docid: dbvdefrq

title: Effect of the Coronavirus Disease 2019 (COVID‐19) Pandemic on the United States Emergency Medical Services System: A Preliminary Report

text: BACKGROUND: Our objective was to quantify trends in Emergency Medical Services (EMS) incidents as the effects of the COVID‐19 pandemic spread across the United States, and to determine if there was an increase in EMS attended deaths. METHODS: We conducted a three‐year comparative retrospective cohort analysis of data from the National EMS Information System. Data were included if care was provided between the 40(th) and 21(st) week of the next year and compared over three‐years. We included incidents identified through 9‐1‐1 where patient contact was made. The total number of EMS incidents per week was used as the denominator to calculate the rate of patient deaths and possible injury. We assessed for temporal and seasonal trends. RESULTS: Starting in the 10(th) week of 2020 there was a decrease in the number of EMS activations in the United States compared to the prior weeks and the same time period in previous years. The number of activations between week 10 and 16 decreased by 140,292 or 26.1%. The portion of EMS activations reporting a patient disposition of death nearly doubled between the 11(th) and 15(th) week of 2020 (1.49% to 2.77% of all activations). The number of EMS activations documenting a possible injury decreased from 18.43% to 15.27% between weeks 10 and 13. CONCLUSION: We found that early in the COVID‐19 outbreak there was a significant decrease in the number of EMS responses across the United States. Simultaneously the rate of EMS attended death doubled, while the rate of injuries decreased.


title: Isolation protocol for a COVID-2019 patient requiring emergent surgical intervention: case presentation

text: BACKGROUND: The concerns of the highly contagious and morbid nature of Coronavirus Disease-2019 (COVID-2019) have prompted healthcare workers to implement strict droplet and contact isolation precautions. Unfortunately, some patients who may be or presumptively or confirmed as infected with COVID-2019 may also require emergent surgical procedures. As such, given the high-risk for exposure of many healthcare workers involved the complex requirements for appropriate isolation must be adhered to. CASE PRESENTATION: We present our experience with a 77-year-old who required emergency cardiac surgery for a presumed acute aortic syndrome in the setting of a presumed, and eventually confirmed, COVID-2019 infection. We outline the necessary steps to maintain strict isolation precautions to limit potential exposure to the surgical Team. CONCLUSIONS: We hereby provide our algorithm for emergent surgical procedures in critically-ill patients with presumptive or confirmed infection with COVID-2019. The insights from this case report can potentially be templated to other facilities in order to uphold high standards of infection prevention and patient safety in surgery during the current COVID-19 pandemic.


title: 11.10 Immunology of the Testis and Male Reproductive Tract

text: A large body of evidence points to the existence of a close, dynamic relationship between the immune system and the male reproductive tract, which has important implications for our understanding of both systems. The testis and the male reproductive tract provide an environment that protects the otherwise highly immunogenic spermatogenic cells and sperm from immunological attack. At the same time, secretions of the testis, including androgens, influence the development and mature functions of the immune system. Activation of the immune system has negative effects on both androgen and sperm production, so that systemic or local infection and inflammation compromise male fertility. The mechanisms underlying these interactions have begun to receive the attention from reproductive biologists and immunologists that they deserve, but many crucial details remain to be uncovered. A complete picture of male reproductive tract function and its response to toxic agents is contingent upon continued exploration of these interactions and the mechanisms involved.


title: Viral ion channel proteins in model membranes: a comparative study by X-ray reflectivity

text: We have investigated the effect of the transmembrane domain of three viral ion channel proteins on the lipid bilayer structure by X-ray reflectivity and scattering from oriented planar bilayers. The proteins show a similar effect on the lipid bilayer structural parameters: an increase in the lipid bilayer hydrophobic core, a decrease in the amplitude of the vertical density profile and a systematic change in the ordering of the acyl chains as a function of protein-to-lipid ratio. These results are discussed in a comparative view.


title: Spatiotemporal variability and key influencing factors of river fecal coliform within a typical complex watershed

text: Abstract Fecal coliform bacteria are a key indicator of human health risks; however, the spatiotemporal variability and key influencing factors of river fecal coliform have yet to be explored in a rural-suburban-urban watershed with multiple land uses. In this study, the fecal coliform concentrations in 21 river sections were monitored for 20 months, and 441 samples were analyzed. Multivariable regressions were used to evaluate the spatiotemporal dynamics of fecal coliform. The results showed that spatial differences were mainly dominated by urbanization level, and environmental factors could explain the temporal dynamics of fecal coliform in different urban patterns except in areas with high urbanization levels. Reducing suspended solids is a direct way to manage fecal coliform in the Beiyun River when the natural factors are difficulty to change, such as temperature and solar radiation. The export of fecal coliform from urban areas showed a quick and sensitive response to rainfall events and increased dozens of times in the short term. Landscape patterns, such as the fragmentation of impervious surfaces and the overall landscape, were identified as key factors influencing urban non-point source bacteria. The results obtained from this study will provide insight into the management of river fecal pollution.


title: Health Care Workers and Researchers Traveling to Developing-World Clinical Settings: Disease Transmission Risk and Mitigation

text: With the recent emphasis on funding and training opportunities for global health and humanitarian aid and the increased interest in the field, many health care workers and medical researchers are traveling from resource-replete to resource-limited settings. This type of travel brings unique disease risks not routinely considered for the business or vacationing traveler. This review provides practical advice for this special population of travelers, targeted to specific health care-related risks (needlestick, hemorrhagic fever viruses, severe viral respiratory disease, and tuberculosis), with suggestions for risk mitigation.


title: SEROEPIDEMIOLOGIC SURVEY OF CORONAVIRUS (STRAIN 229E) INFECTIONS IN A POPULATION OF CHILDREN

text: The indirect hemagglutination (IHA) test for coronavirus 229E antibodies was used for serodiagnostic and seroepidemiologic studies in a population of children. Subjects ranged in age from 5 to 19 years and lived in a home which participated in a longitudinal surveillance of respiratory illness (1960–1968). During this period 1477 respiratory illnesses were observed; 63 (4%) were associated with sero-response (fourfold or greater antibody rises) to 229E. An additional 105 sero-responses were associated with unreported or subclinical illness. The frequency of these infections was cyclical, and 229E and coronavirus OC 43 infections peaked in different years among the same population. Sero-responses occurred mainly in the fall, winter and spring quarters. Preexisting antibody was demonstrated in one-third of the children with 229E seroresponses. Clinical studies indicated that the most frequent complaints with 229E infections were sore throat, coryza and cough, and the most frequent findings were pharyngeal injection, coryza and fever.


title: Registry of patients with congenital bleeding and COVID‐19 in madrid

text: INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID‐19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID‐19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, 2 rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: 42 patients presented symptoms suggestive of infection by COVID‐19 and in 6 cases the disease was confirmed by RT‐PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID‐19 in two patients on prophylaxis with non‐factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognised disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75%of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS‐CoV‐2presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center is essential to make a correct assessment of the risk of haemorrhage/thrombosis.COVID‐19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.


title: Association of HLA class I with severe acute respiratory syndrome coronavirus infection

text: BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.


Biodefense Shield and Avian Influenza


title: Respiratory virus detection and co‐infection in children and adults in a large Australian hospital in 2009–2015

text: AIM: This hospital network‐based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co‐infections, following the introduction of a rapid multiplex molecular diagnostic assay. METHODS: All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis. RESULTS: There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co‐infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co‐infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation. CONCLUSIONS: This study demonstrated a significant difference in the positive detection rate of pathogens and co‐infections between the population groups. Adenovirus had a surprisingly high prevalence as a co‐infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost‐effective manner in the future.


docid: iuhhqcxt

title: Atopic characteristics of wheezing children and responses to prednisolone

text: We wanted to test the hypothesis that the efficacy of systemic corticosteroid is associated with atopic characteristics in wheezing children. A randomized controlled trial comparing oral prednisolone (2 mg/kg/day in 3 divided doses for 3 days) with placebo in hospitalized wheezing children (n = 266, median 1.6 years, range 3 months to 15.2 years) was conducted. In this post‐hoc analysis, we assessed the link between the efficacy of prednisolone and several atopic characteristics, such as atopy, aeroallergen sensitization, total IgE level, number of sensitizations, eczema, atopic eczema, blood or nasal eosinophils, exhaled nitric oxide, positive modified asthma predictive index/asthma, inhaled corticosteroid medication and parental asthma/allergy. Virology was studied comprehensively. Our primary endpoint was the time until ready for discharge, and the most important secondary endpoint was the occurrence of relapses during the following 2 months. For statistics, we used interaction analyses in uni‐ and multivariate regression models. Overall, prednisolone did not decrease any of our predefined clinical endpoints. Neither was the efficacy of prednisolone associated with atopy. However, prednisolone significantly decreased the time until ready for discharge in children with positive modified asthma predictive index/asthma, inhaled corticosteroids, or rhinovirus infection and/or in children without azithromycin treatment. Prednisolone significantly decreased relapses in children with eczema, nasal eosinophilia and rhinovirus infection. The multiple clinical, inflammatory and viral markers associating with the efficacy of prednisolone should be confirmed in prospective trials. It is important that corticosteroid intervention trials have strict design for these potentially confounding factors. Pediatr Pulmonol. 2007; 42:1125–1133. © 2007 Wiley‐Liss, Inc.


title: Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs

text: This review opens a new series entitled “Unreported intrinsic disorder in proteins.” The goal of this series is to bring attention of researchers to an interesting phenomenon of missed (or overlooked, or ignored, or unreported) disorder. This series serves as a companion to “Digested Disorder” which provides a quarterly review of papers on intrinsically disordered proteins (IDPs) found by standard literature searches. The need for this alternative series results from the observation that there are numerous publications that describe IDPs (or hybrid proteins with ordered and disordered regions) yet fail to recognize many of the key discoveries and publications in the IDP field. By ignoring the body of work on IDPs, such publications often fail to relate their findings to prior discoveries or fail to explore the obvious implications of their work. Thus, the goal of this series is not only to review these very interesting and important papers, but also to point out how each paper relates to the IDP field and show how common tools in the IDP field can readily take the findings in new directions or provide a broader context for the reported findings.


title: Characterization of monoclonal antibodies to bovine enteric coronavirus and antigenic variability among Quebec isolates

text: Twenty monoclonal antibodies (MAbs) were prepared against the Mebus strain of bovine enteric coronavirus, 14 of them reacting with the peplomeric S (gp 100) glycoprotein. Competition binding assays allowed the definition of at least 4 distinct antigenic domains for the S glycoprotein, designated as A, B, C, and D; epitopes associated to neutralizing activity being located in sites A, B, and C. One MAb directed to the hemagglutinin HE (gp 140/gp 65) glycoprotein inhibited the hemagglutinating activity of the virus, but had no neutralizing activity. Comparison of Quebec enteropathogenic BCV isolates using polyclonal antiserum and MAbs directed to the S glycoprotein confirmed their close antigenic relationship, but also revealed the occurrence of at least three distinct antigenic subgroups. Antigenic domain D was highly conserved among BCV isolates, as well as non-neutralizing epitopes assigned to antigenic domains A and C. The Minnesota strain of turkey enteric coronavirus could be distinguished from BCV isolates by MAbs directed to epitopes of antigenic domain C, whereas human coronavirus HCV-OC 43 could be distinguished by MAbs directed to epitopes of antigenic domain A. The porcine hemagglutinating encephalomyelitis virus could be distinguished from the other hemagglutinating coronaviruses by neutralizing epitopes located on antigenic domains A, B, and C.


title: Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies

text: Antibody phage display has been pivotal in the quest to generate human monoclonal antibodies for biomedical and research applications. Target antigen preparation is a main bottleneck associated with the panning process. This includes production complexity, downstream purification, quality and yield. In many instances, purified antigens are preferred for panning but this may not be possible for certain difficult target antigens. Here, we describe an improved procedure of affinity selection against crude or non-purified antigen by saturation of non-binders with blocking agents to promote positive binder enrichment termed as Yin-Yang panning. A naïve human scFv library with kappa light chain repertoire with a library size of 10(9) was developed. The improved Yin-Yang biopanning process was able to enrich monoclonal antibodies specific to the MERS-CoV nucleoprotein. Three unique monoclonal antibodies were isolated in the process. The Yin-Yang biopanning method highlights the possibility of utilizing crude antigens for the isolation of monoclonal antibodies by phage display.


title: Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens: Emerging patterns and molecular principles

text: Abstract Attachment of ubiquitin (Ub) or ubiquitin-like (Ubl) modifiers is a reversible post-translational modification that regulates the fate and function of proteins. In particular, proteolytic enzymes with Ub/Ubl processing activity appear to be more widespread than originally anticipated. It is therefore not surprising that bacterial and viral pathogens have exploited many ways to interfere with Ub/Ubl conjugation, but also de-conjugation. On one hand, pathogens were shown to manipulate host encoded enzymes. On the other hand, pathogen derived sequences of proteases specific for Ub/Ubls are emerging as a common feature shared by many viruses, bacteria and protozoa, and we are at an early stage of understanding how these proteases contribute to the pathogenesis of infection. Whereas some of these proteases share a common origin with mammalian cell encoded hydrolases with specific properties towards Ub/Ubls, most of them have ancient intrinsic functions, such as processing pathogen protein components, and may have acquired the specificity for Ub/Ubls by interacting with mammalian hosts and their immune system throughout evolution. Since many of these proteases are clearly distinct from their mammalian counterparts, they represent attractive targets for drug design against infectious diseases.


CHALLENGES IN THE FIGHT AGAINST THE COVID-19 PANDEMIC IN UNIVERSITY HOSPITALS


title: Changes in alcohol use as a function of psychological distress and social support following COVID-19 related University closings

text: Amidst the coronavirus pandemic, universities across the country abruptly closed campuses and transitioned to remote learning. The effects of these unprecedented closures are unknown. The current study examined reported alcohol consumption during the week prior to and after campus closure at a public university in Northeast Ohio. Analysis of data from 1,958 students, who endorsed using alcohol in the past 30 days, demonstrates that alcohol consumption (amount and frequency) increased as time progressed. Those with more symptoms of depression and anxiety reported greater increases in alcohol consumption (assessed via retrospective timeline follow-back) compared to students with fewer symptoms. Furthermore, students with greater perceived social support reported less alcohol consumption. Together, these findings highlight the need for universities to offer services and programs to students that will minimize risk factors and maximize protective factors in order to reduce or prevent alcohol abuse during the coronavirus pandemic.


title: Poor-sleep is associated with slow recovery from lymphopenia and an increased need for ICU care in hospitalized patients with COVID-19: A retrospective cohort study

text: Sleep is known to play an important role in immune function. However, the effects of sleep quality during hospitalization for COVID-19 remain unclear. This retrospective, single-center cohort study was conducted to investigate the effects of sleep quality on recovery from lymphopenia and clinical outcomes in hospitalized patients with laboratory-confirmed COVID-19 admitted to the West District of Wuhan Union Hospital between January 25 and March 15, 2020. The Richards-Campbell sleep questionnaire (RCSQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess sleep quality. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected from electronic medical records and compared between the good-sleep group and poor-sleep group. In all, 135 patients (60 in good-sleep group and 75 in poor-sleep group) were included in this study. There were no significant between-group differences regarding demographic and baseline characteristics, as well as laboratory parameters upon admission and in-hospital treatment. Compared with patients in the good-sleep group, patients in the poor-sleep group had lower absolute lymphocyte count (ALC) (day 14: median, 1.10 vs 1.32, P = 0.0055; day 21: median, 1.18 vs 1.48, P = 0.0034) and its reduced recovery rate (day 14: median, 56.91 vs 69.40, P = 0.0255; day 21: median, 61.40 vs 111.47, P = 0.0003), as well as increased neutrophil-to-lymphocyte ratio (NLR; day 14: median, 3.17 vs 2.44, P = 0.0284; day 21: median, 2.73 vs 2.23, P = 0.0092) and its associated deterioration rate (day 14: median, -39.65 vs -61.09, P = 0.0155; day 21: median, -51.40% vs -75.43, P = 0.0003). Nine [12.0%] patients in the poor-sleep group required ICU care (P = 0.0151); meanwhile, none of the patients in good-sleep group required ICU care. Patients in the poor-sleep group had increased duration of hospital stay (33.0 [23.0–47.0] days vs 25.0 [20.5–36.5] days, P = 0.0116) compared to those in the good-sleep group. An increased incidence of hospital-acquired infection (seven [9.3%] vs one [1.7%]) was observed in the poor-sleep group compared to the good-sleep group; however, this difference was not significant (P = 0.1316). In conclusion, poor sleep quality during hospitalization in COVID-19 patients with lymphopenia is associated with a slow recovery from lymphopenia and an increased need for ICU care.


title: Supplementing a yeast probiotic to pre-weaning Holstein calves: Feed intake, growth and fecal biomarkers of gut health

text: Abstract Diarrhea, resulting from gastrointestinal infection by pathogens, is a common cause of the high mortality and morbidity of neonatal calves. The objective of this study was to evaluate the effects of supplementing a yeast product in milk replacer (MR) on growth and health of calves, and on fecal populations of some targeted microorganisms related to calf health and growth (i.e., total bacteria, Escherichia coli, Clostridium cluster XIVa, Faecalibacterium prausnitzii and Bifidobacterium spp.). We hypothesized that feeding a Saccharomyces cerevisiae var boulardii (SCB) product would improve gastrointestinal health and growth performance of calves. Forty-two Holstein bull calves (42.6±0.77kg at birth) were randomly assigned on day 2 of age to either a control or SCB treatment. The SCB was supplemented in MR and fed at 5g/d per head to supply 10 billion colony-forming units per day. All calves received high quality colostrum (>50mg/mL of immunoglobulin G) during the first 24h of life, and were fed with 8L MR (150g/L mixed with 40°C water) daily from day 2–35, and 4L daily from day 35–42. Calves were also fed calf starter ad libitum from day 7–56. Daily MR and starter offered and refused, daily fecal scores, nasal scores, ear scores, and weekly body weight of calves were recorded. Fecal samples were collected on day 7, 35 and 56 after the first feeding of that day for microbial targets analysis. Overall, there is no serious disease challenge for all the calves during the entire experimental period. No differences were observed in MR intake, starter intake, metabolizable energy (ME) intake, average daily gain, ME intake to gain ratio, fecal score, nasal score, eye score or any targeted microorganisms between treatments throughout the experiment. These results suggest that supplementing SCB in MR has no additive effects on animal growth or fecal biomarkers of gut health when calves do not show deteriorated health status.


title: CEACAMs: their role in physiology and pathophysiology

text: Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) belong to a group of mammalian immunoglobulin-related glycoproteins. They are involved in cell–cell recognition and modulate cellular processes that range from the shaping of tissue architecture and neovascularization to the regulation of insulin homeostasis and T-cell proliferation. CEACAMs have also been identified as receptors for host-specific viruses and bacteria in mice and humans, respectively, making these proteins an interesting example of pathogen–host co-evolution. Forward and reverse genetics in the mouse now provide powerful novel models to elucidate the action of CEACAM family members in vivo.


title: Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding

text: Abstract The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10-fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 μg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25-229 may have potential to be used as a subunit vaccine against PEDV variant strains.


Urticaria in the times of COVID‐19


title: Effective Risk Communication for Public Health Emergency: Reflection on the COVID-19 (2019-nCoV) Outbreak in Wuhan, China

text: Risk communication is critical to emergency management. The objective of this paper is to illustrate the effective process and attention points of risk communication reflecting on the COVID-19 (2019-nCoV) outbreak in Wuhan, China. We provide the timeline of risk communication progress in Wuhan and use a message-centered approach to identify problems that it entailed. It was found that the delayed decision making of the local government officials and the limited information disclosure should be mainly responsible for the ineffective risk communication. The principles for effective risk communication concerning Wuhan’s outbreak management were also discussed. The whole communication process is suggested to integrate the accessibility and openness of risk information, the timing and frequency of communication, and the strategies dealing with uncertainties. Based on these principles and lessons from Wuhan’s case, this paper employed a simplified Government–Expert–Public risk communication model to illustrate a collaborative network for effective risk communication.


title: Clostridium perfringens and C. difficile in parvovirus-positive dogs

text: Abstract The aim of this study was to investigate Clostridium difficile and Clostridium perfringens in 82 diarrheic dogs positive for canine parvovirus type 2 (CPV). Enterotoxigenic C. perfringens type A was isolated from three (3.6%) dogs. One (1.2%) strain was also positive for NetE- and NetF-encoding genes, which are commonly associated with diarrhea in dogs. Toxigenic C. difficile was isolated from one animal (1.2%), which was also positive for A/B toxins. The present study identified C. difficile and C. perfringens infection in CPV-positive dogs. Further studies are necessary to clarify if clostridial infections may predispose or potentiate CPV-infection in dogs or vice versa.


title: Chapter 1 In Vitro Biofabrication of Tissues and Organs

text: In vitro fabrication of tissues and the regeneration of internal organs are no longer regarded as science fiction but as potential remedies for individuals suffering from chronic degenerative diseases. Tissue engineering has generated much interest from researchers in many fields, including cell and molecular biology, biomedical engineering, transplant medicine, and organic chemistry. Attempts to build tissues or organs in vitro have utilized both scaffold and scaffold-free approaches. Despite considerable progress, fabrication of three-dimensional tissue constructs in vitro remains a challenge. In this chapter, we introduce and discus current concepts of tissue engineering with particular focus on future clinical application.


title: Creation of an Interactive Virtual Surgical Rotation for Undergraduate Medical Education During the COVID-19 Pandemic

text: OBJECTIVE: During the COVID-19 pandemic, medical student involvement in direct patient care has been severely limited. Rotations mandatory not only for core curricula but also for informing decisions regarding specialty choice have been postponed during a critical window in the application cycle. Existing virtual rotations are largely observational or lack patient-facing components. SETTING: A virtual Otolaryngology - Head and Neck Surgery rotation at the University of Pennsylvania (Philadelphia, PA) was implemented for medical students, comprising interactive live-streamed surgeries, outpatient telehealth visits, and virtual small group didactics. RESULTS: Medical students enrolled in the virtual surgical rotation were able to engage with attending surgeons and operating room staff while remotely viewing surgical procedures captured with first-person audiovisual technology. Students participated in several different aspects of care delivery in both the inpatient and outpatient setting, similar to their typical responsibilities of an in-person rotation. CONCLUSIONS: The authors will continue to develop the virtual surgical education methodology to further disseminate an interactive video-based medical student elective to other procedural specialties and institutions.


title: Cryptosporidium parvum: Determination of ID50 and the dose–response relationship in experimentally challenged dairy calves

text: Abstract The objectives were to determine the median infective dose (ID50) of Cryptosporidium parvum and to describe the dose–response relationship including associated clinical illness in experimentally challenged dairy calves. Within the first 24h of life, 27 test calves were experimentally challenged with C. parvum oocysts and 3 control calves were sham dosed. Test calves received 1 of 8 possible doses (25, 50, 100, 500, 1×103, 1×104, 1×105, and 1×106 oocysts). All 27 test calves developed diarrhea. Fecal oocyst shedding occurred in 25 (92.6%) test calves and in 0 control calves. The 2 non-shedding test calves both received 25 oocysts. There was an inverse relationship between dose and time to onset of fecal oocyst shedding (P =0.005). There was no relationship found between dose and duration (P =0.2) or cessation (P =0.3) of fecal oocyst shedding. In addition, there was not a significant relationship between log-dose and the log-peak oocysts (P =0.2) or log-total oocysts (P =0.5) counted/g of feces across the dose groups. There was a positive dose–response relationship between log-dose and diarrhea (P =0.01). However, when controlling for other factors, such as onset and cessation of fecal oocyst shedding, dose was not a significant predictor of diarrhea (P =0.5). Onset and cessation of fecal oocyst shedding were found to be the best predictors of diarrhea (P =0.0006 and P =0.04, respectively). The ID50 for fecal oocyst shedding was 5.8 oocysts, for diarrhea was 9.7 oocysts, and for fecal oocyst shedding with diarrhea was 16.6 oocysts. Given that the ID50 of C. parvum is far less than would be excreted into the environment by a naturally infected calf, prevention and control of cryptosporidiosis is a formidable challenge.


title: IFN-stimulated P2Y(13) protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway

text: Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y(13) and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y(13), as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y(13) but not P2Y(1) or P2Y(12), which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregulated by extracellular ADP through the P2Y(13)-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y(13)-mediated antiviral activities. Taken together, our results show that P2Y(13) and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.


Pandemic reflections from Toronto


Let’s conquer COVID-19 and sustain our abilities


title: Itch in the era of COVID‐19 pandemic: An unfolding scenario

text: Coronavirus disease 2019 (COVID‐19) is an infectious disease, caused by severe acute respiratory syndrome (SARS)‐CoV‐2, that broke out in December 2019. In just 4 months it has spread to almost every country in the world and up to April 18, 2020, the virus has infected more than two million people. Itch is the most common symptom in dermatology and a frequent one of systemic diseases. The association of itch and viral diseases has been widely documented; however, the actual prevalence of itch in the patients suffering from new the SARS‐CoV‐2 infection is still unknown. In this paper, we present a review of the available literature on the topic of itch in the affected population. Moreover, we have also analyzed different aspects of itch associated with COVID‐19 pandemic, not directly related to the viral infection. Those included use of chemicals, hand sanitizers, common use of personal protective equipment and psychosocial stress.


Computed tomography scanning in the prone position for a critically hypoxic patient with COVID‐19


The 2019 novel corona virus outbreak – An institutional guideline


title: Propagation of Respiratory Aerosols by the Vuvuzela

text: Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×10(3) per litre for the vuvuzela and 3.7×10(3) per litre for shouting, representing a mean log(10) difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others.


title: An integrated analysis of membrane remodeling during porcine reproductive and respiratory syndrome virus replication and assembly

text: BACKGROUND: Recently, three-dimensional (3D) imaging techniques have been used to detect viral invasion and the appearance of specialized structures established in virus-infected cells. These methods have had a positive impact in the field of virology and helped to further our knowledge of how viruses invade cells. Nearly all positive-strand RNA viruses propagate their viral genomes in part through intracellular membranes. Porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus, accumulates viral RNA that forms replication complexes (RCs) in infected cells. In this study, using immunofluorescence and electron microscopy (EM), we dissected PRRSV-induced membrane structures in infected cells and determined the correlations between PRRSV particles and vesicles stimulated by PRRSV to understand the structural and dynamic aspects of PRRSV infection. METHODS: We identified the appropriate time point by determining the 50% tissue culture infectious dose (TCID50) and using qRT-PCR and Western blotting. The co-localization of viruses and organelles was determined by immunofluorescence and immune-electron microscopy (IEM). The ultrastructure of cells infected by PRRSV was observed using EM and electron tomography (ET). RESULTS: In our study, we found that PRRSV dsRNA was located at the endoplasmic reticulum (ER) and autophagosomes; in addition, the N protein was located at the mitochondria, ER and autophagosomes. Vesicles induced by PRRSV appeared at 16 hours post-infection (h.p.i.) and increased in size with time during the infection period. In addition, our findings demonstrated that the virus vesicles originated from the ER, and these two organelle structures connected with each other to form a reticulovesicular network (RVN) that provided a site for virus replication and assembly. CONCLUSION: Our results revealed that membrane vesicles induced by PRRSV were derived from the ER. The vesicles may provide a location for PRRSV replication and assembly.


title: Literature-based review of the drugs used for the treatment of COVID-19

text: COVID-19 is primarily a respiratory disease caused by a newly discovered SARS-CoV-2 virus and identified in the city of Wuhan, China in December 2019. WHO has declared this disease as a pandemic, and warned other countries. Presently this has affected 216 countries, areas or territories worldwide, spreading of this disease is very fast in USA, Brazil, and Russia than in the country of its origin, China. Like other coronaviruses, this may develop respiratory tract infections in the patients range from mild to fatal illness like pneumonia and acute respiratory distress syndrome (ARDS). As of now, no effective drug, vaccine, or any procedure is available and experiments are underway. However, empirical therapy is being followed to manage and save the lives of the patients. There is a need for pharmacological alternatives to combat this deadly virus and its complications. Based on the previous experiences with similar coronavirus management and present preliminary data from uncontrolled studies, drugs like chloroquine, hydroxychloroquine, remdesivir, lopinavir/ritonavir, and favipiravir have been recommended by the researchers to manage COVID-19. This review had assessed the potential mechanisms, safety profile, availability and cost of these drugs. This review concludes that the drugs mentioned above are having different properties and act differently in combating the COVID-19 viruses. Instead of single drug, combination of antivirals with different mechanism of action may be more effective and at the same time their adverse events should not be underestimated.


HAEMATOLOGICAL VALUES IN VITAMIN B(12) RESPONSIVE CALVES


title: COVID-19 and Advanced Practice Registered Nurses (APRNs): Frontline update #1

text: COVID-19 emerged in 2019 and rapidly became a global pandemic infecting millions, killing hundreds of thousands. The disease altered the practices of hospitals, clinics, and patients. These changes have implications for Advanced Practice Registered Nurses (APRNs). APRNs must remain current on best practices for treatment and diagnosis of COVID-19 while being cognizant of changes to their scope of practice. As the pandemic continues, APRNs will remain on the front lines treating COVID-19 patients while also caring for vulnerable populations within the community. To provide high-quality care, APRNs must utilize a multi-faceted approach that heeds ongoing updates to evidence-based practice.


title: A field‐deployable insulated isothermal RT‐PCR assay for identification of influenza A (H7N9) shows good performance in the laboratory

text: BACKGROUND: Avian influenza A (H7N9) remains circulating in China. For countries at risk of introduction of H7N9, such as Vietnam, early detection of H7N9 virus is essential for the early containment of the virus. Insulated isothermal reverse transcriptase PCR (iiRT‐PCR) is a portable PCR system that can be deployed under field conditions to identify pathogens at the sampling site. Applying PCR at the sampling site will greatly reduce the time to obtain a diagnostic result which allows the veterinary authority to take immediate action to contain disease spreading. OBJECTIVE: To determine analytical and diagnostic sensitivity and specificity of the portable iiRT‐PCR for H7N9 virus detection. METHODS: A panel of 59 virus isolates, including H7N9, avian influenza viruses of subtype H1 to H13, swine and human influenza viruses, Newcastle disease virus, and infectious bursal disease virus, were tested by H7 and N9 iiRT‐PCR reagents, using probes and primers specific to H7 or N9, in comparison with laboratory‐based real‐time RT‐PCR assays to determine analytical sensitivity and specificity. Fifty oropharyngeal samples from experimentally infected chicken and ducks with H7N9 and 50 non‐infected control swabs were tested by the H7 iiRT‐PCR to determine diagnostic sensitivity and specificity. RESULTS: The H7 and N9 iiRT‐PCR reagents yielded comparable levels of analytical sensitivity and specificity with real‐time RT‐PCR for the detection of H7N9 virus. Diagnostic sensitivity and specificity of H7 iiRT‐PCR were 98% and 100%, respectively. CONCLUSION: The observed high sensitivity and specificity of iiRT‐PCR for H7N9 detection show its potential for early detection of H7N9 in risk‐based surveillance.


title: Phytochemical Compositions and Biological Activities of Essential Oils from the Leaves, Rhizomes and Whole Plant of Hornstedtia bella Škorničk

text: The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and whole plant of Hornstedtia bella were investigated. The GC/MS analysis showed that β-pinene, E-β-caryophyllene, and α-humulene were found at high concentrations in the essential oils. The essential oils exhibited (i) inhibition against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis with minimum inhibitory concentrations (MIC) and minimum lethal concentration (MLC) values from 1 to 4% (v/v); (ii) MIC and MLC values from 2 to 16% (v/v) in Candida tropicalis and Candida parapsilosis; (iii) MIC and MLC values from 4 to 16% in Enterococcus faecalis; and (iv) MIC and MLC values from 8 to greater than or equal to 16% (v/v) in the remaining strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, and Candida glabrata. In antitrichomonas activity, the leaves and whole-plant oils of Hornstedtia bella possessed IC(50), IC(90), and MLC values of 0.008%, 0.016%, and 0.03% (v/v), respectively, whilst those of rhizomes oil had in turn, 0.004%, 0.008%, and 0.016% (v/v).Besides, the leaf oil showed a weak cytotoxicity against Vero 76 and MRC-5; meanwhile, rhizomes and whole-plant oils did not exert any toxic effects on cell monolayers. Finally, these oils were not active against EV-A71.


title: A case of COVID-19 patient with the diarrhea as initial symptom and literature review

text: Summary Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.


title: Antigenic detection of Canine rotavirus group A in diarrheic dogs in Ahvaz district, Southwestern Iran

text: The aim of the present survey was to evaluate the prevalence of Canine rotavirus (CRV) infection in companion dogs in Ahvaz district, Iran. The studied dogs were selected between referred cases to Shahid Chamran University of Ahvaz. Fecal samples were collected from 98 diarrheic dogs between December 2011 and August 2013. The dogs were classified according to age, sex, breed, clinical signs, and season. They were divided into three age groups (<3 months, 3–6 months, and >6 months), five different breeds, and another two groups on the basis of clinical symptoms (hemorrhagic and non-hemorrhagic diarrhea) using Chi-square analysis, Fischer’s exact test, and Z test. The prevalence of rotavirus infection was 16.33 % (16 out of 98) (95 % CI for proportion 9.1–23.6 %) by means of immunochromatography assay (ICA) (Catalog No. RG18-03). The infection had significantly more prevalence in dogs less than 3 months (48.15 %; 13 out of 27) compared with dogs between 3 and 6 months (6.06 %; 2 out of 33) and above 6 months (2.63 %; 1 out of 38) (p < 0.05). Prevalence was higher in males (17.54 %; 10 out of 57) than females (14.63 %; 6 out of 41), in winter season (21.74 %; 5 out of 23), and breed of German shepherd (19.05 %; 4 of 21), but the difference was not significant between the prevalence of infection relative to gender, season, and breed (p > 0.05). Nevertheless, infection was significantly higher in none-hemorrhagic diarrheic dogs (23.08 %; 15 of 65) (p < 0.05). The obtained results provide useful information on the epidemiology of Canine rotavirus in this area.


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title: Zinc Supplementation Promotes a Th1 Response and Improves Clinical Symptoms in Fewer Hours in Children With Pneumonia Younger Than 5 Years Old. A Randomized Controlled Clinical Trial

text: Background: Pneumonia caused 704,000 deaths in children younger than 5 years in 2015. Zinc is an important micronutrient due to its role in immune function. Since 2004, WHO recommends zinc supplementation for children with diarrhea to shorten the duration and decrease severity. Zinc supplementation for children with pneumonia is controversial. Methods: A randomized controlled clinical trial was conducted, and 103 children 1 month to 5 years old with pneumonia were included. Zinc or placebo was given during hospitalization. Clinical symptoms were recorded, and a blood draw was obtained to determine serum zinc levels, lymphoproliferation, and cytokines at hospitalization and at discharge of the patient; a nasal wash was obtained to detect viral or bacterial pathogens by multiplex RT-PCR. Results: Zinc supplementation improved in fewer hours the clinical status (76 ± 7 vs. 105 ± 8, p = 0.01), the respiratory rate (37 ± 6 vs. 57 ± 7, p = 0.04), and the oxygen saturation (53 ± 7 vs. 87 ± 9, p = 0.007) compared to the placebo group. An increase in IFNγ and IL-2 after treatment in the zinc group was observed. Conclusions: Zinc supplementation improved some clinical symptoms in children with pneumonia in fewer hours and induced a cellular immune response. Clinical Trial Registration: The trial was retrospectively registered in ClinicalTrials.gov, identifier NCT03690583, URL https://clinicaltrials.gov/ct2/show/NCT03690583?term=zinc+children&cond=Pneumonia&draw=2&rank=1.


title: Folding of Viral Envelope Glycoproteins in the Endoplasmic Reticulum

text: Viral glycoproteins fold and oligomerize in the endoplasmic reticulum of the host cell. They employ the cellular machinery and receive assistance from cellular folding factors. During the folding process, they are retained in the compartment and their structural quality is checked by the quality control system of the endoplasmic reticulum. A special characteristic that distinguishes viral fusion proteins from most cellular proteins is the extensive conformational change they undergo during fusion of the viral and cellular membrane. Many viral proteins fold in conjunction with and dependent on a viral partner protein, sometimes even synthesized from the same mRNA. Relevant for folding is that viral glycoproteins from the same or related virus families may consist of overlapping sets of domain modules. The consequences of these features for viral protein folding are at the heart of this review.


title: The 17-residue transmembrane domain of beta-galactoside alpha 2,6- sialyltransferase is sufficient for Golgi retention

text: beta-Galactoside alpha 2,6-sialyltransferase (ST) is a type II integral membrane protein of the Golgi apparatus involved in the sialylation of N-linked glycans. A series of experiments has shown that the 17-residue transmembrane domain of ST is sufficient to confer localization to the Golgi apparatus when transferred to the corresponding region of a cell surface type II integral membrane protein. Lectin affinity chromatography of chimeric proteins bearing this 17-residue sequence suggests that these chimeric proteins are localized in the trans-Golgi cisternae and/or trans-Golgi network. Further experiments suggest that this 17-residue sequence functions as a retention signal for the Golgi apparatus.


title: Is HIV-1 evolving to a less virulent form in humans?

text: During the rapid spread of HIV-1 in humans, the main (M) group of HIV-1 has evolved into ten distinct subtypes, undergone countless recombination events and diversified extensively. The impact of this extreme genetic diversity on the phenotype of HIV-1 has only recently become a research focus, but early findings indicate that the dominance of HIV-1 subtype C in the current epidemic might be related to the lower virulence of this subtype compared with other subtypes. Here, we explore whether HIV-1 has reached peak virulence or has already started the slow path to attenuation. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro1594) contains supplementary material, which is available to authorized users.


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title: The role of polymerase chain reaction and its newer developments in feline medicine

text: Abstract We give a brief overview on the principles of the polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), quantitative competitive PCR and real-time PCR (TagMan technology). The literature dealing with PCR and its role in the diagnosis, pathogenesis and research of infectious diseases of the domestic cat is reviewed. Cross-contaminations which occasionally occur during handling of amplified DNA may be an important problem in the PCR laboratory. In many infectious diseases, PCR results are difficult to interpret as their predictive positive and negative values are not always known. Newer assays, such as TagMan procedures, are becoming increasingly reliable and cost-effective. It can be expected that additional knowledge on how to interpret PCR results will soon be available.


title: Environment and Health in Children Day Care Centres (ENVIRH) – Study rationale and protocol

text: Abstract Background Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods – study design This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children's respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children's health. A building ventilation model will also be developed. Discussion This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.


title: Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses

text: The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This not only decreases the cost of a vaccine and make it affordable, but also reduces the quantity of the antigen used. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emerging SARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease.


title: An overview and future prospects on aptamers for food safety

text: INTRODUCTION: Many bacteria are responsible for infections in humans and plants, being found in vegetables, water, and medical devices. Most bacterial detection methods are time-consuming and take days to give the result. Aptamers are a promising alternative for a quick and reliable measurement technique to detect bacteria present in food products. Selected aptamers are DNA or RNA oligonucleotides that can bind with bacteria or other molecules with affinity and specificity for the target cells by the SELEX or cell-SELEX technique. This method is based on some rounds to remove the non-ligand oligonucleotides, leaving the aptamers specific to bind to the selected bacteria. Compared with conventional methodologies, the detection approach using aptamers is a rapid, low-cost form of analysis. OBJECTIVE: This review summarizes obtention methods and applications of aptamers in the food industry and biotechnology. Besides, different techniques with aptamers are presented, which enable more effective target detection. CONCLUSION: Applications of aptamers as biosensors, or the association of aptamers with nanomaterials, may be employed in analyses by colorimetric, fluorescence, or electrical devices. Additionally, more efficient ways of sample preparation are presented, which can support food safety to provide human health, with a low-cost method for contaminant detection.


title: Hypofractionated radiotherapy in patients with non‐melanoma skin cancer in the post COVID‐19 era: Time to reconsider its role for most patients

text: The most frequent cancer worldwide is skin cancer, occurring at epidemic rates in countries exposed to high levels of chronic ultraviolet radiation such as Australia and New Zealand (ANZ). Australia has the highest incidence of non‐melanoma skin cancer (NMSC) in the world. NMSC is predominantly a cancer of the middle aged or elderly and accounts for considerable consulting and treatment time in most radiation oncology departments. Many patients also suffer from medical co‐morbidity, an important factor in any treatment decision.


title: First complete genome sequence of European turkey coronavirus suggests complex recombination history related with US turkey and guinea fowl coronaviruses

text: A full-length genome sequence of 27 739 nt was determined for the only known European turkey coronavirus (TCoV) isolate. In general, the order, number and size of ORFs were consistent with other gammacoronaviruses. Three points of recombination were predicted, one towards the end of 1a, a second in 1b just upstream of S and a third in 3b. Phylogenetic analysis of the four regions defined by these three points supported the previous notion that European and American viruses do indeed have different evolutionary pathways. Very close relationships were revealed between the European TCoV and the European guinea fowl coronavirus in all regions except one, and both were shown to be closely related to the European infectious bronchitis virus (IBV) Italy 2005. None of these regions of sequence grouped European and American TCoVs. The region of sequence containing the S gene was unique in grouping all turkey and guinea fowl coronaviruses together, separating them from IBVs. Interestingly the French guinea fowl virus was more closely related to the North American viruses. These data demonstrate that European turkey and guinea fowl coronaviruses share a common genetic backbone (most likely an ancestor of IBV Italy 2005) and suggest that this recombined in two separate events with different, yet related, unknown avian coronaviruses, acquiring their S-3a genes. The data also showed that the North American viruses do not share a common backbone with European turkey and guinea fowl viruses; however, they do share similar S-3a genes with guinea fowl virus.


title: Effectiveness of Computed Tomography in the Diagnosis of Novel Coronavirus-2019

text: Coronaviruses (CoV) belong to the coronavirus genus of the coronaviridae family. All CoVs are pleomorphic RNA viruses containing crown-like peplomers of 80-160 nm in size. This virus is a zoonotic pathogen seen with a wide range of clinical features from asymptomatic state to intensive care in humans. So far, seven human coronaviruses have been identified with the last one being Coronavirus-2019 (COVID-19). These pathogens typically lead to mild disease, but SARS and MERS type coronaviruses have caused severe respiratory disease and even mortality within the last 20 years. COVID-19 virus has rapidly spread worldwide after China and is continuing to cause huge economical and social impacts. Given the scarcity of resources including healthcare staff, hospital capacities, test kits, etc., timely diagnosis and treatment of this virus are of paramount importance. However, there is no vaccination or drug developed for the treatment of this disease up to today. Because the spreading rate of the virus is very high worldwide and there is no definitive treatment, diagnosis becomes even more important. The objective of this review is to evaluate the use of chest computed tomography, one of the commonly used radiologic imaging modalities, in the diagnosis of COVID-19 in light with the current literatüre.


title: Clinical and Immunological Benefits of OM-85 Bacterial Lysate in Patients with Allergic Rhinitis, Asthma, and COPD and Recurrent Respiratory Infections

text: PURPOSE: The aim of this study was to evaluate the efficacy of OM-85 in reducing the incidence of respiratory tract infections (RTIs) in patients with allergic rhinitis, asthma, or chronic obstructive pulmonary disease (COPD), and its effect on immunological parameters, namely serum and secretory IgA levels. METHODS: This was an open-label, prospective, sequential study which included 84 consecutive patients aged 16–65 years, who presented with recurrent (three or more) respiratory infections during the year prior to study entry. In the first year of the study, patients received standard optimized care (SOC), according to their underlying disease condition (asthma, allergic rhinitis, or COPD). In the following year, patients received treatment with OM-85 oral bacterial lysate (one 7 mg capsule daily for ten consecutive days per month, for 3 months), with a 6-month follow-up. Medical history, clinical symptoms, serum, and secretory IgA levels, and the number of infections and exacerbations were evaluated before and after treatment. RESULTS: There was a decrease in the total number of RTIs before the OM-85 treatment period (SOC only) compared to the year before the study start [69/266 (corresponding to a 74 % reduction)] and an additional decrease [38/69 (corresponding to a 45 % reduction)] after OM-85 treatment; p < 0.05. There was also a significant reduction in the total number of exacerbations related to the patients’ underlying medical conditions, which decreased from 55 to 35 during OM-85 (+SOC) treatment, corresponding to a reduction of 36 %. In addition, an increase in serum and secretory IgA levels which coincided with the administration of OM-85 was observed. CONCLUSIONS: Our results showed the clinical benefits of OM-85 in reducing RTIs and exacerbations of the underlying medical condition, in patients with allergic rhinitis, asthma, or COPD.


title: Building toolkits for COPD exacerbations: lessons from the past and present

text: In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago. An ECOPD is ‘an acute worsening of respiratory symptoms that results in additional therapy’. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment.


title: Coronaviruses pandemics: Can neutralizing antibodies help?

text: For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not “to be or not to be” yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.


title: Evaluation of an in-practice test for feline coronavirus antibodies

text: Abstract A commercially available in-practice test for feline coronavirus (FCoV) antibodies (FCoV Immunocomb, Biogal Galed Laboratories) was evaluated by comparison with the gold standard FCoV immunofluorescent antibody (IFA) test. One hundred and three serum or plasma samples were selected and tested: 70 were positive by both tests, 24 were negative by both tests. The in-practice test produced five false positive and four false negative results. The sensitivity of the in-practice test was 95% and the specificity was 83%. When the titres were compared it was found that the in-practice test results were significantly correlated with IFA titres but the degree of correlation was not likely to be clinically useful. The IFA titres of the four false negative samples were found to be low (less than 40) which suggests that even a cat with a false negative result is still unlikely to be excreting FCoV. A negative result with the in-practice assay is likely to be reliable for screening cats prior to entry into an FCoV-free cattery or stud. It would also be useful in the investigation of suspected FIP as most cats with this condition have high IFA titres of antibodies. A strong positive result would be useful in the diagnosis of FIP (in conjunction with other biochemical and cytological testing), but positive results would be of limited value in monitoring FCoV infection in healthy cats as the antibody titre could not be reliably compared with those obtained with IFA. All positive results obtained using the in-practice kit should be confirmed and titrated by IFA. The kit also appeared to work efficiently with ascites samples (n=6) but too few samples were analysed to draw firm conclusions.


COVID-19 Putting Patients at Risk of Unplanned Extubation and Airway Providers at Increased Risk of Contamination


title: Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies

text: The role of cyclooxygenase-2 (COX-2), its lipid metabolite prostaglandin E2 (PGE2), and Eicosanoid (EP) receptors (EP; 1-4) underlying the proinflammatory mechanistic aspects of Burkitt’s lymphoma, nasopharyngeal carcinoma, cervical cancer, prostate cancer, colon cancer, and Kaposi’s sarcoma (KS) is an active area of investigation. The tumorigenic potential of COX-2 and PGE2 through EP receptors forms the mechanistic context underlying the chemotherapeutic potential of nonsteroidal anti-inflammatory drugs (NSAIDs). Although role of the COX-2 is described in several viral associated malignancies, the biological significance of the COX-2/PGE2/EP receptor inflammatory axis is extensively studied only in Kaposi’s sarcoma-associated herpes virus (KSHV/HHV-8) associated malignancies such as KS, a multifocal endothelial cell tumor and primary effusion lymphoma (PEL), a B cell-proliferative disorder. The purpose of this review is to summarize the salient findings delineating the molecular mechanisms downstream of COX-2 involving PGE2 secretion and its autocrine and paracrine interactions with EP receptors (EP1-4), COX-2/PGE2/EP receptor signaling regulating KSHV pathogenesis and latency. KSHV infection induces COX-2, PGE2 secretion, and EP receptor activation. The resulting signal cascades modulate the expression of KSHV latency genes (latency associated nuclear antigen-1 [LANA-1] and viral-Fas (TNFRSF6)-associated via death domain like interferon converting enzyme-like- inhibitory protein [vFLIP]). vFLIP was also shown to be crucial for the maintenance of COX-2 activation. The mutually interdependent interactions between viral proteins (LANA-1/vFLIP) and COX-2/PGE2/EP receptors was shown to play key roles in the biological mechanisms involved in KS and PEL pathogenesis such as blockage of apoptosis, cell cycle regulation, transformation, proliferation, angiogenesis, adhesion, invasion, and immune-suppression. Understanding the COX-2/PGE2/EP axis is very important to develop new safer and specific therapeutic modalities for KS and PEL. In addition to COX-2 being a therapeutic target, EP receptors represent ideal targets for pharmacologic agents as PGE2 analogues and their blockers/antagonists possess antineoplastic activity, without the reported gastrointestinal and cardiovascular toxicity observed with few a NSAIDs.


title: The Zika outbreak of the 21st century

text: Abstract The Zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. This virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by British scientists working at the Yellow Fever Research Laboratory located in the Zika forest area of Uganda, hence its name, and is transmitted primarily by the mosquito vector, Aedes aegypti. The fact that the rhesus macaque is an Asian species being placed in an African forest brings to mind the possibility of rapid adaptation of the virus from an African to Asian species, an issue that has not been considered. Whether such adaptation has played any role in acquiring pathogenicity due to cross species transmission remains to be identified. The first human infection was described in Nigeria in 1954, with only scattered reports of about a dozen human infections identified over a 50-year period. It was not until 2007 that Zika virus raised its ugly head with infections noted in three-quarters of the population on the tiny island of Yap located between the Philippines and Papua New Guinea in the western Pacific Ocean, followed by a major outbreak in French Polynesia in 2013. The virus remained confined to a narrow equatorial band in Africa and Asia until 2014 when it began to spread eastward, first toward Oceania and then to South America. Since then, millions of infected individuals have been identified in Brazil, Colombia, Venezuela, including 25 additional countries in the Americas. While the symptoms associated with Zika virus infection are generally mild, consisting of fever, maculopapular rash, arthralgia and conjunctivitis, there have been reports of more severe reactions that are associated with neurological complications. In pregnant women, fetal neurological complications include brain damage and microcephaly, while in adults there have been several cases of virus-associated Guillain-Barre syndrome. The virus was until recently believed to only be transmitted via mosquitoes. But when the Zika virus was isolated from the semen specimens from a patient in Texas, this provided the basis for the recent report of possible sexual transmission of the Zika virus. Due to the neurological complications, various vectors for infection as well as the rapid spread throughout the globe, it has prompted the World Health Organization to issue a global health emergency. Various governmental organizations have recommended that pregnant women do not travel to countries where the virus is epidemic, and within the countries affected by the virus, recommendations were provided for women of childbearing age to delay pregnancy. The overall public health impact of these above findings highlights the need for a rapid but specific diagnostic test for blood banks worldwide to identify those infected and for the counseling of women who are pregnant or contemplating pregnancy. As of this date, there are neither commercially licensed diagnostic tests nor a vaccine. Because cross-reactivity of the Zika virus with dengue and Chikungunya virus is common, it may pose difficulty in being able to quickly develop such tests and vaccines. So far the most effective public health measures include controlling the mosquito populations via insecticides and preventing humans from direct exposure to mosquitoes.


title: Evolution of olfactory disorders in COVID‐19 patients

text: OBJECTIVES: A high frequency and a strong association of olfactory/gustatory impairment with COVID‐19 were reported. Its spontaneous evolution remains unknown. The aim of this study was to investigate the spontaneous evolution of olfactory disorders in COVID‐19 patients. STUDY DESIGN: Cross‐sectional study METHODS: A total of 229 patients with laboratory‐confirmed COVID‐19 from March 1 through 31, 2020 in our institution were included. Among them, 140 patients (mean age, 38.5 years, 89 women) reported sudden olfactory/gustatory disorders during COVID‐19. All patients were interviewed by phone based on a questionnaire with 16 questions at time of survey. The primary end point was olfactory recovery rate at time of survey. RESULTS: The frequency of patients with olfactory disorders was higher before March 20, 2020 than since (70.3% vs 53.9%, respectively) (p=0.016). At time of survey (26 days of the mean time from anosmia onset), 95.71% reported to start an olfactory recovery. The mean time from olfactory loss onset to recovery onset was 11.6 days. Recovery started between the 4(th) and the 15(th) day after olfactory loss onset in 78.4% of patients. Complete olfactory recovery happened for 51.43% of patients. There was a significant relationship between the complete olfactory recovery and a short time from olfactory loss onset to recovery onset (p=0.0004), absence of nasal obstruction (p=0.023), and absence of sore/dry/tingling feeling in the nose (p=0.007) in COVID‐19 patients. CONCLUSION: Knowledge of spontaneous evolution of olfactory disorders allows reassuring patients and planning therapeutic strategies for persistent olfactory dysfunction after having definitely recovered from COVID‐19.


docid: zplnvbab

title: Clinical features in pediatric COVID‐19


title: Retrospective analysis of seizures associated with feline infectious peritonitis in cats

text: Seizures have been reported frequently in feline infectious peritonitis (FIP) but have not been studied in detail in association with this disease. The purpose of this study was to perform a retrospective analysis of neurological signs in a population of 55 cats with a histopathologically confirmed neurological form of FIP. Seizure patterns were determined and it was attempted to relate occurrence of seizures with age, breed, sex and neuropathological features. Fourteen cats had seizure(s), while 41 cats had no history of seizure(s). Generalised tonic–clonic seizures were seen in nine cats; and complex focal seizures were observed in four patients. The exact type of seizure could not be determined in one cat. Status epilepticus was observed in one patient but seizure clusters were not encountered. Occurrence of seizures was not related to age, sex, breed or intensity of the inflammation in the central nervous system. However, seizures were significantly more frequent in animals with marked extension of the inflammatory lesions to the forebrain (P =0.038). Thus, the occurrence of seizures in FIP indicates extensive brain damage and can, therefore, be considered to be an unfavourable prognostic sign.


title: Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

text: Some patients with positive chest CT findings may present with negative results of real time reverse-transcription–polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening


title: Family-Centered Care During the COVID-19 Era

text: Abstract Family support is more, not less, important during crisis. However, during the COVID-19 pandemic, maintaining public safety necessitates restricting the physical presence of families for hospitalized patients. In response, health systems must rapidly adapt family-centric procedures and tools to circumvent restrictions on physical presence. Strategies for maintaining family integrity must acknowledge clinicians’ limited time and attention to devote to learning new skills. Internet-based solutions can facilitate the routine, predictable, and structured communication which is central to family-centered care. But the reliance on technology may compromise patient privacy and exacerbate racial, socioeconomic, and geographic disparities for populations that lack access to reliable internet access, devices or technological literacy. We provide a toolbox of strategies for supporting family-centered inpatient care during physical distancing responsive to the current clinical climate. Innovations in the implementation of family involvement during hospitalizations may lead to long-term progress in the delivery of family-centered care.


title: Pathogen profiles and molecular epidemiology of respiratory viruses in Japanese inpatients with community-acquired pneumonia

text: Abstract Background The etiological profile of viruses among adult patients with community-acquired pneumonia (CAP) has not been characterized yet. The aim of this study was twofold: first, investigate the pathogen profiles and the molecular epidemiology of respiratory viruses among Japanese CAP patients; and second, explore the clinical significance of viral infections. Methods A cross-sectional observational study was conducted at Kyorin University Hospital. To identify respiratory pathogens, hospitalized CAP patients were enrolled, and reverse transcriptase–polymerase chain reaction technology was applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. CAP patients were divided into four etiological groups (virus alone, bacteria alone, co-detection of virus and bacteria, and not detected) and the clinical findings were compared. Results Seventy-six patients were enrolled. Bacteria alone were detected in 39.5% (n=30) of CAP patients. Virus alone or co-detection were found in 10.5% (n=8) and 11.8% (n=9) of cases, respectively. Streptococcus pneumoniae and human metapneumovirus were the most frequently detected bacterium and virus, respectively. Phylogenetic analyses of human metapneumovirus, human rhinovirus, and human respiratory syncytial virus showed that different subgroups and genotypes might be associated with CAP. Respiratory failure was more common when a virus was detected (both virus alone and co-detection groups; n=17, 100%, p<0.05) than when a bacteria alone was detected (n=17, 56.7%). Conclusion Prevalence of respiratory virus infection in CAP inpatients was 22.3%. The detected viruses display high genetic divergence and correlate with increased respiratory failure.


docid: eiicdxre

title: Detection of Novel duck reovirus (NDRV) using visual reverse transcription loop-mediated isothermal amplification (RT-LAMP)

text: Here we present a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting the gene encoding the σB major outer-capsid protein of novel duck reovirus (NDRV). A set of primers, composed of two outer primers, two inner primers and two loop primers, was designed based on the gene of interest. The LAMP reaction was conducted in a traditional laboratory water bath at 65 °C for 50 min. We compared the performance of calcein/Mn(2+) and SYBR Green I dyes, as well as electrophoresis on agarose gel stained with GoldView nucleic acid dye to detect the RT-LAMP-amplified products and all assays could be employed to discriminate between positive and negative specimens in visible or UV light. Our data showed that there is no cross-reaction with other viruses and the RT-LAMP technique displayed high sensitivity for detecting NDRV with a minimal detection limit of 200 fg RNA input. This assay was more sensitive than conventional PCR in detecting NDRV both in natural and experimental infection. In conclusion, the RT-LAMP technique was remarkably sensitive, specific, rapid, simple and profitable for the identification of NDRV.


Community-wide Outbreak of Infection with a 229E-like Coronavirus in Tecumseh, Michigan


docid: xnfrulbf

title: Artificial Intelligence in Public Health and Epidemiology

text: Objectives: To introduce and summarize current research in the field of Public Health and Epidemiology Informatics. Methods: The 2017 literature concerning public health and epidemiology informatics was searched in PubMed and Web of Science, and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to provide the editorial team with an enlightened vision to select the best papers. Results: Among the 843 references retrieved from PubMed and Web of Science, two were finally selected as best papers. The first one analyzes the relationship between the disease, social/mass media, and public emotions to understand public overreaction (leading to a noticeable reduction of social and economic activities) in the context of a nation-wide outbreak of Middle East Respiratory Syndrome (MERS) in Korea in 2015. The second paper concerns a new methodology to de-identify patient notes in electronic health records based on artificial neural networks that outperformed existing methods. Conclusions: Surveillance is still a productive topic in public health informatics but other very important topics in Public Health are appearing. For example, the use of artificial intelligence approaches is increasing.


title: Self-Replicating RNA Viruses for RNA Therapeutics

text: Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.


title: Fly repellency using deltamethrin may reduce intramammary infections of dairy cows under intensive management

text: Abstract The aim of this study was to assess the possible effect of the fly repellent deltamethrin on the full microbiological profile of the intramammary infections as well as on the somatic cell count in one Greek dairy cattle farm under intensive management, during peak fly season. Fifty five multiparous cows, stabled in the same farm, were randomly divided in three groups; cows of Group A were dressed on their back with deltamethrin, cows of Group B remained untreated within the same pen and cows of Group C remained untreated in a separate pen. Clinical records of the herd showed a history of clinical and subclinical mastitis (especially during spring and early summer) and fly infestation. Deltamethrin reduced fly population, landing on the cows of Group A, facilitating a significant decrease of S. aureus, coagulase negative staplylococci, E. coli intramammary infections and somatic cell count, throughout the study period. Consequently, there is a relationship between fly abundance and transmission of bacteria resulting in intramammary infections and mastitis in dairy cows. The use of the pyrethroid deltamethrin reduced fly abundance and therefore, the possibility of transmitting pathogenic bacteria in the mammary gland.


title: Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network

text: Host cells possess the metabolic assets required for viral infection. Recent studies indicate that control of the host’s metabolic resources is a core host-pathogen interaction. Viruses have evolved mechanisms to usurp the host’s metabolic resources, funneling them towards the production of virion components as well as the organization of specialized compartments for replication, maturation, and dissemination. Consequently, hosts have developed a variety of metabolic countermeasures to sense and resist these viral changes. The complex interplay between virus and host over metabolic control has only just begun to be deconvoluted. However, it is clear that virally induced metabolic reprogramming can substantially impact infectious outcomes, highlighting the promise of targeting these processes for antiviral therapeutic development.


title: Prise en charge nutritionnelle des patients de réanimation ayant une infection COVID-19

text: Résumé Les patients ayant eu des formes sévères de Covid-19 ont posé des problèmes nutritionnels en réanimation. L’immobilisation prolongée en réanimation, associée à une réaction inflammatoire systémique exacerbée, ont été à l’origine d’une faiblesse et d’une fatigue musculaire. Pour pallier ce problème, l’instauration d’une nutrition entérale précoce est recommandée, pour atteindre progressivement la cible énergétique de 25kcal/kg/jour et protéique de 1,3g/kg/jour en 4 jours environ. La survenue d’un syndrome de renutrition inappropriée doit être surveillée. En cas d’intolérance digestive réfractaire à un traitement prokinétique, une nutrition parentérale complémentaire ou totale est indiquée, en favorisant les émulsions lipidiques mixtes (contenant de l’huile de poisson) de nouvelle génération et en surveillant régulièrement la triglycéridémie. La prise en charge nutritionnelle des patients doit se faire en limitant les procédures à risque de contamination pour le personnel soignant. Summary Patients with severe cases of Covid-19 are at high nutritional risk during their ICU stay. Prolonged immobilization associated with an exacerbated systemic inflammatory response is a major provider of ICU-acquired muscle weakness. Early enteral nutrition is recommended to gradually reach the energy target of 25kcal/kg/day and protein target of 1.3g/kg/day around D4. The occurrence of a Refeeding syndrome should be closely monitored. In case of feeding intolerance refractory to a prokinetic treatment, complementary or total parenteral nutrition is advised, favouring new generation mixed lipid emulsions (containing fish oil) and regular monitoring of triglyceridemia. Nutrition care of critically ill patients should be carried out with limited procedures that may pose a risk of contamination for the healthcare staff.


title: Generating Vesicular Stomatitis Virus Pseudotype Bearing the Severe Acute Respiratory Syndrome Coronavirus Spike Envelope Glycoprotein for Rapid and Safe Neutralization Test or Cell‐Entry Assay

text: abstract: We generated a recombinant vesicular stomatitis virus (VSV) pseudotype (VSV Δ G*SG) by replacing the envelope G gene with the GFP gene and complementing with spike glycoprotein (S) of SARS‐CoV in trans. The neutralization and infection blocking tests showed that the VSV Δ G*SG and SARS‐CoV reacted similarly to SARS‐CoV specific antiserum, suggesting the VSVΔ G*SG can be a safe replacement of the live SARS‐CoV for neutralization test and cell‐entry assay.


title: Genotyping coronaviruses associated with feline infectious peritonitis

text: Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP.


title: D-RNA Molecules Associated with Subisolates of the VT Strain of Citrus Tristeza Virus which Induce Different Seedling-Yellows Reactions

text: Citrus tristeza virus (CTV) strains were previously catalogued as seedling-yellows (SY) and non-SY (nSY) types, according to their yellowing and stunting effects on indicator seedlings. Among subisolates of the VT strain, which were selected from chronically infected Alemow plants, there was a correlation between the presence of 2.4-, 2.7- and 4.5-kb D-RNAs, and SY and nSY reactions, respectively. Similarly, plants infected with Mor-T subisolates, which cause SY, contained D-RNAs of 2.6 to 2.8 kb, while nSY subisolates from recovered sour orange tissue contained a major D-RNA of 5.1 kb. Plants harboring the 2.7-kb D-RNA were protected against challenge inoculation with a subisolate harboring the 4.5-kb D-RNA. This study suggests that the nSY reaction results either from the absence of SY gene(s) in the genomes of certain CTV strains or through the suppression of the effects of SY gene(s) by D-RNAs with 5′ parts larger than 4000 nt.