title: Isolation and characterization of microsatellite loci in the western long‐fingered bat, Miniopterus magnater

text: We isolated and characterized 10 microsatellite loci in the western long‐fingered bat, Miniopterus magnater. These loci were tested on 48 individuals from Anhui Province of China, and all loci were highly polymorphic. The mean number of observed alleles per locus was 13.6 (range from six to 27). Observed and expected heterozygosity values ranged from 0.364 to 0.957, and from 0.676 to 0.951, respectively. After Bonferroni correction, four loci deviated significantly from Hardy–Weinberg equilibrium. No pairs of loci were in linkage disequilibrium. These polymorphic markers will be used to examine population structure and genetic diversity in this species.


title: Deconvoluting Virome-Wide Antiviral Antibody Profiling Data

text: The ability to comprehensively characterize exposures and immune responses to viral infections will be critical to better understanding human health and disease. We previously described the VirScan system, a phage-display based technology for profiling antibody binding to a comprehensive library of peptides designed to represent the human virome. The previous VirScan analytical approach did not fully account for disproportionate representation of viruses in the library or for antibody cross-reactivity among sequences shared by related viruses. Here we present the ‘AntiViral Antibody Response Deconvolution Algorithm’ (‘AVARDA’), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection at species-level resolution by considering alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. By comparing acute and convalescent sera, AVARDA successfully confirmed or detected antibody responses to human herpesviruses 1, 3, 4, 5, and 6, thereby improving the rate of diagnosing viral encephalitis in this cohort by 62.5%. We further assessed AVARDA’s utility in the setting of an epidemiological study, demonstrating its ability to determine infections acquired in a child followed prospectively from infancy. We consider ways in which AVARDA’s conceptual framework may be further developed in the future and describe how its analyses may be extended beyond investigations of viral infection. AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases.


title: A 2-year follow-up study of patients with pharyngotonsillitis

text: BACKGROUND: Longtime follow-up studies on patients with pharyngotonsillitis are rare. We aimed to describe the patterns of new visits for a sore throat, complications and tonsillectomy during 2 years in a cohort of patients with pharyngotonsillitis and non-infected controls. METHODS: A retrospective chart review was performed on a cohort of patients with acute sore throat (n = 207), and non-infected controls (n = 108). New visits, complications and tonsillectomy within 2 years was recorded and analyzed in relation to microbiological findings at inclusion. RESULTS: Patients with Group A streptococci (GAS) (12/66) reconsulted more often within 30 days than patients with no GAS (9/141) (p = 0.009) and patients with F. necrophorum (2/29). After 2 years, we observed no significant differences in reconsultations with regard to aetiology at inclusion. A single complication was recorded and 5 patients were planned for tonsillectomy. CONCLUSIONS: Group A streptococci were the sole aetiological agent associated with recurrent sore throat while F. necrophorum did not distinguish itself as a major cause of either recurrent infection or complications in this cohort. More studies, preferably with the focus on adolescents, are needed before F. necrophorum can be considered an important cause of pharyngotonsillitis.


Chilblain y lesiones purpúricas acrales en COVID-19


title: Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems

text: To reveal the putative cellular factors involved in SARS coronavirus replication, the helicase (Hel, nsp13) of SARS coronavirus was used to screen the cDNA library of rat pulmonary epithelial cells using the yeast two-hybrid system. Positively interacting proteins were further tested using a mammalian cell hybrid system and co-immunoprecipitation in the human A549 cell line, which has been shown to support SARS coronavirus replication. Out of the seven positive clones observed by yeast two-hybrid assay, only the Ddx5 (Asp-Glu-Ala-Asp box polypeptide 5) protein showed specific interaction with SARS-CoV helicase. When expression of DdX5 was knocked down by small interfering RNA (siRNA), SARS coronavirus replication was significantly inhibited in fetal rhesus kidney (FRhK-4) cells. Since Ddx5 is a multifunctional protein that plays important roles in transcriptional regulation, its interaction with SARS coronavirus helicase provides interesting clues for studying virus–host cell interactions in SARS-CoV infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-009-0323-y) contains supplementary material, which is available to authorized users.


docid: gwtkwtzx

title: Choroid plexus and the blood–cerebrospinal fluid barrier in disease

text: The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.


title: LIPS method for the detection of SARS‐CoV‐2 antibodies to spike and nucleocapsid proteins

text: Profiling antibodies to SARS‐CoV‐2 can help to assess potential immune response after COVID‐19 disease. Luciferase IP system (LIPS) assay is a sensitive method for quantitative detection of antibodies to antigens in their native conformation. We here describe LIPS to detect antibody responses to SARS‐CoV‐2 spike (S) and nucleocapsid (N) proteins in COVID‐19 patients. The antibodies targeted both S and N fragments and gave a high assay sensitivity by identifying 26 out of 26 COVID‐19 patients with N antigen or with three protein fragments when combined into a single reaction. The assay correlated well with ELISA method and was specific to COVID‐19 as we saw no reactivity among uninfected healthy controls. Our results show that LIPS is a rapid and measurable method to screen antibody responses against SARS‐CoV‐2 antigens.


title: Hospitalization due to human parainfluenza virus–associated lower respiratory tract illness in rural Thailand

text: Background Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. Methods From 2003–2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse‐transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera Results Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children <5 years of age had evidence of HPIV infection (HPIV1=189, HPIV2=54, HPIV3=305, untyped=27). Average adjusted annual incidence of HPIV‐associated hospitalized respiratory illness was greatest in children aged <1 year (485 per 100,000 person years). Conclusions In Thailand, HPIV caused substantial illnesses requiring hospitalization in young children.


title: Distinct infection process of SARS‐CoV‐2 in human bronchial epithelial cells line

text: COVID‐19, caused by SARS‐CoV‐2, leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS‐CoV‐2 can enter these cells through interaction between its membrane‐localized S protein with the ACE2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although mRNA expression of various innate immune signaling molecules is altered in the cells, transcription of IFNα, IFNβ and IFNγ is unchanged. Furthermore, expression of some interleukins related to inflammatory reactions, such as IL‐6, IL‐2 and IL‐8, is maintained at low levels, whereas that of interleukins involved in immune regulation is upregulated. Interestingly, IL‐22, an interleukin that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism. This article is protected by copyright. All rights reserved.


title: Tissue Distribution of the MERS-Coronavirus Receptor in Bats

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.


title: Sequence of the 3′ end of the simian hemorrhagic fever virus genome

text: SHFV is a member of a new virus family which includes the genus arterivirus. We have cloned and sequenced 6,314 nt from the 3′ end of the SHFV genome. This sequence encompasses nine complete ORFs which is three additional ORFs as compared to the other arteriviruses. We have numbered these ORFs 2a, 2b, 3, 4, 5, 6, 7, 8 and 9. At the 5′ end of this sequence is a partial ORF (ORF 1b) of 1590 nt and at the 3′ end is a poly(A) tract preceded by a 76 nt noncoding region. The coding capacity for each of the SHFV ORFs as well as the potential mass, pI and number of N-linked glycosylation sites for each of the encoded peptides was determined.


docid: afaqldqf

title: Food safety risk during the pandemic


title: Correlation analysis of the severity and clinical prognosis of 32 cases of patients with COVID-19

text: • Fibrosis indicators were early warning markers for critical COVID-19 patients. • Dynamic changes of lymphocyte count and CRP levels were related to the prognosis. • Rapid pulmonary consolidation was the major feature for died COVID-19 patients. • Pathological changes included inflammatory exudation and formation of granulomatous nodule.


Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19


title: Review and analysis of current responses to COVID-19 in Indonesia: Period of January to March 2020

text: Abstract The world is under pressure from the novel COVID-19 pandemic. Indonesia is the fourth most populous country in the world and predicted to be affected significantly over a longer time period. Our paper aims to provide detailed reporting and analyses of the present rapid responses to COVID-19, between January and March 2020, in Indonesia. We particularly highlight responses taken by the governments, non-government organisations and the community. We outline gaps and limitations in the responses, based on our rapid analysis of media contents, from government speeches and reports, social and mass media platforms. We present five recommendations toward more rapid, effective, and comprehensive responses.


BSPD issues plea to parents during lockdown


title: Infección por SARS-CoV-2: implicaciones para la salud sexual y reproductiva. Una declaración de posición de la Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA)

text: OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.


title: Carry forward advantages of traditional medicines in prevention and control of outbreak of COVID-19 pandemic

text: Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper manly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10+3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation.


Occurrence of Acute Pulmonary Embolism in COVID-19 – A Case Series


title: Rapid one-step construction of a Middle East Respiratory Syndrome (MERS-CoV) infectious clone system by homologous recombination

text: Abstract Background Viral Infectious clone systems serve as robust platforms to study viral gene or replicative function by reverse genetics, formulate vaccines and adapt a wild type-virus to an animal host. Since the development of the first viral infectious clone system for the poliovirus, novel strategies of viral genome construction have allowed for the assembly of viral genomes across the identified viral families. However, the molecular profiles of some viruses make their genome more difficult to construct than others. Two factors that affect the difficulty of infectious clone construction are genome length and genome complexity. Results This work examines the available strategies for overcoming the obstacles of assembling the long and complex RNA genomes of coronaviruses and reports one-step construction of an infectious clone system for the Middle East Respiratory Syndrome coronavirus (MERS-CoV) by homologous recombination in S. cerevisiae. Conclusions Future use of this methodology will shorten the time between emergence of a novel viral pathogen and construction of an infectious clone system. Completion of a viral infectious clone system facilitates further study of a virus’s biology, improvement of diagnostic tests, vaccine production and the screening of antiviral compounds.


title: The personality types of key catalytic individuals shape colonies' collective behaviour and success

text: Behavioural ecologists often note that one or a few group members appear to shape the collective behaviour of social groups differentially. Our understanding of these keystone individuals is largely taken from meticulous field observations and semi-scientific anecdotes. In this study we experimentally test whether the behavioural tendencies of putative keystone individuals shift the collective behaviour of colonies using the social spider Stegodyphus dumicola. Prior studies on Stegodyphus demonstrated that the single best predictor of colonies' collective behaviour is the behaviour of colonies' boldest individual. Here, we probe the causal relationship between the traits of extremely bold individuals and colonies' collective behaviour by experimentally creating colonies of identical size and personality composition in the laboratory and then adding a single individual of varying boldness (the putative keystone individual). Experimentally adding just one extremely bold individual increased the foraging aggressiveness of entire colonies and altered the total mass gained by fellow group members, relative to the addition of a less bold individual. Additionally, our data suggest that bold individuals are capable of such influence because they catalyse variation in the behavioural tendencies of fellow group members.


Chapter 6 Defensins and Other Antimicrobial Peptides and Proteins


title: On the basic reproduction number and the topological properties of the contact network: An epidemiological study in mainly locally connected cellular automata

text: Abstract We study the spreading of contagious diseases in a population of constant size using susceptible-infective-recovered (SIR) models described in terms of ordinary differential equations (ODEs) and probabilistic cellular automata (PCA). In the PCA model, each individual (represented by a cell in the lattice) is mainly locally connected to others. We investigate how the topological properties of the random network representing contacts among individuals influence the transient behavior and the permanent regime of the epidemiological system described by ODE and PCA. Our main conclusions are: (1) the basic reproduction number (commonly called R 0 ) related to a disease propagation in a population cannot be uniquely determined from some features of transient behavior of the infective group; (2) R 0 cannot be associated to a unique combination of clustering coefficient and average shortest path length characterizing the contact network. We discuss how these results can embarrass the specification of control strategies for combating disease propagations.


title: Infection Prevention in Transplantation

text: The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplant-associated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcare-associated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients.


title: Emergency department triage: an ethical analysis

text: BACKGROUND: Emergency departments across the globe follow a triage system in order to cope with overcrowding. The intention behind triage is to improve the emergency care and to prioritize cases in terms of clinical urgency. DISCUSSION: In emergency department triage, medical care might lead to adverse consequences like delay in providing care, compromise in privacy and confidentiality, poor physician-patient communication, failing to provide the necessary care altogether, or even having to decide whose life to save when not everyone can be saved. These consequences challenge the ethical quality of emergency care. This article provides an ethical analysis of "routine" emergency department triage. The four principles of biomedical ethics - viz. respect for autonomy, beneficence, nonmaleficence and justice provide the starting point and help us to identify the ethical challenges of emergency department triage. However, they do not offer a comprehensive ethical view. To address the ethical issues of emergency department triage from a more comprehensive ethical view, the care ethics perspective offers additional insights. SUMMARY: We integrate the results from the analysis using four principles of biomedical ethics into care ethics perspective on triage and propose an integrated clinically and ethically based framework of emergency department triage planning, as seen from a comprehensive ethics perspective that incorporates both the principles-based and care-oriented approach.


title: MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis

text: Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4(+) and CD8(+) T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4(+) T cells transiently accumulate within the perivascular space, whereas CD8(+) T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4(+) T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4(+) T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4(+) T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4(+) T cells, disease severity was decreased and associated with reduced IFNγ (interferon γ) production. Moreover, decreased CD4(+) T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4(+) T cell access into the CNS parenchyma during acute JHMV encephalitis.


Migratory Pulmonary Infiltrates in a Patient with COVID-19 Infection and the Role of Corticosteroids


title: First retrospective studies with etiological confirmation of porcine transmissible gastroenteritis virus infection in Argentina

text: BACKGROUND: In 2014, a notification of porcine transmissible gastroenteritis virus (TGEV) was made by the National Services of Animal Health of Argentina (SENASA) to the World Organization of Animal Health (OIE). The notification was based on a serological diagnosis in a small farm with a morbidity rate of 2.3% without enteric clinical signs. In order to determine if TGEV was circulating before the official report, a retrospective study on cases of neonatal diarrhea was performed. The selection criteria was a sudden increase in mortality in 1- to 21-day-old piglets with watery diarrhea that did not respond to antibiotics. Based on these criteria, three clinical cases were identified during 2010–2015. RESULTS: All animals that were evaluated presented histological lesions consistent with enteric viral infection. The feces and ultrathin sections of intestine that were evaluated by electron microscopy confirmed the presence of round particles of approximately 80 nm in size and characterized by finely granular electrodense nucleoids consistent with complete particles of coronavirus. The presence of the TGEV antigen was confirmed by monoclonal specific immunohistochemistry, and final confirmation of a metabolically-active virus was performed by in situ hybridization to detect a TGE mRNA encoding spike protein. All sections evaluated in this case were negative for PEDV and rotavirus A. CONCLUSIONS: This is the first case series describing neonatal mortality with etiological confirmation of TGEV in Argentina. The clinical diagnosis of TGEV infections in endemic regions is challenging due to the epidemiological distribution and coinfection with other enteric pathogens that mask the clinical presentation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1615-9) contains supplementary material, which is available to authorized users.


title: COVID-19 in Rheumatic Disease Patients on Immunosuppressive Agents

text: OBJECTIVE: To analyze clinical characteristics and outcome of COVID-19 patients with underlying rheumatic diseases (RD) on immunosuppressive agents. METHOD: A case series of COVID-19 patients with RD on disease modifying anti-rheumatic drugs (DMARDs) were studied by a retrospective chart review. A literature search identified 9 similar studies of single cases and case series, which were also included. RESULTS: There were 4 COVID-19 inpatients with RD from our hospital, and the mean age was 57 ± 21 years. Two patients had a mild infection, and 2 developed severe COVID-19 related respiratory complications, including 1 patient on secukinumab requiring mechanical ventilation and 1 patient on rituximab developing viral pneumonia requiring supplemental oxygenation. All 4 patients had elevated acute phase reactants, 2 patients had mild COVID-19 with lymphopenia, and 2 patients had severe COVID-19 with normal lymphocyte counts, and high levels of IL-6. None of the patients exhibited an exacerbation of their underlying RD. In the literature, there were 9 studies of COVID-19 involving 197 cases of various inflammatory RD. Most patients were on DMARDs or biologics, of which TNFα inhibitors were most frequently used. Two tocilizumab users had a mild infection. Two patients were on rituximab with 1 severe COVID-19 requiring mechanical ventilation. Six patients were on secukinumab with 1 hospitalization. Of the total 201 cases, 12 died, with an estimated mortality of 5.9% CONCLUSION: Patients with RD are susceptible to COVID-19. Various DMARDs or biologics may affect the viral disease course differently. Patients on hydroxychloroquine, TNFα antagonists or tocilizumab may have a mild viral illness. Rituximab or secukinumab could worsen the viral disease. Further study is warranted.


title: Legionnaires' disease mimicking swine influenza (H1N1) pneumonia during the “herald wave” of the pandemic

text: Background New York area hospitals were hit hard by the swine influenza (H1N1) pandemic in spring and summer 2009. During a pandemic, the initial cases may be difficult to recognize, but subsequent clinical diagnoses were relatively straightforward, given the high volume of cases and their typical clinical presentation. Swine influenza pneumonia presents as an influenza-like illness (ILI) with dry cough, fever >102°F and myalgias. A variety of other viral pneumonias, eg, cytomegalovirus, human parainfluenza virus 3 (HPIV 3), and adenovirus, as well as bacterial community-acquired pneumonias (CAPs) that may present with some of the clinical and laboratory features of H1N1 pneumonia. Most adults admitted to hospitals with ILIs during the pandemic had, in fact, definite or probable H1N1 pneumonia. The Infectious Disease Division at Winthrop-University Hospital developed a diagnostic weighted point score to identify probable H1N1 cases in hospitalized adults with rapid negative influenza diagnostic tests (RIDTs). Methods We present a case of an elderly male who presented with an ILI and negative RIDTs during the H1N1 pandemic. He was admitted with a diagnosis of possible H1N1, and placed on influenza precautions and oseltamivir. Although the patient had features consistent with H1N1 pneumonia, Legionnaires' disease was included in the differential diagnosis because of his elevated serum ferritin levels. A Legionella urinary antigen test was positive for Legionella pneumophila (serogroups 01-06). Results The peak seasonal incidence of sporadic Legionnaires' disease occurs in the summer and fall. Even in the midst of a pandemic, clinicians should be on the alert for other infectious diseases that may mimic H1N1 pneumonia. In our experience, the best way to differentiate H1N1 from ILIs or other bacterial CAPs is through the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for H1N1 pneumonia or its rapid simplified version, ie, the diagnostic swine influenza triad. Legionnaires' disease is the atypical CAP pathogen most likely to mimic H1N1 pneumonia. Conclusions Based on this and other nine cases at our institution during the “herald wave” of pandemic, we conclude that Legionnaires' disease may mimic swine influenza (H1N1) pneumonia.


title: Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson's Disease

text: Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.


title: World Health Organization

text: The World Health Organization is the global authority on health issues. Since its inception in 1948, it has made large strides in advancing its goal of the highest attainable level of health for all people. Through the years, the organization has faced many setbacks, but it has also marked numerous achievements. The global forces that necessitated its establishment continue to mold and influence the organization. This article discusses how the World Health Organization started, its functions, and what it is doing to maintain its relevance in the twenty-first century. This article also brings into focus the fight against tropical diseases.


title: Air quality changes during the COVID-19 lockdown over the Yangtze River Delta Region: An insight into the impact of human activity pattern changes on air pollution variation

text: Abstract The outbreak of COVID-19 has spreaded rapidly across the world. To control the rapid dispersion of the virus, China has imposed national lockdown policies to practise social distancing. This has led to reduced human activities and hence primary air pollutant emissions, which caused improvement of air quality as a side-product. To investigate the air quality changes during the COVID-19 lockdown over the YRD Region, we apply the WRF-CAMx modelling system together with monitoring data to investigate the impact of human activity pattern changes on air quality. Results show that human activities were lowered significantly during the period: industrial operations, VKT, constructions in operation, etc. were significantly reduced, leading to lowered SO2, NO x , PM2.5 and VOCs emissions by approximately 16–26%, 29–47%, 27–46% and 37–57% during the Level I and Level II response periods respectively. These emission reduction has played a significant role in the improvement of air quality. Concentrations of PM2.5, NO2 and SO2 decreased by 31.8%, 45.1% and 20.4% during the Level I period; and 33.2%, 27.2% and 7.6% during the Level II period compared with 2019. However, ozone did not show any reduction and increased greatly. Our results also show that even during the lockdown, with primary emissions reduction of 15%–61%, the daily average PM2.5 concentrations range between 15 and 79 μg m−3, which shows that background and residual pollutions are still high. Source apportionment results indicate that the residual pollution of PM2.5 comes from industry (32.2–61.1%), mobile (3.9–8.1%), dust (2.6–7.7%), residential sources (2.1–28.5%) in YRD and 14.0–28.6% contribution from long-range transport coming from northern China. This indicates that in spite of the extreme reductions in primary emissions, it cannot fully tackle the current air pollution. Re-organisation of the energy and industrial strategy together with trans-regional joint-control for a full long-term air pollution plan need to be further taken into account.


title: Functional recombinant human anti-HAV antibody expressed in milk of transgenic mice

text: Hepatitis A virus (HAV) is a wide spread pathogenic agent and is the common cause of acute Hepatitis A worldwide. Passive immunization of HAV plays an extremely important role in post-exposure prophylaxis with clinical applications often requiring large amounts of antibody. As an alternative to the in vitro production of recombinant proteins, expression of monoclonal antibodies (mAbs) in the milk of transgenic animals is currently used being associated with low production costs and high activity. In this paper, eight founder lines of transgenic mice were generated by co-microinjection of the two cassettes encoding the heavy- and light-chains of a neutralizing anti-HAV antibody, respectively. The expressed heavy- and light-chains of the mAb were correctly assembled and modified in the mammary gland as detected by western blotting. High expression levels of the antibody were achieved during the lactation period and found to be independent of the copy numbers of integrated transgenes. The highest level was up to 32.2 mg/ml. The binding specificity and neutralizing activity of the expressed mAb were assayed by ELISA and neutralizing test, showing that it is capable to neutralize the JN strain of Hepatitis A virus efficiently. Therefore, our results suggest that a large-scale and efficient production of the anti-HAV mAb in the milk of transgenic farm animals would be feasible in the future.


title: Efficacy of Listerine(®) Antiseptic in reducing viral contamination of saliva

text: Aim: The anti‐viral efficacy of oral antimicrobial rinses has not been adequately studied in terms of potential clinical significance. As a follow‐up to an in vitro study on the effect of oral antiseptics on Herpes simplex virus, Type 1, this study was undertaken to evaluate the in vivo effect of an essential oil containing oral antiseptic on the reduction of viral titer in saliva during active viral infection. Method: Patients were recruited and evaluated in a single visit protocol at the onset of a perioral outbreak, consistent historically and clinically with recurrent Herpes labialis. Direct immunofluorescence of cytological smears of the lesions/oral fluids was used to confirm Herpes simplex virus types I or II. Patients were randomly assigned to one of two treatment groups: (1) active ingredient and (2) sterile water control. The viral lesion was evaluated as to clinical stage according to standard protocol. Salivary fluid samples were taken: (1) at baseline; (2) immediately following a 30 s rinse; (3) 30 min. after the 30 s rinse; and (4) on the repeat trial, also at 60 min. after the 30 s rinse. All samples were evaluated for viral titer and results compared. Results: In Trial 1, the sample population consisted of 19 males and 21 females with an average age of 29.2 and in Trial 2, 21 males, 19 females with an average age of 28. In both Trials 1 and 2, recoverable infectious virions were reduced to zero after a 30 s experimental rinse; whereas, the control rinse resulted in a non‐significant (p>0.05) reduction. The experimental group also demonstrated a continued significant (p<0.05) reduction 30 min. post rinse when compared with baseline while the control group returned to baseline levels. In Trial 2, the 60 min. post rinse follow‐up demonstrated a 1–2 log residual reduction from baseline in the experimental group; however, this was not significant. Conclusions: There is clinical efficacy in utilizing an oral rinse with the antimicrobial agent Listerine(®) Antiseptic in reducing the presence of viral contamination in oral fluids for at least 30 min. after oral rinse. The risk of viral cross contamination generated from these oral fluids in person to person contact or during dental treatment may be reduced.


title: VirOligo: a database of virus-specific oligonucleotides

text: VirOligo is a database of virus-specific oligonucleotides. The VirOligo database consists of two tables, Common data and Oligo data. The Oligo data table contains PCR primers and hybridization probes used for detection of viral nucleic acids and the Common data table contains the experimental conditions used in their detection. Each oligonucleotide entry contains links to PubMed, GenBank, NCBI Taxonomy databases and BLAST. As of July 2001, the VirOligo database contains a complete listing of oligonucleotides specific to viral agents associated with bovine respiratory disease that were published in English in peer-reviewed journals. The viruses are bovine herpes virus types 1, 3, 4 and 5, bovine viral diarrhea virus, bovine parainfluenza 3 virus, bovine respiratory syncytial virus, bovine adenovirus, bovine rhinovirus, bovine coronavirus, bovine reovirus, bovine enterovirus and alcelaphine herpesvirus-1. The VirOligo database is being expanded to other viruses and can be accessed through the Internet at http://viroligo.okstate.edu/.


title: Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area

text: To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m(2)) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.


title: Coronovirus infection as a novel delusional topic

text: Abstract Delusional topics tend to rapidly incorporate popular hot topical issues. Thus, the current coronavirus COVID-19 pandemic has rapidly reached delusional themes in patients with psychiatric disorders. Here we present the clinical case of a Spanish woman with bipolar disorder that included coronavirus infection in her delusional themes even faster than the real infection reached mainland Spain.


title: 3 vragen over De Covid-19 Verhalenbank

text: Wie: Hugo Schalkwijk (28), adviseur Historisch College Florence Nightingale Instituut (FNI)


title: iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins

text: As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.


title: Interaction of a peptide corresponding to the loop domain of the S2 SARS-CoV virus protein with model membranes

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein is responsible for the fusion between the membranes of the virus and the target cell. In the case of the S2 domain of protein S, it has been found a highly hydrophobic and interfacial domain flanked by the heptad repeat 1 and 2 regions; significantly, different peptides pertaining to this domain have shown a significant leakage effect and an important plaque formation inhibition, which, similarly to HIV-1 gp41, support the role of this region in the fusion process. Therefore, we have carried out a study of the binding and interaction with model membranes of a peptide corresponding to segment 1073–1095 of the SARS-CoV S glycoprotein, peptide SARS(L) in the presence of different membrane model systems, as well as the structural changes taking place in both the lipid and the peptide induced by the binding of the peptide to the membrane. Our results show that SARS(L) strongly partitions into phospholipid membranes and organizes differently in lipid environments, displaying membrane activity modulated by the lipid composition of the membrane. These data would support its role in SARS-CoV mediated membrane fusion and suggest that the region where this peptide resides could be involved in the merging of the viral and target cell membranes.


docid: aobuhwbi

title: Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study

text: We assessed the prevalence and impact of COVID-19 among multiple sclerosis (MS) patients across Europe by leveraging participant data collected as part of the ongoing EU IMI2 RADAR-CNS major programme aimed at finding new ways of monitoring neurological disorders using wearable devices and smartphone technology. In the present study, 399 patients of RADAR-MS have been included (mean age 43.9 years, 60.7% females) with 87/399 patients (21.8%) reporting major symptoms suggestive of COVID-19. A trend for an increased risk of COVID-19 symptoms under alemtuzumab and cladribine treatments in comparison to injectables was observed. Remote monitoring technologies may support health authorities in monitoring and containing the ongoing pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10072-020-04519-x) contains supplementary material, which is available to authorized users.


title: Responsible Return to Essential and Non-Essential Surgery During the COVID-19 Pandemic

text: Non-essential surgery had largely been suspended during the COVID-19 Pandemic. Enormous amounts of resources were utilized to shift surgical practices to a “disaster footing” with most elective surgeons assuming new roles to offset the anticipated burden from surgical and medical personnel delivering acute care. As the number of COVID-19-infected patients began to plateau in the state of Ohio, a four-phase “Responsible Return to Surgery” approach was adopted in concert with the Ohio Department of Health and the Ohio Hospital Association. This approach was adopted understanding that a simple return to the status quo prior to the COVID-19 pandemic might be harmful to patients, providers, and staff. The discrete phases undertaken at our quaternary care institution for a responsible return to non-essential surgery are outlined with the goal of ensuring timely care, minimizing community transmission, and preserving personal protective equipment. Operationalizing these phases relied upon the widespread use of telehealth, systematic COVID-19 testing, and real-time monitoring of hospital and personal protective equipment resources.


title: COVID-19 Outbreak and Surgical Practice: Unexpected Fatality in Perioperative Period

text: Little is known about surgical practice in the initial phase of coronavirus disease 2019 (COVID-19) global crisis. This is a retrospective case series of 4 surgical patients (cholecystectomy, hernia repair, gastric bypass, and hysterectomy) who developed perioperative complications in the first few weeks of COVID-19 outbreak in Tehran, Iran in the month of February 2020. COVID-19 can complicate the perioperative course with diagnostic challenge and a high potential fatality rate. In locations with widespread infections and limited resources, the risk of elective surgical procedures for index patient and community may outweigh the benefit.


title: The phosphorylation of the N protein could affect PRRSV virulence in vivo

text: Abstract The porcine respiratory and reproductive syndrome virus (PRRSV) nucleocapsid (N) protein is a multiphosphorylated protein.It has been proved that the phosphorylation of N protein could regulate the growth ability of PRRSV in Marc-145 cells. However, further investigation is needed to determine whether phosphorylation of the N protein could affect PRRSV virulence in piglets. In this study, we confirmed that the mutations could impair PRRSV replication ability in porcine primary macrophages (PAMs) as they did in Marc-145 cells. The animal experiments suggested that the pathogenicity of the mutated virus (A105-120) was significantly reduced compared with parent strain (XH-GD). Our results suggested that the phosphorylation of the N protein contributes to virus replication and virulence. This study is the first to identify a specific modification involved in PRRSV pathogenicity. Mutation of PTMs sites is also a novel way to attenuate PRRSV virulence. The mutations could be a marker in a vaccine. In conclusion, our study will improve our understanding of the molecular mechanisms of PRRSV pathogenicity.


The Covid-19 Pandemic and People with Disability


title: Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD?

text: BACKGROUND: The SARS-CoV-2 virus continues to spread rapidly across the globe afflicting many with Coronavirus Disease 2019 (COVID-19). As the infection rates rise, a growing number of SARS-CoV-2 positive individuals have been reported to complain of olfactory disturbances at an alarming rate. Postviral olfactory dysfunction (PVOD) is a well-known phenomenon that may explain the olfactory dysfunction reported by SARS-CoV-2 infected individuals. METHODS: A scoping literature review was performed to identify studies that investigated the mechanisms of postviral olfactory dysfunction. Studies demonstrating pathophysiological, histological, immunochemical, and epidemiological outcomes of PVOD were included. RESULTS: Fourteen studies were included in addition to one international news article. Three studies reported destruction of the olfactory epithelium following intranasal inoculation of various viral strains in mice. Three studies isolated pathogenic, anosmia inciting viruses (Parainfluenza virus, Human Coronavirus, Rhinovirus) through nucleic acid amplification. Eleven studies demonstrated female predilection in patients with PVOD and COVID-19 associated olfactory dysfunction, of which the majority were over 50 years old. CONCLUSIONS: PVOD and COVID-19 associated olfactory dysfunction demonstrates considerable similarities in epidemiological trends and disease sequela of other viruses to suggest identical pathophysiological mechanisms. Further studies such as intranasal inoculation and histological biopsies are needed to support our hypothesis.


docid: jngjogrh

title: Disidratazione acuta nel lattante

text: Il lattante al di sotto di un anno, e soprattutto al di sotto di sei mesi, è ad alto rischio di disidratazione, di cui la prima causa è la diarrea. Questa è principalmente di origine virale. La gestione di una disidratazione comporta la correzione di questa e il soddisfacimento delle richieste idriche e nutrizionali. La valutazione della gravità della disidratazione è l’elemento chiave che guiderà la terapia. La perdita di peso, espressa in percentuale del peso corporeo prima dell’episodio di disidratazione, rappresenta il metodo di riferimento, ma è spesso difficile o impossibile da rilevare. Così, i segni clinici come l’alterazione dell’aspetto generale, il prolungamento del tempo di rivascolarizzazione cutanea, la constatazione di una plica cutanea persistente, occhi infossati, una secchezza delle mucose, un’assenza di lacrime sono i principali elementi che, insieme a tachicardia, pressione arteriosa e diuresi, permettono di valutare la gravità della disidratazione. La terapia si basa sulla correzione rapida del deficit del settore extracellulare. Può essere necessaria un’espansione volemica con 20 ml/kg di una soluzione cristalloide isotonica somministrata per via endovenosa o intraossea nella fase iniziale nei casi più gravi (disidratazione >10%). In tutti gli altri cas, la reidratazione per via orale volta a correggere il deficit idrico in quattro ore è la tecnica di elezione, che si è dimostrata efficace, sicura e rapida. Essa utilizza delle soluzioni per reidratazione adattate, che rispondono a criteri specifici. Il loro uso precoce rappresenta la prevenzione più efficace delle forme gravi e deve essere diffuso più ampiamente.


title: Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury

text: Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 μg/kg DON, respectively. We observed significant increases in the diarrhea rates, the villous injury of jejunums and the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in experimental groups compared with control. Additionally, the autophagosome-like vesicles and the autophagy-related protein expressions were also increased in experimental groups. In vitro, we observed that, approximately 2 hrs post-infection, 0.1, 0.5 and 1.0 μM DON promoted PEDV entry (P < 0.05) in IPEC-J2s and resulted in tight junction protein occludin internalization. Knockdown of occludin and CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 μM DON treatment, along with the induction of a complete autophagy. Specifically, deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the induction of autophagy. Furthermore, downregulation of type I interferon revealed that DON contributed PEDV to escape innate immune. Mechanistically, DON-caused innate immune escape was related to the upregulation of LC3B, which further inhibited STING phosphorylation. Taken together, DON could promote PEDV infection by inducing occludin internalization and innate immune escape via triggering p38-mediated autophagy. Porcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic economic loss to the global pig industry. Its primary pathogen is the coronavirus PED virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor of PED outbreaks, other non-infectious factors is also related to this disease. We guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig intestinal epithelial cell stress might encourage the progress and spread of PED. In the present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell line were selected as models to explore the effects of DON on PEDV infection, morbidity and gut barrier. Our results showed that DON exposure can promote PEDV infection in vitro and in vivo, and the underlying mechanism might be related to LC3B-mediated autophagy. Our findings reveal new pathways for developing potential novel antiviral strategies against PEDV infection.


title: Automated degenerate PCR primer design for high-throughput sequencing improves efficiency of viral sequencing

text: BACKGROUND: In a high-throughput environment, to PCR amplify and sequence a large set of viral isolates from populations that are potentially heterogeneous and continuously evolving, the use of degenerate PCR primers is an important strategy. Degenerate primers allow for the PCR amplification of a wider range of viral isolates with only one set of pre-mixed primers, thus increasing amplification success rates and minimizing the necessity for genome finishing activities. To successfully select a large set of degenerate PCR primers necessary to tile across an entire viral genome and maximize their success, this process is best performed computationally. RESULTS: We have developed a fully automated degenerate PCR primer design system that plays a key role in the J. Craig Venter Institute’s (JCVI) high-throughput viral sequencing pipeline. A consensus viral genome, or a set of consensus segment sequences in the case of a segmented virus, is specified using IUPAC ambiguity codes in the consensus template sequence to represent the allelic diversity of the target population. PCR primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the full length of the specified target region. As part of the tiling process, primer pairs are computationally screened to meet the criteria for successful PCR with one of two described amplification protocols. The actual sequencing success rates for designed primers for measles virus, mumps virus, human parainfluenza virus 1 and 3, human respiratory syncytial virus A and B and human metapneumovirus are described, where >90% of designed primer pairs were able to consistently successfully amplify >75% of the isolates. CONCLUSIONS: Augmenting our previously developed and published JCVI Primer Design Pipeline, we achieved similarly high sequencing success rates with only minor software modifications. The recommended methodology for the construction of the consensus sequence that encapsulates the allelic variation of the targeted population and is a key step prior to designing degenerate primers is also formally described.


title: The incidence and management of persistent cystoid macular oedema following uncomplicated cataract surgery—a Scottish Ophthalmological Surveillance Unit study

text: PURPOSE: Post-operative cystoid macular oedema (CMO) can cause deterioration of vision following routine cataract surgery. The incidence of persistent CMO (pCMO; defined as CMO present after 3 months) following uncomplicated surgery is uncertain. We wished to identify the incidence, management and visual outcomes of such patients. METHODS: A Scottish Ophthalmological Surveillance Unit (SOSU) questionnaire was sent monthly to every ophthalmic specialist in Scotland over an 18-month period from 1st January 2018 asking them to report all new patients with pCMO confirmed on OCT scanning following uncomplicated cataract surgery. A follow-up questionnaire was sent 9 months after initial presentation. RESULTS: Fourteen cases of pCMO were reported, giving an incidence of 2.2 cases of pCMO per 10,000 uncomplicated cataract surgeries. Mean age was 74.9 years (SD 10.2; range 44–86) with a male preponderance (72.7%). Two patients developed pCMO in each eye. Six cases (46.2%) had hypertension and one had diabetes. Three eyes required intracameral adjuncts (two iris hooks, one intracameral phenylephrine). Postoperative visual acuity (VA) at 3 months was logMAR 0.48 (0.2–0.8). Average mean central retinal thickness (CRT) at 3 months was 497microns (270–788). The most common initial treatment comprised topical steroids and topical NSAIDs (61.5%). Other management strategies included systemic steroids, intravitreal steroids and oral acetazolamide. At 1-year post-op, mean VA was logMAR 0.18 (0.1–0.3) with average mean CRT of 327microns (245–488). CONCLUSIONS: We identified a low incidence of pCMO following uncomplicated cataract surgery in Scotland (0.02%), with inconsistent and variable management regimes. A nationally agreed treatment protocol is required.


title: Prevalence and Pathogenicity of WU and KI Polyomaviruses in Children, the Netherlands

text: A longitudinal study in 2004 and 2005 detected polyomaviruses WU and KI in 44% and 17% of children with and without respiratory symptoms, respectively, in the Netherlands. In some children both viruses were detected for long periods. In several symptomatic children no other respiratory pathogen was detected.


title: Web-based forecasting system for the airborne spread of livestock infectious disease using computational fluid dynamics

text: Livestock infectious diseases, such as foot-and-mouth disease (FMD), cause substantial economic damage to livestock farms and their related industries. Among various causes of disease spread, airborne dispersion has previously been considered to be an important factor that could not be controlled by preventive measures to stop the spread of disease that focus on direct and indirect contact. Forecasting and predicting airborne virus spread are important to make time for developing strategies and to minimise the damage of the disease. To predict the airborne spread of the disease a modelling approach is important since field experiments using sensors are ineffective because of the rarefied concentrations of virus in the air. The simulation of airborne spread during past outbreaks required improvement both for farmers and for policy decision makers. In this study a free license computational fluid dynamics (CFD) code was used to simulate airborne virus spread. Forecasting data from the Korea Meteorological Administration (KMA) was directly connected in the developed model for real-time forecasting for 48 h in three-hourly intervals. To reduce computation time, scalar transport for airborne virus spread was simulated based on a database for the CFD computed airflow in the investigated area using representative wind conditions. The simulation results, and the weather data were then used to make a database for a web-based forecasting system that could be accessible to users.


Emerging Issues for the Public Health Laboratory


title: Living donor liver transplants for sick recipients during COVID‐19 pandemic‐ An experience from a tertiary center in India

text: The recent outbreak of COVID‐19 has brought elective surgeries including liver transplantation to a standstill. The concerns in Living Donor Liver Transplant (LDLT) were that immunosuppressed recipients and healthy donors would be exposed to nosocomial SARS‐ CoV‐2 infection.(1) However, as patients began to suffer and die, Liver Transplant Society of India (LTSI) revised its guidelines (2) and allowed LDLT for those who were very sick, or had just recovered from a life threatening decompensation (high MELD/ CTP score) or had malignancy. Over 90 % of transplants in India are from live donors as we have a very low donation rate.


title: COVID-19 in solid organ transplantation patients: A systematic review

text: Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were “COVID-19” AND “Transplant.” Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299)


docid: sepawqdp

title: Efficacy of an automated multi-emitter whole room UV-C disinfection system against Coronaviruses MHV and MERS-CoV

text: The virus responsible for Middle Eastern respiratory syndrome, MERS-CoV is a lineage C betacoronavirus similar to the mouse hepatitis virus type A59 (MHV-A59). The first reported case of MERS occurred in Saudi Arabia in 2012 and resulted in 76 deaths(1). Outbreaks of MERS have since occurred not only in the Middle East but South Korea as well(2). Rapid, efficient, and automated methods of disinfecting surfaces contaminated with the MERS-CoV virus may prevent the spread of the virus in the healthcare setting. Here we report on the use of an automated triple-emitter whole room disinfection system to inactivate the MHV-A59 and the MERS-CoV viruses on surfaces with a greater than 5 log(10) reduction on MERS in 5 minutes of UV-C exposure.


title: Rapid discrimination of oseltamivir‐resistant 275Y and ‐susceptible 275H substitutions in the neuraminidase gene of pandemic influenza A/H1N1 2009 virus by duplex one‐step RT‐PCR assay

text: Pandemic influenza A/H1N1 2009 (A/H1N1pdm) virus caused significant outbreaks worldwide last year (2009). A number of oseltamivir‐resistant A/H1N1pdm viruses possessing an H275Y substitution in the neuraminidase (NA) protein were reported sporadically in several countries, including Japan, but they were sensitive to zanamivir and did not spread in the community. In this study, to monitor rapidly and simply oseltamivir‐resistant A/H1N1pdm viruses possessing H275Y, a duplex one‐step RT‐PCR assay (H275Y RT‐PCR assay) was developed based on an endpoint genotyping analysis method. H275Y RT‐PCR assay evaluated using several subtypes/types of influenza A and B viruses and other respiratory pathogenic viruses and shown to have high sensitivity and high specificity. Forty‐four clinical specimens were tested after RNA purification using the H275Y RT‐PCR assay, resulting in one clinical specimen being found to contain a virus possessing the H275Y mutation. Seventy‐three clinical isolates were then tested with the H275Y assay by using clinical isolates in the cultured supernatants of cells directly, without RNA purification, and the results were consistent with the NA sequencing. Since the H275Y RT‐PCR assay could detect the H275Y mutation in clinical isolates without RNA purification, as well as a H275Y mutated virus in clinical specimens after RNA purification, the assay was considered a powerful tool for surveillance screening of oseltamivir‐resistant A/H1N1pdm virus activity. J. Med. Virol. 83:1121–1127, 2011. © 2011 Wiley‐Liss, Inc.


Sentiment analysis of Social Media Response on the Covid19 outbreak


Early evolution and the origin of eukaryotes


title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function

text: Abstract Severe acute respiratory syndrome virus (SARS-CoV) was the causative agent of the SARS outbreaks in 2002–2003. A safer in vitro system is desirable for conducting research on SARS-CoV and to screen for antiviral drugs against the virus. Based on the infectious cDNA clone of rSARS-CoV-ΔE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. Successful replication was achieved as evident from continuous expression of eGFP detected by both fluorescence and Western blot. Treatment with antiviral drugs demonstrated that the replication could be significantly inhibited by 0.4mg/ml of cysteine proteinase inhibitor E-64D, but not by ribavirin. The same replicons containing further deletion of the coding regions for non-structural proteins (nsp) 1, 2 or 16 confirmed previous observation that nsp16, but not nsp1 or nsp2, was essential for efficient viral replication or transcription.


title: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays

text: BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003), and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03). 48 of 157(30.57%) HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu) A were the most common viruses detected (more than 35%) in HCoV co-infections. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.


title: A Comparative Process Mining Analysis of Road Trauma Patient Pathways

text: In this paper we report on key findings and lessons from a process mining case study conducted to analyse transport pathways discovered across the time-critical phase of pre-hospital care for persons involved in road traffic crashes in Queensland (Australia). In this study, a case is defined as being an individual patient’s journey from roadside to definitive care. We describe challenges in constructing an event log from source data provided by emergency services and hospitals, including record linkage (no standard patient identifier), and constructing a unified view of response, retrieval, transport and pre-hospital care from interleaving processes of the individual service providers. We analyse three separate cohorts of patients according to their degree of interaction with Queensland Health’s hospital system (C1: no transport required, C2: transported but no Queensland Health hospital, C3: transported and hospitalisation). Variant analysis and subsequent process modelling show high levels of variance in each cohort resulting from a combination of data collection, data linkage and actual differences in process execution. For Cohort 3, automated process modelling generated ’spaghetti’ models. Expert-guided editing resulted in readable models with acceptable fitness, which were used for process analysis. We also conduct a comparative performance analysis of transport segment based on hospital ‘remoteness’. With regard to the field of process mining, we reach various conclusions including (i) in a complex domain, the current crop of automated process algorithms do not generate readable models, however, (ii) such models provide a starting point for expert-guided editing of models (where the tool allows) which can yield models that have acceptable quality and are readable by domain experts, (iii) process improvement opportunities were largely suggested by domain experts (after reviewing analysis results) rather than being directly derived by process mining tools, meaning that the field needs to become more prescriptive (automated derivation of improvement opportunities).


title: Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China

text: BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. METHODS: We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. RESULTS: Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. CONCLUSIONS: SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.


title: Phosphorylation and membrane association of the Rubella virus capsid protein is important for its anti‐apoptotic function

text: Rubella virus (RV), a member of Togaviridae, is an important human pathogen that can cause severe defects in the developing fetus. Compared to other togaviruses, RV replicates very slowly suggesting that it must employ effective mechanisms to delay the innate immune response. A recent study by our laboratory revealed that the capsid protein of RV is a potent inhibitor of apoptosis. A primary mechanism by which RV capsid interferes with programmed cell death appears to be through interaction with the pro‐apoptotic Bcl‐2 family member Bax. In the present study, we report that the capsid protein also blocks IRF3‐dependent apoptosis induced by the double‐strand RNA mimic polyinosinic‐polycytidylic acid. In addition, analyses of cis‐acting elements revealed that phosphorylation and membrane association are important for its anti‐apoptotic function. Finally, the observation that hypo‐phosphorylated capsid binds Bax just as well as wild‐type capsid protein suggests that interaction with this pro‐apoptotic host protein in and of itself is not sufficient to block programmed cell death. This provides additional evidence that this viral protein inhibits apoptosis through multiple mechanisms.


title: “Runde“ virus, a coronavirus-like agent associated with seabirds and ticks

text: From 206I. uriae collected in the seabird colonies at Runde, Norway, two identical virus strains demonstrating no antigenic relationships to major arbovirus groups were isolated. The new strains demonstrated a corona-virus like morphology, haemagglutinated chicken red cells and were sensitive to sodium desoxycholate. Multiplication with CPE was demonstrated in BHK 21/c13 and BSC-1 cells, and without CPE in Vero and GMK cell cultures. The mouse pathogenicity was relatively low. In gel precipitation three to five specific lines were seen. Precipitating antibodies have been found in seabird species commonly infested byI. uriae. The ecological circumstances of the isolates indicate an earlier unrecognized arbovirus circulating between seabirds andI. uriae. This corona-like virus has been tentatively termed Runde virus.


docid: tovaxufu

title: Deep learning system to screen coronavirus disease 2019 pneumonia

text: Radiographic patterns on CT chest scans have shown higher sensitivity and specificity compared to RT-PCR detection of COVID-19 which, according to the WHO has a relatively low positive detection rate in the early stages. We technically review a study that compared multiple convolutional neural network (CNN) models to classify CT samples with COVID-19, Influenza viral pneumonia, or no-infection. We compare this mentioned study with one that is developed on existing 2D and 3D deep-learning models, combining them with the latest clinical understanding, and achieved an AUC of 0.996 (95%CI: 0.989–1.00) for Coronavirus vs Non-coronavirus cases per thoracic CT studies. They calculated a sensitivity of 98.2% and a specificity of 92.2%.


Healthcare Settings as Amplifiers of Infectious Disease


title: Hypolipidemia is associated with the severity of COVID-19

text: Abstract Background Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. Objective In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. Methods A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age and gender-matched normal subjects (n=50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. Results LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (p<0.001). There were significant and gradual decreases in levels of LDL-c (median (IQR) in mg/dL, mild: 91 (76, 104); severe 86 (69, 102); critical: 69 (48, 81); p<0.02) and TC (mild: 173 (148, 203); severe 167 (138, 197); critical: 125 (95, 162); p<0.05) across all three groups. HDL-c levels only decreased significantly in critical cases as compared to levels in mild and severe cases. LDL-c and TC levels inversely correlated with C-reactive protein and IL-6, and positively correlated with the number of lymphocytes in patients. Conclusions Development of hypolipidemia starts in patients with mild symptoms. It progressively becomes worse in an association with the disease severity.


title: The macrodomain family: Rethinking an ancient domain from evolutionary perspectives

text: The reasons why certain domains evolve much slower than others is unclear. The notion that functionally more important genes evolve more slowly than less important genes is one of the few commonly believed principles of molecular evolution. The macro-domain (also known as the X domain) is an ancient, slowly evolving and highly conserved structural domain found in proteins throughout all of the kingdoms and was first discovered nearly two decades ago with the isolation and cloning of macroH2A1. Macrodomains, which are functionally promiscuous, have been studied intensively for the past decade due to their importance in the regulation of cellular responses to DNA damage, chromatin remodeling, transcription and tumorigenesis. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the evolutionary advantage of concentrating such a plethora of diverse functions into the macrodomain and of how macrodomains could perform so many functions. In this article, we focus on macrodomains that are evolving slowly and broadly discuss the potential relationship between the biological evolution and functional diversity of macrodomains.


Skin amidst COVID‐19 pandemic


title: Niclosamide Blocks Rice Leaf Blight by Inhibiting Biofilm Formation of Xanthomonas oryzae

text: Rice (Oryza sativa) is the leading source of nutrition for more than half of the world’s population, and by far it is the most important commercial food crop. But, its growth and production are significantly hampered by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) which causes leaf blight disease. Earlier studies have reported the antibacterial ability of FDA-approved niclosamide drug against Xoo. However, the underlying mechanism by which niclosamide blocks the growth of Xoo remained elusive. In the present study, by employing the microbiological, microscopical, molecular, bioinformatics and analytical tools we found that niclosamide can directly inhibit the growth of the Xoo by hampering the biofilm formation and the production of xanthomonadin and exopolysaccharide substances (EPS) required for relentless growth and virulence of Xoo. Interestingly, niclosamide was found to specifically suppress the growth of Xoo without affecting other bacteria like Escherichia coli. Our electron microscopic observations disclosed that niclosamide disrupts the membrane permeability of Xoo and causes the release of intracellular components. Similarly, the molecular docking analysis disclosed the molecular interaction of niclosamide with the biofilm, virulence and quorum sensing related proteins, which was further substantiated by relative gene expression analysis where niclosamide was found to significantly downregulate the expression of these key regulatory genes. In addition, considerable changes in chemical structures were detected by Fourier Transform Infrared Spectroscopy (FTIR) in response to niclosamide treatment. Overall, our findings advocate the utilization of niclosamide as a safe and potent alternative antibacterial compound to control bacterial blight disease in rice.


title: High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea

text: Summary Background Effective countermeasures against emerging infectious diseases require an understanding of transmission rate and basic reproduction number (R 0). R 0 for severe acute respiratory syndrome is generally considered to be >1, whereas that for Middle East respiratory syndrome (MERS) is considered to be <1. However, this does not explain the large-scale outbreaks of MERS that occurred in Kingdom of Saudi Arabia (KSA) and South Korean hospitals. Aim : To estimate R 0 in nosocomial outbreaks of MERS. Methods R 0 was estimated using the incidence decay with an exponential adjustment model. The KSA and Korean outbreaks were compared using a line listing of MERS cases compiled using publicly available sources. Serial intervals to estimate R 0 were assumed to be six to eight days. Study parameters [R 0 and countermeasures (d)] were estimated by fitting a model to the cumulative incidence epidemic curves using Matlab. Findings The estimated R 0 in Korea was 3.9 in the best-fit model, with a serial interval of six days. The first outbreak cluster in a hospital in Pyeongtaek had an R 0 of 4.04, and the largest outbreak cluster in a hospital in Samsung had an R 0 of 5.0. Assuming a six-day serial interval, the KSA outbreaks in Jeddah and Riyadh had R 0 values of 3.9 and 1.9, respectively. Conclusion R 0 for the nosocomial MERS outbreaks in KSA and South Korea was estimated to be in the range of 2–5, which is significantly higher than the previous estimate of <1. Therefore, more comprehensive countermeasures are needed to address these infections.


title: Diabetes and COVID-19: IDF perspective in the Western Pacific Region

text: Abstract The World Health Organization (WHO) declared a pandemic, the highest risk level in the infectious disease alert phase, on 11 March 2020. In the Western Pacific Region (WPR), 192,016 confirmed cases with 7,125 deaths had been reported as of 8 June 2020. In people with diabetes COVID-19 can be more difficult to treat due to the wide fluctuations in blood glucose levels or presence of comorbidities such as diabetes complications, including cardiovascular disease and renal damage, which are recognized risks for adverse outcomes. National diabetes associations and governments have established guidelines for subjects with diabetes in relation to COVID-19, and are trying to supply emergency and their regularly required medical products for them. The WPR is so large and composed of such diverse countries and COVID-19 situations, no one conclusion or program applies. Instead we could see a diverse COVID-19 pandemic profile in the WPR, and several creative diagnostic and therapeutic measures undertaken. This includes drive-through screening facilities, high-speed RT-PCR technologies, convalescent patients’ plasma therapy, which potentially had some positive contributions in combatting COVID-19 in the WPR as well as globally. Although the numbers of confirmed cases are currently decreasing in the region, the COVID-19 pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of COVID-19.


title: Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways

text: Abstract The acute phase of respiratory distress caused by porcine reproductive and respiratory syndrome virus (PRRSV) is likely a consequence of the release of inflammatory cytokines in the lung. IL-8, the main chemokine and activator of neutrophils, might be related to the lung injury upon PRRSV infection. In this study, we showed that PRRSV induced IL-8 expression in vivo and in vitro. Subsequently, we demonstrated that JNK and NF-κB pathways were activated upon PRRSV infection and required for the enhancement of IL-8 expression. We further verified that PRRSV-activated TAK-1 was essential for the activation of JNK and NF-κB pathways and IL-8 expression. Moreover, we revealed an AP-1 binding motif in the cloned porcine IL-8 (pIL-8) promoter, and deletion of this motif abolished the pIL-8 promoter activity. Finally, we found that the JNK-activated AP-1 subunit c-Jun was critical for the up-regulation of IL-8 expression by PRRSV. These data suggest that PRRSV-induced IL-8 production is likely through the TAK-1/JNK/AP-1 pathways.


title: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study

text: INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398.


Chilblain‐like lesions on feet and hands during the COVID‐19 Pandemic


title: The history of monoclonal antibody development – Progress, remaining challenges and future innovations

text: As medicine progresses into a new era of personalised therapy, the use of monoclonal antibodies to treat a wide range of diseases lies at the heart of this new forefront. Since the licencing of the first monoclonal antibody for clinical use 30 years ago, the monoclonal antibody industry has expanded exponentially and is now valued at billions of dollars. With major advances in genetic sequencing and biomedical research, much research into monoclonal antibodies now focuses on identifying new targets for development and maximising their efficacy for use in clinical practice. However, a balance has to be struck with regards to reducing numbers of side-effects and overall economic cost, which arguably somewhat blighted their early clinical and commercial successes. Nowadays, there are approximately 30 monoclonal antibodies that have been approved for use in clinical practice with many more currently being tested in clinical trials. Some of the current major limitations include: the use of inefficient models for generation, a lack of efficacy and issues of cost-effectiveness. Some of the current research focuses on ways to improve the efficacy of existing monoclonal antibodies through optimising their effects and the addition of beneficial modifications. This review will focus on the history of monoclonal antibody development – how it has increasingly moved away from using laborious animal models to a more effective phage display system, some of the major drawbacks from a clinical and economical point of view and future innovations that are currently being researched to maximise their effectiveness for future clinical use.


title: Magnetically enhanced nucleic acid delivery. Ten years of magnetofection—Progress and prospects

text: Abstract Nucleic acids carry the building plans of living systems. As such, they can be exploited to make cells produce a desired protein, or to shut down the expression of endogenous genes or even to repair defective genes. Hence, nucleic acids are unique substances for research and therapy. To exploit their potential, they need to be delivered into cells which can be a challenging task in many respects. During the last decade, nanomagnetic methods for delivering and targeting nucleic acids have been developed, methods which are often referred to as magnetofection. In this review we summarize the progress and achievements in this field of research. We discuss magnetic formulations of vectors for nucleic acid delivery and their characterization, mechanisms of magnetofection, and the application of magnetofection in viral and nonviral nucleic acid delivery in cell culture and in animal models. We summarize results that have been obtained with using magnetofection in basic research and in preclinical animal models. Finally, we describe some of our recent work and end with some conclusions and perspectives.


title: Astroviruses☆

text: Abstract Astroviruses are positive-sense, single-stranded RNA viruses. Their genomes contain three open reading frames, but the exact number of encoded proteins remains unknown. Astroviruses were originally identified in association with childhood diarrhea; subsequently, they have been identified as a common enteric virus infecting children under the age of 2. Infection is not restricted to humans, however, and astroviruses have been found in widespread mammalian and avian species. Generally, infection causes a mild, self-limiting gastroenteritis, although infection can result in nephritis, hepatitis, and encephalitis in certain host species. Astrovirus pathogenicity and immune response is only poorly characterized and may differ between mammalian and avian species. In this article, the current knowledge of astroviruses is reviewed, including their molecular virology, viral evolution, pathogenesis, and immune response.


title: A dynamic model for the p53 stress response networks under ion radiation

text: P53 controls the cell cycle arrest and cell apoptosis through interaction with the downstream genes and their signal pathways. To stimulate the investigation into the complicated responses of p53 under the circumstance of ion radiation (IR) in the cellular level, a dynamic model for the p53 stress response networks is proposed. The model can be successfully used to simulate the dynamic processes of generating the double-strand breaks (DSBs) and their repairing, ataxia telangiectasia mutated (ATM) activation, as well as the oscillations occurring in the p53-MDM2 feedback loop.


title: Discovery and antitumor activities of constituents from Cyrtomium fortumei (J.) Smith rhizomes

text: BACKGROUND: Cyrtomium fortumei (J.) Smith is an important Chinese herbal medicine because of its biological functions. However, systematic and comprehensive studies on the phytochemicals from Cyrtomium fortumei (J.) Smith and their bioactivity are limited. RESULTS: Using the bioassay-guided technique, the ethyl acetate and n-BuOH extracts of the rhizomes of Cyrtomium fortumei (J.) Smith were shown to exhibit good antitumor activities, consequently leading to the isolation of 23 compounds. All compounds were isolated from the plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells MGC-803, PC3, and A375 in vitro by MTT (thiazolyl blue tetrazolium bromide) assay, and the results showed that pimpinellin (3) had potent cytotoxic activities against the three cell lines, with the IC(50) values of 14.4 ± 0.3 μM, 20.4 ± 0.5 μM, and 29.2 ± 0.6 μM, respectively. The mechanism of the antitumor action indicated that pimpinellin inhibited the growth of MGC-803 cells via the induction of tumor cell apoptosis, with apoptosis ratio of 27.44% after 72 h of treatment at 20 μM. CONCLUSIONS: This study suggests that most of the compounds from the roots of Cyrtomium fortumei (J.) Smith could inhibit the growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis.