The structures of isolates were elucidated by NMR, MS, UV, IR spectra, and optical rotation. IL-17A protein and gene expressions were also evaluated in the Th17 cell model and luciferase reporter assay, respectively. Results Two indole alkaloids, including one new indigodole D and cephalandole B, were isolated from Qing Dai. Indigodole D could inhibit IL-17A protein production during the Th17 polarization (EC50: 2.16 μg/mL) or after the polarization (EC50: 5.99 μg/mL) without cytotoxicity toward Th17 cells. Cephalandole B did not inhibit the IL-17A protein secretion. Nevertheless, both isolates notably inhibited IL-17A gene expression, especially cephalandole B, in a dose-dependent manner in Jukat cells with IL-17A luciferase reporter. Conclusions Indole alkaloids, indigodoles A, C, D, tryptanthrin, and indirubin could contribute to anti-IL 17A properties of Qing Dai. The possible biogenetic mechanisms of above-mentioned indoles were also speculated in this investigation for further promising anti-IL-17 lead drugs development.


title: Commensal and mutualistic relationships of reoviruses with their parasitoid wasp hosts

text: Abstract During evolution, certain endoparasitoid wasps have developed mechanisms to suppress the defence systems of their hosts. For this purpose, these species, all of which belong to the families Ichneumonidae and Braconidae, inject various kinds of virus-like particles. The most studied of these particles are classified as polydnaviruses (family Polydnaviridae) which are symbiotic viruses. Over the past decade, it has also been shown that several wasp species harbour reoviruses (family Reoviridae), and that two of these suppress host defence, allowing the development of the parasitoid eggs. In this paper, we summarize the key features of these viruses and their relationships with their wasp hosts. Five reoviruses are known that appear to be non-pathogenic for the wasps. Three of these, McRVLP, HeRV, OpRVLP, use their wasp hosts as vectors, and do not appear to be involved in host defence suppression. The fourth, DpRV-1, is a commensal reovirus detected in most field populations of the wasp, Diadromus pulchellus. This reovirus is always found associated with an ascovirus, DpAV-4a, which is indispensable for host immune suppression. Although DpRV-1 has not been shown to directly increase D. pulchellus parasitic success, it may contribute to this success by retarding DpAV-4a replication in the wasp. The fifth reovirus, DpRV-2, occurs in a specific population of D. pulchellus in which DpRV-1 and DpAV-4 are absent. This virus has a mutualistic relationship with its wasp host, as its injection by females during oviposition is essential for host immunosuppression. Interestingly, these viruses belong to several different reovirus genera.


title: Recurrent mutations associated with isolation and passage of SARS coronavirus in cells from non‐human primates

text: Four clinical isolates of SARS coronavirus were serially passaged in two primate cell lines (FRhK4 and Vero E6). Viral genetic sequences encoding for structural proteins and open reading frames 6–8 were determined in the original clinical specimen, the initial virus isolate (passage 0) and at passages 5, 10, and 15. After 15 passages, a total of 15 different mutations were identified and 12 of them were non‐synonymous mutations. Seven of these mutations were recurrent mutation and all located at the spike, membrane, and Orf 8a protein encoding sequences. Mutations in the membrane protein and a deletion in ORF 6–8 were already observed in passage 0, suggesting these amino acid substitutions are important in the adaptation of the virus isolate in primate cell culture. A mutation in the spike gene (residue 24079) appeared to be unique to adaptation in FRhK4 cells. It is important to be aware of cell culture associated mutations when interpreting data on molecular evolution of SARS coronavirus. J. Med. Virol. 76:435–440, 2005. © 2005 Wiley‐Liss, Inc.


title: Respiratory Muscle Performance Screening for Infectious Disease Management Following COVID-19: A Highly Pressurized Situation

text: Abstract The 2019-2020 coronavirus pandemic elucidated how a single highly infectious virus can overburden healthcare systems of even highly economically developed nations. A leading contributor to these concerning outcomes is a lack of available intensive care unit (intensive care unit) beds and mechanical ventilation support. Poorer health is associated with a higher risk for severe respiratory complications from the coronavirus. We hypothesize that impaired respiratory muscle performance is an underappreciated factor contributing to poor outcomes unfolding during the coronavirus pandemic. While impaired respiratory muscle performance is considered to be rare, it is more frequently encountered in patients with poorer health, in particular obesity. However, measures of respiratory muscle performance are not routinely performed in clinical practice, including those with symptoms such as dyspnea. The purpose of this perspective paper is to discuss the potential role of respiratory muscle performance from the perspective of the coronavirus pandemic. We also provide a theoretical patient management model to screen for impaired respiratory muscle performance and intervene if identified with the goal of unburdening healthcare systems during future pandemic crises. • Poor baseline health increases the risk of acute respiratory distress syndrome due to coronavirus infection and poorer outcomes. • Patients with poorer baseline health, notably obesity, are more likely to demonstrate impaired respiratory muscle performance, and poorer outcomes following intensive care unit admission and mechanical ventilation. • This relationship indicates respiratory muscle performance may contribute to outcomes related to acute respiratory distress syndrome from coronavirus infection in patients with poor baseline health.


A proposed scoring system for triaging patients who require vascular access creation in times of COVID-19


title: Cross protective immune responses in nursing piglets infected with a US spike-insertion deletion porcine epidemic diarrhea virus strain and challenged with an original US PEDV strain

text: We investigated cross-protective immunity of a US spike-insertion deletion porcine epidemic diarrhea virus (PEDV) Iowa106 (S-INDEL) strain against the original US PEDV (PC21A) strain in nursing piglets. Piglets were inoculated orally with S-INDEL, PC21A or mock. At 20–29 days post-inoculation (dpi), all pigs were challenged with the PC21A strain. The S-INDEL-inoculated pigs had lower ileal IgA antibody secreting cells, serum IgA and neutralizing antibody titers compared with PC21A-inoculated pigs. No pigs in the PC21A-group developed diarrhea, whereas 81 and 100% of pigs in the S-INDEL and mock-groups had diarrhea post challenge, respectively. S-INDEL induced partial protective immunity against the original US PEDV strain.


docid: dhaznivq

title: Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula

text: BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities. DATA AND METHODS: This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities. CONCLUSION: Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.


title: Identification of a CD4+ T Cell Epitope within the M Protein of a Neurotropic Coronavirus

text: Abstract A significant CD4+ T cell response against the transmembrane (M) protein can be detected in the spleens of C57BI/6 mice infected intraperitoneally with a sublethal injection of the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM), but not in those of mice with the chronic demyelinating encephalomyelitis caused by this virus. With the ultimate goal of determining the role of the M-specific response in the pathogenesis of MHV-JHM-induced neurological diseases, CD4+ T cell epitopes within the M protein were identified using vaccinia virus recombinants expressing truncated forms of the protein and peptides spanning most of the M protein in cell proliferation assays. Peptides covering residues 128-147 contain at least one CD4+ T cell epitope for MHV-JHM. Within this region is a sequence (residues 135-143) which matches the recently described MHC class II I-Ab binding motif. Delineation of this epitope should facilitate analysis of the role of the M-specific CD4+ T cell response in the development of acute and chronic neurological infections caused by MHV-JHM.


title: Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19)

text: BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60–200), and the median length of the trial periods was 179 d (IQR: 94–366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.


title: From Low-Skilled to Key Workers: The Implications of Emergencies for Immigration Policy

text: The COVID-19 pandemic has increased public awareness of the extent to which the economy relies on a low-wage workforce. Many of those lower-waged occupations that have been recognised as essential in the emergency are heavily dependent on migrant workers. We explore the implications of the COVID-19 pandemic for future immigration policies and provide an example using data for the UK. We suggest that there are three key considerations for governments in this context. First, whether the management of emergencies themselves requires a certain type of immigration policy. Second, whether the experience of the current pandemic brings to light new information about the ‘value’ of certain types of immigration. Finally, whether immigration is the right response to pandemic-driven increases in labour demand.


title: Imaging in corona virus disease 2019 (COVID-19)—A scoping review

text: Coronavirus Disease-2019 (COVID-19) originated in the Wuhan, Hubei Province, China in November 2019 and has since been declared a pandemic by the WHO. COVID-19 is an acute infectious disease, primarily affecting the respiratory system. Currently, real-time reverse transcription polymerase chain reaction (RT-PCR) performed on respiratory specimens is considered the reference by which to diagnose COVID-19. However, the limitations of RT-PCR, specifically, the fact that it is time-consuming and inadequate for the assessment of disease severity, have affected the process of epidemiological disease containment and has taken a toll on the healthcare management chain. As the risk of infection for other patients and personnel must be kept to a minimum, the indications for imaging have to be carefully considered. Imaging is primarily performed in patients with a negative RT-PCR, but a high clinical suspicion of COVID-19, or, in patients with diagnosed COVID-19 who are suffering from moderate to severe symptoms. In this article, we review the typical imaging findings in COVID-19, the differential diagnoses, and common complications.


title: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists

text: Abstract Context The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Objective To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. Evidence acquisition A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. Evidence synthesis A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. Conclusions PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes.


Trombo en aurícula derecha tras neumonía por COVID-19


title: HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex

text: During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.


docid: kdnfnpla

title: Coronaviruses: An Overview of Their Replication and Pathogenesis

text: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).


title: Gaseous pollutant transmission through windows between vertical floors in a multistory building with natural ventilation

text: Abstract Natural ventilation is an effective strategy to control thermal comfort in buildings, and can be enhanced depending on the window style. The combination of natural ventilation and window can also facilitate the removal or dilution of gaseous pollutants from indoor sources in newly decorated buildings. However, the windows on the same facade may cause gaseous pollutant cross-transmission during single-sided natural ventilation between households on different floors close to the source. Although some research has focused on the pollutant cross-transmission in buildings, the simplification of windows into rectangular openings often affects accurate knowledge of pollutant transmission characteristics. Therefore, this investigation explored gaseous pollutant cross-transmission through real windows during single-sided, buoyancy-driven ventilation in a multistory building. Six types of windows were modeled for the indoor pollutant of gaseous formaldehyde (HCHO). Computational fluid dynamics (CFD) was utilized to solve characteristics of pollutant transmission inside and outside the multistory building. The results indicated that the ventilation rates, thermal profiles and pollutant transmission inside and outside the building varied for each window type, although the open window areas were identical. The re-entry ratio of exhausted air entering upper floors and the infection risk of epidemic viruses caused by airborne cross-transmission was sensitive to ventilation rates and window configurations, while the sensitivities for window configurations varied case by case. The comparisons also revealed that the specification of ambient temperature and pollutant release rate ultimately did not affect the evaluation of pollutant cross-transmission using CFD.


title: The COVID‐19 outbreak in dermatologic surgery: resetting clinical priorities

text: Emilia‐Romagna was one of the Italian regions mostly affected by the COVID‐19 pandemic and lockdown measures were taken to slow the COVID‐19 outbreak. All routine activities in Modena hospitals were suspended; however, urgent procedures were still to be performed. Setting the priority of procedures in oncological dermatology in the COVID‐19 era is challenging.


title: Serum KL‐6 can distinguish between different phenotypes of severe COVID‐19

text: We read the article by D'Alessandro Miriana et al. with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen‐6 (KL‐6) as a prognostic biomarker of severe coronavirus disease 2019 (COVID‐19).(1) This article is protected by copyright. All rights reserved.


title: Detection of hepatitis C virus by an improved loop-mediated isothermal amplification assay

text: An improved, sensitive, specific, and rapid one-step reverse transcription loop-mediated isothermal amplification (LAMP) assay targeting the 5′ untranslated region (UTR) was developed to detect hepatitis C virus (HCV) infection. Based on an accelerating primer (AP), the present assay, named AP-LAMP, has the advantages of rapidity and sensitivity over the routine LAMP method. The possible AP-based amplification pathway during the reaction was revealed by restriction enzyme digestion and eletrophoresis. The detection limit of the AP-LAMP assay was approximately 84 IU/ml, and no cross-detection was observed. The assay was evaluated further with 126 clinical specimens, and the results indicated the suitability and simplicity of the test as a rapid diagnostic tool for detection of HCV RNA.


title: Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness

text: BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009–2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses.


Comment on “Is the type of diabetes treatment relevant to outcome of COVID‐19?”


title: Proofreading-deficient coronaviruses adapt over long-term passage for increased fidelity and fitness without reversion of exoribonuclease-inactivating mutations

text: The coronavirus (CoV) RNA genome is the largest among single-stranded positive sense RNA viruses. CoVs encode a proofreading 3′→5′exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in SARS-CoV and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold decreased fidelity, and increased susceptibility to nucleoside analogs. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with WT-MHV. Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication, reduced susceptibility to nucleoside analogs, and increased competitive fitness. However, passage did not select for complete or partial reversion at the ExoN-inactivating mutations. We identified novel amino acid changes within the RNA-dependent RNA polymerase (nsp12-RdRp) and nsp14 of MHV-ExoN(-) P250 that partially account for the observed changes in replication, susceptibility to nucleoside analogs, and competitive fitness observed in the passaged virus population, indicating that additional determinants can compensate for the activities of nsp14-ExoN. Our results suggest that while selection favors restoration of replication fidelity in ExoN(-) CoVs, there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and identify additional candidate proteins that may regulate CoV replication fidelity. Unique among RNA viruses, CoVs encode a proofreading exoribonuclease (ExoN) in nsp14 that mediates high-fidelity RNA genome replication. Proofreading-deficient CoVs with disrupted ExoN activity [ExoN(-)] are either non-viable or have significant defects in replication, RNA synthesis, fidelity, fitness, and virulence. In this study, we show that ExoN(-) murine hepatitis virus can adapt over long-term passage for increased replication and fitness without reverting the ExoN-inactivating mutations. Passage-adapted ExoN(-) mutants also demonstrate increasing resistance to nucleoside analogs that is only partially explained by secondary mutations in nsp12 and nsp14. These data suggest that enhanced resistance to nucleoside analogs is mediated by the interplay of multiple replicase proteins and support the proposed link between CoV fidelity and fitness.


title: Influence of supercritical water treatment on heavy metals in medical waste incinerator fly ash

text: Abstract In this work, medical waste (MW) incinerator fly ashes from different types of incinerators were subjected to supercritical water (SCW) and SCW+H2O2 (SCWH) treatments. Sequential extraction experiments showed that, after SCW treatment, heavy metals in exchangeable and carbonate forms in the ashes could be transferred into other relatively stable forms, e.g., Ba and Cr into residual fraction, Cu and Pb into organic matter fraction. SCWH treatment could stabilize heavy metals in Fe–Mn oxides and residual fractions. However, the behavior of As was quite different from heavy metals, which could be leached out from residue fraction after SCW and SWCH treatments. The leached As tended to absorb onto Fe–Mn oxides and organic matters under near neutral environment, but it could react with Ca2+ at lower pH, increasing the mobility of this element. Therefore, it is necessary to neutralize acidic ash to near neutral condition before subjecting it to SCW and SCWH treatments so as to effectively stabilize hazardous elements in the ash. Consequently, it is believed that SCWH treatment is an effective alternative for hazardous elements detoxification in MW fly ash.


The psychological effects of quarantining a city


title: Weathering the Storm: Managing Older Adults With Breast Cancer Amid COVID-19 and Beyond

text: Caring for older patients with breast cancer presents unique clinical considerations due to preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the “new normal” for the approximately 30% of breast cancer patients age 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.


title: Using design thinking to respond to crises: B2B lessons from the 2020 COVID-19 pandemic

text: Abstract We examine the value of design thinking in times of crisis. Drawing on examples of firm innovations during the 2020 Covid-19 lockdown, we propose that disruptive events represent wicked problems that require managers to break out of established patterns of thinking. Design thinking, or the problem solving approaches and tools of designers, represents one such approach. Drawing on extant research, we identify a three-stage process of design thinking: disrupt, develop and deliver, and transform. We examine each stage, identifying how careful disruptive thinking with a focus on understanding problems within their context can give rise to innovative solutions, resulting in a more resilient organisation.


title: Identification of a peptide derived from the heptad repeat 2 region of the porcine epidemic diarrhea virus (PEDV) spike glycoprotein that is capable of suppressing PEDV entry and inducing neutralizing antibodies

text: Abstract Heptad repeat (HR) regions are highly conserved motifs located in the glycoproteins of enveloped viruses that form a six-helix bundle structure and is important in the process of virus fusion. Peptides derived from the HR regions of some viruses have also been shown to inhibit viral entry. Porcine epidemic diarrhea virus (PEDV) was predicted to have HR regions (HR1 and HR2) in the spike glycoprotein S2 subunit. Based on this analysis, six peptides derived from HR1 and HR2 were selected, expressed in Escherichia coli, purified, and characterized. Three peptides (HR2M, HR2L and HR2P) were identified as potential competitive inhibitors in PEDV in vitro infection assays, with the HR2P peptide representing the most potent inhibitor. Further study indicated that immunization of HR2P in mice elicited antibodies capable of neutralizing PEDV infection in vitro. These results demonstrate that the HR2P peptide and anti-HR2P antibody can serve as a tool for dissecting the fusion mechanism of PEDV, guiding the search for potent inhibitors with therapeutic value against PEDV infection.


title: Afectación De La Pandemia Por Covid-19 En Los Servicios Médico Forenses De Madrid (España)

text: ABSTRACT The Community of Madrid has been the hardest hit by the COVID-19 pandemic.The recent launch of Madrid´s Institute of Legal Medicine and Forensic Sciences, has forced its precarious structure to manage this situation, through the establishment of agreements and operational guidelines, which have prevented it from collapsing.These measures, also promoted by the different Services, but in particular, those adopted by the Pathology Service, have helped to avoid this situation.Special measures had to be adopted for the management of corpses in the Community of Madrid, with the opening of temporary morgues to deal with the high number of deaths.A comparative study of the number of deaths, according to forensic medical aetiology, was carried out between 2019 and 2020, in the period between March 9 to April 20.


title: Anatomy of a viral entry platform differentially functionalized by integrins α3 and α6

text: During cell invasion, human papillomaviruses use large CD151 patches on the cell surface. Here, we studied whether these patches are defined architectures with features for virus binding and/or internalization. Super-resolution microscopy reveals that the patches are assemblies of closely associated nanoclusters of CD151, integrin α3 and integrin α6. Integrin α6 is required for virus attachment and integrin α3 for endocytosis. We propose that CD151 organizes viral entry platforms with different types of integrin clusters for different functionalities. Since numerous viruses use tetraspanin patches, we speculate that this building principle is a blueprint for cell-surface architectures utilized by viral particles.


title: CT features of SARS-CoV-2 pneumonia according to clinical presentation: a retrospective analysis of 120 consecutive patients from Wuhan city

text: OBJECTIVES: To characterize the chest computed tomography (CT) findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to clinical severity. We compared the CT features of common cases and severe cases, symptomatic patients and asymptomatic patients, and febrile and afebrile patients. METHODS: This was a retrospective analysis of the clinical and thoracic CT features of 120 consecutive patients with confirmed SARS-CoV-2 pneumonia admitted to a tertiary university hospital between January 10 and February 10, 2020, in Wuhan city, China. RESULTS: On admission, the patients generally complained of fever, cough, shortness of breath, and myalgia or fatigue, with diarrhea often present in severe cases. Severe patients were 20 years older on average and had comorbidities and an elevated lactate dehydrogenase (LDH) level. There were no differences in the CT findings between asymptomatic and symptomatic common type patients or between afebrile and febrile patients, defined according to Chinese National Health Commission guidelines. CONCLUSIONS: The clinical and CT features at admission may enable clinicians to promptly evaluate the prognosis of patients with SARS-CoV-2 pneumonia. Clinicians should be aware that clinically silent cases may present with CT features similar to those of symptomatic common patients. KEY POINTS: • The clinical features and predominant patterns of abnormalities on CT for asymptomatic, typic common, and severe cases were summarized. These findings may help clinicians to identify severe patients quickly at admission. • Clinicians should be cautious that CT findings of afebrile/asymptomatic patients are not better than the findings of other types of patients. These patients should also be quarantined. • The use of chest CT as the main screening method in epidemic areas is recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06854-1) contains supplementary material, which is available to authorized users.


title: Corticosteroid administration for viral pneumonia: COVID-19 and beyond

text: BACKGROUND: Corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome (ARDS) by many clinicians due to their perceived anti-inflammatory effects. However, for patients with severe viral pneumonia, the corticosteroid treatment is highly controversial. OBJECTIVES: The purpose of this review is to systematically evaluate the effect and potential mechanism of corticosteroid administration in pandemic viral pneumonia. SOURCES: We comprehensively searched all manuscripts on corticosteroids therapy for influenza, SARS, MERS and SARS-CoV-2 viral pneumonia from the PubMed, EMBASE, Web of Science and Cochrane Library databases. CONTENT: We systematic summarized the effects of corticosteroids therapy for pandemic viral pneumonia and the potential mechanism of corticosteroid worked in COVID-19. IMPLICATIONS: Observational studies showed that corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delay virus clearance for SARS-CoV and MERS-CoV. Limited data on corticosteroid therapy for COVID-19 were reported. Corticosteroids were used in about a fifth of patients (670/2995, 22.4%). Although clinical observational studies reported the improvement in symptoms and oxygenation for the severe COVID-19 patients received corticosteroids therapy, case fatality rate in the corticosteroid group was significantly higher than that in the non-corticosteroid group (69/443, 15.6% vs 56/1310, 4.3%). Compared with non-severe patients, severe patients were more likely to receive corticosteroid therapy (201/382, 52.6% vs 201/1310, 15.3%). Although there is no evidence of corticosteroid therapy reduce the mortality of COVID-19 patients, some improvements in clinical symptoms and oxygenation were reported in some clinical observational studies. Excessive inflammatory response and lymphopenia might be critical factors associated with disease severity and mortality of COVID-19. Sufficiently powered randomized controlled trials with rigorous inclusion/exclusion criteria and standardized dose and duration of corticosteroids are needed to verify the effectiveness and safety of corticosteroid therapy.


title: Multiple sclerosis: experimental models and reality

text: One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that “Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis”. However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system. However, the relevance of results from such models for MS pathogenesis has to be critically validated. Current EAE models are mainly based on inflammation, induced by auto-reactive CD4(+) T-cells, and these models reflect important aspects of MS. However, pathological data and results from clinical trials in MS indicate that CD8(+) T-cells and B-lymphocytes may play an important role in propagating inflammation and tissue damage in established MS. Viral models may reflect key features of MS-like inflammatory demyelination, but are difficult to use due to their very complex pathogenesis, involving direct virus-induced and immune-mediated mechanisms. Furthermore, evidence for a role of viruses in MS pathogenesis is indirect and limited, and an MS-specific virus infection has not been identified so far. Toxic models are highly useful to unravel mechanisms of de- and remyelination, but do not reflect other important aspects of MS pathology and pathogenesis. For all these reasons, it is important to select the right experimental model to answer specific questions in MS research.


title: Melatonin: Roles in influenza, Covid‐19, and other viral infections

text: There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid‐19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial “cytokine storm”, as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl‐coenzyme A (acetyl‐CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian “resetting” of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl‐CoA is a necessary cosubstrate for arylalkylamine N‐acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus‐ and cytokine‐storm‐driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus‐and cytokine storm‐driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short‐chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid‐19 and other viral infections.


title: Biological and genetic characterization of a hemagglutinating coronavirus isolated from a diarrhoeic child

text: The coronavirus strain HECV‐4408 was isolated from diarrhea fluid of a 6‐year‐old child with acute diarrhea and propagated in human rectal tumor (HRT‐18) cells. Electron microscopy revealed coronavirus particles in the diarrhea fluid sample and the infected HRT‐18 cell cultures. This virus possessed hemagglutinating and acetylesterase activities and caused cytopathic effects in HRT‐18 cells but not in MDBK, GBK and FE cells. One of four S‐specific monoclonal antibodies reacted in Western blots with HECV‐4408, BCV‐L9 and BCV‐LY138 but not with HCV‐OC43, and two reacted with BCV‐L9 but not with HECV‐4408, BCV‐LY138 and HCV‐OC43. One S‐specific and two N‐specific monoclonal antibodies reacted with all of these strains. cDNA encompassing the 3′ 8.5 kb of the viral RNA genome was isolated by reverse transcription followed by polymerase chain reaction amplification had size and restriction endonuclease patterns similar to those of BCV‐L9 and BCV‐LY138. In contrast, the M gene of HCV‐OC43 differed in restriction patterns from HECV‐4408 and BCV. A genomic deletion located between the S and M within the nonstructural genes of HCV‐OC43 was not detected in HECV‐4408. DNA sequence analyses of the S and HE genes revealed more than 99% nucleotide and deduced amino acid homologies between HECV‐4408 and the virulent wild‐type BCV. Forty‐nine nucleotide and 22 amino acid differences were found between the HE genes of HECV‐4408 and HCV‐OC43, while only 16 nucleotide and 3 amino acid differences occurred between the HE genes of HECV‐4408 and BCVLY138. We thus conclude that the strain HECV‐4408 is a hemagglutinating enteric coronavirus that is biologically, antigenically and genomically more closely related to the virulent BCVLY138 than to HCV‐OC43. © 1994 Wiley‐Liss, Inc.


docid: mjfpnvoy

title: Sequence analysis of gene 3, gene 4 and gene 5 of avian infectious bronchitis virus strain CU-T2

text: Abstract We have previously reported the nucleotide sequences of gene 2 (spike (S) protein gene), gene 6 (nucleocapsid (N) protein gene), and the 3′ end untranslated region of a novel avian infectious bronchitis virus (IBV) strain, CU-T2 [Jia et al. (1995) Arch. Virol. 140, 259–271]. In the present report we describe the sequences of the remaining genes of this strain (gene 3, 4 and 5) with the exception of gene 1 (RNA polymerase gene). Gene 3 contained three open reading frames (ORFs), 3a, 3b and 3c of 174, 195 and 282 nucleotides (nt), respectively. Gene 4 (membrane (M) protein gene) consisted of 749 nt with a single ORF of 687 nt. Gene 5 contained two ORFs, 5a and 5b, with 198 and 249 nt, respectively. Thus, in total, there were 7349 nt from the 5′ end of S protein gene to the 3′ end of the CU-T2 genome. The overall nt sequence homologies between gene 3, 4, and 5 of CU-T2 and those of other strains were between 84.1–90.8%, 85.8–88.8% and 90.4–96.4%, respectively. The predicted amino acid (aa) sequence homologies revealed that gene 3b and 5b were more conserved than 3a, 3c and 5a. Each individual gene of CU-T2 strain (with the exception of the RNA polymerase gene) had a different level of homology with the homologous gene of other strains, suggesting that the evolution of IBV strains in general has been a complex, and as yet, poorly understood process. © 1997 Elsevier Science B.V. All rights reserved.


title: Multiple regions of the murine coronavirus spike glycoprotein influence neurovirulence

text: The spike (S) glycoprotein of mouse hepatitis virus (MHV) is a major determinant of neurovirulence. Using targeted recombination we previously demonstrated that the S gene of the highly neurovirulent MHV-4 conferred a dramatic increase in neurovirulence to the mildly neurovirulent MHV-A59. To identify the genetic determinants of neurovirulence within the MHV-4 spike, we generated isogenic recombinant viruses containing various MHV-4/MHV-A59 chimeric spike genes, and studied their phenotypes in vivo. The MHV-4/MHV-A59 chimeric spike genes consisted of either reciprocal exchanges between the S1 and S2 spike subunits, or smaller exchanges specifically in the hyper-variable region (HVR) of S1. The chimeric spike gene containing recombinants all exhibited efficient replication in vitro, yet many were severely attenuated for virulence in vivo. Furthermore, these attenuated recombinants exhibited decreased titers of infectious virus in the brain relative to the parental recombinant viruses containing the full-length MHV-4 or MHV-A59 spike genes. This is the first report that compares the neurovirulence and pathogenesis of isogenic viruses with defined alterations in the MHV spike protein. From these studies, it appears that the interactions of multiple regions of the MHV spike, including the HVR, act in concert to allow for efficient infection of and virulence in the murine central nervous system.


Re: Androgen-deprivation Therapies for Prostate Cancer and Risk of Infection by SARS-CoV-2: A Population-based Study (n = 4532)


title: Non-encapsidation activities of the capsid proteins of positive-strand RNA viruses

text: Abstract Viral capsid proteins (CPs) are characterized by their role in forming protective shells around viral genomes. However, CPs have additional and important roles in the virus infection cycles and in the cellular responses to infection. These activities involve CP binding to RNAs in both sequence-specific and nonspecific manners as well as association with other proteins. This review focuses on CPs of both plant and animal-infecting viruses with positive-strand RNA genomes. We summarize the structural features of CPs and describe their modulatory roles in viral translation, RNA-dependent RNA synthesis, and host defense responses.


title: Regulation of the nucleocytoplasmic trafficking of viral and cellular proteins by ubiquitin and small ubiquitin-related modifiers

text: Nucleocytoplasmic trafficking of many cellular proteins is regulated by nuclear import/export signals as well as post-translational modifications such as covalent conjugation of ubiquitin and small ubiquitin-related modifiers (SUMOs). Ubiquitination and SUMOylation are rapid and reversible ways to modulate the intracellular localisation and function of substrate proteins. These pathways have been co-opted by some viruses, which depend on the host cell machinery to transport their proteins in and out of the nucleus. In this review, we will summarise our current knowledge on the ubiquitin/SUMO-regulated nuclear/subnuclear trafficking of cellular proteins and describe examples of viral exploitation of these pathways.


title: Silent geographical spread of the H7N9 virus by online knowledge analysis of the live bird trade with a distributed focused crawler

text: Unlike those infected by H5N1, birds infected by the newly discovered H7N9 virus have no observable clinical symptoms. Public health workers in China do not know where the public health threat lies. In this study, we used a distributed focused crawler to analyze online knowledge of the live bird trade in first-wave provinces, namely, Jiangsu, Zhejiang, Anhui, and Shanghai, to track the new H7N9 virus and predict its spread. Of the 18 provinces proposed to be at high risk of infection, 10 reported human infections and one had poultry specimens that tested positive. Five provinces (Xinjiang, Yunnan, Guizhou, Shaanxi, and Tibet) as well as Hong Kong, Macao, and Taiwan were proposed to have no risk of H7N9 virus infection from the live bird trade. These data can help health authorities and the public to respond rapidly to reduce damage related to the spread of the virus.