docid: zbxiaofl

title: Treatment with proteasome inhibitor bortezomib enhances antigen-specific CD8+ T-cell-mediated antitumor immunity induced by DNA vaccination

text: There is an urgent need to develop new innovative therapies for the control of cancer. Antigen-specific immunotherapy and the employment of proteasome inhibitors have emerged as two potentially plausible approaches for the control of cancer. In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) with the proteasome inhibitor, bortezomib, for their ability to generate E7-specific immune responses and antitumor effects in vaccinated mice. We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor-bearing mice compared to monotherapy. Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CD8+ T cells. Our data have significant implications for future clinical translation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-008-0370-y) contains supplementary material, which is available to authorized users.


title: Web services in the life sciences

text: Web services provide a standard way of publishing applications and data sources over the internet, enabling mass dissemination of knowledge. In the life sciences, the web-service approach is seen as being a road to standardizing the multitude of tools available from different providers. In this article, we present an overview of the technology (focusing on life-science applications), we list the currently available service providers and we discuss advanced issues raised by the concept.


title: Measuring and Comparing Municipal Policy Responses to COVID-19

text: Municipal governments are experts in social non-distancing. From swimming pools to libraries, streetcars to public parks, municipalities bring residents together and move them around—services vital to a vibrant community in ordinary times, but potentially disastrous in a pandemic. Municipal decisions to shutter these services and enforce social distancing are thus crucial for a successful COVID-19 response.


title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK

text: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R(0), the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a “lockdown” was implemented across the UK. We compared measured contact patterns during the “lockdown” to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R(0) from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37–0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22–0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.


title: Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling

text: Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC(50) = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC(50) of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.


title: Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy

text: We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802–0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.


title: Social stigma in the time of Coronavirus

text: The COVID-19 pandemic has dramatically changed the lives of people around the globe since it appeared in Wuhan, China, at the beginning of December 2019. The burden of disease and its death toll have had an unprecedented impact on the healthcare, economic, and financial systems of low-, middle-, and high-income countries [1–3]. Peoples’ lives have been disrupted and negatively impacted by COVID-19-related suffering and lockdowns at community and household level.


title: Biowarfare Pathogens. Is the Research Flavor Different Than That of Clinically Relevant Pathogens?

text: Publisher Summary This chapter introduces four chemical warfare agents: bacillus anthracis (anthrax), yersinia pestis (plague), variola major (smallpox), and francesella tularensis (tularemia). Anthrax is a dimorphic bacterium that normally exists as spores. The clinical presentation can be as cutaneous, inhalational or gastrointestinal forms that are fortuitously not transmissible from person to person. The insidious nature of anthrax has both vegetative and spore morphology. The vegetative state, being the growth phase, is typically responsive to most classes of antibiotics, while the spore phase is not. Plague is caused by a bacterium carried by a rodent flea. While current antibiotics are effective against plague, the worry is the possibility of a bioengineered chimeric construct that would be resistant to all classes of antibiotics. Tularemia is a zoonosis that occurs naturally in the United States, with animal transmission to man. Sometimes an insect vector may also be the primary route of infection. It is highly pathogenic and the inhalation of 10 organisms would be adequate for infection. Smallpox is the most feared of all biowarfare pathogens, primarily due to its high transmissibility versus other pathogens whose etiologic affects are episodic.


title: Chapter 17 Viral Evolution It Is All About Mutations

text: Abstract Viral infection is a highly dynamic process, which lead to constant evolutionary changes on both sides of the viral–host interface. The high mutation rates of viruses, coupled with short generation times and large population sizes, allow viruses to rapidly adapt to the host environment. However, this high mutation rate also comes at a cost to the viral population, as deleterious mutations are constantly created, leading to a plethora of defective genomes. Here, we will discuss the basic tenets that govern the evolution of viruses: mutation rates, population size, selection, the multiplicity of infection, and how these factors modulate infection as viruses evolve within a host, during transmission to novel susceptible hosts, and as viruses establish infections in new host species.


Impact of Covid-19 pandemic on Asia-Europe relations


Pneumomediastinum in mechanically ventilated COVID-19 patients


title: Influenza-like illness in pregnant women during summertime: clinical, epidemiological and microbiological features

text: It is not known whether influenza-like illnesses (ILI) in pregnant women caused by influenza virus, specifically, those caused by the 2009 Influenza A H1N1 virus (nH1N1), can be clinically distinguished from those caused by other agents. From 1st July 2009 until 20th September 2009, an observational study including all pregnant women presenting at Hospital Universitario La Paz with an ILI was carried out. A specific reverse-transcriptase polymerase chain reaction (RT-PCR) for nH1N1 in nasopharyngeal swabs was prospectively carried out in all patients. Retrospectively, samples were analysed for multiple respiratory virus panel (RT-PCR microarray). Clinical, demographical and other microbiological variables were evaluated as well. A total of 45 pregnant women with ILI were admitted. Of these, 14 (31.1%) women had nH1N1 infection and 11 with a non-influenza ILI (35.48%) were positive for other viruses (five rhinovirus, four parainfluenza virus, one bocavirus and one adenovirus). In 20 patients, no aetiologic agent was identified. The clinical course of nH1N1 was mild, without deaths or severe complications. No significant differences were found when comparing the clinical presentation and course of patients with and without nH1N1 infection. Six women with nH1N1 infection received oseltamivir. Influenza and non-influenza ILI were clinically indistinguishable among pregnant women. Many ILI in pregnant women remain undiagnosed, despite undergoing an RT-PCR microarray for several respiratory viruses.


title: Earliest cases of coronavirus disease 2019 (COVID‐19) identified in solid organ transplant recipients in the United States

text: With the rapidly expanding pandemic of SARS‐CoV‐2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID‐19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID‐19, including two hospitalized patients and two patients managed entirely in the outpatient setting.


title: Mortality prediction to hospitalized patients with influenza pneumonia: PO(2)/FiO(2) combined lymphocyte count is the answer

text: INTRODUCTION: Community‐acquired pneumonia (CAP) severity scores perform well in predicting mortality of CAP patients, but their applicability in influenza pneumonia is powerless. OBJECTIVES: The aim of our research was to test the efficiency of PO(2)/FiO(2) and CAP severity scores in predicting mortality and intensive care unit (ICU) admission with influenza pneumonia patients. METHODS: We reviewed all patients with positive influenza virus RNA detection in Beijing Chao‐Yang Hospital during the 2009–2014 influenza seasons. Outpatients, inpatients with no pneumonia and incomplete data were excluded. We used receiver operating characteristic curves (ROCs) to verify the accuracy of severity scores or indices as mortality predictors in the study patients. RESULTS: Among 170 hospitalized patients with influenza pneumonia, 30 (17.6%) died. Among those who were classified as low‐risk (predicted mortality 0.1%–2.1%) by pneumonia severity index (PSI) or confusion, urea, respiratory rate, blood pressure, age ≥65 year (CURB‐65), the actual mortality ranged from 5.9 to 22.1%. Multivariate logistic regression indicated that hypoxia (PO(2)/FiO(2) ≤ 250) and lymphopenia (peripheral blood lymphocyte count <0.8 × 10(9)/L) were independent risk factors for mortality, with OR value of 22.483 (95% confidence interval 4.927–102.598) and 5.853 (95% confidence interval 1.887–18.152), respectively. PO(2)/FiO(2) combined lymphocyte count performed well for mortality prediction with area under the curve (AUC) of 0.945, which was significantly better than current CAP severity scores of PSI, CURB‐65 and confusion, respiratory rate, blood pressure, age ≥65 years for mortality prediction (P < 0.001). The scores or indices for ICU admission prediction to hospitalized patients with influenza pneumonia confirmed a similar pattern and PO(2)/FiO(2) combined lymphocyte count was also the best predictor for predicting ICU admission. CONCLUSION: In conclusion, we found that PO(2)/FiO(2) combined lymphocyte count is simple and reliable predictor of hospitalized patients with influenza pneumonia in predicting mortality and ICU admission. When PO(2)/FiO(2) ≤ 250 or peripheral blood lymphocyte count <0.8 × 10(9)/L, the clinician should pay great attention to the possibility of severe influenza pneumonia.


title: Varied clinical presentation and outcome of SARS‐CoV‐2 infection in liver transplant recipients: initial experience at a single center in Madrid, Spain

text: BACKGROUND: Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) infection in liver transplant (LT) recipients? METHODS: We attempted to address this question by reviewing our single‐center experience during the first two months of the pandemics at a high incidence area. RESULTS: Nineteen adult patients (5 females) were diagnosed by May 5th, 2020. Median age was 58 (range 55‐72), and median follow‐up since transplantation was 83 (range 20‐183) months. Cough (84.2%), fever (57.9%) and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in X‐ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon β in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient, and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow‐up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function. CONCLUSIONS: Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID‐19, with a favorable outcome in most of them without needing to modify baseline IS.


Infarto pulmonar secundario a tromboembolia pulmonar en COVID-19 diagnosticado con angiotomografía computarizada pulmonar con energía dual


title: Ubiquitin in the activation and attenuation of innate antiviral immunity

text: Viral infection activates danger signals that are transmitted via the retinoic acid–inducible gene 1–like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression.


title: Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes

text: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2–7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-α, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.


title: Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2

text: A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development.


Recommendations for resetting the food system


Novel Coronavirus Pneumonia and Cardiomyopathy: A Case Report.


title: From genome to drug lead: Identification of a small-molecule inhibitor of the SARS virus

text: Virtual screening, a fast, computational approach to identify drug leads [Perola, E.; Xu, K.; Kollmeyer, T. M.; Kaufmann, S. H.; Prendergast, F. G. J. Med. Chem.2000, 43, 401; Miller, M. A. Nat. Rev. Drug Disc.2002, 1 220], is limited by a known challenge in crystallographically determining flexible regions of proteins. This approach has not been able to identify active inhibitors of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using solely the crystal structures of a SARS-CoV cysteine proteinase with a flexible loop in the active site [Yang, H. T.; Yang, M. J.; Ding, Y.; Liu, Y. W.; Lou, Z. Y. Proc. Natl. Acad. Sci. U.S.A.2003, 100, 13190; Jenwitheesuk, E.; Samudrala, R. Bioorg. Med. Chem. Lett.2003, 13, 3989; Rajnarayanan, R. V.; Dakshanamurthy, S.; Pattabiraman, N. Biochem. Biophys. Res. Commun.2004, 321, 370; Du, Q.; Wang, S.; Wei, D.; Sirois, S.; Chou, K. Anal. Biochem.2005, 337, 262; Du, Q.; Wang, S.; Zhu, Y.; Wei, D.; Guo, H. Peptides2004, 25, 1857; Lee, V.; Wittayanarakul, K.; Remsungenen, T.; Parasuk, V.; Sompornpisut, P. Science (Asia)2003, 29, 181; Toney, J.; Navas-Martin, S.; Weiss, S.; Koeller, A. J. Med. Chem.2004, 47, 1079; Zhang, X. W.; Yap, Y. L. Bioorg. Med. Chem.2004, 12, 2517]. This article demonstrates a genome-to-drug-lead approach that uses terascale computing to model flexible regions of proteins, thus permitting the utilization of genetic information to identify drug leads expeditiously. A small-molecule inhibitor of SARS-CoV, exhibiting an effective concentration (EC(50)) of 23 μM in cell-based assays, was identified through virtual screening against a computer-predicted model of the cysteine proteinase. Screening against two crystal structures of the same proteinase failed to identify the 23-μM inhibitor. This study suggests that terascale computing can complement crystallography, broaden the scope of virtual screening, and accelerate the development of therapeutics to treat emerging infectious diseases such as SARS and Bird Flu.


title: Markers and Biomarkers of Endothelium: When Something Is Rotten in the State

text: Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.


title: Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

text: WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient.


title: Descriptive distribution and phylogenetic analysis of feline infectious peritonitis virus isolates of Malaysia

text: The descriptive distribution and phylogeny of feline coronaviruses (FCoVs) were studied in cats suspected of having feline infectious peritonitis (FIP) in Malaysia. Ascitic fluids and/or biopsy samples were subjected to a reverse transcription polymerase chain reaction (RT-PCR) targeted for a conserved region of 3'untranslated region (3'UTR) of the FCoV genome. Eighty nine percent of the sampled animals were positive for the presence of FCoV. Among the FCoV positive cats, 80% of cats were males and 64% were below 2 years of age. The FCoV positive cases included 56% domestic short hair (DSH), 40% Persian, and 4% Siamese cats. The nucleotide sequences of 10 selected amplified products from FIP cases were determined. The sequence comparison revealed that the field isolates had 96% homology with a few point mutations. The extent of homology decreased to 93% when compared with reference strains. The overall branching pattern of phylogenetic tree showed two distinct clusters, where all Malaysian isolates fall into one main genetic cluster. These findings provided the first genetic information of FCoV in Malaysia.


title: A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice

text: Viral protein neutralizing antibodies have been developed but they are limited only to the targeted virus and are often susceptible to antigenic drift. Here, we present an alternative strategy for creating virus-resistant cells and animals by ectopic expression of a nucleic acid hydrolyzing catalytic 3D8 single chain variable fragment (scFv), which has both DNase and RNase activities. HeLa cells (SCH7072) expressing 3D8 scFv acquired significant resistance to DNA viruses. Virus challenging with Herpes simplex virus (HSV) in 3D8 scFv transgenic cells and fluorescence resonance energy transfer (FRET) assay based on direct DNA cleavage analysis revealed that the induced resistance in HeLa cells was acquired by the nucleic acid hydrolyzing catalytic activity of 3D8 scFv. In addition, pseudorabies virus (PRV) infection in WT C57BL/6 mice was lethal, whereas transgenic mice (STG90) that expressed high levels of 3D8 scFv mRNA in liver, muscle, and brain showed a 56% survival rate 5 days after PRV intramuscular infection. The antiviral effects against DNA viruses conferred by 3D8 scFv expression in HeLa cells as well as an in vivo mouse system can be attributed to the nuclease activity that inhibits viral genome DNA replication in the nucleus and/or viral mRNA translation in the cytoplasm. Our results demonstrate that the nucleic-acid hydrolyzing activity of 3D8 scFv confers viral resistance to DNA viruses in vitro in HeLa cells and in an in vivo mouse system.


title: Pathophysiology of viral-induced exacerbations of COPD

text: Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation.


title: Binding site analysis of potential protease inhibitors of COVID-19 using AutoDock

text: Recent outbreak of COVID-19 caused by SARS-CoV-2 in December 2019 raised global health concerns. Re-purposing the available protease inhibitor drugs for immediate use in treatment in SARS-CoV-2 infections could improve the currently available clinical management. The current study, aims to predict theoretical structure for protease of COVID-19 and to explore further whether this protein can serve as a target for protease inhibitor drugs such as remdesivir, nelfinavir, lopinavir, ritonavir and α-ketoamide. While the 3D structure of protease was predicted using SWISS MODEL server, molecular interaction studies between protein and ligands were performed using AutoDock software. The predicted protease model was reasonably good based on reports generated by different validation servers. The study further revealed that all the protease inhibitor drugs got docked with negative dock energy onto the target protein. Molecular interaction studies showed that protease structure had multiple active site residues for remdesivir, while for remaining ligands the structure had only one active site residue each. From the output of multiple sequence alignment, it is evident that ligand binding sites were conserved. The current in silico study thus, provides structural insights about the protease of COVID-19 and also its molecular interactions with some of the known protease inhibitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-020-00585-z) contains supplementary material, which is available to authorized users.


title: Geographic risk assessment of COVID-19 transmission using recent data: An observational study

text: BACKGROUND: The US Centers for Disease Control and Prevention (CDC) regularly issues “travel health notices” that address disease outbreaks of novel coronavirus disease (COVID)-19 in destinations worldwide. The notices are classified into 3 levels based on the risk posed by the outbreak and what precautions should be in place to prevent spreading. What objectively observed criteria of these COVID-19 situations are required for classification and visualization? This study aimed to visualize the epidemic outbreak and the provisional case fatality rate (CFR) using the Rasch model and Bayes's theorem and developed an algorithm that classifies countries/regions into categories that are then shown on Google Maps. METHODS: We downloaded daily COVID-19 outbreak numbers for countries/regions from the GitHub website, which contains information on confirmed cases in more than 30 Chinese locations and other countries/regions. The Rasch model was used to estimate the epidemic outbreak for each country/region using data from recent days. All responses were transformed by using the logarithm function. The Bayes's base CFRs were computed for each region. The geographic risk of transmission of the COVID-19 epidemic was thus determined using both magnitudes (i.e., Rasch scores and CFRs) for each country. RESULTS: The top 7 countries were Iran, South Korea, Italy, Germany, Spain, China (Hubei), and France, with values of {4.53, 3.47, 3.18, 1.65, 1.34 1.13, 1.06} and {13.69%, 0.91%, 47.71%, 0.23%, 24.44%, 3.56%, and 16.22%} for the outbreak magnitudes and CFRs, respectively. The results were consistent with the US CDC travel advisories of warning level 3 in China, Iran, and most European countries and of level 2 in South Korea on March 16, 2020. CONCLUSION: We created an online algorithm that used the CFRs to display the geographic risks to understand COVID-19 transmission. The app was developed to display which countries had higher travel risks and aid with the understanding of the outbreak situation.


title: Risk of Virus Contamination Through Surgical Smoke During Minimally Invasive Surgery: A Systematic Review of Literature on a Neglected Issue Revived in the COVID-19 Pandemic Era

text: CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the safety of laparoscopy due to the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diffusion in surgical smoke. Although no case of SARS-CoV-2 contagion related to surgical smoke has been reported, several international surgical societies recommended caution or even discouraged the use of a laparoscopic approach. OBJECTIVE: To evaluate the risk of virus spread due to surgical smoke during surgical procedures. EVIDENCE ACQUISITION: We searched PubMed and Scopus for eligible studies, including clinical and preclinical studies assessing the presence of any virus in the surgical smoke from any surgical procedure or experimental model. EVIDENCE SYNTHESIS: We identified 24 studies. No study was found investigating SARS-CoV-2 or any other coronavirus. About other viruses, hepatitis B virus was identified in the surgical smoke collected during different laparoscopic surgeries (colorectal resections, gastrectomies, and hepatic wedge resections). Other clinical studies suggested a consistent risk of transmission for human papillomavirus (HPV) in the surgical treatments of HPV-related disease (mainly genital warts, laryngeal papillomas, or cutaneous lesions). Preclinical studies showed conflicting results, but HPV was shown to have a high risk of transmission. CONCLUSIONS: Although all the available data come from different viruses, considering that the SARS-CoV-2 virus has been shown in blood and stools, the theoretical risk of virus diffusion through surgical smoke cannot be excluded. Specific clinical studies are needed to understand the effective presence of the virus in the surgical smoke of different surgical procedures and its concentration. Meanwhile, adoption of all the required protective strategies, including preoperative patient nasopharyngeal swab for COVID-19, seems mandatory. PATIENT SUMMARY: In this systematic review, we looked at the risk of virus spread from surgical smoke exposure during surgery. Although no study was found investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or any other coronavirus, we found that the theoretical risk of virus diffusion through surgical smoke cannot be excluded.


title: Comparison of serum immunoglobulin G half-life in dairy calves fed colostrum, colostrum replacer or administered with intravenous bovine plasma

text: Abstract In calves, passive immunity of immunoglobulins can be acquired through ingestion of colostrum or colostrum replacers. Plasma can been used to supplement immunoglobulins in healthy or sick calves. Serum half-life of colostral derived immuglobulin G (IgG) is estimated to be 20 days. Half-life of IgG is important in determining response to antigens and timing of vaccination in calves. To date studies evaluating half-life of colostrum replacer or plasma derived IgG are lacking. The objectives of this study were to compare the serum half-life of IgG derived from colostrum, colostrum replacer and plasma in dairy calves reared up to 35 days of age. Thirty Jersey calves were randomly assigned to receive colostrum or colostrum replacer by oroesophageal tubing or plasma by intravenous administration. Serum samples were collected at 2, 5, 7, 10, 14, 21, 28 and 35 days. Serum IgG concentrations were determined by radial immunodiffusion. The results indicated that half-life for IgG in colostrum fed (28.5 days) or plasma transfused calves (27.3 days) was longer than colostrum replacer fed calves (19.1 days). Further studies are required to evaluate pathogen specific immunoglobulins in order to recommend vaccination timing in calves fed colostrum replacers.


docid: jgfthsvy

title: COVID-19: From the short term crisis mode to a long term maintainance mode, International Medical Assistance to reinvent?


title: Editorial Perspective: Perils and promise for child and adolescent sleep and associated psychopathology during the COVID‐19 pandemic

text: It is anticipated that the novel coronavirus disease 2019 (COVID‐19) pandemic and associated societal response will have wide‐ranging impacts on youth development and mental health. Sleep is crucial for child and adolescent health and well‐being, and the potential for sleep problems to emerge or worsen during and following the pandemic is high. This may be particularly true for children and adolescents who are at heightened risk for the onset of sleep and mental health disturbances and for those whom developmental changes impacting sleep are rapidly occurring. Youth with preexisting psychopathologies (including anxiety and depression) and neurodevelopmental conditions (including attention‐deficit/hyperactivity disorder and autism spectrum disorder) could be especially vulnerable to disturbed sleep during this period of change and uncertainty. It is thus imperative that sleep considerations be part of research and clinical initiatives aimed at understanding and mitigating the impact of the COVID‐19 pandemic in children and adolescents. This article considers ways in which the pandemic may impact sleep, including research and clinical implications.


A16 A distributed pan-viral typing framework


title: Drainage systems, an occluded source of sanitation related outbreaks

text: BACKGROUND: Drainage systems and its role in sanitation related outbreaks are evident but still occluded once it has been installed. This current review evaluates if drainage systems can cause infections and thus be of clinical concern. METHOD: A review of the literature was analyzed. Papers, guidelines, and quality management systems have been considered. RESULTS: Adequate sanitation is fundamental and a prerequisite for safe life and productivity. In contrast, malfunctioning sanitation has been reported to cause outbreaks all over the world. In areas with no sanitation, diarrheal mortality is high and has been shown to decrease by 36% after interventions to improve sanitation. Often, infections are faeces associated and when present in wastewater and sewage sludge poses a high risk of infection upon exposure. Hence, there are working safety guidelines and in industries where infection reduction is essential strict quality assurance systems, i.e. HACCP (hazard analysis critical control points) and GMP (Good Manufacturing Practice) must be complied. Healthcare has recently taken interest in the HACCP system in their efforts to reduce healthcare associated infections as a response to increasing number of ineffective antibiotics and the threat of mortality rate like the pre-antibiotic era. The last few years have called for immediate action to contain the emergence of increasing resistant microorganisms. Resistance is obtained as a result of overuse and misuse of antibiotics in both healthcare and agriculture. Also, by the discharge of antibiotics from manufacturers, healthcare and society. One mechanism of development of novel resistant pathogens has been shown to be by effortless sharing of genetic mobile elements coding for resistance from microbes in the environment to human microbes. These pathogens have been sampled from the drainage systems. These were noticed owing to their possession of an unusual antibiotic resistance profile linking them to the outbreak. Often the cause of sanitation related outbreaks is due to inadequate sanitation and maintenance. However, in general these infections probably go unnoticed. CONCLUSION: Drainage systems and its maintenance, if neglected, could pose a threat in both community and healthcare causing infections as well as emergence of multi-resistant bacteria that could cause unpredictable clinical manifestations.


docid: eeoelafd

title: Recombinant Live Attenuated Influenza Vaccine Viruses Carrying Conserved T Cell Epitopes of Human Adenoviruses Induce Functional Cytotoxic T Cell Responses and Protect Mice against both Infections

text: Human adenoviruses (AdVs) are one of the most common causes of acute respiratory viral infections worldwide. Multiple AdV serotypes with low cross-reactivity circulate in the human population, making the development of an effective vaccine very challenging. In the current study, we designed a cross-reactive AdV vaccine based on the T-cell epitopes conserved among various AdV serotypes, which were inserted into the genome of a licensed cold-adapted live attenuated influenza vaccine (LAIV) backbone. We rescued two recombinant LAIV-AdV vaccines by inserting the selected AdV T-cell epitopes into the open reading frame of full-length NA and truncated the NS1 proteins of the H7N9 LAIV virus. We then tested the bivalent vaccines for their efficacy against influenza and human AdV5 in a mouse model. The vaccine viruses were attenuated in C57BL/6J mice and induced a strong influenza-specific antibody and cell-mediated immunity, fully protecting the mice against virulent influenza virus infection. The CD8 T-cell responses induced by both LAIV-AdV candidates were functional and efficiently killed the target cells loaded either with influenza NP(366) or AdV DBP(418) peptides. In addition, high levels of recall memory T cells targeted to an immunodominant H2(b)-restricted CD8 T-cell epitope were detected in the immunized mice after the AdV5 challenge, and the magnitude of these responses correlated with the level of protection against pulmonary pathology caused by the AdV5 infection. Our findings suggest that the developed recombinant vaccines can be used for combined protection against influenza and human adenoviruses and warrant further evaluation on humanized animal models and subsequent human trials.


title: Viral etiology of respiratory infections in children under 5 years old living in tropical rural areas of Senegal: The EVIRA project

text: Acute respiratory infection is one of the leading causes of child morbidity, especially in developing countries. Viruses are recognized as the predominant causative agents of acute respiratory infections. In Senegal, few data concerning the causes of respiratory infections are available, and those known relate mainly to classical influenza infections. Clinical and virological surveillance of acute respiratory infections was carried out in a rural community in children less than 5 years old. A standardized questionnaire was used and a nasopharyngeal swab sample was collected from each patient. These samples were tested for the detection of 20 respiratory viruses by multiplex RT‐PCR or by viral culture. A total of 82 acute respiratory episodes were included, and 48 (58.5%) were found to be positive, with a total of 55 viral detections; several samples were positive for two (n = 5) or 3 (n = 1) viruses. Ten different viruses were identified: influenza viruses A, B, and C (n = 25), human respiratory syncytial virus type A (n = 13), rhinoviruses (n = 8), human coronaviruses type 229E and NL63 (n = 6), parainfluenza viruses 3 and 4 (n = 2), and bocavirus (n = 1). These results provide evidence on the importance and the diversity of viruses as causative agents of acute respiratory infections in children living in a rural community in Senegal. The establishment of sentinel surveillance sites could help estimate the burden of acute respiratory infection in the pediatric population and should help prepare the health care systems to identify and respond to new viral respiratory emergencies. J. Med. Virol. 82:866–872, 2010. © 2010 Wiley‐Liss, Inc.


title: A Transfected Sialyltransferase That Is Elevated in Breast Cancer and Localizes to the medial/trans-Golgi Apparatus Inhibits the Development of core-2–based O-Glycans

text: The α2,3 sialyltransferase, α2,3 SAT (O), catalyzes the transfer of sialic acid to Galβ1,3 N-acetyld-galactosamine (GalNAc) (core-1) in mucin type O-glycosylation, and thus terminates chain extension. A Core-2 branch can also be formed from core-1 by the core-2 β1,6 N-acetyl-d-glucosamine transferase (β1,6 GlcNAc T) that leads to chain extension. Increased levels of the α2,3 SAT (O) and decreased levels of the core-2 β1,6 GlcNAc T are seen in breast cancer cells and correlate with differences in the structure of the O-glycans synthesized (Brockhausen et al., 1995; Lloyd et al., 1996). Since in mucin type O-glycosylation sugars are added individually and sequentially in the Golgi apparatus, the position of the transferases, as well as their activity, can determine the final structure of the O-glycans synthesized. A cDNA coding for the human α2,3 SAT (O) tagged with an immunoreactive epitope from the myc gene has been used to map the position of the glycosyltransferase in nontumorigenic (MTSV1-7) and malignant (T47D) breast epithelial cell lines. Transfectants were analyzed for expression of the enzyme at the level of message and protein, as well as for enzymic activity. In T47D cells, which do not express core-2 β1,6 GlcNAc T, the increased activity of the sialyltransferase correlated with increased sialylation of core-1 O-glycans on the epithelial mucin MUC1. Furthermore, in MTSV1-7 cells, which do express core-2 β1,6 GlcNAc T, an increase in sialylated core-1 structures is accompanied by a reduction in the ratio of GlcNAc: GalNAc in the O-glycans attached to MUC1, implying a decrease in branching. Using quantitative immunoelectron microscopy, the sialyltransferase was mapped to the medial- and trans-Golgi cisternae, with some being present in the TGN. The data represent the first fine mapping of a sialyltransferase specifically active in O-glycosylation and demonstrate that the structure of O-glycans synthesized by a cell can be manipulated by transfecting with recombinant glycosyltransferases.


title: Public awareness of coronavirus in Al-Jouf region, Saudi Arabia

text: AIM: Since 2012 and to date, outbreak/new cases of Middle East respiratory syndrome-related coronavirus (MERS-CoV) were always reported in Saudi Arabia. Al-Jouf region is considered as one of the most vulnerable areas to the disease outbreak. This research aimed to assess (to the best of our knowledge), for the first time, the current level of awareness towards MERS-CoV among the Al-Jouf region population through a well-designed multistage questionnaire. SUBJECTS AND METHODS: A cross-sectional study of 384 participants recruited from various places in Al-Jouf government was conducted through a valid and reliable questionnaire including sociodemographic and MERS-CoV knowledge data. RESULTS: The majority of the participants showed generally moderate knowledge about MERS-CoV. Age, education, and occupation were the only significant predictors of the level of low awareness concern. Also, the public awareness about the nature, communicability, and lethal effect of the disease was good overall; however, knowledge about incubation period, clinical picture, and epidemiology of the disease needs more governmental concern. The Ministry of Health was the main source of information. CONCLUSION: Empowering public information regarding the incubation period and epidemiology of the disease is needed. Frequent communication between healthcare providers and both school students and non-educated individuals is recommended to help the Saudi government in controlling the disease outbreak. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10389-020-01209-y) contains supplementary material, which is available to authorized users.


Getting it right: PPE demonstration videos


title: Challenges and strategies in management of osteoporosis and fragility fracture care during COVID-19 pandemic

text: BACKGROUND: COVID-19 has resulted in restriction of face to face consultations and mechanisms to access health care. Osteoporosis and fragility fractures forms a significant proportion of adult trauma and orthopaedic workload even during the pandemic. AIMS: We assess the challenges and strategies used in the management of osteoporosis and fragility fracture care during the COVID-19 pandemic. METHODS: We have done a comprehensive review of the literature using suitable keywords on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the first week of May 2020 on developments and guidance during the current COVID-19 pandemic. RESULTS: Osteoporosis and fragility fractures management has been hampered by lock down and infection transmission strategies used to contain the COVID-19 pandemic. Access to diagnostic tests, treatment facilities with the need to use clinical and prediction tools to guide management Telemedicine has an evolving role. CONCLUSION: Osteoporosis and fragility fractures in elderly individuals pose a real challenge for an appropriate diagnosis and management, during the COVID-19 pandemic. A clinical decision along with use of clinical prediction tools for osteoporosis should be used to direct treatment. Obligatory fractures such as hip fractures require operative intervention. Non-obligatory fractures such as distal radius fractures can be managed conservatively with use of telemedicine applications in monitoring both types of patients.


title: Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus

text: The cotranslational folding is recognized as a very cooperative process that occurs after the nearly completion of the polypeptide sequence of a domain. Here we investigated the challenges faced by polypeptide segments of a non-vectorial β-barrel fold. Besides the biological interest behind the SARS coronavirus non-structural protein 1 (nsp1, 117 amino acids), this study model has two structural features that motivated its use in this work: 1- its recombinant production is dependent on the temperature, with greater solubility when expressed at low temperatures. This is an indication of the cotranslational guidance to the native protein conformation. 2- Conversely, nsp1 has a six-stranded, mixed parallel/antiparallel β-barrel with intricate long-range interactions, indicating it will need the full-length protein to fold properly. We used non-denaturing purification conditions that allowed the characterization of polypeptide chains of different lengths, mimicking the landscape of the cotranslational fold of a β-barrel, and avoiding the major technical hindrances of working with the nascent polypeptide bound to the ribosome. Our results showed partially folded states formed as soon as the amino acids of the second β-strand were present (55 amino acids). These partially folded states are different based on the length of polypeptide chain. The native α-helix (amino acids 24–37) was identified as a transient structure (~20–30% propensity). We identified the presence of regular secondary structure after the fourth native β-strand is present (89 amino acids), in parallel to the collapse to a non-native 3D structure. Interestingly the polypeptide sequences of the native strands β2, β3 and β4 have characteristics of α-helices. Our comprehensive analyses support the idea that incomplete polypeptide chains, such as the ones of nascent proteins much earlier than the end of the translation, adopt an abundance of specific transient folds, instead of disordered conformations.


title: Re-engineering the Cypriot healthcare service system

text: BACKGROUND: The Cypriot healthcare system has undergone a number of major transformations since the induction of the Republic of Cyprus in the European Union over 10 years ago. Currently Cyprus is undergoing a major reform, namely the introduction of a primary care driven national healthcare system. The aim of the study was to assess the existing state of training, support, quality, guidelines and infrastructure towards a better healthcare system in Cyprus. METHODS: This is a mixed-methods study combining statistical data until October 2016 and workshop discussions delivered in Cyprus in November 2015. We used anonymised data provided: (1a) by the Cyprus Medical Association of all registered medical doctors up to October 2016; (1b); by the Ministry of Health (MoH) Health Monitoring Unit up to October 2016; (2) during a workshop organised with representatives from the Royal College of Physicians, the European Commission and the Health Insurance Organization. RESULTS: The gender ratio of men over women is disproportionate, with over 85% of the medical doctors undertaking their training in Greece, Eastern Europe and neighbouring countries, while the current record does not hold a relevant specialty information for 4 out of 10 doctors. The results show lack of statutory inspection systems, application of revalidation principles or implementation of peer-review clinical services on the island. There are eight proposed recommendations made by the workshop participants towards the transformation of the Cypriot healthcare system and the development of the Cyprus Quality Improvement Institute. These are aimed at addressing gaps in quality of care, adherence to clinical guidelines and implementation of audits, development of doctors’ revalidation and peer-review of clinical services, accreditation of service implementation, establishment of a statutory inspection system as well as the set-up of an incentives program as part of the general healthcare system (GHS) of Cyprus. CONCLUSIONS: Current efforts for the implementation of the new GHS in Cyprus call for adequate training and support of the medical workforce, transparent and safer quality of care provision through the implementation of clinical guidelines and capacity-building infrastructure.


title: Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response

text: Coronavirus MHV‐JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV‐JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG† B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down‐regulation of this protein, possibly mediated by anti‐S antibodies.


title: The computation of case fatality rate for novel coronavirus (COVID-19) based on Bayes theorem: An observational study

text: BACKGROUND: When a new disease such starts to spread, the commonly asked questions are how deadly is it? and how many people are likely to die of this outbreak? The World Health Organization (WHO) announced in a press conference on January 29, 2020 that the death rate of COVID-19 was 2% on the case fatality rate (CFR). It was underestimated assuming no lag days from symptom onset to deaths while many CFR formulas have been proposed, the estimation on Bays theorem is worthy of interpretation. Hence, it is hypothesized that the over-loaded burdens of treating patients and capacities to contain the outbreak (LSBHRS) may increase the CFR. METHODS: We downloaded COVID-19 outbreak numbers from January 21 to February 14, 2020, in countries/regions on a daily basis from Github that contains information on confirmed cases in >30 Chinese locations and other countries/regions. The pros and cons were compared among the 5 formula of CFR, including [A] deaths/confirmed; [B] deaths/(deaths + recovered); [C] deaths/(cases x days ago); [D] Bayes estimation based on [A] and the outbreak (LSBHRS) in each country/region; and [E] Bayes estimation based on [C] deaths/(cases x days ago). The coefficients of variance (CV = the ratio of the standard deviation to the mean) were applied to measure the relative variability for each CFR. A dashboard was developed for daily display of the CFR across each region. RESULTS: The Bayes based on (A)[D] has the lowest CV (=0.10) followed by the deaths/confirmed (=0.11) [A], deaths/(deaths + recoveries) (=0.42) [B], Bayes based on (C) (=0.49) [E], and deaths/(cases x days ago) (=0.59) [C]. All final CFRs will be equal using the formula (from, A to E). A dashboard was developed for the daily reporting of the CFR. The CFR (3.7%) greater than the prior CFR of 2.2% was evident in LSBHRS, increasing the CFR. A dashboard was created to present the CFRs on COVID-19. CONCLUSION: We suggest examining both trends of the Bayes based on both deaths/(cases 7 days ago) and deaths/confirmed cases as a reference to the final CFR. An app developed for displaying the provisional CFR with the 2 CFR trends can improve the underestimated CFR reported by WHO and media.


title: Effect of bovine viral diarrhea virus in the feedlot

text: It could be argued that bovine viral diarrhea virus (BVDV) is one of the most economically significant infectious pathogens of feedlot cattle. Although the direct economic losses caused by this virus have not been well quantified, the role it plays as an immunosuppressive agent and as a potentiator for other diseases, most notably bovine respiratory disease, have been well documented. It is also a difficult disease for the feedlot veterinarian to control effectively. Individual cattle persistently infected with BVDV often serve as the source of infectious virus within a group of feedlot cattle, and the ultimate responsibility for preventing persistent infections in cattle rests with the cow-calf producer and not with the feedlot owner. The enormous impact of the virus on the livestock industry has led the Academy of Veterinary Consultants to draft a position statement that resolves that the beef and dairy industries adopt measures to control and target eventual eradication of BVDV from North America.


title: Implementation of an Emergency Use Authorization Test During an Impending National Crisis

text: Abstract The laboratory response to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may be termed heroic. From the identification of the novel coronavirus to implementation of routine laboratory testing around the world to the development of potential vaccines, laboratories have played a critical role in the efforts to curtail this pandemic. In this brief report, we review our own effort at a mid-sized, rural, academic medical center to implement a molecular test for the virus; and, we share insights and lessons learned from that process which might be helpful in similar situations in the future.


title: Sequence analysis of the S gene of recombinant MHV-2/A59 coronaviruses reveals three candidate mutations associated with demyelination and hepatitis

text: Coronaviruses, mouse hepatitis virus (MHV) strains, exhibit various degrees of neurotropism and hepatotropism following intracerebral (IC) infection of 4-week-old C57Bl/6 mice. Whereas MHV-A59 produces acute meningitis, encephalitis, hepatitis, and chronic demyelination, a closely related strain, MHV-2, produces only acute meningitis and hepatitis. We previously reported that the spike glycoprotein gene of MHV contains determinants of demyelination and hepatitis. To further investigate the site of demyelination and hepatitis determinants within the S gene, we sequenced the S gene of several nonde-myelinating recombinant viruses. We found that three encephalitis-positive, demyelination-negative, hepatitis-negative recombinant viruses have an MHV-A59-derived S gene, which contains three identical point mutations (I375M, L652I, and T1087N). One or more of the sites of these mutations in the MHV-A59 genome are likely to contribute to demyelination and hepatitis.


title: Impact of coronavirus pandemic crisis in endoscopic clinical practice: Results from a national survey in Brazil

text: Background and study aims In March 2020, the World Health Organization declared coronavirus disease of 2019 (COVID-19) as a pandemic, mobilizing all countries to contain the disease spread. Activity in endoscopy centers globally was severely affected. We conducted a national survey aiming to assess the impact of the COVID-19 outbreak on endoscopic clinical practice in Brazil. Methods In April 2020, 3,719 associate members of SOBED (Brazilian Society of Digestive Endoscopy) were invited to respond to an electronic survey. An Internet link was established to provide access to the online questionnaire with 40 questions regarding personal profile, endoscopy unit logistics and schedule, availability and use of personal protective equipment (PPE), financial impact, and exposure to COVID-19. Results A total of 2,131 individuals (67 %) accessed the questionnaire and 1155 responses were received. After review, 980 responses were considered valid. According to almost 90 % of respondents, endoscopy activity was restricted to urgent procedures, in both public and private hospitals. All respondents increased PPE use after the outbreak, however, institutions provided adequate PPE to only 278 responders (28.7 %). Significant income loss was universally reported. A total of 10 practitioners (1 %) reported COVID-19 infection and attributed the contamination to endoscopic procedures. Conclusions Based on this nationwide survey with almost 1,000 respondents, the COVID-19 pandemic substantially reduced the activity of endoscopy units in private and public settings. The pandemic increased awareness of PPE use, but its availability was not universal and 1 % of the respondents became infected with COVID-19, allegedly due to exposure during endoscopic procedures.


title: COVID-19-related self-harm and suicidality among individuals with mental disorders

text: Abstract The coronavirus disease (COVID-19) pandemic has created an unprecedented public health emergency Extraordinary measures have been implemented to reduce the spread of the virus, including mass quarantines and social distancing However, these preventive measures come at a price Economic stress, social isolation, decreased access to community activities, etc , is the new reality for a large part of the global community, and may have detrimental effects on mental health


title: Identify-Isolate-Inform: A Tool for Initial Detection and Management of Measles Patients in the Emergency Department

text: Measles (rubeola) is a highly contagious airborne disease that was declared eliminated in the U.S. in the year 2000. Only sporadic U.S. cases and minor outbreaks occurred until the larger outbreak beginning in 2014 that has become a public health emergency. The “Identify-Isolate-Inform” tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Measles typically presents with a prodrome of high fever, and cough/coryza/conjunctivitis, sometimes accompanied by the pathognomonic Koplik spots. Two to four days later, an erythematous maculopapular rash begins on the face and spreads down the body. Suspect patients must be immediately isolated with airborne precautions while awaiting laboratory confirmation of disease. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases.


title: Perceptions and practices among Zambian sheep and goat traders concerning small ruminant health and disease

text: Trade in animals and animal products is a key factor in the transmission of infectious diseases. Livestock traders play an important role in this process, yet there is little knowledge of traders’ perceptions of animal disease or their associated actions. The aim of this study was to investigate perceptions and practices of Zambian small ruminant traders with regard to sheep and goat health and disease. It also analysed how existing perceptions and practices might affect risks of disease transmission through trade. A case study was performed at the two largest small livestock markets in Zambia: the Lusaka market in the capital and the Kasumbalesa market near the border with the Democratic Republic of Congo. Semi-structured interviews with 47 traders performed in April-May and September 2018 represent the core material. Zambian small ruminant traders frequently trade animals that have clinical signs of disease, either because they appear unaware or indifferent to the associated risks, experience financial constraints or assign responsibility for disease prevention to other value chain actors. In their decision about whether or not to sell a visibly sick small ruminant, traders appear to consider whether the clinical sign is perceived as ‘natural’ or the result of an illness, whether the buyer is aware of the animal’s health condition, and whether the animal is sold for consumption or breeding purposes. Traders appear to regard the veterinary certificate required to transport small ruminants in Zambia as proof of health, placing the responsibility for potential disease in traded animals on the veterinary authorities. In their description of a model trader, taking good care of and being sensitive to customer needs was emphasized, indicating that an efficient way to encourage traders to change their behaviour is to influence customer demands. In contrast to the focus in previous studies on identifying and filling knowledge gaps, the present study show that lack of knowledge is not central to why traders engage in disease-transmitting behaviour. Greater awareness of other reasons for certain perceptions and practices could lead to the formulation of risk communication strategies and mitigation measures that are relevant for the local context, as well as alternative strategies for changing trader behaviour.


title: Viruses are a dominant driver of protein adaptation in mammals

text: Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001


title: Embryo importation and cryobanking strategies for laboratory animals and wildlife species

text: Abstract The transportation of embryos obtained from animal models, endangered species and nondomestic farmed animals (e.g., deer) can reduce/eliminate the need for shipping postnatal animals and thus has gained the interest of the biomedical and conservation fields. Efficient movement of germ plasm worldwide requires established cryobanks. Embryo cryopreservation has become a routinely successful technology for many species and efforts to develop usable cryobanks for many target species are ongoing. Recommended regulations for the movement of embryos from nontraditional (i.e. other than domestic livestock) species are nonexistent. Efforts are underway to establish domestic and international handling guidelines and to recommend suitable quarantine conditions to facilitate embryo importation. Further basic research on specific zona pellucida-pathogen interactions is encouraged to support embryo movement efforts.


Keeping on the high quality of healthcare in Greek Inflammatory Bowel Disease patients in the SARS-CoV-2 era


title: RNA elements required for RNA recombination function as replication enhancers in vitro and in vivo in a plus‐strand RNA virus

text: RNA replication requires cis‐acting elements to recruit the viral RNA‐dependent RNA polymerase (RdRp) and facilitate de novo initiation of complementary strand synthesis. Hairpins that are hot spots for recombination in the genomic RNA of turnip crinkle virus (TCV) and satellite (sat)‐RNA C, a parasitic RNA associated with TCV infections, stimulate RNA synthesis 10‐fold from a downstream promoter sequence in an in vitro assay using partially purified TCV RdRp. Artificial hairpins had an inhibitory effect on transcription. RNA accumulation in single cells was enhanced 5‐ to 10‐fold when the natural stem‐loop structures were inserted into a poorly accumulating sat‐RNA. The effect of the stem‐loop structures on RNA replication was additive, with insertion of three stem‐loop RNA elements increasing sat‐RNA accumulation to the greatest extent (25‐fold). These stem‐loop structures do not influence the stability of the RNAs in vivo, but may serve to recruit the RdRp to the template.


title: One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus and canine kobuvirus

text: To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10(2.1) TCID(50) for CDV, 10(1.9) TCID(50) for CPV and 10(3) copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.


title: Recommendations for general surgery activities in a pandemic scenario (SARS‐CoV‐2)

text: Challenging times


Protein portal: Enzyme acts as door for the sars virus


title: CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration

text: The smallest Cas13 family protein, CasRx, has a high cleavage activity and targeting specificity, offering attractive opportunity for therapeutic applications. Here we report that delivery of CasRx by adeno-associated virus via intravitreal injection could efficiently knockdown Vegfa transcripts and significantly reduce the area of laser-induced choroidal neovascularization in a mouse model of age-related macular degeneration. Thus, RNA-targeting CRISPR system could be used for in vivo gene therapy.


title: Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses

text: BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation. RESULTS: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation. CONCLUSION: This report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.


title: Genetic characterization of infectious bronchitis viruses in Thailand, 2014–2016: identification of a novel recombinant variant

text: Abstract Infectious bronchitis (IB) causes severe economic losses to the poultry industry worldwide owing to frequent emergence of novel infectious bronchitis virus (IBV) variants, which potentially affect the effectiveness of the currently used IBV vaccine. Therefore, continuous monitoring of IBV genotypes and lineages recently circulating in chickens worldwide is essential. In this study, we characterized the complete S1 gene from 120 IBVs circulating in chickens in Thailand from 2014 to 2016. Phylogenetic analysis of the complete S1 gene of 120 Thai IBVs revealed that the 2014–2016 Thai IBVs were divided into 3 lineages (GI-1, GI-13, and GI-19) and a novel IBV variant. Our results also showed that GI-19 lineage has become the predominant lineage of IBV circulating in chicken flocks in Thailand from 2014 to 2016. It is interesting to note that a novel IBV variant, which was genetically different from the established IBV lineages, was identified in this study. The recombination analysis demonstrated that this novel IBV variant was a recombinant virus, which was originated from the GI-19 and GI-13 lineage viruses. In conclusion, our data demonstrate the circulation of different lineages of IBV and the presence of a novel recombinant IBV variant in chicken flocks in Thailand. This study highlights the high genetic diversity and continued evolution of IBVs in chickens in Thailand, and the importance of continued IBV surveillance for effective control and prevention of IB.


title: Conocimiento sobre la infección por SARS-CoV-2 de Gastroenterólogos y Endoscopistas de Latino América

text: Abstract Introduction: After the World Health Organization declared the COVID-19 outbreak a pandemic, the number of patients with confirmed SARS-CoV-2 infection (COVID-19) has increased exponentially, and gastroenterologists and other specialists most likely will be involved in the care of those patients. Aim: To evaluate the knowledge Latin American gastroenterologists and endoscopists (staff physicians and residents) have about the characteristics of COVID-19, as well as the prevention measures to be taken during endoscopic procedures. Materials and methods: We conducted a cross-sectional study that included gastroenterologists and endoscopists from 9 Latin American countries. An electronic questionnaire was applied that was designed to evaluate the knowledge of symptoms, risk groups for severe disease, prevention measures, and the reprocessing of endoscopes utilized in patients with COVID-19. Results: Information was obtained from 133 physicians. Ninety-five percent of them correctly identified the most frequent symptoms of the virus, and 60% identified the 3 risk groups for severe disease. Sixty-six percent of those surveyed did not consider it necessary to use standard precautions during endoscopic procedures, and 30% did not consider contact precautions necessary. Forty-eight percent of the participants surveyed were not familiar with the protocol for reprocessing the endoscopes utilized in patients with COVID-19. Conclusion: The majority of the gastroenterologists and endoscopists surveyed were familiar with the signs and symptoms of COVID-19 and the populations at risk for complications. There was a lack of knowledge about prevention measures (during clinical care and endoscopic procedures) and the reprocessing of endoscopic equipment by 70% and 48%, respectively, of those surveyed. Dissemination and teaching strategies that increase the knowledge of specific biosafety measures must be carried out.


Community Respiratory Viral Infections in the Immunocompromised Host: Past, Present, and Future Directions


docid: mshopzer

title: Importance of a Travel History in Evaluation of Respiratory Infections

text: PURPOSE OF REVIEW: International travel has increased at a fast pace and will continue to rapidly rise. Concomitantly, with this increase in travel is the increase in post travel-related diseases, such as respiratory illnesses. Identifying the cause of the posttravel respiratory illness is a complex challenge for many healthcare professionals because similar presentations occur for both infectious and noninfectious causes. Not only is diagnosis important but also transmission prevention. In the last two decades, there have been several severe infectious respiratory syndromes that have spread through international travel causing epidemics in many countries. RECENT FINDINGS: A detailed travel history with the chronology of symptoms paired with the patient's medical risk factors and exposures along with some basic knowledge of infectious respiratory illnesses will help facilitate clinical decision making. This framework will help create a broad, but appropriate differential diagnosis to guide clinical workup, prevent delays in diagnosis, and implement the appropriate precautions to prevent transmission if appropriate. SUMMARY: The foundation to diagnosing a travel-related respiratory illness lies within integrating the patient's travel history, comorbid conditions, clinical presentation, exposures, and mode of transmission. A timely and accurate diagnosis benefits not only the patient but also the surrounding community to prevent further individual transmission, epidemics, and pandemics.


title: Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex

text: Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.


docid: lxvnamda

title: Psychiatrists, patients favor telemedicine; challenges exist

text: Despite some drawbacks, the transition to telemedicine in the early weeks of the COVID‐19 pandemic went more smoothly than expected, according to a majority of outpatient psychiatrists interviewed in a qualitative analysis published online in Psychiatric Services. Patients, they said, have also expressed satisfaction with virtual care.


title: Persistent Infection and Promiscuous Recombination of Multiple Genotypes of an RNA Virus within a Single Host Generate Extensive Diversity

text: Recombination and reassortment of viral genomes are major processes contributing to the creation of new, emerging viruses. These processes are especially significant in long-term persistent infections where multiple viral genotypes co-replicate in a single host, generating abundant genotypic variants, some of which may possess novel host-colonizing and pathogenicity traits. In some plants, successive vegetative propagation of infected tissues and introduction of new genotypes of a virus by vector transmission allows for viral populations to increase in complexity for hundreds of years allowing co-replication and subsequent recombination of the multiple viral genotypes. Using a resequencing microarray, we examined a persistent infection by a Citrus tristeza virus (CTV) complex in citrus, a vegetatively propagated, globally important fruit crop, and found that the complex comprised three major and a number of minor genotypes. Subsequent deep sequencing analysis of the viral population confirmed the presence of the three major CTV genotypes and, in addition, revealed that the minor genotypes consisted of an extraordinarily large number of genetic variants generated by promiscuous recombination between the major genotypes. Further analysis provided evidence that some of the recombinants underwent subsequent divergence, further increasing the genotypic complexity. These data demonstrate that persistent infection of multiple viral genotypes within a host organism is sufficient to drive the large-scale production of viral genetic variants that may evolve into new and emerging viruses.


title: Applied modern biotechnology for cultivation of Ganoderma and development of their products

text: A white-rot basidiomycete Ganoderma spp. has long been used as a medicinal mushroom in Asia, and it has an array of pharmacological properties for immunomodulatory activity. There have been many reports about the bioactive components and their pharmacological properties. In order to analyze the current status of Ganoderma products, the detailed process of cultivation of Ganoderma spp. and development of their products are restated in this review article. These include the breeding, cultivating, extracting bioactive component, and processing Ganoderma products, etc. This article will expand people’s common knowledge on Ganoderma, and provide a beneficial reference for research and industrial production.


title: Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus

text: Porcine epidemic diarrhea (PED) has re-emerged in recent years and has already caused huge economic losses to the porcine industry all over the world. Therefore, it is urgent for us to find out efficient ways to prevent and control this disease. In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. We found that even at a very low concentration, Caerin1.1 has the ability to destroy the integrity of the virus particles to block the release of the viruses, resulting in a considerable decrease in PEDV infections. In addition, Caerin1.1 showed powerful antiviral activity without interfering with the binding progress between PEDV and the receptor of the cells, therefore, it could be used as a potential antiviral drug or as a microbicide compound for prevention and control of PEDV.


title: Role of pharmacist during the COVID-19 pandemic: A scoping review

text: BACKGROUND: Since the start of the new Coronavirus (COVID-19) outbreak in December 2019, pharmacists worldwide are playing a key role adopting innovative strategies to minimize the adverse impact of the pandemic. OBJECTIVES: To identify and describe core services provided by the pharmacist during the COVID-19 pandemic. METHODS: A literature search was performed in MEDLINE, Embase, Scopus, and LILACS for studies published between December 1st, 2019 and May 20th, 2020 without language restriction. Studies that reported services provided by pharmacists during the COVID-19 pandemic were included. Two independent authors performed study selection and data extraction with a consensus process. The pharmacist's intervention identified in the included studies were described based on key domains in the DEPICT v.2. RESULTS: A total of 1189 records were identified, of which 11 studies fully met the eligibility criteria. Most of them were conducted in the United States of America (n = 4) and China (n = 4). The most common type of publication were letters (n = 4) describing the workplace of the pharmacist in hospitals (n = 8). These findings showed the different roles of pharmacists during the COVID-19 pandemic, such as disease prevention and infection control, adequate storage and drug supply, patient care and support for healthcare professionals. Pharmacists' interventions were mostly conducted for healthcare professionals and patients (n = 7), through one-to-one contact (n = 11), telephone (n = 6) or video conference (n = 5). The pharmacists' main responsibility was to provide drug information for healthcare professionals (n = 7) as well as patient counseling (n = 8). CONCLUSIONS: A reasonable number of studies that described the role of the pharmacists during the COVID-19 pandemic were found. All studies reported actions taken by pharmacists, although without providing a satisfactory description. Thus, future research with more detailed description as well as an evaluation of the impact of pharmacist intervention is needed in order to guide future actions in this and/or other pandemic.


title: Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis

text: BACKGROUND: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear. RESEARCH QUESTION: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score–matching (PSM) analysis. STUDY DESIGN AND METHODS: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients’ outcomes and PSM analysis to further validate the abovementioned effect. RESULTS: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709–6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients’ mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19. CONCLUSION: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.


title: Human factors and ergonomics at time of crises: the Italian experience coping with COVID19

text: Several of the key organizational issues that we have had to face with the emergence of COVID-19 crisis are related to Human Factors/Ergonomics (HFE) and the safety culture. During the crisis the main activities of the healthcare services have been profoundly affected. Patient safety and risk management units have also experienced the need to adapt rapidly. What can we do as HFE experts, now that the scenario has completely changed? We contend that: We can favour and support the heuristics that are applied to manage the load of psycho-cognitive stress; We can observe, collect strategies and develop analytic schemes, thereby creating a memory of the organization for improvement in the future; And we can support in educating and engaging the public. This crisis has forced the community of healthcare experts to broaden their reflections: for the future to come, our communities of experts in the field of risk management HF/E, quality and safety of care and public health should play together an important role from the very beginning, from the time of peace.


title: High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020

text: Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30–60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.


title: Bacterial Infections: Overview

text: Bacterial infections have a large impact on public health. Disease can occur at any body site and can be caused by the organism itself or by the body's response to its presence. Bacteria are transmitted to humans through air, water, food, or living vectors. The principal modes of transmission of bacterial infection are contact, airborne, droplet, vectors, and vehicular. Preventive measures have a dramatic impact on morbidity and mortality. Such measures include water treatment, immunization of animals and humans, personal hygiene measures, and safer sex practices. Bacterial resistance to antibiotics is a growing concern mandating their prudent use.


title: FORECASTING COVID-19 PANDEMIC: A DATA-DRIVEN ANALYSIS

text: In this paper, a new Susceptible-Exposed-Symptomatic Infectious-Asymptomatic Infectious-Quarantined-Hospitalized-Recovered-Dead (SEI(D)I(U)QHRD) deterministic compartmental model has been proposed and calibrated for interpreting the transmission dynamics of the novel coronavirus disease (COVID-19). The purpose of this study is to give a tentative prediction of the epidemic peak for Russia, Brazil, India and Bangladesh which could become the next COVID-19 hotspots in no time by using a Trust-region-reflective (TRR) algorithm which one of the well-known real data fitting techniques. Based on the publicly available epidemiological data from late January until 10 May, it has been estimated that the number of daily new symptomatic infectious cases for the above mentioned countries could reach the peak around the beginning of June with the peak size of ∼ 15, 774 (95% CI, 12,814-16,734) symptomatic infectious cases in Russia, ∼ 26, 449 (95% CI, 25,489-31,409) cases in Brazil, ∼ 9, 504 (95% CI, 8,378-13,630) cases in India and ∼ 2, 209 (95% CI, 2,078-2,840) cases in Bangladesh. As of May 11, 2020, incorporating the infectiousness capability of asymptomatic carriers, our analysis estimates the value of the basic reproduction number (R(0)) as of May 11, 2020 was found to be ∼ 4.234 (95% CI, 3.764-4.7) in Russia, ∼ 5.347 (95% CI, 4.737-5.95) in Brazil, ∼ 5.218 (95% CI, 4.56-5.81)in India, ∼ 4.649 (95% CI, 4.17-5.12) in the United Kingdom and ∼ 3.53 (95% CI, 3.12-3.94) in Bangladesh. Moreover, Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) which is a global sensitivity analysis (GSA) method is applied to quantify the uncertainty of our model mechanisms, which elucidates that for Russia, the recovery rate of undetected asymptomatic carriers, the rate of getting home-quarantined or self-quarantined and the transition rate from quarantined class to susceptible class are the most influential parameters, whereas the rate of getting home-quarantined or self-quarantined and the inverse of the COVID-19 incubation period are highly sensitive parameters in Brazil, India, Bangladesh and the United Kingdom which could significantly affect the transmission dynamics of the novel coronavirus. Our analysis also suggests that relaxing social distancing restrictions too quickly could exacerbate the epidemic outbreak in the above-mentioned countries.


A glimpse of enzymology within the idea of systems


title: Assessment of the SARS-CoV-2 basic reproduction number, R 0, based on the early phase of COVID-19 outbreak in Italy

text: Abstract As of March 12th Italy has the largest number of SARS-CoV-2 cases in Europe as well as outside China. The infections, first limited in Northern Italy, have eventually spread to all other regions. When controlling an emerging outbreak of an infectious disease it is essential to know the key epidemiological parameters, such as the basic reproduction number R 0, i.e. the average number of secondary infections caused by one infected individual during his/her entire infectious period at the start of an outbreak. Previous work has been limited to the assessment of R 0 analyzing data from the Wuhan region or Mainland China. In the present study the R 0 value for SARS-CoV-2 was assessed analyzing data derived from the early phase of the outbreak in Italy. In particular, the spread of SARS-CoV-2 was analyzed in 9 cities (those with the largest number of infections) fitting the well-established SIR-model to available data in the interval between February 25–March 12, 2020. The findings of this study suggest that R 0 values associated with the Italian outbreak may range from 2.43 to 3.10, confirming previous evidence in the literature reporting similar R 0 values for SARS-CoV-2.


Overview of mental health issues of COVID-19: need of the hour


title: High-throughput interrogation of programmed ribosomal frameshifting in human cells

text: Programmed ribosomal frameshifting is the controlled slippage of the translating ribosome to an alternative frame. This tightly regulated process is widely employed by human viruses such as HIV and SARS coronavirus and is critical for their life cycle and virulence. It is also utilized from yeast to human to implement a feedback control mechanism to regulate polyamine levels. Here, we developed a high-throughput, fluorescence-based approach to assess the frameshifting potential of a sequence. We designed and tested >12,000 sequences based on 15 viral and human frameshifting events, allowing us to elucidate the rules governing ribosomal frameshifting in a systematic way and to discover novel regulatory inputs based on amino acid properties and tRNA availability. We assessed the natural variation in HIV gag-pol frameshifting rates by testing >500 clinical isolates and identified subtype-specific differences as well as associations between viral load in patients and the optimality of gag-pol frameshifting rates. We further devised computational models that accurately predict frameshifting potential (up to auROC=0.93) and frameshifting rates (up to Pearson r=0.81) of novel variants, including subtle differences between HIV clinical isolates (r=0.60). Taken together, this systematic approach can contribute to the development of antiviral agents acting on programmed ribosomal frameshifting.


title: Crystal structure of the natural anion-conducting channelrhodopsin GtACR1

text: The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta, exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools.


title: Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex

text: AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/ microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. METHODS: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. CONCLUSION: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.