title: Exploring the Prospects of Engineered Newcastle Disease Virus in Modern Vaccinology

text: Many traditional vaccines have proven to be incapable of controlling newly emerging infectious diseases. They have also achieved limited success in the fight against a variety of human cancers. Thus, innovative vaccine strategies are highly needed to overcome the global burden of these diseases. Advances in molecular biology and reverse genetics have completely restructured the concept of vaccinology, leading to the emergence of state-of-the-art technologies for vaccine design, development and delivery. Among these modern vaccine technologies are the recombinant viral vectored vaccines, which are known for their incredible specificity in antigen delivery as well as the induction of robust immune responses in the vaccinated hosts. Although a number of viruses have been used as vaccine vectors, genetically engineered Newcastle disease virus (NDV) possesses some useful attributes that make it a preferable candidate for vectoring vaccine antigens. Here, we review the molecular biology of NDV and discuss the reverse genetics approaches used to engineer the virus into an efficient vaccine vector. We then discuss the prospects of the engineered virus as an efficient vehicle of vaccines against cancer and several infectious diseases of man and animals.


title: Early forecasting of the potential risk zones of COVID-19 in China's megacities

text: Recently, the coronavirus disease 2019 (COVID-19) has become a worldwide public health threat. Early and quick identification of the potential risk zones of COVID-19 infection is increasingly vital for the megacities implementing targeted infection prevention and control measures. In this study, the communities with confirmed cases during January 21–February 27 were collected and considered as the specific epidemic data for Beijing, Guangzhou, and Shenzhen. We evaluated the spatiotemporal variations of the epidemics before utilizing the ecological niche models (ENM) to assemble the epidemic data and nine socioeconomic variables for identifying the potential risk zones of this infection in these megacities. Three megacities were differentiated by the spatial patterns and quantities of infected communities, average cases per community, the percentages of imported cases, as well as the potential risks, although their COVID-19 infection situations have been preliminarily contained to date. With higher risks that were predominated by various influencing factors in each megacity, the potential risk zones coverd about 75% to 100% of currently infected communities. Our results demonstrate that the ENM method was capable of being employed as an early forecasting tool for identifying the potential COVID-19 infection risk zones on a fine scale. We suggest that local hygienic authorities should keep their eyes on the epidemic in each megacity for sufficiently implementing and adjusting their interventions in the zones with more residents or probably crowded places. This study would provide useful clues for relevant hygienic departments making quick responses to increasingly severe epidemics in similar megacities in the world.


title: Rapid detection of taxonomically important fatty acid methyl ester and steroid biomarkers using in situ thermal hydrolysis/methylation mass spectrometry (THM-MS): implications for bioaerosol detection

text: Abstract Implications for the rapid interrogation of biological materials collected from the atmosphere using a simple, one step, sample preparation technique was explored. For this purpose, various samples of whole bacteria, fungi, pollen, media contaminated with viruses, and proteins were treated with an aliquot of methanolic tetramethylammonium hydroxide prior to thermal introduction into the ion source of a triple quadrupole mass spectrometer. Molecular and fragment ions, consistent with fatty acid methyl esters (FAMEs) and steroids (non-methylated and methylated), generated during electron ionization (70 eV) of the volatile hydrolysates were subsequently detected. The varying distributions and relative intensities of these ions were used to discriminate between the different biological samples. More specifically, it was found that polyunsaturated FAMEs and steroids could be used to differentiate eukaryotic cells from prokaryotic cells since the latter do not generally synthesize either of these lipid membrane constituents. Further discrimination of the different eukaryotic samples was made based on the detection of ergosterol for fungi, cholesterol for the viral media, and C18:3Me for pollen. Multivariate statistical analysis was employed to evaluate and compare the large set of mass spectra generated during the study and to build a trained model for predicting the class membership of test samples entered as unknowns. Of 132 different samples subjected to the model as unknowns, 131 were correctly classified into their proper biological categories. Moreover, 29 out of 30 bacteria test samples representing five species of pathogenic bacteria were correctly classified at the species level.


H1N1 influenza pandemic: What we did and what we learnt?


title: Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

text: Respiratory syncytial virus (RSV) can cause recurrent infection in people because it does not stimulate a long-lived immunological memory. There is an urgent need to develop a safe and efficacious vaccine against RSV that would induce immunological memory without causing immunopathology following natural RSV infection. We have previously generated two recombinant live attenuated influenza vaccine (LAIV) viruses that encode immunodominant T-cell epitopes of RSV M2 protein in the neuraminidase or NS1 genes. These chimeric vaccines afforded protection against influenza and RSV infection in mice, without causing pulmonary eosinophilia or inflammatory RSV disease. The current study assessed the formation of influenza-specific and RSV-specific CD4 and CD8 T-cell responses in the lungs of mice, with special attention to the lung tissue-resident memory T cell subsets (T(RM)). The RSV epitopes did not affect influenza-specific CD4 effector memory T cell (Tem) levels in the lungs. The majority of these cells formed by LAIV or LAIV-RSV viruses had CD69(+)CD103(-) phenotype. Both LAIV+NA/RSV and LAIV+NS/RSV recombinant viruses induced significant levels of RSV M2(82) epitope-specific lung-localized CD8 Tem cells expressing both CD69 and CD103 T(RM) markers. Surprisingly, the CD69(+)CD103(+) influenza-specific CD8 Tem responses were augmented by the addition of RSV epitopes, possibly as a result of the local microenvironment formed by the RSV-specific memory T cells differentiating to T(RM) in the lungs of mice immunized with LAIV-RSV chimeric viruses. This study provides evidence that LAIV vector-based vaccination can induce robust lung-localized T-cell immunity to the inserted T-cell epitope of a foreign pathogen, without altering the immunogenicity of the viral vector itself.


title: Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings

text: PURPOSE: To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings. METHODS: Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings. RESULTS: Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype. CONCLUSION: Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types.


title: Lung, Heart, Vascular, and Diaphragm Ultrasound Examination of COVID-19 Patients: A Comprehensive Approach

text: Lung ultrasound (LU) has a multitude of features and capacities that make it a useful medical tool to assist physicians contending with the pandemic spread of novel coronavirus disease-2019 (COVID-19) caused by coronavirus SARS-CoV-2. Thus, a LU approach to patients with suspected COVID-19 is being implemented worldwide. In non-critical COVID-19 patients, two new LU signs have been described and proposed: the “waterfall” and the “light beam” signs. Both signs have been hypothesized to increase the diagnostic accuracy of LU for COVID-19 interstitial pneumonia. In critically-ill patients, a distinct pattern of LU changes seems to follow the disease's progression, and this information can be used to guide decisions about when a patient needs to be ventilated, as occurs in other disease states similar to COVID-19. Furthermore, a new algorithm has been published, which enables the automatic detection of B-lines as well as quantification of the percentage of the pleural line associated with lung disease. In COVID-19 patients, a direct involvement of cardiac function has been demonstrated, and ventilator-induced diaphragm dysfunction might be present due to the prolonged mechanical ventilation often involved, as reported for similar diseases. For this reason, cardiac and diaphragm ultrasound evaluation is highly important. Last but not least, due to the thrombotic tendency of COVID-19 patients, particular attention should also be paid to vascular ultrasound. This review is primarily devoted to the study of LU in COVID-19 patients. We explain the significance of its “light and shadows”, bearing in mind the context in which LU is being used: the emergency department and the intensive care setting. The use of cardiac, vascular, and diaphragm ultrasound is also discussed, as a comprehensive approach to patient care.


title: Pulmonary embolism in patients with Covid-19 pneumonia

text: We report an overall 24%(95% CI; 17–32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients


title: Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

text: Abstract The factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. Taken together, these results may partially explain why smokers are particularly susceptible to severe SARS-CoV-2 infections. Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive-feedback loops that increase ACE2 levels and facilitate viral dissemination.


title: Electron microscopy in the diagnosis of viral gastroenteritis in hospitalised children in the Czech Republic

text: Our study has been aimed at demonstrating the main role of viruses in the aetiology of acute gastroenteritis in children less than 5 years old and at pointing out the diagnostic potential of electron microscopy in the diagnosis of viral gastroenteritis. A prospective study was conducted to analyse the aetiology of diarrhoeal diseases in children less than 5 years of age admitted to the Department of Infectious Diseases between September 2006 and December 2008. All children were tested by faecal culture, latex agglutination and electron microscopy. A total of 832 children were included in the study. An aetiological agent was detected in 788 children (94.6 %). A bacterial aetiology was found in 22 (2.6 %) children and bacterial–viral co-infection was found in 146 (17.6 %) patients. The most frequent causative agents of gastroenteritis in children were viruses, which were detected in 620 (74.5 %) patients. The main causes of viral gastroenteritis were rotaviruses (detected in 410 children), followed by caliciviruses (42), coronaviruses (28), adenoviruses (19) and astroviruses (14). Dual viral infections were detected in 107 children, with rotavirus–calicivirus co-infection being the most common. Electron microscopy proved to be a more sensitive method in comparison with the latex agglutination test for the diagnosis of rotaviruses and adenoviruses. The major role of viruses in diarrhoeal diseases among children under 5 years of age in the Czech Republic has been confirmed. The diagnostic potential of electron microscopy, particularly in small outbreaks of gastroenteritis, was clearly shown.


title: Tracheotomy in the SARS‐CoV‐2 pandemic

text: The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. As such, surgeons will be called upon to perform tracheotomy for a subset of these chronically intubated patients. As seen during the SARS and the SARS‐CoV‐2 outbreaks, aerosol‐generating procedures (AGP) have been associated with higher rates of infection of medical personnel and potential acceleration of viral dissemination throughout the medical center. Therefore, a thoughtful approach to tracheotomy (and other AGPs) is imperative and maintaining traditional management norms may be unsuitable or even potentially harmful. We sought to review the existing evidence informing best practices and then develop straightforward guidelines for tracheotomy during the SARS‐CoV‐2 pandemic. This communication is the product of those efforts and is based on national and international experience with the current SARS‐CoV‐2 pandemic and the SARS epidemic of 2002/2003.


title: Inhibition in vivo of both infective Leishmania major and L. mexicana amazonensis mediated by a single monoclonal antibody

text: Abstract Monoclonal antibodies raised against a strain of Leishmania infantum isolated in Greece were produced and tested for their protective effect in an in vivo system (in BALB/C mice). A single monoclonal antibody, IgG2b isotype, can prevent the development of two Leishmania strains in vivo: one of L. major and one of L. mexicana amazonensis. This antibody-mediated protection may be dependent on complement.


title: Enabling Medicine Reuse Using a Digital Time Temperature Humidity Sensor in an Internet of Pharmaceutical Things Concept

text: Medicinal waste due to improper handling of unwanted medicines creates health and environmental risks. However, the re-dispensing of unused prescribed medicines from patients seems to be accepted by stakeholders when quality and safety requirements are met. Reusing dispensed medicines may help reduce waste, but a comprehensive validation method is not generally available. The design of a novel digital time temperature and humidity indicator based on an Internet of Pharmaceutical Things concept is proposed to facilitate the validation, and a prototype is presented using smart sensors with cloud connectivity acting as the key technology for verifying and enabling the reuse of returned medicines. Deficiency of existing technologies is evaluated based on the results of this development, and recommendations for future research are suggested.


title: Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits

text: Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice. Male C57BL/6 mice fed 0.3% cuprizone for 12 weeks exhibited CC atrophy with chronic demyelination, astrogliosis, and microglial activation. Syngeneic iNSCs were transplanted into the CC after ending cuprizone and perfused for neuropathology 2 weeks later. Magnetic resonance imaging (MRI) sequences for magnetization transfer ratio (MTR), diffusion-weighted imaging (T2), and diffusion tensor imaging (DTI) quantified CC pathology in live mice before and after iNSC transplantation. Each MRI technique detected progressive CC pathology. Mice that received iNSCs had normalized DTI radial diffusivity, and reduced astrogliosis post-imaging. A motor skill task that engages the CC is Miss-step wheel running, which demonstrated functional deficits from cuprizone demyelination. Transplantation of iNSCs resulted in marked recovery of running velocity. Neuropathology after wheel running showed that iNSC grafts significantly increased host oligodendrocytes and proliferating oligodendrocyte progenitors, while modulating axon damage. Transplanted iNSCs differentiated along astrocyte and oligodendrocyte lineages, without myelinating, and many remained neural stem cells. Our findings demonstrate the applicability of neuroimaging and functional assessments for pre-clinical interventional trials during chronic demyelination and detect improved function from iNSC transplantation. Directly reprogramming fibroblasts into iNSCs facilitates the future translation towards exogenous autologous cell therapies.


title: Clematis montana lectin, a novel mannose-binding lectin from traditional Chinese medicine with antiviral and apoptosis-inducing activities

text: A novel mannose-binding lectin (designated CML) was isolated from Clematis montana Buch.-Ham stem (Ranunculaceae) using ion exchange and gel filtration chromatographies on DEAE-Sepharose and Sephacryl S-100. The purified C. montana lectin was a homodimer of 11,968.9 Da subunits as determined by gel filtration and MS. The hemagglutinating activity of CML was inhibited by branched oligomannosides. The N-terminal 15-amino acid sequence of CML, DNVKYSGQVKNTGSA, has not been reported for other lectins. Also, the peptide mass fingerprinting assay confirmed that there is no match result of similar plant lectins for CML, indicating CML may be a novel plant lectin. CML showed marked antiviral activity against various viruses in cell culture. Subsequently, CML was also found to exhibit remarkable inhibitory effect on L929, HeLa, MCF7 and HepG2 cells. Furthermore, CML specially induced L929 cell apoptosis in dose-dependent manner as evidenced by MTT, fluorescent microscopy, LDH activity-based cytotoxicity assays and DNA ladder. Moreover, due to both caspase inhibitors and Western blot analyses, caspase was also found to play the important role in the potential apoptotic mechanism of CML. When the carbohydrate-binding site was fully inhibited by sugars, cytotoxicity was abruptly decreased and apoptotic phenomenon in L929 cells was not observed, suggesting a significant correlation between mannose-binding-specific activity and the antineoplastic mechanism.


title: Setting up and maximising the usage of an Urgent Dental Care Centre in Blackpool. Sharing our experiences

text: An integrated Urgent Dental Care Centre with Tier 2 Oral Surgery support was set up in Blackpool starting 24(th) March 2020. This was in reaction to the COVID-19 pandemic. In the first month 1433 patients had telephone consultations and 713 extractions were performed. The challenges surrounding set up and continuity of care are discussed.


title: Application of ProteinChip Array Profiling in Serum Biomarker Discovery for Patients Suffering From Severe Acute Respiratory Syndrome

text: A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients’ serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip® Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.


title: Gendered effects on inflammation reaction and outcome of COVID‐19 patients in Wuhan

text: BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID‐19) has turned into a public health emergency of international concern. Epidemiological research showed that gender was associated with the severity of COVID‐19, but the underlying mechanism of gender predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID‐19. METHODS: In this retrospective study, we enrolled 548 COVID‐19 inpatients from Tongji Hospital from January 26 to February 5, 2020, and followed up to March 3, 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. Cox proportional hazard regression model was applied to identify gendered effect on mortality of COVID‐19 after adjusting age, comorbidity and smoking history. Multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs. 10.4%), with the HR of 1.923 (95% CI, 1.181‐3.130); elder age and comorbidity were significantly associated with decease of COVID‐19 patients. Excess inflammation reaction was related to severity of COVID‐19. Male patients had greater inflammation reaction, with higher levels of IL‐10, TNF‐α, LDH, ferritin and hsCRP, but lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Gender, age, and comorbidity are critical risk factors for mortality of COVID‐19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males especially elder males to develop cytokine storm, causing potential ARDS, multiple organ failure and decease. This article is protected by copyright. All rights reserved.


title: Sensing social interactions through BLE beacons and commercial mobile devices

text: Wearable sensing devices can provide high-resolution data useful to characterise and identify complex human behaviours. Sensing human social interactions through wearable devices represents one of the emerging field in mobile social sensing, considering their impact on different user categories and on different social contexts. However, it is important to limit the collection and use of sensitive information characterising individual users and their social interactions in order to maintain the user compliance. For this reason, we decided to focus mainly on physical proximity and, specifically, on the analysis of BLE wireless signals commonly used by commercial mobile devices. In this work, we present the SocializeME framework designed to collect proximity information and to detect social interactions through heterogeneous personal mobile devices. We also present the results of an experimental data collection campaign conducted with real users, highlighting technical limitations and performances in terms of quality of RSS, packet loss, and channel symmetry, and how they are influenced by different configurations of the user’s body and the position of the personal device. Specifically, we obtained a dataset with more than 820.000 Bluetooth signals (BLE beacons) collected, with a total monitoring of over 11 h. The dataset collected reproduces 4 different configurations by mixing two user posture’s layouts (standing and sitting) and different positions of the receiver device (in hand, in the front pocket and in the back pocket). The large number of experiments in those different configurations, well cover the common way of holding a mobile device, and the layout of a dyad involved in a social interaction. We also present the results obtained by SME-D algorithm, designed to automatically detect social interactions based on the collected wireless signals, which obtained an overall accuracy of 81.56% and F-score 84.7%. The collected and labelled dataset is also released to the mobile social sensing community in order to evaluate and compare new algorithms.


title: The Relationship of Rhinovirus-Associated Asthma Hospitalizations with Inhaled Corticosteroids and Smoking

text: BackgroundAlthough rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic association between this virus and severe exacerbations, as well as the clinical characteristics of adults at risk for RV-associated asthma that necessitates hospitalization, have not been established MethodsDuring 1999–2003, we conducted a cohort study of 101 adults prospectively enrolled at hospital admission for an asthma exacerbation. Patient characteristics and frequencies of RV in nasal specimens were analyzed, by reverse-transcription polymerase chain reaction (RT-PCR), at asthma-related hospital admission and at a 3-month convalescent follow-up visit ResultsRV was detected by RT-PCR in 21% of hospitalized patients over a 4-year period and in 1.3% of patients who returned for a 3-month follow-up visit. RV detection was strongly associated with hospitalization for asthma (adjusted odds ratio [OR], 15.1 [95% confidence interval {CI}, 1.88–121.4]). After adjustment for baseline asthma severity, RV-positive patients were more likely than RV-negative patients to be current smokers and nonusers of inhaled corticosteroids (ICSs) (adjusted OR, 11.18 [95% CI, 2.37–52.81]; P=.002) ConclusionsRV respiratory infection is an etiologic agent in severe asthma exacerbations necessitating hospitalization in adults. Compared with hospitalized patients with asthma who were RV negative, RV-positive patients were significantly more likely to be smokers and nonusers of ICSs


title: Meeting critical challenges and striving for urban sustainability in China

text: Abstract China has experienced outstanding economic growth during the last three decades through urbanization. But at the same time, many ecological and social issues have been marginalized, leading to problems in public safety, health, and social equity. Such a pattern of development is unlikely to be sustainable. In this article, we examine these issues and the challenges that come with resolving them, and advocate a holistic and pragmatic approach to the research and practice of urban sustainability in China.


title: Translating transmissibility measures into recommendations for coronavirus prevention

text: The rapid increase in clinical cases of the new coronavirus disease, COVID-19, suggests high transmissibility. However, the estimates of the basic reproductive number reported in the literature vary widely. Considering this, we drew the function of contact-rate reduction required to control the transmission from both detectable and undetectable sources. Based on this, we offer a set of recommendations for symptomatic and asymptomatic populations during the current pandemic. Understanding the dynamics of transmission is essential to support government decisions and improve the community’s adherence to preventive measures.


Considerations Left behind Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreaks in Republic of Korea


Chapter 2 Emergency Management of Poisoning


title: Atualização em pneumonia comunitária viral()

text: Viral pneumonia is a prevalent cause of respiratory infection in immunocompetent adults. It has varied presentation, from mild to severe respiratory failure, requiring mechanical ventilation. However, in Brazil, there have been few studies on the clinical presentation and diagnosis of this infection. Thus, the authors of the present article intend to review the main viral agents that cause community-acquired pneumonia and to discuss the currently available diagnostic and therapeutic methods.


title: An updated analysis of turning point, duration and attack rate of COVID-19 outbreaks in major Western countries with data of daily new cases

text: As coronavirus spreads around the world, the study of its effects is of great practical significance. We collated data on daily new cases of the COVID-19 outbreaks in the six Western countries of the Group of Seven and the dates of governments’ interventions. We studied the periods before and after the dates of major governments’ interventions integrally based on a segmented Poisson model. The relevant results are published in the paper of “Predicting turning point, duration and attack rate of COVID - 19 outbreaks in major Western countries” [1]. Our method can be used to update prediction daily as COVID-19 outbreaks evolve. In this article, we illustrate an updated analysis with our method to facilitate reproducibility. Both datasets used and updated are provided.


title: Nrf2 Activator PB125® as a Potential Therapeutic Agent Against COVID-19

text: Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-α the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the “cytokine storm” observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm.


title: A perspective on hydrothermal processing of sewage sludge

text: Abstract The US annually produces 79 million dry tons of liquid organic waste including sewage sludge. Anaerobic digestion can only reduce the sludge volume by 50% in mass, leaving the other half as a growing waste management and hygienic problem. Hydrothermal processing (HTP), a set of several chemical digestion processes, could be used to convert sewage sludge into valuable products and minimize potential environmental pollution risks. Specifically, hydrothermal carbonization and hydrothermal liquefaction have been extensively studied to sustainably manage sludge. Two of the main reasons for this are the high upscalability of HTP for public waste management and that it is estimated that HTP can recover eleven times more energy from waste products than landfilling. An integration of HTP with anaerobic digestion or recycling the soluble organics (in the HTP aqueous products) into the HTP process could lead to a higher overall rate of energy recovery for municipal sewage sludge.


title: Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

text: We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.


title: Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein

text: The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins.


title: Considerations for Development and Use of AI in Response to COVID-19

text: Artificial intelligence (AI) is playing a key supporting role in the fight against COVID-19 and perhaps will contribute to solutions quicker than we would otherwise achieve in many fields and applications. Since the outbreak of the pandemic, there has been an upsurge in the exploration and use of AI, and other data analytic tools, in a multitude of areas. This paper addresses some of the many considerations for managing the development and deployment of AI applications, including planning; unpredictable, unexpected, or biased results; repurposing; the importance of data; and diversity in AI team membership. We provide implications for research and for practice, according to each of the considerations. Finally we conclude that we need to plan and carefully consider the issues associated with the development and use of AI as we look for quick solutions.


title: GI-16 lineage (624/I or Q1), there and Back Again: the history of one of the major threat for poultry farming of our era

text: The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.


title: Association between social support and recovery from post-traumatic stress disorder after flood: a 13–14 year follow-up study in Hunan, China

text: BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric disorders among survivors of traumatic events. It is well established that social support has been related to the onset of PTSD after natural disasters. However, very little is known whether or not social support has had an influence on the recovery from the PTSD that was diagnosed after floods. This study, therefore, made a follow-up assessment of PTSD in flood victims 13–14 years after they were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD among them and identify the association between social support and their recovery from PTSD. METHODS: Victims who had experienced Dongting Lake flood in 1998 and had been diagnosed as having PTSD in 2000 were enrolled in this study. A follow-up survey was done between the years 2013 and 2014 to diagnose the victims again of PTSD using the DSM-IV criteria. Social support and its three dimensions were measured using the Chinese version of Social Support Rating Scale (SSRS), including objective support, subjective support and support utilization. Data were collected through face-to-face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were used to examine the relationship between social support and the recovery from PTSD after flood. RESULTS: Out of 321 subjects with prior PTSD, 51 (15.89 %) were diagnosed as still having PTSD. Logistic regression analyses indicated that the recovery from prior PTSD was significantly associated with social support (odds ratio (OR) =0.202, 95 % confidence interval (95 % CI): 0.047–0.878), subjective support (OR = 0.236, 95 % CI: 0.080–0.694) and support utilization (OR = 0.245, 95 % CI: 0.071–0.844). CONCLUSIONS: The prevalence rate of current PTSD indicates that natural disasters, such as floods, may affect the mental health of victims for a long time. Social support was significantly associated with the recovery from prior PTSD, especially subjective support and support utilization.


title: Sinusitis in the common cold

text: Abstract Background: Acute community-acquired sinusitis is considered a bacterial complication of the common cold. Radiologic abnormalities in sinuses occur, however, in most patients with upper respiratory virus infections. Objective: Assessment of the occurrence, clinical profile, laboratory findings, and outcome of radiologically confirmed sinusitis was carried out as part of a common cold study in young adults. Methods: Clinical examinations and radiography of the paranasal sinuses were carried out on days 1, 7, and 21 in 197 patients with the common cold. The symptoms were recorded on diary cards on days 1 to 20. Ten viruses and 5 bacteria were studied as etiologic agents of common cold as reported earlier. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and total white blood cell counts with differentials were determined in 40 randomized subjects on day 7. The effect of 6 days of intranasal fluticasone propionate treatment of the common cold in the prevention of sinusitis was analyzed. Results: On day 7, 39% of patients with the common cold in the placebo group (n = 98) had sinusitis, which we would prefer to call viral sinusitis. The symptoms of patients with sinusitis and those without it were not clinically distinguishable. Viral infection was detected in 81.6% of patients with sinusitis. No significantly increased levels of antibodies to bacteria were detected. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and white blood cell counts were low in patients with sinusitis. All patients made a clinical recovery within 21 days without antibiotic treatment. Fluticasone propionate treatment tended to prevent paranasal sinusitis, especially in rhinovirus-positive subjects. Conclusion: Viral sinusitis frequently occurs in the early days of the common cold, but it is a self-limited illness. The sinuses should not be imaged in patients with the common cold if the signs and symptoms of illness gradually become less severe and no specific signs suggestive of bacterial sinusitis occur. (J Allergy Clin Immunol 1998;102:403-8.)


title: The transcriptional and translational landscape of equine torovirus

text: The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order Nidovirales) encompasses a range of species that infect domestic ungulates including cattle, sheep, goats, pigs and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV) we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyse the relative expression levels of the known torovirus proteins and transcripts, chimaeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle) and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilises a unique combination of discontinuous and non-discontinuous RNA synthesis to produce its subgenomic RNAs; indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated ORFs, located within the so-called 5’ UTR. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens. Toroviruses infect cattle, goats, pigs and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens including severe acute respiratory syndrome (SARS) coronavirus and they share some common features, however the mechanism that they use to produce subgenomic RNA molecules differs. Here we performed deep sequencing to determine how equine torovirus produces subgenomic RNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.


title: Production of a Monoclonal Antibody Targeting the M Protein of MERS-CoV for Detection of MERS-CoV Using a Synthetic Peptide Epitope Formulated with a CpG–DNA–Liposome Complex

text: The Middle East respiratory syndrome-related coronavirus (MERS-CoV) contains four major structural proteins, the spike glycoprotein, nucleocapsid phosphoprotein, membrane (M) glycoprotein and small envelope glycoprotein. The M protein of MERS-CoV has a role in the morphogenesis or assembly of the virus and inhibits type I interferon expression in infected cells. Here, we produced a monoclonal antibody specific against the M protein of MERS-CoV by injecting BALB/c mice with a complex containing the epitope peptide and CpG–DNA encapsulated with a phosphatidyl-β-oleoyl-γ-palmitoyl ethanolamine (DOPE):cholesterol hemisuccinate (CHEMS). The monoclonal antibody was reactive to the epitope peptide of the M protein of MERS-CoV which was confirmed by western blotting and immunoprecipitations. Indirect immunofluorescence assay and confocal image analysis showed that the monoclonal antibody binds specifically to the M protein of MERS-CoV in the virus-infected cells. Further studies using this monoclonal antibody may provide important information on the function of the M protein and its future application in diagnostics.


title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models

text: BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.


European Resuscitation Council Guidelines for Resuscitation 2010 Section 2. Adult basic life support and use of automated external defibrillators


title: Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients Recommendations of Centers for Disease Control, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation

text: Abstract CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood-or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients. Biol Blood Marrow Transplant 2000;6(6a):659-713; 715; 717-27; quiz 729-33.


title: Electrowetting-on-Dielectric System for COVID-19 Testing

text: The ongoing viral outbreak labeled COVID-19 is spreading rapidly across states and is posing a great threat to public health. Rapid identification of the virus in the population plays a crucial role in isolating the individual and breaking the transmission chain, apart from initiating an appropriate treatment procedure. Here, we discuss an electrowetting-on-dielectric (EWOD) technology that uses a microprocessor-controlled electrode array to merge a possibly infected sample carried by a liquid drop with a drop of a reagent to carry out the testing process. Changes in color occurring during the mixing process of the drops are imaged using a camera.


title: Immunohistological study of the immune system cells in paraffin-embedded tissues of conventional pigs

text: Abstract The distribution of different cells of the immune system has been studied in formalin-fixed paraffin-embedded tissues from conventionally reared healthy pigs, using immunohistological techniques. The samples collected were: lungs, tonsils, lymph nodes (mediastinal, mesenteric, inguinal and submandibular), pancreas, spleen, liver, kidney, adrenal gland, ileum and stomach. A total of six primary antibodies anti-CD3, anti-CD79α, Mac 387, anti-lysozyme, anti-CD45RA (3C3/9) and anti-SLA-II-DQ (BL2H5) were used with a standard avidin–biotin peroxidase (ABC) method. Anti-CD3 and anti-CD79α mAb-reacted, respectively with cells located in T cell areas and B cell areas. Mac 387 recognised circulating polymorphonuclear leukocytes, while anti-lysozyme-stained resident macrophages in all tissues. 3C3/9 and BL2H5, were assessed in formalin-fixed paraffin-embedded tissues for the first time. 3C3/9 identified B lymphocytes, in primary follicles and mantle zones, a subpopulation of T cells, especially located in the marginal zone of the spleen and a variable number of immunoblasts, in the germinal centres. BL2H5 reacted with B cells in the mantle zones of the follicles of lymphoid tissues, with dendritic and interdigitating cells in all studied lymphoid tissues and with a variable number of resting and activated T cells in the periarteriolar lymphoid sheath (PALs), marginal zone and red pulp of the spleen. Furthermore, it stained Kupffer and perivascular macrophages in the liver This study represents a detailed histological study of the distribution of the most important subpopulations of immune system cells in conventional, healthy pigs. In our view, these tools should be useful for future comparative studies in disease conditions.


title: Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: Experience from mobile SARS containment teams, 2003

text: BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.


title: The defective RNAs of Closteroviridae

text: The family Closteroviridae consists of two genera, Closterovirus and Ampelovirus with monopartite genomes transmitted respectively by aphids and mealybugs and the Crinivirus with bipartite genomes transmitted by whiteflies. The Closteroviridae consists of more than 30 virus species, which differ considerably in their phytopathological significance. Some, like beet yellows virus and citrus tristeza virus (CTV) were associated for many decades with their respective hosts, sugar beets and citrus. Others, like the grapevine leafroll-associated ampeloviruses 1, and 3 were also associated with their grapevine hosts for long periods; however, difficulties in virus isolation hampered their molecular characterization. The majority of the recently identified Closteroviridae were probably associated with their vegetative propagated host plants for long periods and only detected through the considerable advances in dsRNA isolation and sequencing of PCR amplified replicons. Molecular characterization of CTV and several other Closteroviridae revealed that, in addition to genomic and subgenomic RNAs, infected plants contain several different subviral defective RNAs (dRNAs). The roles and biological functions of dRNAs associated with Closteroviridae remain terra incognita.


title: Molecular characterisation and risk factor analysis of Cryptosporidium spp. in calves from Italy

text: To provide up-to-date information on the occurrence of Cryptosporidium in pre-weaned calves from Sardinia (Italy), the species implicated and their zoonotic potential, 147 faecal samples from 22 cattle herds were microscopically examined for Cryptosporidium oocysts; positive isolates were molecularly characterised. A questionnaire was developed to identify risk factors for Cryptosporidium infection. Overall, the percentage of positive calves and farms was 38.8 and 68.2%, respectively. The SSU rRNA-based PCR identified two Cryptosporidium species, Cryptosporidium parvum (95.8%) and C. bovis (4.2%). Sequence analyses of the glycoprotein (gp60) gene revealed that all C. parvum isolates belonged to the subtype family IIa (IIaA15G2R1 and IIaA16G3R1), with the exception of three isolates that belonged to the subtype family IId (IIdA20G1b and IIdA20). Mixed logistic regression results indicated that calves aged 15–21 days were more likely to be Cryptosporidium-positive. The risk of being positive was also significantly higher in herds from Central Sardinia and in farms using non-slatted flooring. In addition, the application of disinfectants and milk replacers was significantly associated with higher Cryptosporidium prevalence. In contrast, the risk of being positive was significantly reduced in halofuginone-treated calves. Our results reveal that a significant percentage of suckling calves are carriers of zoonotic subtypes of C. parvum. Thus, both healthy and diarrhoeic calves younger than 1 month may represent a risk for the transmission of cryptosporidiosis in humans and animals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-018-6000-x) contains supplementary material, which is available to authorized users.


title: Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

text: BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8(+) T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.


title: Application of the LAMP Assay as a Diagnostic Technique for Rapid Identification of Thrips tabaci (Thysanoptera: Thripidae)

text: Rapid and accurate identification of potentially invasive taxa that may cause high economic losses or environmental damage is of critical importance. The onion thrips, Thrips tabaci Lindeman, ranks as one of the world’s most destructive agricultural pests and commonly found in imported agricultural products and field samples, but is prone to undetected transport because of its minute size as well as cryptic behavior. Although traditional taxonomic methods are pretty useful in straightforward assignment of specimens to the genus Thrips , identification in the species level is much more difficult and requires expertise, knowledge, and experience. Furthermore, it is often difficult or impossible to identify or distinguish this species from other thrips by using material from other stages of development. Based on the foregoings, use of a molecular technique known as loop-mediated isothermal amplification (LAMP) as a rapid and robust alternative species diagnostic tool would be valuable. In this study, a relatively quick and simple method was used to detect the presence of onion thrips DNA rapidly and discriminate it from other species, by using material from different stages of development. Not only LAMP itself required less than 1 h to complete but also amounts of DNA as little as that recovered from a single specimen were adequate for the detection. Another advantage of this identification system is that nonspecialists will be able to make faster and cheaper identifications.


title: Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (Arctocephalus spp.)

text: In some regions, little is known about exposure to viruses in coastal marine mammals. The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. tropicalis). Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. Circovirus DNA fragments were detected in six animals of the same species. Two were phylogenetically similar to the Circovirus genus, whereas the other four nucleotide fragments showed no similarity to any of the known genera within the family Circoviridae. RNA fragments indicating the presence of coronavirus, vesivirus, and morbillivirus were not detected. These findings suggest that adenoviruses and circoviruses are circulating in fur seal populations found along the coast of Rio Grande do Sul State, Brazil.


title: Introduction: microbes, networks, knowledge—disease ecology and emerging infectious diseases in time of COVID-19

text: This is an introduction to the topical collection Microbes, Networks, Knowledge: Disease Ecology in the twentieth Century, based on a workshop held at Queen Mary, University London on July 6–7 2016. More than twenty years ago, historian of science and medicine Andrew Mendelsohn asked, “Where did the modern, ecological understanding of epidemic disease come from?” Moving beyond Mendelsohn’s answer, this collection of new essays considers the global history of disease ecology in the past century and shows how epidemics and pandemics have made “microbes complex”.


title: Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: Evidence for membrane cycling from Golgi to ER

text: Abstract In cells treated with brefeldin A (BFA), movement of newly synthesized membrane proteins from the endoplasmic reticulum (ER) to the Golgi apparatus was blocked. Surprisingly, the glycoproteins retained in the ER were rapidly processed by cis/medial Golgi enzymes but not by trans Golgi enzymes. An explanation for these observations was provided from morphological studies at both the light and electron microscopic levels using markers for the cis/medial and trans Golgi. They revealed a rapid and dramatic redistribution to the ER of components of the cis/medial but not the trans Golgi in response to treatment with BFA. Upon removal of BFA, the morphology of the Golgi apparatus was rapidly reestablished and proteins normally transported out of the ER were efficiently and rapidly sorted to their final destinations. These results suggest that BFA disrupts a dynamic membrane-recycling pathway between the ER and cis/medial Golgi, effectively blocking membrane transport out of but not back to the ER.


title: Methodologies for measuring travelers' risk perception of infectious diseases: A systematic review

text: Summary Numerous studies in the past have stressed the importance of travelers' psychology and perception in the implementation of preventive measures. The aim of this systematic review was to identify the methodologies used in studies reporting on travelers' risk perception of infectious diseases. A systematic search for relevant literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There were 39 studies identified. In 35 of 39 studies, the methodology used was that of a knowledge, attitude and practice (KAP) survey based on questionnaires. One study used a combination of questionnaires and a visual psychometric measuring instrument called the ‘pictorial representation of illness and self-measurement” or PRISM. One study used a self-representation model (SRM) method. Two studies measured psychosocial factors. Valuable information was obtained from KAP surveys showing an overall lack of knowledge among travelers about the most frequent travel-associated infections and associated preventive measures. This methodological approach however, is mainly descriptive, addressing knowledge, attitudes, and practices separately and lacking an examination of the interrelationships between these three components. Another limitation of the KAP method is underestimating psychosocial variables that have proved influential in health related behaviors, including perceived benefits and costs of preventive measures, perceived social pressure, perceived personal control, unrealistic optimism and risk propensity. Future risk perception studies in travel medicine should consider psychosocial variables with inferential and multivariate statistical analyses. The use of implicit measurements of attitudes could also provide new insights in the field of travelers’ risk perception of travel-associated infectious diseases.


title: Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

text: The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel(®) 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ. However, pre-dissolved cellulosic polymer in the phosphate dissolution medium (pH 7.5) modified the dissolution profile of NTZ when starting from the cocrystals, achieving transient drug supersaturation. Subsequent dissolution studies under sink conditions of polymer-based pharmaceutical powder formulations with NTZ-SUC cocrystals gave a significant improvement of the apparent solubility of NTZ when compared with analogous formulations of pure NTZ and the physical mixture of NTZ and SUC. Scanning electron microscopy and powder X-ray diffraction analysis of samples recovered after the powder dissolution studies showed that the cocrystals undergo fast dissolution, drug supersaturation and precipitation both in the absence and presence of polymer, suggesting that the solubilization enhancement is due to polymer-induced delay of nucleation and crystal growth of the less soluble NTZ form. The study demonstrates that the incorporation of an appropriate excipient in adequate concentration can be a key factor for inducing and maintaining the solubilization of poorly soluble drugs starting from co-crystallized solid forms. In such a way, cocrystals can be suitable for the development of solid dosage forms with improved bioavailability and efficacy in the treatment of important parasitic and viral diseases, among others.


A review of feline infectious peritonitis virus infection: 1963–2008


title: Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China

text: BACKGROUND/OBJECTIVES: To evaluate the prevalence of malnutrition and its related factors in elderly patients with COVID-19 in Wuhan, China. SUBJECTS/METHODS: In a cross-sectional study, we evaluated the nutritional status of elderly inpatients with COVID-19 using the Mini Nutritional Assessment (MNA). Based on MNA scores, patients were divided into non-malnutrition group (MNA ≥ 24), the group with risk of malnutrition (MNA 17–23.5) and malnutrition group (MNA score < 17). Regression analysis was conducted to screen for risk factors for malnutrition. RESULTS: A total of 182 patients were included in the study, of which 27.5% were in the group with malnutrition risk and 52.7% were in the malnutrition group. There were statistical differences in the incidence of comorbid diabetes mellitus, body mass index (BMI), calf circumference,albumin, hemoglobin, and lymphocyte counts among the three groups. Further regression analysis suggested that combined diabetes, low calf circumference, and low albumin were independent risk factors for malnutrition. CONCLUSIONS: The prevalence of malnutrition in elderly patients with COVID-19 was high, and nutritional support should be strengthened during treatment, especially for those with diabetes mellitus, low calf circumference, or low albumin.


title: Urban-Rural Disparity in Helicobacter Pylori Infection–Related Upper Gastrointestinal Cancer in China and the Decreasing Trend in Parallel with Socioeconomic Development and Urbanization in an Endemic Area

text: Abstract Background Globally China has the largest urban-rural disparity in socioeconomic development, and the urban-rural difference in upper gastrointestinal cancer (UGIC) is similar to the difference between developed and developing countries. Objectives To describe urban-rural disparity in UGIC and to emphasize prevention by socioeconomic development and urbanization in China. Methods Age-standardized incidence rates (ASRs) of cancers in 2012 were compared between urban Shijiazhuang city and rural Shexian County, and trends from 2000-2015 in Shexian County were analyzed. Findings Compared with urban Shijiazhuang city, the ASR of gastroesophageal cancers in rural Shexian County was 5.3 times higher in men (234.1 vs 44.2/100,000, P < .01) and 9.1 times higher in women (107.7 vs 11.8/100,000, P < .01). This rural-urban disparity in UGIC is associated with differences in socioeconomic development in annual gross domestic product (GDP) per capita of US$2700 vs US$6965, in urbanization rate of 48% vs 100%, and in adult Helicobacter pylori infection prevalence of 75% vs 50%. From 2000-2015, the GDP per capita in Shexian County increased from US$860 to US$3000, urbanization rate increased from 22.4% to 54.8%, and prevalence of H pylori infection among 3- to 10-year-old children decreased from 60% to 46.1% (P < .01). Meanwhile, the biennial ASR of esophagogastric cancer decreased 42% in men, from 313.5 to 182.1 per 100,000 (P < .01), and 57% in women, from 188.6 to 80.4 per 100,000 (P = .00). However, lung, colorectal, and gallbladder cancers and leukemia in both sexes and breast, ovary, thyroid, and kidney cancer in women increased significantly. Despite this offset, ASR of all cancers combined decreased 25% in men (from 378.2 to 283.0/100,000, P = .00) and 19% in women (from 238.5 to 193.6/100,000, P = .00). Conclusions Urban-rural disparity in UGIC is related to inequity in socioeconomic development. Economic growth and urbanization is effective for prevention in endemic regions in China and should be a policy priority.


title: The rippled newsvendor: A new inventory framework for modelling supply chain risk severity in the presence of risk propagation

text: How should managers take into account the propagation of supply chain disruptions and risks (i.e. the ripple effect) when they design their inventory policies? For over 60 years, various extensions and applications to the popular newsvendor model have been suggested, where cost/profit are often the focal objective. We propose a new version of the traditional single-period newsvendor model - the ”Rippled Newsvendor” - with supply chain severity (i.e. risk propagation) as the primary objective while taking into account network structure. Our model considers exogenous and endogenous risk(s) of disruption while exploring the tension between under-supply and ”wear-and-tear” (i.e system breakdown). To model the intricacies of this trade-off whilst minimizing the potential spread of risk, we leverage a Bayesian Network whereby the conditional probability distributions are functions of the inventory ordering decisions. We use a simulation study to understand the nature of our objective function as well as to gain insight into the potential optimal ordering policies of this new model. Furthermore, the simulation seeks to understand how the various factors in our system impact total risk severity, and if they do so in different ways. Our simulations indicate that local exogenous risk is of greater importance than non-local exogenous risk. Furthermore, we show that the type of risk, as well as the structural characteristics of the supply chain and inventory system, impact risk severity differently.


title: Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage

text: Abstract The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV.


title: Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades

text: BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. OBJECTIVE: To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. METHODS: A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. RESULTS: HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P <.001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.


title: Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil

text: BACKGROUND: The cattle industry is one of the most important Brazilian agribusiness sectors and is a strong contributor to the national economy. Annually about 44.6 million calves are bred, which makes the optimal management of these animals extremely important. Several diseases can affect the initial stages of the bovine production chain, being the bovine respiratory syncytial virus (BRSV) one of the most relevant pathogens. This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. For that, 1243 blood samples were collected of animals from 26 farms and a questionnaire about possible risk factors for BRSV prevalence was performed. The obtained blood sera were analyzed using virus neutralization test (VNT). RESULTS: VNT results showed high BRSV prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. CONCLUSIONS: The study showed that adult animals over 1 year old are an important risk factor for the high seroprevalence of BRSV in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests that biosecurity measures should be applied in order to reduce viral dissemination. Additionally, the natural suckling may be an important management to protect calves from high BRSV seroprevalence.


title: Chapter 18 Viral Epidemiology Tracking Viruses with Smartphones and Social Media

text: Abstract The science of epidemiology has been developed over the last 200years, using traditional methods to describe the distribution of diseases by person, place, and time. However, in the last several decades, a new set of technologies has become available, based on the methods of computer sciences, systems biology, and the extraordinary powers of the Internet. Technological and analytical advances can enhance traditional epidemiological methods to study the emergence, epidemiology, and transmission dynamics of viruses and associated diseases. Social media are increasingly used to detect the emergence and geographic spread of viral disease outbreaks. Large-scale population movement can be estimated using satellite imagery and mobile phone use, and fine-scale population movement can be tracked using global positioning system loggers, allowing estimation of transmission pathways and contact patterns at different spatial scales. Advances in genomic sequencing and bioinformatics permit more accurate determination of viral evolution and the construction of transmission networks, also at different spatial and temporal scales. Phylodynamics links evolutionary and epidemiological processes to better understand viral transmission patterns. More complex and realistic mathematical models of virus transmission within human and animal populations, including detailed agent-based models, are increasingly used to predict transmission patterns and the impact of control interventions such as vaccination and quarantine. In this chapter, we will briefly review traditional epidemiological methods and then describe the new technologies with some examples of their application.


title: Identification of protective T-cell antigens for smallpox vaccines

text: Abstract E3L is an immediate-early protein of vaccinia virus that is detected within 0.5 hours of infection, potentially before the many immune evasion genes of vaccinia can exert their protective effects. E3L is highly conserved among orthopoxviruses and hence could provide important protective T-cell epitopes that should be retained in any subunit or attenuated vaccine. We have therefore evaluated the immunogenicity of E3L in healthy VV vaccinated donors. Peripheral blood mononuclear cells from healthy volunteers (n=13) who had previously received a smallpox vaccine (Dryvax®) were activated and expanded using overlapping E3L peptides and their function, specificity and anti-viral activity was analyzed. E3L-specific T-cells were expanded from 7 of 12 (58.3%) vaccinated healthy donors. 25% of these produced CD8+ T-cell responses and 87.5% produced CD4+ T-cells. We identified epitopes restricted by HLA-B35 and HLA-DR15. E3L-specific T-cells killed peptide-loaded target cells as well as vaccinia-infected cells but only CD8+ T-cells could prevent the spread of infectious virus in virus inhibition assays. The epitopes recognized by E3L-specific T-cells were shared with monkeypox and although there was a single amino acid change in the variola epitope homolog, it was recognized by vaccinia-specific T-cells. Therefore it might be important to include E3L in any deletion mutant or subunit vaccine and E3L could provide a useful antigen to monitor protective immunity in humans.


title: The Role of Clinical Virology Laboratory and the Clinical Virology Laboratorian in Ensuring Effective Surveillance for Influenza and Other Respiratory Viruses: Points to Consider and Pitfalls to Avoid

text: Influenza and respiratory viruses have a global impact on public health. Clinical virology laboratories and laboratorians play an important role in not only the diagnosis but also the surveillance of these pathogens. Surveillance for influenza and other respiratory pathogens is important, as it informs public health decision making in terms of influenza vaccine and antiviral effectiveness, informs clinicians and public health practitioners about the pathogenicity of specific viral strains, guides clinical practice, and supports laboratory panning activities. Key background issues include the following: the fact that the laboratory is only one of several data providers to a surveillance system, the biologic nature of influenza and respiratory viruses and the laboratory needs to keep up to date on the diagnosis of these agents, the need for laboratorians to be involved in case definition development, the impact of push and pull data flow models on laboratory resources, and the fact that laboratories may be asked to provide more than just test results to surveillance programs. This review also identifies some key issues or questions that arise during the pre-analytic, analytic, and post-analytic phases that could impact on the ability of the laboratory to link to surveillance programs. Finally, issues surrounding virus characterization programs and how they link to surveillance programs are identified and discussed.


title: A predictive nomogram for predicting improved clinical outcome probability in patients with COVID-19 in zhejiang province, china

text: The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), Acute Physiology and Chronic Health Evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931–0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.


“COVID-19 Leading to Acute Encephalopathy in a Heart Transplant Patient”


title: Energy Return on Investment (EROI) and Life Cycle Analysis (LCA) of biofuels in Ecuador

text: In Ecuador, the net energy contribution of biofuels is unknown or unnoticed. To address this issue, we determined the Energy Return on Investment (EROI) for bioethanol and biodiesel. The selection of raw materials relied on their productive capacity, export and import records, and historical yields. Consequently, the scope included three raw materials for ethanol (sugar cane, corn, and forest residues) and four for biodiesel (African palm, pinion, bovine fat, and swine fat). Using a method based on the Life Cycle Analysis (LCA) of each biofuel, we assessed the entire production chain through statistical processing of primary and secondary information. Then we calculated the calorific values in the laboratory, compared energy inputs/outputs, and finally obtained the energetic returns. EROIs for bioethanol were: 1.797 for sugarcane, 1.040 for corn, and 0.739 for wood. The results for biodiesel were: 3.052 for African palm, 2.743 for pinion, 2.187 for bovine fat, and 2.891 for swine fat. These values suggest feasibility only for sugarcane in the case of ethanol. In contrast, biodiesel has better prospects because all the feedstocks analyzed had EROIs higher than two. Nevertheless, biodiesel is not available for trading in Ecuador because energy policy has overlooked systems based on higher energy return. Future studies should consider more comprehensive variables such as climate change, land use, and water management.


title: Increasing Access to Care: Telehealth During COVID-19

text: The COVID-19 public health emergency has amplified both the potential value and the challenges with health care providers deploying telehealth solutions. As people across the country find ways to stay at home, telehealth preserves an opportunity to obtain necessary healthcare services. Further, telehealth can help individuals avoid COVID-19 infection, free up hospital beds and other resources for those patients most in need and prevent infected individuals from spreading that infection. Federal and state regulators have recognized this potential of telehealth and have quickly changed a variety of laws and regulations to enable health care providers to deploy solutions quickly. These changes can provide lasting benefits for the use of telehealth well after the current crisis. However, to best realize telehealth’s benefits further legal and regulatory action are necessary. Specifically, lawmakers and regulators should focus on six areas: reimbursement, privacy/cybersecurity, liability, licensure, technology access, and AI.


title: Vergesellschaftung unter Ansteckenden – für eine Körpergeschichte der Seuche

text: This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. Being a “trauma of mankind” epidemics have been a major subject of historical research for a long time and regarding every historical period. Recurring to the concept of Rudolf Schlögl (“Vergesellschaftung unter Anwesenden”) my proposal is to research epidemics as a history of the communicating body and thus including the contagium as part of this communication.


title: Antiseptic properties of two calix[4]arenes derivatives on the human coronavirus 229E

text: Abstract Facing the lack in specific antiviral treatment, it is necessary to develop new means of prevention. In the case of the Coronaviridae this family is now recognized as including potent human pathogens causing upper and lower respiratory tract infections as well as nosocomial ones. Within the purpose of developing new antiseptics molecules, the antiseptic virucidal activity of two calix[4]arene derivatives, the tetra-para-sulfonato-calix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arene (C[4]S-BTZ) were evaluated toward the human coronavirus 229E (HCoV 229E). Comparing these results with some obtained previously with chlorhexidine and hexamidine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C[4]S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C[4]S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4log10 reduction in viral titer after 5min of contact with 10−3 molL−1 solutions of C[4]S-BTZ and chlorhexidine, respectively. Thus, the C[4]S-BTZ appeared as a promising virucidal (antiseptic) molecule.


title: Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection

text: Crimean-Congo hemorrhagic fever virus (CCHFV) infection can result in a severe hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs.


COVID-19—What we know and what we need to know: There are more questions than answers


title: Recent advances and perspectives of nucleic acid detection for coronavirus

text: The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people’s lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler operation. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection.


title: Under‐folded proteins: Conformational ensembles and their roles in protein folding, function, and pathogenesis

text: For decades, protein function was intimately linked to the presence of a unique, aperiodic crystal‐like structure in a functional protein. The two only places for conformational ensembles of under‐folded (or partially folded) protein forms in this picture were either the end points of the protein denaturation processes or transiently populated folding intermediates. Recent years witnessed dramatic change in this perception and conformational ensembles, which the under‐folded proteins are, have moved from the shadow. Accumulated to date data suggest that a protein can exist in at least three global forms–functional and folded, functional and intrinsically disordered (nonfolded), and nonfunctional and misfolded/aggregated. Under‐folded protein states are crucial for each of these forms, serving as important folding intermediates of ordered proteins, or as functional states of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs), or as pathology triggers of misfolded proteins. Based on these observations, conformational ensembles of under‐folded proteins can be classified as transient (folding and misfolding intermediates) and permanent (IDPs and stable misfolded proteins). Permanently under‐folded proteins can further be split into intentionally designed (IDPs and IDPRs) and unintentionally designed (misfolded proteins). Although intrinsic flexibility, dynamics, and pliability are crucial for all under‐folded proteins, the different categories of under‐foldedness are differently encoded in protein amino acid sequences. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 870–887, 2013.


title: Musculoskeletal and Neurologic Diseases

text: Ferrets may exhibit neurologic signs as a result of various conditions that may be of nervous or muscular origin. Neurologic examination follows the same principles as in small animal medicine. One of the main defect that may be screened during clinical examination is deafness. Congenital deafness in ferrets is associated with coat color patterns such as white markings and premature graying.In this species, paresis is a common presentation and may reflect a generalized weakness. Spinal disorder, intervertebral disk disease, and neoplasia are among the differential diagnosis. Diagnostic exams usually include advance diagnostic imaging such as CT-scan associated with myelography. Seizure is usually associated with hypoglycemia and insulinoma, but other causes such as hypocalcemia or intracranial disorders have been described. Ferrets are sensitive to various neurotropic infectious disease such as rabies, distemper, aleutian disease, or systemic coronavirus. Finally, muscular disorder such as disseminated idiopathic myofasciitis and myasthenia gravis have been recently described, and potential treatments have been intended.


title: Distinct Structural Elements and Internal Entry of Ribosomes in mRNA3 Encoded by Infectious Bronchitis Virus

text: Abstract Infectious bronchitis virus (IBV) mRNA3 encodes three small proteins, 3a, 3b, and 3c, at its 5′ end. Recently, it was demonstrated that initiation of protein 3c is dependent on the upstream sequence. Monte Carlo simulations of RNA folding in this tricistronic mRNA3 indicate that a highly significant folding region occurs prior to the initiator AUG of 3c. The unusual folding region (UFR) of 265 nucleotides (nt) contains the coding sequences of proteins 3a and 3b. Details of the structural analyses show that five highly significant RNA stem-loops in the UFR can be modeled into a compact superstructure by the interaction of two predicted pseudoknot structures. The folded superstructure comprising nt 44 to 330, with additional 22 nt downstream from this UFR, is suggested to serve as a ribosome landing pad (or an internal ribosomal entry site) in the cap-independent translation of the 3c of IBV. Intriguingly, the proposed structural motif of this coronavirus shares structural features similar to those proposed in a number of picornavirus mRNAs. Based on the common structural features, a plausible base pairing model between mRNA3 and 18 S rRNA is suggested, which is consistent with a general mechanism for regulation of internal initiation described in many picornaviruses.