docid: seirbkiq

title: Effect of air travel on the spread of an avian influenza pandemic to the United States

text: Abstract The highly pathogenic avian influenza (HPAI) strain H5N1, which first appeared in Hong Kong in 1997, achieved bird-to-human transmission, causing a severe disease with high mortality to humans [18]. According to the World Health Organization (WHO), a total of 637 cases were reported in fifteen countries, including 378 deaths, corresponding to a case fatality rate of nearly 60% [19]. Avian influenza continues to be one of the deadliest diseases that jumps from animals to humans. Epidemiologists believe that it is likely to cause the next major global pandemic that could kill millions of people. The 2002 outbreak of severe acute respiratory syndrome (SARS) demonstrated that international air travel can significantly influence the global spread of an infectious disease. This paper studies the effects of air travel on the spread of avian influenza from Asian and Australian cities to the United States. A two-city mathematical model involving a pandemic strain is used to derive the basic reproduction number ( R 0 ), which determines if the disease will spread and persist ( R 0 > 1 ) or go extinct ( R 0 < 1 ). Real air travel data is used to model the disease spread by individuals who are susceptible to or are infected with pandemic avian influenza. Analysis of the two-city model helps understand the dynamics of the spread of pandemic influenza when the cities are connected by air travel. Understanding these effects can help public health officials and policy-makers select the appropriate disease control measures. Also, it can provide guidance to decision-makers on where to implement control measures while conserving precious resources.


title: Real-time location and inpatient care systems based on passive RFID

text: Abstract RFID technology meets identification and tracking requirements in healthcare environments with potential to speed up and increase reliability of involved processes. Due to this, high expectations for this integration have emerged, but hospital and medical centers interested in adoption of RFID technology require prior knowledge on how to squeeze RFID capabilities, real expectations and current challenges. In this paper, we show our lab tested solutions in two specific healthcare scenarios. On the one hand, we analyze the case of a medical equipment tracking system for healthcare facilities enabling both real-time location and theft prevention. Worth-noting aspects such as possible EMI interferences, technology selection and management of RFID data from hospital information system are analyzed. Lab testing of system reliability based on passive UHF RFID is provided for this case. On the other hand, we analyze and provide a solution for care and control of patients in a hospital based on passive HF RFID with the result of a fully functional demonstrator. Our prototype squeezes RFID features in order to provide a backup data source from patient's wristband. It also provides an offline working mode aiming to increase application reliability under network fail down and therefore, improving patient's safety. Considerations regarding lessons learned and challenges faced are exposed.


ESICM LIVES 2016: part two: Milan, Italy. 1–5 October 2016


title: Epidemiological Trends of Coronavirus Disease 2019 in China

text: Background: The Coronavirus Disease 2019 (COVID-19) epidemic broke out in Wuhan, China, and it spread rapidly. Since January 23, 2020, China has launched a series of unusual and strict measures, including the lockdown of Wuhan city to contain this highly contagious disease. We collected the epidemiological data to analyze the trend of this epidemic in China. Methods: We closely tracked the Chinese and global official websites to collect the epidemiological information about COVID-19. The number of total and daily new confirmed cases of COVID-19 in China was presented to illustrate the trend of this epidemic. Results: On January 23, 2020, 835 confirmed COVID-19 cases were reported in China. On February 6, 2020, there were 31,211 cases. By February 20, 2020, the number reached as high as 75,993. Most cases were distributed in and around Wuhan, Hubei province. Since January 23, 2020, the number of daily new cases in China except Hubei province reached a peak of 890 on the eleventh day and then it declined to a low level of 34 within two full-length incubation periods (28 days), and the number of daily new cases in Hubei also started to decrease on the twelfth day, from 3,156 on February 4, 2020 to 955 on February 15, 2020. Conclusion: The COVID-19 epidemic has been primarily contained in China. The battle against this epidemic in China has provided valuable experiences for the rest of the world. Strict measures need to be taken as earlier as possible to prevent its spread.


title: A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity

text: Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity.


title: Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response

text: The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. These systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-41) contains supplementary material, which is available to authorized users.


title: A 10-year surveillance of antimicrobial susceptibility patterns in Shigella sonnei isolates circulating in Jiangsu Province, China

text: Abstract Objectives The rapid emergence of drug-resistant Shigella sonnei is a serious public health problem. This study aimed to characterise the antimicrobial resistance patterns, molecular subtypes, and integron types and resistance gene cassettes in S. sonnei from Jiangsu Province, China. Methods In total, 340 S. sonnei were collected in 2002–2011 throughout Jiangsu Province. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), PCR amplification of integrons, restriction fragment length polymorphism (RFLP) and DNA sequencing of cassette regions were performed. Results Resistance rates to ampicillin (67.7%), nalidixic acid (75.2%), tetracycline (73.7%) and trimethoprim/sulfamethoxazole (68.7%) remained high. Strains from Centre and South Jiangsu showed higher resistance and multiresistance rates compared with the North. PFGE analysis indicated that large-scale clonal transmission among different cities occurred several times during 10 years. Among all strains, 55.9% (190/340) harboured class 1 integrons, 80.3% (273/340) harboured class 2 integrons and 49.4% (168/340) harboured an atypical class 1 integron. Resistance rates to nine antimicrobials in the class 1 integron-positive group were significantly higher than in the negative group (P < 0.05). Seven different gene cassettes were detected in class 1 integrons. The most prevalent type was aacA4–cmlA1 (114/286). Class 2 integrons carried the gene cassette array dfrA1–sat1–aadA1, and the atypical class 1 integron carried bla OXA-30–aadA1. Conclusions The increasing antimicrobial resistance and significant clonal transmission of S. sonnei circulating in Jiangsu were closely related to the high prevalence of integrons and gene cassettes. Long-term cross-regional monitoring of antimicrobial resistance is urgently required for S. sonnei.


title: Inhibition of herpes simplex virus type 1 by small interfering RNA

text: Background. RNA interference, a conserved mechanism in which a sequence‐specific gene‐silencing process is mediated by small interfering RNA (siRNA), is a promising method of gene therapy in treating a variety of viral diseases. Aim. To investigate the antiviral effects of siRNA on herpes simplex virus type 1 (HSV‐1) replication in Vero cells. Methods. The antiviral effects of siRNA duplexes targeting the VP16 and DNA polymerase genes of HSV‐1 were evaluated by yield‐reduction and plaque‐reduction assays. The effect of siRNA on the expression of target genes was measured by real‐time quantitative reverse transcription PCR. Results. Two siRNA duplexes (siRNA‐1, targeting VP16, and siRNA‐4, targeting DNA polymerase), were found to be highly effective in inhibiting HSV‐1 replication. siRNA‐1 and siRNA‐4 reduced HSV‐1 replication by around 2 log(10) and 1 log(10) in the yield‐‐reduction assay and by ∼85% and ∼70% in the plaque‐reduction assay, respectively. Significant decreases in the mRNA level of VP16 and DNA polymerase genes were detected after viral infection in the Vero cells pretreated with siRNA‐1 and siRNA‐4, respectively. Conclusion. These results indicate that siRNA can potently inhibit HSV‐1 replication in vitro, suggesting that siRNA‐based antiviral therapy may be a potential effective therapeutic alternative for patients with HSV‐1 infection.


Combined anti-influenza virus effect of a plant polyphenol-rich extract and rimantadine


title: Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2

text: We evaluated the performance of the BioFire® Respiratory Panel 2.1 (RP2.1) in the detection of SARS CoV-2 in comparison against three other SARS CoV-2 EUA assays. In these studies, the RP2.1 panel had 98% positive percent agreement (48/49) and 100% negative percent agreement (49/49). Since 30% of nasopharyngeal swab specimens have a SARS CoV-2 Ct >30 and thus detection of virus in low titers is clinically relevant, a sample with a high titer was diluted and each 10 fold dilution was tested in triplicate and compared against 6 other EUA approved SARS CoV-2 assays. These data suggested that the BioFire® RP2.1 panel, along with four other SARS CoV-2 assays (Roche cobas, Cepheid Xpert Xpress, BioFire® Defense COVID19, and NECoV19), consistently detected viral RNA at the 10-7 dilution. Overall, these studies suggest that the BioFire® RP2.1 assay can be used to detect acute cases of SARS CoV2 in addition to patients with low viral titer later in disease presentation.


title: Susceptibility of rodent cell lines to rat coronaviruses and differential enhancement by trypsin or DEAE-dextran

text: Cell lines of rodent origin were tested for susceptibility to infection with rat coronavirus (RCV), including sialodacryoadenitis virus (SDAV) and Parker's rat coronavirus (PRCV). LBC rat mammary adenocarcinoma cells were susceptible only if the cells were treated with diethylaminoethyl-dextran (DEAE-D). A recent report that RCVs grow well in L2 mouse fibroblast cells was confirmed and expanded. RCV infection of L2 cells was substantially enhanced by treatment of cells with trypsin but not by treatment with DEAE-D. Primary isolation of SDAV from experimentally infected rats was accomplished using trypsin-treated L2 cells. One of 13 additional cell lines tested (rat urinary bladder epithelium, RBL-02) supported growth of RCVs, and growth was slightly enhanced by DEAE-D, but not by trypsin. These refinements of in vitro growth conditions for RCVs should facilitate further studies of their basic biology and improve options for primary isolation.


title: Lung transplant infection

text: Lung transplantation has become an accepted therapeutic procedure for the treatment of end‐stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection‐ and rejection‐related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.


title: Soziale Arbeit und „Corona“: Einige „blinde Flecken“ in der Pandemiediskussion

text: Soziale Arbeit geriet in den Diskussionen und Planungen um die Eindämmung der Corona-Pandemie erst langsam und nach deutlichen Interventionen in den Blick. Und bis heute sind weder alle Handlungsfelder als „systemrelevant“ anerkannt, noch werden Expert_innen der Sozialen Arbeit in die Beratungsgremien der Politik berufen. Hinzu kommen nationalstaatliche Orientierungen, die für Internationale Soziale Arbeit eine Herausforderung darstellen.


COVID-19–Associated Pediatric Multisystem Inflammatory Syndrome


title: Bacteria and Viruses The Bogeymen in the Intensive Care Unit

text: This article covers the frequently encountered bacteria and viruses in the ICU. It focuses on recognition, management, and prevention. Emerging and difficult-to-treat organisms are covered in detail.


title: Molecular Characterization of the ORF3 and S1 Genes of Porcine Epidemic Diarrhea Virus Non S-INDEL Strains in Seven Regions of China, 2015

text: In an effort to trace the evolution of porcine epidemic diarrhea virus (PEDV), S1 and ORF3 genes of viruses identified in 41 pig farms from seven regions (North, Northeast, Northwest, Central, East, South West, and South, respectively) of China in 2015 were sequenced and analyzed. Sequence analysis revealed that the 41 ORF3 genes and 29 S1 genes identified in our study exhibited nucleotide homologies of 98.2%–100% and 96.6%–100%, respectively; these two genes exhibited low nucleotide sequence similarities with classical CV777 strain and early Chinese strain LZC. Phylogenetic analysis indicated that the identified PEDV strains belonged to global non S-INDEL strains, and exhibited genetic diversity; S1 gene of the HLJ2015/DP1-1 strain harbored an unique deletion of 12 nucleotides (A(1130)CAACTCCACTG(1141)); while the Chinese PEDV S-INDEL reference strains included two types of the “CV777” S-INDEL as well as the “US” S-INDEL, and all co-circulated with Chinese non S-INDEL strains. Of 29 identified S1 genes, the SS2 epitope (Y(748)SNIGVCK(755)) was highly conserved, while the SS6 epitope (L(764)QDGQVKI(771)) and pAPN receptor-binding region (aa 490–615) exhibited amino substitutions. Nine possible recombination events were identified between the 29 identifed S1 genes and the 3 S1 reference genes from early Chinese PEDV strains. The complete S genes of selected Chinese PEDV field strains (2011–2015) showed 5.18%–6.07% nucleotide divergence, which is far higher than the divergence observed in early Chinese PEDV strains (3.1%) (P<0.05). Our data provide evidence that PEDV non S-INDEL strains with genetic diversities and potential recombination circulate in seven regions of China in 2015; Chinese PEDV S-INDEL strains exhibit genetic diversity and co-circulate with non S-INDEL strains.


title: The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases

text: Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.


title: Cell culture propagation of bovine coronavirus

text: Although most field strains of bovine coronavirus (BCV) grow poorly in cell culture and fail to produce cytopathic effects (CPE) until after blind passage, primary calf kidney (PCK) and Vero cells have permitted primary isolation of virus. Cell culture-adapted strains of BCV replicate in PCK, bovine embryonic lung, bovine fetal thyroid, bovine fetal brain, bovine skin cells, ovine fetal kidney cells, and the cell lines pig kidney K3 and 15, Vero, human embryonic lung fibroblasts, HRT-18, MDBK and BEK-1, with trypsin useful for enhancing replication. Organ culture as well as suckling mouse, rat, and hamster brains also support the growth of cell culture-adapted BCV strains. Viral growth is most commonly detected by CPE, immunofluorescence, hemagglutination, and hemadsorption assays or electron microscopy of supernatants from infected cells. In this report, the optimal conditions for the growth and plaque assay of the NCDV strain of BCV in MDBK cells are described.


title: Harnessing HLA‐E‐restricted CD8 T lymphocytes for adoptive cell therapy of severe COVID‐19 patients

text: SARS‐CoV‐2 is spreading worldwide, and is a pandemic virus that has infected almost 5 million individuals and causing 300.000 deaths, as of mid‐May 2020. Because SARS‐CoV‐2 is a new virus in humans there are currently no vaccines, monoclonal antibodies (mAbs) or even effective drugs available. Human convalescent plasma transfusion is an option for either prophylactic or therapeutic treatment of COVID‐19 patients, but its administration to patients who are affected by severe pulmonary disease is associated with increased risk of transfusion‐related acute lung injury (TRALI).


docid: jodnluhh

title: Logistics and procurement outsourcing in the healthcare sector: A comparative analysis

text: Abstract As outsourcing ventures become more complex, opportunities for synergies and efficiencies increase, but also create longer and more fragmented supply chains which could have disastrous consequences, particularly in a healthcare context. This study investigates the implications of outsourcing on healthcare supply chains by comparing two alternatives: outsourcing from public-to-private and outsourcing from public-to-public. A conceptual framework, adapted from previous literature, has been employed to provide a comprehensive overview of the phenomenon and consider the implications of logistics and procurement outsourcing on the healthcare supply chain structure and performance. The study presents a European cross-country comparison, analysing both the National Health Service (NHS) outsourcing in England (public-to-private outsourcing) and the Regional Health Service (RHS) outsourcing in the Tuscany region (Italy) (public-to-public outsourcing). Specificities and commonalities of the two outsourcing experiences provide suggestions for managers and policy-makers and enhance the current knowledge of outsourcing in the public healthcare sector.


title: Novel coronavirus transmission to water bodies; risk of COVID-19 pneumonia to aquatic mammals

text: [Figure: see text]


title: Virus and virus-like particles observed in the intestinal contents of the possum,Trichosurus vulpecula

text: Intestinal contents derived from the Australian brush-tailed possum,Trichosurus vulpecula, were examined by negative stain electron microscopy for the presence of viruses. Out of 100 samples, 23 contained at least one type of vertebrate virus or virus-like particle. Adenovirus was identified in six samples, herpesvirus in two samples, coronavirus in four samples, and coronavirus-like particles in 14 samples. To date no viruses of the brush-tailed possum have been isolated in tissue culture but these results indicate that this species is probably host to several viral species.


Medicina Nuclear en la pandemia por Covid-19


title: SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications

text: Abstract The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world – this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death. To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease. Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body. The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization. We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.


title: Sequence-Based Human Leukocyte Antigen—B Typing of Patients Infected with Ebola Virus in Uganda in 2000: Identification of Alleles Associated with Fatal and Nonfatal Disease Outcomes

text: The Sudan species of Ebola virus (SEBOV) causes severe, often fatal infection in ∼50% of infected humans. We sought to determine whether the human leukocyte antigen—B (HLA-B) locus has a role in the outcome of SEBOV disease by typing 77 cases from an outbreak in northern Uganda in 2000–2001. Sequence-based HLA-B typing was performed using leukocytes isolated from 77 patients. Statistical analysis and a predictive discriminant analysis (PDA) were applied to typing data. Epitope prediction software was also applied to SEBOV sequences. Statistically significant associations were found between certain sets of alleles and either fatal or nonfatal disease outcomes. Alleles B*67 and B*15 were associated with fatal outcomes, whereas B*07 and B*14 were associated with nonfatal outcomes. The PDA-derived functions that were produced were 81.8% accurate in classifying patients into their correct outcome group. Several epitopes predicted to bind strongly to HLA-B*07 molecules were identified in the viral polymerase, nucleoprotein, and VP35 protein. HLA-B alleles associated with either fatal or nonfatal outcomes of SEBOV disease were identified and can be used in a predictive model. Studies of HLA-B—restricted epitopes could contribute to characterization of protective host responses and to vaccine development.


title: From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS‐CoV‐2 and the changes in SARS‐CoV‐2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA‐dependent RNA polymerase and main protease (Mpro) of SARS‐CoV‐2, Beta‐CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS‐CoV‐2 prefers pyrimidine rich codons to purines. Most high‐frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS‐CoV‐2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS‐CoV‐2 structural proteins. SARS‐CoV‐2 encoded the highest number of over‐biased and negatively biased codons. Pangolin Beta‐CoV showed little differences with SARS‐CoV‐2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS‐CoV‐2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.


title: The fecal virome of domesticated animals

text: Next-generation sequencing is a new research tool in our hands helping us to explore still unknown fields of human and veterinary virology. Metagenomic analysis has enabled the discovery of putative novel pathogens and the identification of the etiologic agents of several diseases, solving long-standing mysteries caused by divergent viruses. This approach has been used in several studies investigating fecal samples of livestock, and companion animal species, providing information on the diversity of animal fecal virome, helping the elucidation of the etiology of diarrheal disease in animals and identifying potential zoonotic and emerging viruses.


title: The effect of protected areas on pathogen exposure in endangered African wild dog (Lycaon pictus) populations

text: Abstract Infectious diseases impact African wild dogs (Lycaon pictus), but the nature and magnitude of this threat likely varies among populations according to different factors, such as the presence and prevalence of pathogens and land-use characteristics. We systematically evaluated these factors to assist development of locally appropriate strategies to mitigate disease risk. Wild dogs from 16 sites representing five unconnected populations were examined for rabies virus, canine distemper virus (CDV), canine parvovirus, canine coronavirus, and Babesia spp. exposure. Analyses revealed widespread exposure to viral pathogens, but Babesia was never detected. Exposure to CDV was associated with unprotected and protected-unfenced areas where wild dogs likely have a high probability of domestic dog contact and, in the case of protected-unfenced areas, likely reside amongst high wildlife densities. Our findings also suggest that domestic dog contact may increase rabies and coronavirus exposure risk. Therefore, domestic dogs may be a source of CDV, rabies and coronavirus, while wildlife may also play an important role in CDV transmission dynamics. Relatively high parvovirus seroprevalence across land-use types suggests that it might persist in the absence of spillover from domestic dogs. Should intervention be needed to control pathogens in wild dogs, efforts to prevent rabies and coronavirus exposure might be directed at reducing infection in the presumed domestic dog reservoir through vaccination. If prevention of CDV and parvovirus infections were deemed a management necessity, control of disease in domestic dogs may be insufficient to reduce transmission risks, and vaccination of wild dogs themselves may be the optimal strategy.


Health measures to travelers and cruise ships in response to COVID-19


title: Adipositas erhöht Risiko für schweren Verlauf von COVID-19: Corona-Pandemie

text: Eine retrospektive Kohortenstudie zeigt, dass Adipositas das Risiko für eine Beatmungspflichtigkeit im Verlauf einer COVID-19-Erkrankung stark erhöht. Übergewichtige Menschen müssen sich also besonders aufmerksam an präventive Maßnahmen halten.


Covid-19: outbreak could last until spring 2021 and see 7.9 million hospitalised in the UK


title: A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19

text: The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.


title: Telehealth for High-Risk Pregnancies in the Setting of the COVID-19 Pandemic

text: As New York City became an international epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic, telehealth was rapidly integrated into prenatal care at Columbia University Irving Medical Center, an academic hospital system in Manhattan. Goals of implementation were to consolidate in-person prenatal screening, surveillance, and examinations into fewer in-person visits while maintaining patient access to ongoing antenatal care and subspecialty consultations via telehealth virtual visits. The rationale for this change was to minimize patient travel and thus risk for COVID-19 exposure. Because a large portion of obstetric patients had underlying medical or fetal conditions placing them at increased risk for adverse outcomes, prenatal care telehealth regimens were tailored for increased surveillance and/or counseling. Based on the incorporation of telehealth into prenatal care for high-risk patients, specific recommendations are made for the following conditions, clinical scenarios, and services: (1) hypertensive disorders of pregnancy including preeclampsia, gestational hypertension, and chronic hypertension; (2) pregestational and gestational diabetes mellitus; (3) maternal cardiovascular disease; (4) maternal neurologic conditions; (5) history of preterm birth and poor obstetrical history including prior stillbirth; (6) fetal conditions such as intrauterine growth restriction, congenital anomalies, and multiple gestations including monochorionic placentation; (7) genetic counseling; (8) mental health services; (9) obstetric anesthesia consultations; and (10) postpartum care. While telehealth virtual visits do not fully replace in-person encounters during prenatal care, they do offer a means of reducing potential patient and provider exposure to COVID-19 while providing consolidated in-person testing and services. Key Points: Telehealth for prenatal care is feasible. Telehealth may reduce coronavirus exposure during prenatal care. Telehealth should be tailored for high risk prenatal patients.


title: The Activity of Influenza and Influenza-like Viruses in Individuals Aged over 14 in the 2015/2016 Influenza Season in Poland

text: Infections in every epidemic season induced by respiratory viruses, especially by the influenza virus, are the cause of many illnesses and complications which often end in death. The aim of this study was to determine the activity of influenza and influenza-like viruses in individuals aged over of 14 in Poland during the 2015/2016 epidemic season. A total of 5070 specimens taken from patients were analyzed. The presence of the influenza virus was confirmed in 40.2% of cases, among which the subtype A/H1N1/pdm09 (62.6% positive samples) predominated. The analysis of confirmed influenza and influenza-like viruses in individuals divided into four age-groups demonstrate that the highest morbidity was reported for the age ranges: 45–64 (13.1%) and 26–44 (12.6%) years. An increase in the number of influenza type B cases (23.7% positive samples), which was the main cause of morbidity in the age group 15–25 years, was noticeable. Given the epidemiological and virological data, the 2015/2016 season in Poland was characterized by increased activity of the influenza virus compared to the previous season. In the 2015/2016 season, there were more than 3.8 million cases and suspected cases of influenza and influenza-like illness, more than 15,000 hospitalizations, and up to 140 deaths.


title: Point-of-care testing (POCT): Current techniques and future perspectives

text: Abstract Point-of-care testing (POCT) is a laboratory-medicine discipline that is evolving rapidly in analytical scope and clinical application. In this review, we first describe the state of the art of medical-laboratory tests that can be performed near the patient. At present, POCT ranges from basic blood-glucose measurement to complex viscoelastic coagulation assays. POCT shortens the time to clinical decision-making about additional testing or therapy, as delays are no longer caused by transport and preparation of clinical samples, and biochemical-test results are rapidly available at the point of care. Improved medical outcome and lower costs may ensue. Recent, evolving technological advances enable the development of novel POCT instruments. We review the underlying analytical techniques. If new instruments are not yet in practical use, it is often hard to decide whether the underlying analytical principle has real advantage over former methods. However, future utilization of POCT also depends on health-care trends and new areas of application. But, even today, it can be assumed that, for certain applications, near-patient testing is a useful complement to conventional laboratory analyses.


title: Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis

text: Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4(+) and CD8(+) T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8(+) T cells. However, these mice established fewer CD8(+) tissue-resident memory T (T(RM)) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8(+) T cells and slows viral RNA clearance but promotes CD8(+) T(RM) cell establishment.


title: Chapter 7 Long-term virus evolution in nature

text: Abstract Viruses spread to give rise to epidemics and pandemics, and some key parameters that include virus and host population numbers determine virus persistence or extinction in nature. Viruses evolve at different rates depending on the polymerase copying fidelity during genome replication and a number of environmental influences. Calculated rates of evolution in nature vary depending on the time interval between virus isolations. In particular, intrahost evolution is generally more rapid that interhost evolution, and several possible mechanisms for this difference are considered. The mechanisms by which the error-prone viruses evolve are very unlikely to render the operation of a molecular clock (constant rate of incorporation of mutations in the evolving genomes), although a clock is assumed in many calculations. Several computational tools permit the alignment of viral sequences and the establishment of phylogenetic relationships among viruses. The evolution of the virus in the form of dynamic mutant clouds in each infected individual, together with multiple environmental parameters renders the emergence and reemergence of viral pathogens an unpredictable event, another facet of biological complexity.


title: Feline coronavirus isolates from a part of Brazil: insights into molecular epidemiology and phylogeny inferred from the 7b gene

text: The Feline coronavirus (FCoV) can lead to Feline infectious peritonitis (FIP), which the precise cause is still unknown. The theory of internal mutation suggests that a less virulent biotype of FCoV (FECV) would lead to another more pathogenic biotype (FIPV) capable of causing FIP. In this work, the 7b gene was amplified from 51 domestic cat plasma samples by semi-nested PCR and tested through phylogenetic and phylogeographical approaches. The 7b gene of Brazilian isolates displayed high conservation, a strong correlation between the geographic origin of the viral isolates and their genealogy, and its evolution was possibly shaped by a combination of high rates of nucleotide substitution and purifying selection.


title: Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China

text: Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the “three uniformities and three combinations,” and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease.


title: Design, Synthesis, and Bioevaluation of Viral 3C and 3C-Like Protease Inhibitors

text: A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, α-ketoamide, bisulfite adduct, and α-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities.


Repurposing therapeutic agents and herbal medicines to defeat viral nemesis


title: DPP4 inhibition: preventing SARS‐CoV‐2 infection and/or progression of COVID‐19?

text: Dipeptidyl peptidase 4 (DPP4), also known as cluster of differentiation 26 (CD26), is a serine exopeptidase expressed ubiquitously in several tissues, including but not limited to lung, kidney, liver, gut, and immune cells. The question has been raised on whether DPP4 modulation or inhibition may prevent infection and/or progression of the COVID‐19. A docked complex model of the SARS‐CoV‐2 spike glycoprotein and DPP4 has been proposed, showing a large interface between the proteins and proposing close similarity with other coronaviruses using DPP4 as functional receptor. In absence of experimental validation, these data should be interpreted with caution. Nevertheless, this observation may rise the question on whether DPP4 is directly involved in SARS‐CoV‐2 cell adhesion/virulence, and whether DPP4 inhibition might be a therapeutic strategy for preventing infection. Although a direct involvement of DPP4 in SARS‐CoV‐2 infection needs to be clarified, there is also evidence suggesting that DPP4i modulate inflammation and exert anti‐fibrotic activity. These properties may be of potential use for halting progression to the hyperinflammatory state associated with severe COVID‐19. Taken together these findings may suggest a potential role for DPP4 inhibition or modulation in one or more steps of COVID‐19 immunopathogenesis. This article is protected by copyright. All rights reserved.


title: Pediatric cancer research: Surviving COVID‐19

text: A diverse panel of pediatric cancer advocates and experts, whose collective experience spans the continuum of international academic medicine, industry, government research, and cancer advocacy, recently discussed challenges for pediatric cancer research in the context of coronavirus disease 2019 (COVID‐19). Specifically, this special report addresses the following focus areas: (a) the critical role that translational research has played in transforming pediatric cancer outcomes; (b) the current and potential future impact of COVID‐19 on pediatric cancer research; (c) target areas of COVID‐19 research that may have application in immunity, oncogenesis, and therapeutic discovery; and (d) future considerations and directions in maintaining pediatric cancer research during and after COVID‐19.


title: Root response in Pisum sativum under naproxen stress: Morpho-anatomical, cytological, and biochemical traits

text: Non-steroidal anti-inflammatory drugs as an important group of emerging environmental contaminants in irrigation water and soils can influence biochemical and physiological processes essential for growth and development in plants as non-target organisms. Plants are able to take up, transport, transform, and accumulate drugs in the roots. Root biomass in ten-days old pea plants was lowered by 6% already under 0.1 mg/L naproxen (NPX) due to a lowered number of lateral roots, although 0.5 mg/L NPX stimulated the total root length by 30% as against control. Higher section area (by 40%) in root tip, area of xylem (by 150%) or stele-to-section ratio (by 10%) in zone of maturation, and lower section area in zone of lateral roots (by 18%) prove the changes in primary root anatomy and its earlier differentiation at 10 mg/L NPX. Accumulated NPX (up to 10 μg/g DW at 10 mg/L) and products of its metabolization in roots increased the amounts of hydrogen peroxide (by 33%), and superoxide (by 62%), which was reflected in elevated lipid peroxidation (by 32%), disruption of membrane integrity (by 89%) and lowering both oxidoreductase and dehydrogenase activities (by up to 40%). Elevated antioxidant capacity (SOD, APX, and other molecules) under low treatments decreased at 10 mg/L NPX (both by approx. 30%). Naproxen was proved to cause changes at both cellular and tissue levels in roots, which was also reflected in their anatomy and morphology. Higher environmental loading through drugs thus can influence even the root function.


title: Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein

text: Abstract Severe acute respiratory syndrome-coronavirus nucleocapsid (SARS-CoV N) protein has been found to be important to the processes related to viral pathogenesis, such as virus replication, interference of the cell process and modulation of host immune response; detection of the antigen has been used for the early diagnosis of infection. We have used recombinant N protein expressed in insect cells to generate 17 mAbs directed against this protein. We selected five mAbs that could be used in various diagnostic assays, and all of these mAbs recognized linear epitopes. Three IgG2b mAbs were recognized within the N-terminus of N protein, whereas the epitope of two IgG1 mAbs localized within the C-terminus. These mAbs were found to have significant reactivity with both non-phosphorylated and phosphorylated N proteins, which resulted in high reactivity with native N protein in virus-infected cells; however, they did not show cross-reactivity with human coronavirus. Therefore, these results suggested that these mAbs would be useful in the development of various diagnostic kits and in future studies of SARS-CoV pathology.


docid: lgprrwee

title: Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids

text: All lifeforms have developed highly sophisticated systems equipped to detect altered self and non-self nucleic acids (NA). In vertebrates, NA-sensing receptors safeguard the integrity of the organism by detecting pathogens, dyshomeostasis and damage, and inducing appropriate responses to eliminate pathogens and reconstitute homeostasis. Effector mechanisms include i) immune signaling, ii) restriction of NA functions such as inhibition of mRNA translation, and iii) cell death pathways. An appropriate effector response is necessary for host defense, but dysregulated NA-sensing can lead to devastating autoimmune and autoinflammatory disease. Their inherent biochemical similarity renders the reliable distinction between self NA under homeostatic conditions and altered or exogenous NA particularly challenging. In this review, we provide an overview of recent progress in our understanding of the closely coordinated and regulated network of innate immune receptors, restriction factors, and nucleases to effectively respond to pathogens and maintain host integrity.


title: Biodegradable polymers for modern vaccine development

text: Abstract Most traditional vaccines are composed either of a whole pathogen or its parts; these vaccines, however, are not always effective and can even be harmful. As such, additional agents known as adjuvants are necessary to increase vaccine safety and efficacy. This review summarizes the potential of biodegradable materials, including synthetic and natural polymers, for vaccine delivery. These materials are highly biocompatible and have minimal toxicity, and most biomaterial-based vaccines delivering antigens or adjuvants have been shown to improve immune response, compared to formulations consisting of the antigen alone. Therefore, these materials can be applied in modern vaccine development.


Evaluation of potential therapeutic options for COVID‐19


title: Preparedness and management of global public health threats at points of entry in Ireland and the EU in the context of a potential Brexit

text: Health security in the European Union (EU) aims to protect citizens from serious threats to health such as biological agents and infectious disease outbreaks- whether natural, intentional or accidental. Threats may include established infections, emerging diseases or chemical and radiological agents. Co-ordinated international efforts attempt to minimize risks and mitigate the spread of infectious disease across borders. We review the current situation (March 2019) with respect to detection and management of serious human health threats across Irish borders- and what may change for Ireland if/when the United Kingdom (UK) withdraws from the EU (Brexit). Specifically, this paper reviews international legislation covering health threats, and its national transposition; and EU legislation and processes, especially the relevant European Decision No. 1082/2013/EU of the European Parliament and of the Council on serious cross border threats to health with repeal of Decision No 2119/98/EC. We enumerate European surveillance systems and agencies which relate to port health security; we consider consortia and academic arrangements within the EU framework and established collaboration with the World Health Organization. We describe current Health Services Executive port health structures in Ireland which address preparedness and management of human health threats at points of entry. We appraise risks which Brexit could bring, reviewing literature on shared concerns about these risks, and we evaluate post-Brexit challenges for the EU, and potential opportunities to remain within current structures in shared health threat preparedness and response. It is imperative that the UK, Ireland and the EU work together to mitigate these risks using some agreed joint coordination mechanisms for a robust, harmonised approach to global public health threats at points of entry.


title: In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection

text: BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. FINDINGS: A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. CONCLUSION: Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.


title: The Perceived Threat of SARS and its Impact on Precautionary Actions and Adverse Consequences: A Qualitative Study Among Chinese Communities in the United Kingdom and the Netherlands

text: BACKGROUND: Although the SARS outbreak involved few probable cases of infection in Europe, swift international spread of infections raised the possibility of outbreaks. In particular, SARS presented a sociopsychological and economic threat to European Chinese communities because of their close links with the outbreak’s origins. METHODS: A qualitative study was conducted among Chinese residents in the United Kingdom and the Netherlands to identify the origins of SARS risk perceptions and their impact on precautionary actions and adverse consequences from the perspective of vulnerable communities living in unaffected regions. Analysis was informed by protection motivation theory. RESULTS: Results revealed that information from affected Asia influenced risk perceptions and protective behavior among the Chinese in Europe when more relevant local information was absent. When high risk perceptions were combined with low efficacy regarding precautionary measures, avoidance-based precautionary action appeared to dominate responses to SARS. These actions may have contributed to the adverse impacts of SARS on the communities. CONCLUSIONS: Experiences of European Chinese communities suggest that practical and timely information, and consistent implementation of protective measures from central governments are essential to protect vulnerable populations in unaffected regions from unnecessary alarm and harm during outbreaks of emerging infections.


title: Commentary: COVID in Care Homes—Challenges and Dilemmas in Healthcare Delivery

text: The COVID-19 pandemic has disproportionately affected care home residents internationally, with 19–72% of COVID-19 deaths occurring in care homes. COVID-19 presents atypically in care home residents and up to 56% of residents may test positive whilst pre-symptomatic. In this article, we provide a commentary on challenges and dilemmas identified in the response to COVID-19 for care homes and their residents. We highlight the low sensitivity of PCR testing and the difficulties this poses for blanket screening and isolation of residents. We discuss quarantine of residents and the potential harms associated with this. Personal Protective Equipment (PPE) supply for care homes during the pandemic has been suboptimal and we suggest that better integration of procurement and supply is required. Advance care planning has been challenged by the pandemic and there is a need to for healthcare staff to provide support to care homes with this. Finally, we discuss measures to implement augmented care in care homes, including treatment with oxygen and subcutaneous fluids, and the frameworks which will be required if these are to be sustainable. All of these challenges must be met by healthcare, social care and government agencies if care home residents and staff are to be physically and psychologically supported during this time of crisis for care homes.


A novel human coronavirus OC43 genotype detected in mainland China


title: Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection

text: In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, “crazy-paving” pattern and the “reverse halo” sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).


title: Detection of biological objects using dynamic characteristics of double-walled carbon nanotubes

text: This study explores double-walled carbon nanotubes as the sensing devices for biological objects including viruses and bacteria. The biological objects studied include alanine with amino terminal residue, deoxyadenosine with free residue, Coronaviridae and Bartonella bacilliformis. An expression has been articulated to identify the mass of biological objects from the shift of frequency. Sensitivity of the sensor has been calculated when subjected to such biological objects. Molecular structural mechanics approach has been used for investigating the vibrational responses of zigzag and armchair double-walled carbon nanotube-based nano biosensors. The elastic properties of beam element are calculated by considering mechanical characteristics of covalent bonds between the carbon atoms in the hexagonal lattice. Spring elements are used to describe the interlayer interactions between the inner and outer tubes caused due to the van der Waals forces. The mass of each beam element is assumed as point mass at nodes coinciding with carbon atoms at inner and outer wall of DWCNT. Based on the sensitivity and the frequency shift it can be concluded that cantilever zigzag DWCNTs are better candidates for detecting the biological objects.


title: Regulated and prolonged expression of mIFNα in immunocompetent mice mediated by a helper-dependent adenovirus vector

text: A major goal in gene therapy is to develop efficient gene transfer protocols that allow tissue-specific, long-term and tightly regulated expression of the desired transgene. This objective is becoming more attainable through the co-evolution of gene transfer vectors and regulation systems. The ideal vector should efficiently transduce non-dividing cells with minimal toxicity, thus endowing the system with persistent transgene expression. The helper-dependent adenovirus vectors meet these requirements, as demonstrated in various studies in the literature. The most promising regulation system is the tet-on system, which has low basal transcriptional activity and high inducibility. To explore the regulated transgene expression in the context of a helper-dependent vector, we constructed the HD-TET-IFN vector, containing the mIFNα gene under the control of the tetracycline inducible transactivator rtTA2(s)-S2. Mice injected with HD-TET-IFN showed high levels of serum mIFNα only upon transcriptional activation. The transgene expression was reinducible to the same high level up to 3 months p.i., and the amount of expressed cytokine could be regulated by dosing doxycycline. Transcriptional activation of mIFNα induced by doxycycline resulted in prolonged survival and reduced liver damage in HD-TET-IFN-injected mice challenged with a lethal dose of coronavirus. Activation of antiviral genes mediated by doxycycline-dependent mIFNα expression was also observed at low HD-TET-IFN doses. The possibility of controlling gene expression by the combination of HD vectors and the latest tet-on transactivator also holds promise for studying gene function in other animal models.


title: Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

text: Abstract Ethnopharmacological relevance Pulmonary fibrosis (PF) is a chronic, debilitating and often lethal lung disorder. Despite the molecular mechanisms of PF are gradually clear with numerous researchers’ efforts, few effective drugs have been developed to reverse human PF or even halt the chronic progression to respiratory failure. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years especially in China, often exerts wider action spectrum than previously attempted options in treating human diseases. Recent data have shown the anti-fibrotic benefits of the active ingredients from TCM in this field, which may represent an attractive source of the drug discovery against PF. Aim of the review This review summarizes the pre-clinical and clinical evidence on the benefits of TCM and their active ingredients, and provides a comprehensive information and reliable basis for the exploration of new treatment strategies of botanical drugs in the therapy of PF. Methods The literature information was obtained from the scientific databases on ethnobotany and ethno medicines (up to Aug 2016), mainly from the Pubmed, Web of Science and CNKI databases, and was to identify the experimental studies on the anti-fibrotic role of the active agents from TCM and the involved mechanisms. The search keywords for such work included: “lung fibrosis” or “pulmonary fibrosis”, and “traditional Chinese medicine”, “extract” or “herb”. Results A number of studies have shown that the active agents of single herbs and TCM formulas, particularly the flavonoids, glycosides and alkaloids, exhibit potential benefits against PF, the mechanisms of which appear to involve the regulation of inflammation, oxidant stress, and pro-fibrotic signaling pathways, etc. Besides, the processing methods for discovering TCM in treating PF were prospectively discussed. Conclusion These research work have shown the therapeutic benefits of TCM in the treatment of PF. However, more continued researches should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights provided in present review will be needed for further exploration of botanical drugs in the development of PF therapy.


title: Chapter 1 The Human Toll of Viral Diseases Past Plagues and Pending Pandemics

text: Abstract This chapter profiles some examples of past and current viral infections that have levied a high toll in human misery and mortality, and derives a number of lessons about the dynamics of viral pandemics. Viral epidemics can be very disruptive to civil society, and—conversely—civil disasters can trigger viral epidemics. Furthermore, viruses likely play an insidious role in initiating a number of chronic diseases whose burden is ever increasing. Evolving technologies have led to much more rapid detection of emerging viral diseases anywhere in the world. However, current efforts to mitigate the toll of viral diseases are less than satisfactory, and futurists predict the emergence of new pandemics particularly of zoonotic origin. Pathogenesis—the subject of this book—informs ongoing efforts to mitigate the toll of viral disease.


title: Prognostic Factors for Severe Coronavirus Disease 2019 in Daegu, Korea

text: BACKGROUND: Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS: We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS: Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90–193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35–88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45–452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64–1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION: In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.


title: Chapter 8 Mechanisms of Cell and Tissue Damage

text: Many infections are associated with damage inflicted either directly or indirectly by invading pathogens. Although some infections do not result in host damage, it is often a natural consequence of the activities of virulence factors produced by the pathogens in order to facilitate survival, and proliferation in the host or onward transmission to another host. The damage often manifests itself as the symptoms of disease which can be useful for diagnosis and for informing appropriate treatments. A wide array of different types of toxins which cause damage to the host are produced by different bacterial pathogens. Here we provide examples of well-characterised toxins and describe their mechanisms of action, and potential function with regard to pathogenesis. In addition we describe indirect damage to the host in the form of inflammation or immunopathology, typically the result of the host's own immune response. Finally, we discuss diarrhoea as a special case and list some of the major pathogens and the toxins associated with this devastating disease.


title: Virus recognition of glycan receptors

text: Attachment of viruses to cell-surface receptors is the initial step in infection. Many mammalian viruses have evolved to recognize receptors that are glycans on cell-surface glycoproteins or glycolipids. Although glycans are a ubiquitous component of mammalian cells, the types of terminal structures expressed vary among different cell-types and tissues, and even between comparable cells and tissues from different species, frequently leading to specific tissue and species tropisms as a direct consequence of glycan receptor recognition. Covering the majority of known virus families, this review provides an overview of mammalian viruses that use glycans as receptors, and their roles in determining in host recognition and tropism.


docid: ejgkrxoe

title: Replication of Synthetic Defective Interfering RNAs Derived from Coronavirus Mouse Hepatitis Virus-A59

text: Abstract We have analyzed the replication of deletion mutants of defective interfering (DI) RNAs derived from the coronavirus mouse hepatitis virus (MHV)-A59 in the presence of MHV-A59. Using two parental DI RNAs, MIDI and MIDIΔH, a twin set of deletion mutants was generated with progressively shorter stretches of 5′ sequence colinear with the genomic RNA. All deletion mutants contained in-frame ORFs. We show that in transfected cells and after one passage the DI RNAs were detectable and that their accumulation was positively correlated with the length of 5′ sequence they contained. However, accumulation of two twin mutants, Δ2, in which sequences from nucleotide position 467 were fused to those from position 801, was undetectable. In passage 4 cells, but not in transfected or in passage 1 cells, recombination with genomic RNA led to the appearance of the parental DI RNAs. The accumulation of these parental RNAs was inversely correlated with the length of 5′ sequence on the deletion mutants and was highest in the Δ2 samples. In sharp contrast to the data reported for MHV-JHM-derived DI RNAs, we show that MHV-A59-derived mutant RNAs do not require an internal sequence domain for replication. The data suggest that coronavirus replication involves an RNA superstructure at the 5′ end of the genome or one comprising both ends of the genomic RNA. We also conclude from the recombination data that in-frame mutants with impaired replication signals are more fit than out-frame mutants with intact replication signals.


title: Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (γ penetrene)

text: BACKGROUND: Borna disease virus (BDV) is the type member of the Bornaviridae, a family of viruses that induce often fatal neurological diseases in horses, sheep and other animals, and have been proposed to have roles in certain psychiatric diseases of humans. The BDV glycoprotein (G) is an extensively glycosylated protein that migrates with an apparent molecular mass of 84,000 to 94,000 kilodaltons (kDa). BDV G is post-translationally cleaved by the cellular subtilisin-like protease furin into two subunits, a 41 kDa amino terminal protein GP1 and a 43 kDa carboxyl terminal protein GP2. RESULTS: Class III viral fusion proteins (VFP) encoded by members of the Rhabdoviridae, Herpesviridae and Baculoviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Proteomics computational analyses suggest that the structural/functional motifs that characterize class III VFP are located collinearly in BDV G. Structural models were established for BDV G based on the post-fusion structure of a prototypic class III VFP, vesicular stomatitis virus glycoprotein (VSV G). CONCLUSION: These results suggest that G encoded by members of the Bornavirdae are class III VFPs (gamma-penetrenes).


title: Dataset of Vietnamese teachers’ perspectives and perceived support during the COVID-19 pandemic

text: The COVID-19 pandemic has caused unprecedented damage to the educational system worldwide. Besides the measurable economic impacts in the short-term and long-term, there is intangible destruction within educational institutions. In particular, teachers – the most critical intellectual resources of any schools – have to face various types of financial, physical, and mental struggles due to COVID-19. To capture the current context of more than one million Vietnamese teachers during COVID-19, we distributed an e-survey to more than 2,500 randomly selected teachers from two major teacher communities on Facebook from 6th to 11th April 2020. From over 373 responses, we excluded the observations which violated our cross-check questions and retained 294 observations for further analysis. This dataset includes: (i) Demographics of participants; (ii) Teachers' perspectives regarding the operation of teaching activities during the pandemic; (iii) Teachers' received support from their schools, government bodies, other stakeholders such as teacher unions, and parents' associations; and (iv) teachers' evaluation of school readiness toward digital transformation. Further, the dataset was supplemented with an additional question on the teachers' primary source of professional development activities during the pandemic.


title: Febuxostat therapy in outpatients with suspected COVID‐19: A clinical trial

text: BACKGROUND: The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID‐19 infection. METHODS: We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID‐19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalization, clinical and laboratory data including fever, cough, breathing rate, C‐Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment. RESULTS: Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnea (44.4%), dyspnea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID‐19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings. CONCLUSION: This trial suggests that FBX is as an alternative treatment to HCQ for COVID‐19 infection and may be considered in patients with a contraindication or precaution to HCQ.


title: A novel variant of the infectious bronchitis virus resulting from recombination events in Italy and Spain

text: Infectious bronchitis is considered to be one of the most devastating diseases in poultry. Control of its spread is typically attempted through biosecurity measures and extensive vaccination. However, the remarkable genetic and antigenic variability of the virus, which originate from both mutations and recombination events, represents an unsolved challenge for this disease. The present study reports on the emergence and spread of recombinant clusters detected in Italy and Spain between 2012 and 2014. A total of 36 Spanish and Italian infectious bronchitis virus (IBV) field strains were investigated and genetically characterized using phylogenetic, molecular, recombination and selection pressure analyses of the complete S1 gene. Based on the partial S1 sequencing, 27 IBV strains originating from Spain and nine from Italy were initially classified as being closely related to the Guandong/Xindadi (XDN) genotype. Phylogenetic analysis of the complete S1 gene revealed that the XDN strains formed a homogeneous clade with the Spanish IBV isolates within the QX genotype, whereas there was higher variability within the Italian strains. Recombination analysis determined that these strains belonged to four groups, which originated from independent recombination events between the QX and 793B IBV genotypes. Our data support the hypothesis of two different scenarios: firstly, in Spain, the large and homogeneous clade probably originated from a single offspring of the recombinant founder, which became dominant and spread throughout the country. Secondly, the nine Italian recombinants, which are characterized by three different recombination patterns, probably represent less fitted strains, because they were less viable with respect to their recombinant parents.


Skin check partner assistance for melanoma skin self-examination by at-risk patients: it takes two to identify melanomas


title: H1N1 infection and acute respiratory failure: can we give non-invasive ventilation a chance?

text: Abstract In 2009, a novel H1N1 Influenza virus has emerged and on June 11 the World Health Organization declared it as pandemic. It may cause acute respiratory failure ranging from severe Acute Respiratory Distress Syndrome to exacerbations of airflow limitation. Non-invasive ventilation is now considered first-line intervention for different causes of acute respiratory failure and may be considered in the context of H1N1 pandemic. Although infection control issues have been arisen, non-invasive ventilation was effective and safe during the Severe Acute Respiratory Syndrome in Asia. It is reasonable to recommend non-invasive ventilation in H1N1-related exacerbations of chronic respiratory diseases, especially in negative-pressure wards. Treatment of early Acute Respiratory Distress Syndrome associated with H1N1 using non-invasive ventilation could be tried rapidly identifying those who fail without delaying endotracheal intubation. Considering the high demand for critical care beds during the pandemic, non-invasive ventilation may have a role in reducing the estimated load.


Maoist public-health campaigns, Chinese medicine, and SARS


title: Type III IFN Receptor Expression and Functional Characterisation in the Pteropid Bat, Pteropus alecto

text: Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs) represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To obtain further insight into the type III IFN system in bats, we describe the characterization of the type III IFN receptor (IFNλR) in the black flying fox, P. alecto with the characterization of IFNλR1 and IL10R2 genes that make up the type III IFN receptor complex. The bat IFNλR complex has a wide tissue distribution and at the cellular level, both epithelial and immune cells are responsive to IFN-λ treatment. Furthermore, we demonstrate that the bat IFNλR1 chain acts as a functional receptor. To our knowledge, this report represents the first description of an IFN receptor in any species of bat. The responsiveness of bat cells to IFN-λ support a role for the type III IFN system by epithelial and immune cells in bats.


Toward sustainable and effective control: Experience of China Ebola Treatment Center in Liberia


title: Genes involved in mitochondrial biogenesis and function may not show synchronised responses to mitochondria in shell gland of laying chickens under infectious bronchitis virus challenge

text: BACKGROUND: Egg formation takes place in the oviduct of laying hens over a 24 h period. Infectious bronchitis virus (IBV) causes pathological lesions in the chicken oviduct. In the current study, mitochondrial counts were determined in three different segments of the oviduct during egg formation in laying chickens challenged with IBV T strain. Nuclear DNA encoded genes that are involved in mitochondrial biogenesis, fission and function were studied in the shell gland of the oviduct undergoing virus multiplication. RESULTS: In the shell gland, the mitochondrial count was significantly lower (P < 0.05) in the challenged group, compared with the control group. However, it did not vary in response to IBV challenge in the isthmus and magnum regions of the oviduct. The gene succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA) was down-regulated in the shell gland by IBV challenge (P < 0.05), while other genes being studied did not show responses to the challenge (P > 0.05). Differential expression of the genes was observed at different time-points of egg-shell formation. The expression levels of citrate synthase (CS), cytochrome C, somatic (CYC, S) and sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase) genes were significantly higher, while those of SDHA and dynamin related protein 1 (Drp1) genes were significantly lower, at 15 h compared with 5 h following oviposition of the previous egg. The expression level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) did not show significant change at different time-points. CONCLUSIONS: It was concluded that IBV T strain infection in laying hens reduced mitochondrial counts only in the shell gland region of the oviduct. The genes involved in mitochondrial biogenesis or function may not show synchronised responses to that of mitochondria in the shell gland of chickens under T strain of IBV challenge.


title: How to worry better

text: As the coronavirus outbreak continues, the science of dealing with uncertainty can help us make better decisions, says Rachel McCloy


title: COVID-19 Contact Tracing Apps: A Stress Test for Privacy, the GDPR and Data Protection Regimes

text: Digital surveillance has played a key role in containing the COVID-19 outbreak in China, Singapore, Israel and South Korea. Google and Apple recently announced the intention to build interfaces to allow Bluetooth contact tracking using Android and iPhone devices. In this article we look at the compatibility of the proposed Apple/Google Bluetooth exposure notification system with Western privacy and data protection regimes and principles, including the General Data Protection Regulation (GDPR). Somewhat counter-intuitively, the GDPR’s expansive scope is not a hindrance, but rather an advantage in conditions of uncertainty such as a pandemic. Its principle-based approach offers a functional blueprint for system design that is compatible with fundamental rights. By contrast, narrower, sector-specific rules such as the US Health Insurance Portability and Accountability Act (HIPAA), and even the new California Consumer Privacy Act (CCPA), leave gaps that may prove difficult to bridge in the middle of an emergency.


docid: rmlklqwo

title: Beating severe covid-19

text: We are beginning to understand how the virus kills – and how to stop it


title: Severe ARDS in COVID-19-infected pregnancy: obstetric and intensive care considerations

text: Abstract Since the emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of December 2019, its infection – COVID-19 – has been associated with severe morbidity and mortality and has left world governments, healthcare systems and providers caring for vulnerable populations, such as pregnant women, wrestling with the optimal management strategy. Unique physiologic and ethical considerations negate a one-size-fits-all approach to the care of critically ill pregnant women with COVID-19, and few resources exist to guide the multi-disciplinary team through decisions regarding optimal maternal-fetal surveillance, intensive care procedures, and delivery timing. We present a case of rapid clinical decompensation and development of severe Acute Respiratory Distress Syndrome (ARDS) in a woman at 31 weeks’ gestation to highlight these unique considerations and present an algorithmic approach to the disease’s diagnosis and management.


Association of Enterotoxigenic Bacteroides fragilis with Diarrheal Disease in Calves


title: Air pollution in Ontario, Canada during the COVID-19 State of Emergency

text: Abstract In March of 2020, the province of Ontario declared a State of Emergency (SOE) to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19). This disruption to the economy provided an opportunity to measure change in air pollution when the population spends more time at home with fewer trips. Hourly air pollution observations were obtained for fine particulate matter, nitrogen dioxide, nitrogen oxides and ozone from the Ontario air monitoring network for 2020 and the previous five years. The analysis is focused on a five-week period during the SOE with a previous five-week period used as a control. Fine particulate matter did not show any significant reductions during the SOE. Ozone concentrations at 12 of the 32 monitors were lower than any of the previous five-years; however, four locations were above average. Average ozone concentrations were 1 ppb lower during the SOE, but this ranged at individual monitors from 1.5 ppb above to 4.2 ppb below long-term conditions. Nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario, and both pollutants displayed their lowest concentrations for 22 of 29 monitors. Individual monitors ranged from 1 ppb (nitrogen dioxide) and 5 ppb (nitrogen oxides) above average to 4.5 (nitrogen dioxide) and 7.1 ppb (nitrogen oxides) below average. Overall, both nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario in response to the COVID-19 SOE, ozone concentrations suggested a possible reduction, and fine particulate matter has not varied from historic concentrations.


title: Identification of a novel linear B-cell epitope in the M protein of avian infectious bronchitis coronaviruses

text: This report describes the identification of a novel linear B-cell epitope at the C-terminus of the membrane (M) protein of avian infectious bronchitis virus (IBV). A monoclonal antibody (MAb) (designated as 15E2) against the IBV M protein was prepared and a series of 14 partially-overlapping fragments of the IBV M gene were expressed with a GST tag. These peptides were subjected to enzyme-linked immunosorbent assay (ELISA) and western blotting analysis using MAb 15E2 to identify the epitope. A linear motif, (199)FATFVYAK(206), which was located at the C-terminus of the M protein, was identified by MAb 15E2. ELISA and western blotting also showed that this epitope could be recognized by IBV-positive serum from chicken. Given that 15E2 showed reactivity with the (199)FATFVYAK(206) motif, expressed as a GST fusion protein, in both western blotting and in an ELISA, we proposed that this motif represented a linear B-cell epitope of the M protein. The (199)FATFVYAK(206) motif was the minimal requirement for reactivity as demonstrated by analysis of the reactivity of 15E2 with several truncated peptides that were derived from the motif. Alignment and comparison of the 15E2-defined epitope sequence with the sequences of other corona-viruses indicated that the epitope is well conserved among chicken and turkey coronaviruses. The identified epitope should be useful in clinical applications and as a tool for the further study of the structure and function of the M protein of IBV.


title: Natural immune response to Plasmodium vivax alpha-helical coiled coil protein motifs and its association with the risk of P. vivax malaria

text: Protein α-helical coiled coil structures are known to induce antibodies able to block critical functions in different pathogens. In a previous study, a total of 50 proteins of Plasmodium vivax erythrocytic asexual stages containing α-helical coiled coil structural motifs were identified in silico, and the corresponding peptides were chemically synthesized. A total of 43 peptides were recognized by naturally acquired antibodies in plasma samples from both Papua New Guinea (PNG) and Colombian adult donors. In this study, the association between IgG antibodies to these peptides and clinical immunity was further explored by measuring total IgG antibody levels to 24 peptides in baseline samples from a longitudinal study of children aged 1–3 years (n = 164) followed for 16 months. Samples were reactive to all peptides tested. Eight peptides were recognized by >50% of individuals, whereas only one peptide had < 20% reactivity. Children infected at baseline were seropositive to 23/24 peptides. No significant association was observed between antibody titers and age or molecular force of infection, suggesting that antibody levels had already reached an equilibrium. There was a strong association between antibody levels to all peptides and protection against P. vivax clinical episodes during the 16 months follow-up. These results suggest that the selected coiled coil antigens might be good markers of both exposure and acquired immunity to P. vivax malaria, and further preclinical investigation should be performed to determine their potential as P. vivax vaccine antigens.


title: Identification of an antilymphocyte transformation substance from Pasteurella multocida

text: Pasteurella multocida is one of the most important bacteria responsible for diseases of animals. Crude extracts from sonicated P. multocida strain Dainai‐1, which is serotype A isolated from bovine pneumonia, were found to inhibit proliferation of mouse spleen cells stimulated with Con A. The crude extract was purified by cation and anion exchange chromatography and hydroxyapatite chromatography. Its molecular weight was 27 kDa by SDS‐PAGE and it was named PM27. PM27 was found to inhibit proliferation of mouse spleen cells stimulated with Con A as effectively as did the crude extract; however, its activity was lost after heating to 100°C for 20 min. PM27 did not directly inhibit proliferation of HT‐2 cells, which are an IL‐2‐dependent T cell line, nor did it modify IL‐2 production by Con A‐stimulated mouse spleen cells. The N‐terminal amino acid sequence of PM27 was determined and BLAST analysis revealed its identity to uridine phosphorylase (UPase) from P. multocida. UPase gene from P. multocida Dainai‐1 was cloned into expression vector pQE‐60 in Escherichia coli XL‐1 Blue. Recombinant UPase (rUPase) tagged with His at the C‐terminal amino acid was purified with Ni affinity chromatography. rUPase was found to inhibit proliferation of mouse spleen cells stimulated with Con A; however, as was true for PM27, its activity was lost after heating to 100°C for 20 min. Thus, PM27/UPase purified from P. multocida has significant antiproliferative activity against Con A‐stimulated mouse spleen cells and may be a virulence factor.


docid: zwjrcaab

title: Distinct Patterns of B-Cell Activation and Priming by Natural Influenza Virus Infection Versus Inactivated Influenza Vaccination

text: Background. The human B-cell response to natural influenza virus infection has not been extensively investigated at the polyclonal level. Methods. The overall B-cell response of patients acutely infected with the 2009 pandemic influenza A(H1N1)pdm09 virus (A[H1N1]pdm09) was analyzed by determining the reactivity of plasmablast-derived polyclonal antibodies (PPAbs) to influenza proteins. Recipients of inactivated influenza vaccine containing the same A(H1N1)pdm09 strain were studied for comparison. Results. During acute infection, robust plasmablast responses to the infecting virus were detected, characterized by a greater PPAb reactivity to the conserved influenza virus nuclear protein and to heterovariant and heterosubtypic hemagglutinins, in comparison to responses to the inactivated A(H1N1)pdm09 vaccine. In A(H1N1)pdm09 vaccinees, the presence of baseline serum neutralizing antibodies against A(H1N1)pdm09, suggesting previous exposure to natural A(H1N1)pdm09 infection, did not affect the plasmablast response to vaccination, whereas repeated immunization with inactivated A(H1N1)pdm09 vaccine resulted in significantly reduced vaccine-specific and cross-reactive PPAb responses. Conclusions. Natural A(H1N1)pdm09 infection and inactivated A(H1N1)pdm09 vaccination result in very distinct patterns of B-cell activation and priming. These differences are likely to be associated with differences in protective immunity, especially cross-protection against heterovariant and heterosubtypic influenza virus strains.


title: Between Securitisation and Neglect: Managing Ebola at the Borders of Global Health

text: In 2014 the World Health Organization (WHO) was widely criticised for failing to anticipate that an outbreak of Ebola in a remote forested region of south-eastern Guinea would trigger a public health emergency of international concern (pheic). In explaining the WHO’s failure, critics have pointed to structural restraints on the United Nations organisation and a leadership ‘vacuum’ in Geneva, among other factors. This paper takes a different approach. Drawing on internal WHO documents and interviews with key actors in the epidemic response, I argue that the WHO’s failure is better understood as a consequence of Ebola’s shifting medical identity and of triage systems for managing emerging infectious disease (EID) risks. Focusing on the discursive and non-discursive practices that produced Ebola as a ‘problem’ for global health security, I argue that by 2014 Ebola was no longer regarded as a paradigmatic EID and potential biothreat so much as a neglected tropical disease. The result was to relegate Ebola to the fringes of biosecurity concerns just at the moment when the virus was crossing international borders in West Africa and triggering large urban outbreaks for the first time. Ebola’s fluctuating medical identity also helps explain the prominence of fear and rumours during the epidemic and social resistance to Ebola control measures. Contrasting the WHO’s delay over declaring a pheic in 2014, with its rapid declaration of pheics in relation to H1N1 swine flu in 2009 and polio in 2014, I conclude that such ‘missed alarms’ may be an inescapable consequence of pandemic preparedness systems that seek to rationalise responses to the emergence of new diseases.


title: Countrywide Survey for MERS-Coronavirus Antibodies in Dromedaries and Humans in Pakistan

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n = 776) and serum (n = 1050) samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged > 10 years (81.37%) followed by those aged 3.1–10 years (78.65%) and ≤ 3 years (58.19%). Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016–2017. Among the sampled population, 840 humans were camel herders. Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.


title: Nonpharmaceutical Interventions for Pandemic Influenza, International Measures

text: Since global availability of vaccine and antiviral agents against influenza caused by novel human subtypes is insufficient, the World Health Organization (WHO) recommends nonpharmaceutical public health interventions to contain infection, delay spread, and reduce the impact of pandemic disease. Virus transmission characteristics will not be completely known in advance, but difficulties in influenza control typically include peak infectivity early in illness, a short interval between cases, and to a lesser extent, transmission from persons with incubating or asymptomatic infection. Screening and quarantining entering travelers at international borders did not substantially delay virus introduction in past pandemics, except in some island countries, and will likely be even less effective in the modern era. Instead, WHO recommends providing information to international travelers and possibly screening travelers departing countries with transmissible human infection. The principal focus of interventions against pandemic influenza spread should be at national and community levels rather than international borders.