title: Technique, radiation safety and image quality for chest X-ray imaging through glass and in mobile settings during the COVID-19 pandemic

text: The COVID-19 pandemic in 2020 has led to preparations within our hospital for an expected surge of patients. This included developing a technique to perform mobile chest X-ray imaging through glass, allowing the X-ray unit to remain outside of the patient’s room, effectively reducing the cleaning time associated with disinfecting equipment. The technique also reduced the infection risk of radiographers. We assessed the attenuation of different types of glass in the hospital and the technique parameters required to account for the glass filtration and additional source to image distance (SID). Radiation measurements were undertaken in a simulated set-up to determine the appropriate position for staff inside and outside the room to ensure occupational doses were kept as low as reasonably achievable. Image quality was scored and technical parameter information collated. The alternative to imaging through glass is the standard portable chest X-ray within the room. The radiation safety requirements for this standard technique were also assessed. Image quality was found to be acceptable or borderline in 90% of the images taken through glass and the average patient dose was 0.02 millisieverts (mSv) per image. The majority (67%) of images were acquired at 110 kV, with an average 5.5 mAs and with SID ranging from 180 to 300 cm. With staff positioned at greater than 1 m from the patient and at more than 1 m laterally from the tube head outside the room to minimise scatter exposure, air kerma values did not exceed 0.5 microgray (µGy) per image. This method has been implemented successfully.


Detection of respiratory pathogens with the RespiFast RG Panel, in comparison with an in-house real-time PCR assay


title: Classic and Nonclassic Renin-Angiotensin Systems in the Critically Ill

text: Classic and nonclassic renin-angiotensin systems (RAS) are 2 sides of an ubiquitous endocrine/paracrine cascade regulating blood pressure and homeostasis. Angiotensin II and angiotensin-converting enzyme (ACE) levels are associated with severity of disease in the critically ill, and are central to the physiology and the pathogenesis of circulatory shock. Angiotensin (1–7) and ACE2 act as an endogenous counterregulatory arm to the angiotensin II/ACE axis. The tissue-based RAS has paracrine effects dissociated from those of the circulating RAS. Exogenous angiotensin II or ACE2 may improve the outcome of septic shock and acute respiratory distress syndrome, respectively.


Telomere formation in yeast


docid: tgddzwgt

title: A laboratory study of the expiratory airflow and particle dispersion in the stratified indoor environment

text: Understanding the role of human expiratory flows on respiratory infection in ventilated environments is useful for taking appropriate interventions to minimize the infection risk. Some studies have predicted the lock-up phenomenon of exhaled flows in stratified environments; however, there is a lack of high-quality experimental data to validate the theoretical models. In addition, how thermal stratification affects the transport of exhaled particles has not been explored so far. In this study, a water tank experiment was conducted according to the similarity protocols to mimic how the expiratory airflow and particles behaved in both uniform and stratified environments. The lock-up phenomenon was visualized and compared with the predicted results by an integral model. Results showed that our previously developed theoretical model of a respiratory airflow was effective to predict the airflow dispersion in stratified environments. Stratification frequency (N) of the background fluid and the Froude Number [Formula: see text] of the thermal flow jointly determined the lock-up layer in a power law. For the particle dispersion, it indicated that small particles such as fine droplets and droplet nuclei would be ‘locked’ by indoor thermal stratification, and disperse with the thermal flow over a long distance, potentially increasing the long-range airborne infection risk. Large particles such as large droplets can deposit within a short distance, hardly affected by thermal stratification, however, droplet infection could happen to the susceptible people at a close contact with the infector. This study could give some guidance in view of cross-infection control indoors for stratified environment.


title: miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1)

text: Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.


docid: nogoqyxl

title: Transcriptome altered by latent human cytomegalovirus infection on THP-1 cells using RNA-seq

text: Abstract Human cytomegalovirus (HCMV) has been recognized as a cause of severe, sometimes life-threatening disease in congenitally infected newborns as well as in immunocompromised individuals. However, the molecular mechanisms of the host-virus interaction remain poorly understood. Here, we profiled the expression of mRNAs and long noncoding RNAs (lncRNAs) in THP-1 cells using the emerging RNA-seq to investigate the transcriptional changes during HCMV latent infection. At 4 days post HCMV infection, a total of 169,008,624 sequence reads and 180,616 transcripts were obtained, respectively. Of these transcripts, 1,354 noncoding genes and 12,952 protein-coding genes were observed in Refseq database. Differential gene expression analysis identified 2,153 differentially expressed genes (DEGs) between HCMV-infected and mock-infected THP-1 cells, including 1,098 up-regulated genes and 1,055 down-regulated genes. These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. In addition, 646 lncRNAs (208 known lncRNAs and 438 novel lncRNAs) were upregulated and 424 (140 known and 284 novel) were downregulated in infected THP-1 cells. These findings have provided a dynamic scenario of DE candidate genes and lncRNAs at the virus-host interface and clearly warrant further experimental investigation associated with HCMV infection.


Preterm delivery in pregnant woman with critical COVID‐19 pneumonia and vertical transmission


docid: todyvwsj

title: Disease and age‐related inequalities in paediatric research, funding and communication: lessons from the COVID‐19 pandemic

text: COVID‐19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children’s role in transmitting the disease. The serious impact that restrictive measures have had on children’s lives have not been fully considered. Because children are less affected by COVID‐19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.


title: Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020

text: Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.


title: Incorporating Risk Stratification into the Practice of Pediatric Preventive Cardiology

text: Atherosclerosis in its earliest stages is associated with the same traditional cardiovascular disease (CVD) risk factors as are associated with manifest CVD events in adulthood. Clustering of risk factors is associated with exponential increases in atherosclerotic burden from a young age. Some medical conditions and risk behaviors occurring in children can either increase the likelihood of higher levels of risk factors (such as chronic kidney disease) or the presence of risk factor clustering (such as obesity and cardiometabolic syndrome), or are associated with acquired coronary artery pathology (such as Kawasaki disease). This creates a milieu for, or increases the impact of, accelerated atherosclerosis that in turn increases the likelihood of premature CVD. This review highlights the importance of considering the total risk factor and risk condition profile of pediatric patients. An algorithm is provided for stratifying patients into high, moderate and at risk categories, and practical examples are provided as to how the evaluation and management of one risk factor or risk condition might need to be intensified in the context of additional risk factors or risk conditions. For example, for treatment of an adolescent with familial hypercholesterolemia, the target low-density lipoprotein cholesterol level might be lowered by the concomitant presence of low high-density lipoprotein cholesterol or elevated lipoprotein(a) levels. As awareness of cardiovascular risk and atherosclerosis in pediatric patients increases, new at risk conditions that warrant consideration are emerging. The identification and management of high risk individuals is an important part of the overall practice of pediatric preventive cardiology.


title: Forensic DNA testing during the SARS-CoV-2 pandemic

text: The aggressive nature of the new SARS-2 corona virus now referred to as SARS-CoV-2 ; the seriousness and length of the period of infection; the fast and far-reaching transmissibility via liquid droplets that become air-borne when someone coughs, sneezes or speaks with increasing evidence to support actual airborne transmission; the presence of viral particles especially in body fluids and tissues, of viral positive individuals; and the persistence of the virus on different types of surfaces pose serious concerns for forensic practitioners, including forensic DNA analysts. Many forensic laboratories and law enforcement agencies need to address the inevitable changes that must be made in forensic DNA testing. In this article, we explore the effects of the COVID-19 pandemic on the collection, handling, storage and transport of biological samples for downstream DNA testing. This paper aims to open discussions on the urgency of balancing the need to conduct investigations in order to maintain public order with the requirements of effective biosafety protocols specifically formulated to protect human resources within the forensic science community.


title: State-of-the-art methods for inverse design of an enclosed environment

text: Abstract The conventional design of enclosed environments uses a trial-and-error approach that is time consuming and may not meet the design objective. Inverse design concept uses the desired enclosed environment as the design objective and inversely determines the systems required to achieve the objective. This paper discusses a number of backward and forward methods for inverse design. Backward methods, such as the quasi-reversibility method, pseudo-reversibility method, and regularized inverse matrix method, can be used to identify contaminant sources in an enclosed environment. However, these methods cannot be used to inversely design a desired indoor environment. Forward methods, such as the CFD-based adjoint method, CFD-based genetic algorithm method, and proper orthogonal decomposition method, show the promise in the inverse design of airflow and heat transfer in an enclosed environment. The CFD-based adjoint method is accurate and can handle many design parameters without increasing computing costs, but the method may find a locally optimal design that could meet the design objective with constrains. The CFD-based genetic algorithm method, on the other hand, can provide the global optimal design that can meet the design objective without constraints, but the computing cost can increase dramatically with the number of design parameters. The proper orthogonal decomposition method is a reduced-order method that can significantly lower computing costs, but at the expense of reduced accuracy. This paper also discusses the possibility to reduce the computing costs of CFD-based design methods.


title: Prediction of SARS-CoV-2 epitopes across 9360 HLA class I alleles

text: Elucidating antiviral CD8 T lymphocyte responses to SARS-CoV-2 may shed light on the heterogeneity of clinical outcomes and inform vaccine or therapeutic approaches. To facilitate the evaluation of antiviral CD8 T cell responses to SARS-CoV-2, we generated a publicly accessible database of epitopes predicted to bind any class I HLA protein across the entire SARS-CoV-2 proteome. While a subset of epitopes from earlier betacoronaviruses, such as SARS-CoV (SARS), have been validated experimentally, validation systems are often biased toward specific HLA haplotypes (notably HLA-A*02:01) that only account for a fraction of the haplotypes of individuals affected by the SARS-CoV-2 pandemic. To enable evaluation of epitopes across individuals with a variety of HLA haplotypes, we computed the predicted binding affinities between 9-mer peptides derived from the annotated SARS-CoV-2 peptidome across 9,360 MHC class I HLA-A, -B, and -C alleles. There were 6,748 unique combinations of peptides and HLA alleles (pMHCs) with a predicted binding affinity of less than 500nM, including 1,103 unique peptides and 1,022 HLA alleles, spanning 11 annotated superfamilies. These peptides were derived from all 11 proteins spanning the SARS-CoV-2 peptidome, including peptides that have previously been validated experimentally. We also show evidence that these previously validated epitopes may be relevant in other HLA contexts. This complete dataset is available publicly: gs://pici-covid19-data-resources/mhci/peptide_predictions.


title: Golgi Structure and Function in Health, Stress, and Diseases

text: The Golgi apparatus is a central intracellular membrane-bound organelle with key functions in trafficking, processing, and sorting of newly synthesized membrane and secretory proteins and lipids. To best perform these functions, Golgi membranes form a unique stacked structure. The Golgi structure is dynamic but tightly regulated; it undergoes rapid disassembly and reassembly during the cell cycle of mammalian cells and is disrupted under certain stress and pathological conditions. In the past decade, significant amount of effort has been made to reveal the molecular mechanisms that regulate the Golgi membrane architecture and function. Here we review the major discoveries in the mechanisms of Golgi structure formation, regulation, and alteration in relation to its functions in physiological and pathological conditions to further our understanding of Golgi structure and function in health and diseases.


title: Treatment of AG129 mice with antisense morpholino oligomers increases survival time following challenge with dengue 2 virus

text: OBJECTIVES: To determine the antiviral activity of phosphorodiamidate morpholino oligomers (PMO) and peptide-conjugated PMO (PPMO) in AG129 mice infected with dengue 2 virus (DENV-2). METHODS: Antisense PMO and PPMO were designed against the 5′ terminal region (5′SL) or the 3′-cyclization sequence region (3′CS) of DENV genomic RNA and administered to AG129 mice before and/or after infection with DENV-2. In addition, cell culture evaluations designed to determine optimum PPMO length, and pharmacokinetic and toxicity analysis of PPMO were also carried out. RESULTS: Mock-treated AG129 mice lived for 9–17 days following intraperitoneal (ip) infection with 10(4)–10(6)pfu of DENV-2 (strain New Guinea C). Intraperitoneal administration of 5′SL or 3′CS PPMO before and after DENV infection produced an increase in the average survival time of up to 8 days. Animals receiving only post-infection PPMO treatment did not benefit significantly. Cell culture studies showed that PPMO of 22–24 bases long produced substantially higher DENV titre reductions than did PPMO that were either shorter or longer. Pharmacokinetic and toxicology analysis with non-infected animals showed that nine consecutive once‐daily ip treatments of 10 mg/kg PPMO resulted in high concentrations of PPMO in the liver and caused little impact on overall health. CONCLUSIONS: The data indicate that PPMO had considerable antiviral efficacy against DENV-2 in the AG129 mouse model and that PPMO treatment early in the course of an infection was critical to extending the survival times of DENV-2-infected mice in the AG129 model system.


title: Transmission and Control of Respiratory Viral Infections in the Healthcare Setting

text: PURPOSE OF THE REVIEW: Viral respiratory infections have been recognized as a cause of severe illness in immunocompromised and non-immunocompromised hosts. This acknowledgement is a consequence of improvement in diagnosis and better understanding of transmission. Available vaccines and antiviral drugs for prophylaxis and treatment have been developed accordingly. Viral respiratory pathogens are increasingly recognized as nosocomial pathogens as well. The purpose of this review is to describe the most frequent and relevant nosocomial viral respiratory infections, their mechanisms of transmission and the infection control measures to prevent their spread in the healthcare setting. RECENT FINDINGS: Although most mechanisms of transmission and control measures of nosocomial viral infections are already known, improved diagnostic tools allow better characterization of these infections and also lead to the discovery of new viruses such as the coronavirus, which is the cause of the Middle East Respiratory Syndrome, or the human bocavirus. Also, the ability to understand better the impact, dissemination and prevention of these viruses, allows us to improve the measures to prevent these infections. SUMMARY: Healthcare viral respiratory infections increase patient morbidity. Each virus has a different mechanism of transmission; therefore, early detection and prompt implementation of infection control measures are very important in order to avoid their transmission in the hospital setting.


title: Clinical characteristics of emergency surgery patients-infected COVID-19 pneumonia in Wuhan, China

text: OBJECTIVE: We aimed to investigate clinical symptom and epidemiological features of ESP-infected COVID-19 SUMMARY BACKGROUND DATA: Almost one million of 2019 novel coronavirus disease (COVID-19) patients were diagnosed in the world wide from December 2019 to now. Thousands of emergency operations were carried out in the interim. However no one focused on the clinical symptom of emergency surgery patients (ESP) with COVID-19 pneumonia. METHODS: Retrospective cohort study of 164 ESP with or without COVID-19 pneumonia in Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 20, 2020. The final date of follow-up was February 5, 2020. The associated clinical, laboratory, epidemiological, demographic, radiological and outcome data were collected and analyzed. RESULTS: Of 164 ESP, the median age was 41 years old (interquartile range (IQR), 29-89) and 136 (82.9%) were women. Associated main clinical symptom including fever (93 [56.7%]), dry cough (56 [34.2%]), fatigue (86 [52.4%]), nausea (78 [47.6%]) and dizziness (77 [47%]). Of 54 ESP-infected COVID-19 patients, the median age was 46 (IQR: 25-89) and 45 (83.3%) were women. The pathological clinical symptoms including fever (54 [100%]), fatigue (48 [88.9%]), nausea (52 [96.3%]), dizziness (46 [85.2%]) and dry cough (44 [81.5%]) were investigated; the lymphopenia (0.37×10(9)/L [IQR: 0.23-0.65]) and increased C-reactive protein (24.7×10(9)/L [IQR: 13.57-38]) were observed. The preoperative fever and postoperative fever in ESP with or without COVID-19 pneumonia were analyzed in this study. Of 54 ESP with COVID-19 patients, 15 (27.8%) patients showed preoperative fever, 54 (100%) had the postoperative fever; Of 110 non-COVID-19 of ESP, 5 (4.5%) patients had preoperative fever, 31 (28.2%) patients had the postoperative fever. The fever in ESP with COVID-19 lasted more than 7 days, markedly exceeded the non-COVID-19 patients (lasted about 3 days). Furthermore, 43 health care workers were infected from exposed to ESP with COVID-19 pneumonia. CONCLUSION: In our study, the clinical symptoms of ESP-infected COVID-19 displayed marked differences from those reported common COVID-19 pneumonia cases. Additionally, the health care workers were confirmed to expose great risk in ESP with COVID-19 pneumonia. Management guidelines of ESP were described in our paper.


Review of Joshua Gans (forthcoming 2020). Economics in the Age of Covid-19: Cambridge, MA: MIT Press. DOI 10.21428/a11c83b7.c48fa91b (E-Book)


title: THE IL-6 (−174, C/C) GENOTYPE PREDICTS GREATER RHINOVIRUS ILLNESS

text: INTRODUCTION: In adults and children with RSV infection, a polymorphism in the IL-6 promoter at position −174 predicted illness magnitude. Also, polymorphisms in the IL-10, TNFα and INFγ genes were associated with immune responsiveness and the frequency of complications. Here, the effect of these polymorphisms on illness and seroconversion during infection with rhinovirus type 39 (RV39) was evaluated. METHODS: Seventy-two adults were genotyped for the selected polymorphisms, experimentally exposed to RV39 and followed for infection, seroconversion and symptoms/signs of illness. Regression analysis was used to determine if these polymorphisms predicted seroconversion and illness magnitude in 57 infected subjects. RESULTS: The low production IL-6 (−174, C/C) phenotype was associated with greater symptom magnitudes and the INFγ (+874) phenotype predicted the frequency of seroconversion. No relationship between the IL-10 or TNFα polymorphisms and any measured outcome was documented. IL-6 protein measured in nasal wash fluids of 51 subjects was positively correlated with symptom magnitude but was independent of the IL-6 (−174) genotypes representing high and low production phenotypes. CONCLUSIONS: These results document significant associations between the IL-6 (−174) and INFγ (+874) gene polymorphisms and specific responses to experimental RV39 infection. For the IL-6 (−174) polymorphism, the results replicate those for RSV infection.


title: The cutting edge of thoracic anesthesia during the 2019 coronavirus disease (COVID-19) outbreak

text: Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.


title: Highlights from the 5(th) annual meeting of the Italian society of virology

text: The 5(th) National Congress of the Italian Society of Virology (SIV) was attended by junior‐ and senior‐level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus‐host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti‐viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was “HIV: determinants of pathogenicity and clinical implications.” The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.


docid: czeyghyy

title: Chapter 4 Antiviral Immunity and Prophylaxis

text: Publisher Summary This chapter argues that antiviral immunity in animals is mediated by both cellular and humoral factors, and the nature of the immune response generated by different individuals infected with the same virus can be different, depending on the individual's genetic constitution, environmental influences, and other factors that can determine the course and pathogenesis of the infection. Innate immune defenses exhibit neither antigen specificity nor memory, but they provide a critical line of first defense against viral infections because they are constantly present and are operational immediately after viral infection. Innate immunity is often considered separate from acquired immune responses, but they are inextricably linked, and innate responses modulate subsequent acquired responses in many ways. Viruses that are transmitted horizontally between individuals must first breach the barriers at their portal of entry before they can cause infection in their respective hosts. In the ongoing war and détente between virus and host, viruses have developed remarkably sophisticated mechanisms to avoid the various host protective responses. Vaccination is the most effective way of preventing viral diseases. There are some important differences between vaccination practices in humans and animals. The immunogenicity of inactivated vaccines, especially that of purified protein vaccines and synthetic peptides, usually needs to be enhanced; this may be achieved by mixing the antigen with an adjuvant, incorporation of the antigen in liposomes, or incorporation of the antigen in an immunostimulating complex.


Covid‐19: Time for a paradigm change


title: Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

text: Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.


title: Vaccination Management of Beef Cattle Delayed Vaccination and Endotoxin Stacking

text: Vaccination is a critical component of cattle health management. Effective cattle vaccine programs should consider the timing of vaccination in relation to expected disease challenge, risk for wild-type exposure of various bovine pathogens, and host factors during vaccination. Nearly all consulting veterinarians recommend vaccination of stressed, high-risk calves on feedlot arrival. However, this recommendation fails to consider several factors associated with vaccine efficiency. Further research evaluating vaccine interactions in stressed cattle and potential additive effects of endotoxin from multiple bacterin administration may reveal new evidence-based vaccination guidelines for cattle in the various segments of beef and dairy production systems.


title: Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats

text: BACKGROUND: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. RESULTS: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. CONCLUSIONS: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection.


title: Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments – the importance of immunofocusing in subunit vaccine design

text: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of “immunofocusing”.


title: A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus

text: Since its emergence in 2012, more than 900 laboratory-confirmed cases of Middle East respiratory syndrome (MERS) have been reported with a fatality rate of more than 30%. However, no antigen detection assay for commercial use is available for diagnosis. In this study, the full-length nucleocapsid protein (NP) gene of MERS coronavirus (MERS-CoV) was cloned and expressed in Escherichia coli. A MERS-CoV NP capture enzyme-linked immunosorbent assay (ELISA) using two MERS-CoV-NP-specific monoclonal antibodies (MAbs) generated was developed. The ELISA was evaluated using 129 nasopharyngeal aspirates (NPAs) positive for various respiratory viruses and simulated positive NPAs by adding serial dilutions of MERS-CoV. Using a cutoff OD of 0.19, all 129 NPAs positive for respiratory viruses showed very low OD, with a specificity of 100%. For the two simulated MERS-CoV-positive NPAs with serial dilutions of live MERS-CoV, all samples with ≥10 50% tissue culture infective dose (TCID(50))/0.1 mL showed positive results. For the 10 additional NPAs with 20 and 200 TCID(50)/0.1 mL of live MERS-CoV added, all were positive. A highly sensitive and specific MAbs-based antigen capture ELISA has been developed for MERS. This sensitive and specific antigen capture ELISA should be useful for detection of MERS-CoV in human and dromedaries and in field studies.


title: Teaching-practice as a critical bridge for narrowing the research-practice gap

text: Abstract Management researchers and management practitioners increasingly appear to be talking past each other. A solution lies in understanding that interactive management education has an important role to play in bridging this divide, but for some reason this mode of academic exchange is often forgotten. Our paper broadens the stakeholder value perspective to explore how and why the interests of researchers and practitioners have diverged, before going on to present illustrative cases of programs attempting to bridge such differences. Current conditions suggest that the dissonance between different cycle-times of research and practice is not sustainable with the inevitable outcome of a shrinking commons. Generating new knowledge and propagating it rapidly through education and teaching-practice is an important way of disseminating higher-order research and findings. In a world where academic relevance is under threat, enabling academics to better cross such a divide is critical. Marketing-management researchers and teachers ironically have their own challenge of taking what can be a complex theory (the marketing academic equivalent of a “sausage”) and making it “sizzle”.


title: Tetraspanin CD81 regulates HSV-1 infection

text: Different members of the tetraspanin superfamily have been described to regulate different virus infectious cycles at several stages: viral entry, viral replication or virion exit or infectivity. In addition, tetraspanin CD81 regulates HIV reverse transcription through its association with the dNTP hydrolase SAMHD1. Here we aimed at analysing the role of CD81 in Herpes simplex virus 1 infectivity using a neuroblastoma cell model. For this purpose, we generated a CD81 KO cell line using the CRISPR/Cas9 technology. Despite being CD81 a plasma membrane protein, CD81 KO cells showed no defects in viral entry nor in the expression of early protein markers. In contrast, glycoprotein B and C, which require viral DNA replication for their expression, were significantly reduced in CD81 KO infected cells. Indeed, HSV-1 DNA replication and the formation of new infectious particles were severely compromised in CD81 KO cells. We could not detect significant changes in SAMHD1 total expression levels, but a relocalization into endosomal structures was observed in CD81 KO cells. In summary, CD81 KO cells showed impaired viral DNA replication and produced greatly diminished viral titers.


docid: sbuxbclx

title: Complexity theory and geographies of health: a critical assessment

text: Abstract The interest of social scientists in complexity theory has developed rapidly in recent years. Here, I consider briefly the primary characteristics of complexity theory, with particular emphasis given to relations and networks, non-linearity, emergence, and hybrids. I assess the ‘added value’ compared with other, existing perspectives that emphasise relationality and connectedness. I also consider the philosophical underpinnings of complexity theory and its reliance on metaphor. As a vehicle for moving away from reductionist accounts, complexity theory potentially has much to say to those interested in research on health inequalities, spatial diffusion, emerging and resurgent infections, and risk. These and other applications in health geography that have invoked complexity theory are examined in the paper. Finally, I consider some of the missing elements in complexity theory and argue that while it is refreshing to see a fruitful line of theoretical debate in health geography, we need good empirical work to illuminate it.


title: SNAD: sequence name annotation-based designer

text: BACKGROUND: A growing diversity of biological data is tagged with unique identifiers (UIDs) associated with polynucleotides and proteins to ensure efficient computer-mediated data storage, maintenance, and processing. These identifiers, which are not informative for most people, are often substituted by biologically meaningful names in various presentations to facilitate utilization and dissemination of sequence-based knowledge. This substitution is commonly done manually that may be a tedious exercise prone to mistakes and omissions. RESULTS: Here we introduce SNAD (Sequence Name Annotation-based Designer) that mediates automatic conversion of sequence UIDs (associated with multiple alignment or phylogenetic tree, or supplied as plain text list) into biologically meaningful names and acronyms. This conversion is directed by precompiled or user-defined templates that exploit wealth of annotation available in cognate entries of external databases. Using examples, we demonstrate how this tool can be used to generate names for practical purposes, particularly in virology. CONCLUSION: A tool for controllable annotation-based conversion of sequence UIDs into biologically meaningful names and acronyms has been developed and placed into service, fostering links between quality of sequence annotation, and efficiency of communication and knowledge dissemination among researchers.


title: Demography, Hunting Ecology, and Pathogen Exposure of Domestic Dogs in the Isoso of Bolivia

text: Abstract: Disease is increasingly recognized as a threat to the conservation of wildlife, and in many cases the source of disease outbreaks in wild carnivores is the domestic dog. For disease to spill over from a domestic to a wild population, three conditions must be satisfied: susceptibility of the wild species, presence of the disease agent in the domestic population, and contact between the two populations of interest. We investigated the potential for disease spillover from the domestic dog population to the wild carnivore population in the Isoso of Bolivia, an area of tropical dry forest contiguous with a national park. Using questionnaires and discussions with residents, we gathered data on the demography of dogs in the Isoso, including adult and neonatal mortality, litter size, and hunting frequency. We analyzed a large data set containing self‐recorded information on hunting in various communities of the Isoso to determine the extent of dog participation in hunting and the duration of hunting trips. Finally, we took blood samples from dogs in the Isoso for a serosurvey of common canine pathogens. More than 95% of dogs had positive titers to canine distemper virus and canine parvovirus. There was also a high seroprevalence in dogs for other pathogens, a high population turnover of dogs (which may allow diseases to be maintained endemically), and frequent opportunities for contact between domestic and wild carnivores. Based on our results and the susceptibility of wild species previously reported in the literature, domestic dogs represent a disease risk for wildlife in the Bolivian Isoso.


title: Controllable inhibition of hepatitis B virus replication by a DR1-targeting short hairpin RNA (shRNA) expressed from a DOX-inducible lentiviral vector

text: As a highly efficient delivery system, lentiviral vectors (LVs) have become a powerful tool to assess the antiviral efficacy of RNA drugs such as short hairpin RNA (shRNA) and decoys. Furthermore, recent advanced systems allow controlled expression of the effector RNA via coexpression of a tetracycline/doxycycline (DOX) responsive repressor (tTR-KRAB). Herein, this system was utilized to assess the antiviral effects of LV-encoded shRNAs targeting three conserved regions on the pregenomic RNA of hepatitis B virus (HBV), namely the region coding for the reverse transcriptase (RT) domain of the viral polymerase (LV-HBV-shRNA1), the core promoter (CP; LV-HBV-shRNA2), and the direct repeat 1 (DR1; LV-HBV-shRNA3). Transduction of just the LV-HBV-shRNA vectors into the stably HBV expressing HepG2.2.15 cell line showed significant reductions in secreted HBsAg and HBeAg, intracellular HBcAg as well as HBV RNA and DNA replicative intermediates for all vectors, however, most pronouncedly for the DR1-targeting shRNA3. The corresponding vector was therefore applied in the DOX-controlled system. Notably, strong interference with HBV replication was found in the presence of the inducer DOX whereas the antiviral effect was essentially ablated in its absence; hence, the silencing effect of the shRNA and consequently HBV replication could be strictly regulated by DOX. This newly established system may therefore provide a valuable platform to study the antiviral efficacy of RNA drugs against HBV in a regulated manner, and even be applicable in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-013-0886-2) contains supplementary material, which is available to authorized users.


title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses

text: The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.


title: COVID-19 Transmission Within a Family Cluster by Presymptomatic Carriers in China

text: We report a family cluster of coronavirus disease 2019 (COVID-19) caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Among the 8 patients, 1 adult and a 13-month-old infant were asymptomatic, and 1 adult was diagnosed as having severe pneumonia.


title: Revisión de nuevas evidencias acerca de la posible transmisión vertical de la COVID-19

text: ABSTRACT Objective: To conduct a systematic review of original peer-reviewed studies, containing data on the identification of SARS-CoV-2 in clinical samples of amniotic fluid, placenta or membranes, umbilical cord blood, and human milk, from women with a clinically or confirmed diagnosis of COVID-19. These studies should have been published after the guide for the management of patients with COVID-19 from World Health Organization guide (available in March 13, 2020). Results: Seventeen studies were included, in which 143 clinical samples were identified (38 of amniotic fluid; 34 of placentas or membranes; 39 from umbilical cord blood and 32 from human milk). Among the 143 samples, nine were positive for SARS-CoV-2 RNA (one amniotic fluid sample obtained before rupturing the membranes; six samples of placenta or membranes, although authors indicate the possibility of contamination by maternal blood in three of these, and two samples of human milk). Conclusions: Following our search criteria, we found no studies that demonstrate the detection of SARS-CoV-2, in conjunction with viral isolation and the evaluation of the infective capacity of viral particles, in clinical samples of amniotic fluid, placenta or membranes, umbilical cord blood and human milk, from women with a confirmed or clinical diagnosis of COVID-19. However, vertical transmission cannot be ruled out, larger studies are required that ideally locate in situ RNA and protein of SARS-CoV-2, as well as isolation that demonstrate the infective capacity of the viral particles.


“I have beard permission for all the patients!”


title: Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV)

text: Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.


title: Minimally invasive urologic surgery is safe during COVID-19: experience from two high-volume centers in Italy

text: Potential risks of COVID-19 spread during minimally invasive procedures caused several concerns among surgeons, despite the lack of high-level evidence. Urological robotic and laparoscopic surgery is performed in elective setting in almost all occasions, thus allowing adequate planning and stratification. Two high-volume urological centers in Italy performed 77 robotic and laparoscopic surgeries during the “lockdown” period and adopted various strategies to prevent contamination. First of all, all patients were tested negative with nasopharyngeal swab before the surgical intervention. Patients and personnel were provided adequate personal protective equipment and intraoperative strategies to prevent smoke formation and pneumoperitoneum spread were adopted. No patients nor staff members tested positive for COVID-19 during a 15-day follow-up period. In conclusion, minimally invasive urologic surgery can be safely performed during the pandemic period with adequate planning. We believe that renouncing the benefits of it would be counterproductive, especially in a scenario of long-lasting cohabitation with the virus.


title: Using heat to kill SARS‐CoV‐2

text: The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS‐CoV‐2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.


title: In der Pandemie: Wo sind all die Herzinfarkte geblieben?

text: Berichte über besorgniserregende Rückgänge bei den Klinikaufnahmen von Patienten mit akutem Herzinfarkt nehmen in der COVID-19-Pandemie zu.


title: Olfactory and taste disorders in COVID-19: a systematic review()()

text: INTRODUCTION: The SARS-CoV-2 virus causes COVID-19, and it is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The classic symptoms of the disease have been well defined by the World Health Organization; however, olfactory/gustatory disorders have been reported in some studies, but there are still several missing points in the understanding and in the consensus about the clinical management of these cases. OBJECTIVE: To identify evidence in the scientific literature about olfactory/gustatory disorders, their clinical presentation, prevalence and possible specific treatments associated with COVID-19. METHODS: A systematic review of articles published up to April 25, 2020 was performed in Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus and Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine and Reasearch Gate. Inclusion criteria: (1) Studies on patients with COVID-19; (2) Records of COVID-19 signs/symptoms, and olfactory/gustatory functions. Exclusion criteria: (1) Studies on non-human coronavirus; (2) Review articles; (3) Experimental studies (in animals or in vitro); (4) Olfactory/gustatory disorders initiated prior to SARS-CoV-2 infection. The risk assessment of bias of the selected studies was performed using the Newcastle-Ottawa scale. RESULTS: Six articles from the 1788 records met the inclusion criteria and were analyzed. A total of 1457 patients of different ethnicities were assessed; of them, 885 (60.7%) and 822 (56.4%) had smell and taste disorders, respectively, with women being most often affected. There were olfactory/gustatory disorders even without nasal obstruction/rhinorrhea and beginning even before the signs/symptoms of COVID-19; the recovery of smell/taste, when it occurs, usually happened in the first two weeks after COVID-19 resolution. There is evidence that olfactory/gustatory disorders are strong predictors of infection by SARS-CoV-2, and it is possible to recommend patient isolation, as early as of the medical consultation, preventing the spread of the virus. No scientific evidence has been identified for effective treatments for any of the disorders. CONCLUSION: Olfactory/gustatory disorders may occur at varying intensities and prior to the general symptoms of COVID-19 and should be considered as part of the clinical features of COVID-19, even in mild cases. There is still no scientific evidence of specific treatments for such disorders in COVID-19 disease.


title: Zinc Deficiency‐Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency

text: BACKGROUND: Zinc deficiency‐like (ZDL) syndrome is an inherited defect of Fleckvieh calves, with striking similarity to bovine hereditary zinc deficiency (BHZD). However, the causative mutation in a phospholipase D4 encoding gene (PLD4) shows no connection to zinc metabolism. OBJECTIVES: To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype. ANIMALS: Nine hospitalized calves with crusting dermatitis and confirmed mutation in PLD4 and medical records from 25 calves with crusting dermatitis or suspected zinc deficiency. METHODS: Prospective and retrospective case series. RESULTS: The 9 calves (age: 5–53 weeks) displayed a moderate to severe crusting dermatitis mainly on the head, ventrum, and joints. Respiratory and digestive tract inflammations were frequently observed. Zinc supplementation did not lead to remission of clinical signs in 4 calves. Laboratory variables revealed slight anemia in 8 calves, hypoalbuminemia in 6 calves, but reduced serum zinc concentrations in only 3 calves. Mucosal erosions/ulcerations were present in 7 calves and thymus atrophy or reduced thymic weights in 8 calves. Histologically, skin lesions were indistinguishable from BHZD. Retrospective analysis of medical records revealed the presence of this phenotype since 1988 and pedigree analysis revealed a common ancestor of several affected calves. CONCLUSIONS AND CLINICAL IMPORTANCE: ZDL syndrome should be suspected in Fleckvieh calves with crusting dermatitis together with diarrhea or respiratory tract inflammations without response to oral zinc supplementation. Definite diagnosis requires molecular genetic confirmation of the PLD4 mutation.


docid: oxybanjl

title: Viromimetic STING Agonist‐Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus

text: The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.


title: The evolving field of biodefence: therapeutic developments and diagnostics

text: The threat of bioterrorism and the potential use of biological weapons against both military and civilian populations has become a major concern for governments around the world. For example, in 2001 anthrax-tainted letters resulted in several deaths, caused widespread public panic and exerted a heavy economic toll. If such a small-scale act of bioterrorism could have such a huge impact, then the effects of a large-scale attack would be catastrophic. This review covers recent progress in developing therapeutic countermeasures against, and diagnostics for, such agents.


title: Porcine epidemic diarrhea virus S1 protein is the critical inducer of apoptosis

text: BACKGROUND: Porcine Epidemic Diarrhea (PED) is an acute and highly contagious enteric disease caused by PED virus (PEDV), characterized by vomitting, watery diarrhea and fatal dehydration with high mortality in sucking piglets of one week of age. Although PEDV induced cell apoptosis has been established in vitro and in vivo, the functional protein that contributes to this event remains unclear. METHODS: The activation or cleavage of main apoptosis-associated molecular such as AIFM1, caspase-3, caspase-8, caspase-9 and PARP in PEDV infected host cells were analyzed by western blotting. The nuclear change of infected cell was monitored by confocal immunofluorescence assay. The overexpressing plasmids of 16 non-structural proteins (Nsp1–16) and 6 structural proteins (M, N, E, ORF3, S1 and S2) were constructed by cloning. Cell apoptosis induced by PEDV or overexpression non-structural or structural proteins was measured by the flow cytometry assay. RESULTS: PEDV could infect various host cells including Vero, Vero-E6 and Marc-145 and cause obvious cytopathic effects, including roundup, cell fusion, cell membrane vacuolation, syncytium formation and cause apparent apoptosis. In infected cells, PEDV-induced apoptosis is accompanied by nuclear concentration and fragmentation as a result of caspase-3 and caspase-8 activation and AIFM1 and PARP cleavage. Overexpression of S1 Spike protein of PEDV SM98 strain effectively induced host cell apoptosis, while the expression of the other non-structure proteins (Nsp1–16) and structural proteins (M, N, E, S2 and ORF3) has no or less effect on cell apoptosis. Similarly, expression of S1 protein from wild-type strain BJ2011 or cell-adapted strain CV777, also induce apoptosis in transfected cells. Finally, we demonstrated that the S1 proteins from various coronavirus family members such as TGEV, IBV, CCoV, SARS and MERS could also induce Vero-E6 cells apoptosis. CONCLUSION: S1 Spike protein is one of the most critical functional proteins that contribute to cell apoptosis. Expression of S1 proteins of the coronavirus tested in this study could all induce cell apoptosis suggesting S1 maybe is an effective inducer in Coronavirus-induced cell apoptosis and targeting S1 protein expression probably is a promising strategy to inhibit coronavirus infection and thus mediated apoptosis on host cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1078-4) contains supplementary material, which is available to authorized users.


title: Host-directed therapies for bacterial and viral infections

text: Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2017.162) contains supplementary material, which is available to authorized users.


Role modelling and active apprenticeship during the COVID‐19 pandemic


title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension?

text: PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. RECENT FINDINGS: In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. SUMMARY: From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.


title: History of the HIV Epidemic in China

text: PURPOSE OF REVIEW: This study aims to review the history of the human immunodeficiency virus (HIV) infection epidemic in China. RECENT FINDINGS: The HIV infection epidemic in China has evolved significantly over the past 35 years, from initially exclusively within people who inject drugs (PWID), to outbreaks due to plasma collection contamination in the mid-1990s, to now almost exclusive transmission via sexual contact. The number of newly-diagnosed cases and the number HIV-related deaths have increased each year since 2004, coinciding with a massive scale-up of both HIV testing and antiretroviral therapy initiation. The proportion of cases diagnosed later in their disease progression has remained constant. SUMMARY: The initial outbreaks of HIV across China were identified quickly and the overall trends have been monitored. While the HIV epidemic among PWID has been well managed, the growing HIV epidemic via sexual contact has grown more complex and even more difficult to control.


title: Proprotein convertases: Key players in inflammation-related malignancies and metastasis

text: Abstract Many cancers occur from locations of inflammation due to chronic irritation and/or infection. Tumor microenvironment contains various different inflammatory cells and mediators that orchestrate diverse neoplastic processes, including proliferation, survival, adhesion and migration. In parallel, tumor cells have adapted some of the signaling molecules used by inflammatory cells, such as selectins and chemokines as well as their receptors for invasion, extravasation and subsequently metastasis. Expression and/or activation of the majority of these molecules is mediated by the proprotein convertases (PCs); proteases expressed by both tumor cells and inflammatory cells. This review analyzes the potential role of these enzymatic system in inflammation-associated cancer impacting on the malignant and metastatic potential of cancer cells, describing the possible use of PCs as a new anti-inflammatory therapeutic approach to tumor progression and metastasis.


title: Endosomal association of a protein phosphatase with high dephosphorylating activity against a coronavirus nucleocapsid protein

text: Abstract On the assumption that dephosphorylation of the neurotropic coronavirus JHM (JHMV) nucleocapsid protein (N) may be connected with initiation of the infectious cycle we searched for a relevant host enzyme activity. Analysis of subcellular fractions from L-2 murine fibroblasts, separated by dual Percoll density gradients, revealed the presence of a phosphoprotein phosphatase (PPPase), co-sedimenting with the endososomal/prelysosomal material, which possesses high activity against N. With purified [22P]N as substrate it was demonstrated that this PPPase, distinguishable from acid and alkaline phosphatases, acts optimally at neutral pH in the presence of Mn2+ following treatment with a detergent. Complete inhibition with okadaic acid at 0.9–4.5 μM but not at 1–10 nM relegates this PPase to a type I protein phosphatase. Similar PPPase activity for N was present in the endosome fraction of a rat Roc-1 astrocytoma-oligodendrocyte cell line and in homogenates of brain and cultured oligodendrocytes. Our data suggest that the phosphorylated N of the inoculum may be modified by the endosomal PPPase in host cells, including those from the CNS so as to facilitate the JHMV infectious process.


title: COVID‐19: how it can look on the skin. Clinical and pathological features in twenty COVID‐19 patients observed in Bologna, northeastern Italy

text: Global public health is currently dealing with the explosive spread of the novel Coronavirus disease 2019 (COVID‐19) [1]. This new type of viral pneumonia, spread from its first focus in Wuhan (Hubei, China) to across all the world, until a pandemic condition was declared. Clinically. the most common symptoms of the disease are cough and fever. More than 80% of patients have asymptomatic to moderate disease, but about 15% get severe pneumonia and 5% develope a multi‐organ failure [2].


Emergency Medical System calls during Italy’s COVID-19 lockdown.


title: Lack of association between HLA‐A, ‐B and ‐DRB1 alleles and the development of SARS: a cohort of 95 SARS‐recovered individuals in a population of Guangdong, southern China

text: Severe acute respiratory syndrome (SARS), caused by infection with a novel coronavirus (SARS‐CoV), was the first major novel infectious disease at the beginning of the 21st century, with China especially affected. SARS was characterized by high infectivity, morbidity and mortality, and the confined pattern of the disease spreading among the countries of South‐East and East Asia suggested the existence of susceptible factor(s) in these populations. Studies in the populations of Hong Kong and Taiwan showed an association of human leucocyte antigen (HLA) polymorphisms with the development and/or severity of SARS, respectively. The aim of the present study was to define the genotypic patterns of HLA‐A, ‐B and ‐DRB1 loci in SARS patients and a co‐resident population of Guangdong province, southern China, where the first SARS case was reported. The samples comprised 95 cases of recovered SARS patients and 403 unrelated healthy controls. HLA ‐A, ‐B and ‐DRB1 alleles were genotyped using polymerase chain reaction with sequence‐specific primers. The severity of the disease was assessed according to the history of lung infiltration, usage of assisted ventilation and occurrence of lymphocytopenia. Although the allelic frequencies of A23, A34, B60, DRB1*12 in the SARS group were slightly higher, and A33, ‐B58 and ‐B61 were lower than in the controls, no statistical significance was found when the Pc value was considered. Similarly, no association of HLA alleles with the severity of the disease was detected. Thus, variations in the major histocompatibility complex are unlikely to have contributed significantly to either the susceptibility or the severity of SARS in the population of Guangdong.


title: Restriction fragment length polymorphism analysis of open reading frame 5 gene of porcine reproductive and respiratory syndrome virus isolates in Korea

text: The genetic variability of porcine reproductive and respiratory syndrome virus (PRRSV) was studied by restriction fragment length polymorphism (RFLP) of polymerase chain reaction (PCR)-amplified fragments among 50 Korean isolates from open reading frame 5. All Korean PRRSVs were isolated from the field cases after the marketing of an U.S. ATCC VR2332-derived modified live PRRSV vaccine. Combining the restriction enzyme digestion patterns obtained with MluI, HincII, SacII, and HaeIII, we observed 19 distinct RFLP patterns. Seventeen out of 50 PRRSV isolates (34%) exhibited the modified live PRRSV vaccine RFLP pattern. The genomic variations that have been identified in the present study seemed to represent characteristic features of the Korean PRRSV isolates. PCR-based RFLP analysis using several restriction enzymes provides a good genetic estimate for isolate differentiation.


title: The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study

text: OBJECTIVES: This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. METHODS: A retrospective epidemiological approach was used where data was obtained from the department of pathology registry files and pathology reports. The records of all patients registered from January 2005 to December 2014 with a diagnosis of primary CNS tumor (brain and spinal cord) were selected. Data about sex, age, tumor location, and histologic type were collected. The classification was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3). RESULTS: Nine hundred and ninety-two (992) cases of primary CNS tumors throughout the ten years (2005 to 2014) were reviewed. There were 714 (71.97%) adults and 278 (28.02%) in the pediatric age group. Nonmalignant tumors dominated the adult population (60.08%) while malignant tumors were more frequent in the pediatric population. Gliomas constituted the most common neoplastic category in children and adults. The most common single tumor entity was meningioma (26.99%, ICD-O-3 histology codes 9530/0, 9539/1, and 9530/3). Medulloblastomas (ICD-O-3 histology codes 9470, 9471, and 9474) were the most common single tumor entity in the pediatric age group (26.62%). CONCLUSIONS: This is an institution-based, detailed, and descriptive epidemiological study of patients with primary CNS tumors in Saudi Arabia. In contrast to other regional and international studies, the medulloblastomas in our institution are more frequent than pilocytic astrocytomas. Limitations to our study included the referral bias and histology-based methodology.


title: «Suspects» in Etiology of Endemic Nephropathy: Aristolochic Acid versus Mycotoxins

text: Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T®T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed.


title: Shared Common Ancestry of Rodent Alphacoronaviruses Sampled Globally

text: The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.


title: Bovine Respiratory Disease Diagnosis: What Progress Has Been Made in Infectious Diagnosis?

text: When it is desired to identify infectious agents involved in an outbreak of bovine respiratory disease, a variety of possible sampling methods may be used. For field use, the deep nasopharyngeal swab, transtracheal wash, and nonendoscopic bronchoalveolar lavage are most feasible. At present, bacterial culture and polymerase chain reaction testing are most commonly used to identify infectious agents. Interpretation of test results can be challenging, particularly for opportunistic pathogens. Evidence-based guidelines for precise interpretation of microbiologic tests results are lacking; however, approaches that have been practically useful for the management of bovine respiratory disease outbreaks are presented.


title: A novel human enterovirus C (EV-C118) identified in two children hospitalised because of acute otitis media and community-acquired pneumonia in Israel

text: Abstract We report the discovery of a novel enterovirus C (EV-C118) identified in two Israeli children hospitalised for acute otitis media and community-acquired pneumonia. The highest pair-wise sequence identity scores with the EV-C109 and EV-C117 reference strains were, respectively, 63.5% and 63.6% nucleotide identity, and 82.5% and 79.9% amino acid identity.


title: Interrupting COVID-19 transmission by implementing enhanced traffic control bundling: Implications for global prevention and control efforts

text: Abstract We argue that enhanced Traffic Control Bundling (eTCB) can interrupt the community-hospital-community transmission cycle, thereby limiting COVID-19’s impact. Enhanced TCB is an expansion of the traditional TCB that proved highly effective during Taiwan’s 2003 SARS outbreak. TCB’s success derived from ensuring that Health Care Workers (HCWs) and patients were protected from fomite, contact and droplet transmission within hospitals. Although TCB proved successful during SARS, achieving a similar level of success with the COVID-19 outbreak requires adapting TCB to the unique manifestations of this new disease. These manifestations include asymptomatic infection, a hyper-affinity to ACE2 receptors resulting in high transmissibility, false negatives, and an incubation period of up to 22 days. Enhanced TCB incorporates the necessary adaptations. In particular, eTCB includes expanding the TCB transition zone to incorporate a new sector – the quarantine ward. This ward houses patients exhibiting atypical manifestations or awaiting definitive diagnosis. A second adaptation involves enhancing the checkpoint hand disinfection and gowning up with Personal Protective Equipment deployed in traditional TCB. Under eTCB, checkpoint hand disinfection and donning of face masks are now required of all visitors who seek to enter hospitals. These enhancements ensure that transmissions by droplets, fomites and contact are disrupted both within hospitals and between hospitals and the broader community. Evidencing eTCB effectiveness is Taiwan’s success to date in containing and controlling the community-hospital-community transmission cycle.


title: Chapter 3 Viral Emerging Pathogen Evolution

text: Abstract The emergence of emerging and reemerging infectious diseases throughout history has been the product of the interaction of infectious agents, immunity, selective pressure, and environmental factors. The origin of the viral ancestors remains controversial, the debate remains whether the viruses existed before their host cells, evolved as molecular structures that adapted to the intracellular development or of the cells that infected or housed them as hosts. The nature of the viruses could propose a hypothetical evolutionary model based on the way they parasitize cells and the way they fuse with their host cells. So far there are no “universal” viral genes that have not allowed the hypotheses of the “common viral ancestor” to be conclusive. Insects have a special role in understanding viral evolution and how they became pathogens, suggesting a coevolutionary scenario of colonization that would initially allow the survival of viruses and later an ecological niche required for the cycle of virus replication. The coevolution of viruses and defense systems of hosts represents a fundamental role in the evolution of both viruses and host cells, a kind of arms race between viruses and hosts, and the deescalation of that war could explain the coexistence of viruses and hosts. Viruses are playing an important role in the understanding of cell evolution and have earned the right to be included in the tree of life. The aim of this chapter is to review the viral evolution and the insects as host.


docid: bmsxoiuy

title: Ventilación mecánica no invasiva y oxigenoterapia de alto flujo en la pandemia COVID-19: el valor de un empate


1 Category Definitions


Prey in Heroes’ Capes


title: Update on Vaccine-Derived Poliovirus Outbreaks — Worldwide, July 2019–February 2020

text: Circulating vaccine-derived polioviruses (cVDPVs) can emerge in areas with low poliovirus immunity and cause outbreaks* of paralytic polio (1-5). Among the three types of wild poliovirus, type 2 was declared eradicated in 2015 (1,2). The use of trivalent oral poliovirus vaccine (tOPV; types 1, 2, and 3 Sabin strains) ceased in April 2016 via a 1-month-long, global synchronized switch to bivalent OPV (bOPV; types 1 and 3 Sabin strains) in immunization activities (1-4). Monovalent type 2 OPV (mOPV2; type 2 Sabin strain) is available for cVDPV type 2 (cVDPV2) outbreak response immunization (1-5). The number and geographic breadth of post-switch cVDPV2 outbreaks have exceeded forecasts that trended toward zero outbreaks 4 years after the switch and assumed rapid and effective control of any that occurred (4). New cVDPV2 outbreaks have been seeded by mOPV2 use, by both suboptimal mOPV2 coverage within response zones and recently mOPV2-vaccinated children or contacts traveling outside of response zones, where children born after the global switch are fully susceptible to poliovirus type 2 transmission (2-4). In addition, new emergences can develop by inadvertent exposure to Sabin OPV2-containing vaccine (i.e., residual response mOPV2 or tOPV) (4). This report updates the January 2018-June 2019 report with information on global cVDPV outbreaks during July 2019-February 2020 (as of March 25, 2020)† (2). Among 33 cVDPV outbreaks reported during July 2019-February 2020, 31 (94%) were cVDPV2; 18 (58%) of these followed new emergences. In mid-2020, the Global Polio Eradication Initiative (GPEI) plans to introduce a genetically stabilized, novel OPV type 2 (nOPV2) that has a lower risk for generating VDPV2 than does Sabin mOPV2; if nOPV2 is successful in limiting new VDPV2 emergences, GPEI foresees the replacement of Sabin mOPV2 with nOPV2 for cVDPV2 outbreak responses during 2021 (2,4,6).


title: Response to ‘the association between D‐dimer in COVID‐19 patients and mortality remains beset of uncertainties’

text: We appreciate the opportunity to respond Dr. Gris and colleagues who still have doubts about the predictive of D‐dimer in COVID‐19[1, 2]. We totally understand the concerns from Dr. Gris and colleagues who just want to manage their patients better. We are trying to explain the potential influence factors here, hope to provide any useful information for managing the COVID‐19 patients.


title: Silver Nanoparticles as Potential Antiviral Agents

text: Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.


title: Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia

text: BACKGROUND: Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated. OBJECTIVES: The aim of this study was to investigate the occurrence of viral co‐infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co‐infections. ANIMALS: Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB). METHODS: Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays. RESULTS: CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co‐infection. CONCLUSION AND CLINICAL IMPORTANCE: Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co‐infection.


title: Surveillance for severe acute respiratory infections in Southern Arizona, 2010–2014

text: BACKGROUND: The Binational Border Infectious Disease Surveillance program began surveillance for severe acute respiratory infections (SARI) on the US–Mexico border in 2009. Here, we describe patients in Southern Arizona. METHODS: Patients admitted to five acute care hospitals that met the SARI case definition (temperature ≥37·8°C or reported fever or chills with history of cough, sore throat, or shortness of breath in a hospitalized person) were enrolled. Staff completed a standard form and collected a nasopharyngeal swab which was tested for selected respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: From October 2010–September 2014, we enrolled 332 SARI patients. Fifty‐two percent were male and 48% were white non‐Hispanic. The median age was 63 years (47% ≥65 years and 5·2% <5 years). During hospitalization, 51 of 230 (22%) patients required intubation, 120 of 297 (40%) were admitted to intensive care unit, and 28 of 278 (10%) died. Influenza vaccination was 56%. Of 309 cases tested, 49 (16%) were positive for influenza viruses, 25 (8·1%) for human metapneumovirus, 20 (6·5%) for parainfluenza viruses, 16 (5·2%) for coronavirus, 11 (3·6%) for respiratory syncytial virus, 10 (3·2%) for rhinovirus, 4 (1·3%) for rhinovirus/enterovirus, 3 (1·0%) for enteroviruses, and 3 (1·0%) for adenovirus. Among the 49 influenza‐positive specimens, 76% were influenza A (19 H3N2, 17 H1N1pdm09, and 1 not subtyped), and 24% were influenza B. CONCLUSION: Influenza viruses were a frequent cause of SARI in hospitalized patients in Southern Arizona. Monitoring respiratory illness in border populations will help better understand the etiologies. Improving influenza vaccination coverage may help prevent some SARI cases.


title: Lessons from the Severe Acute Respiratory Syndrome Outbreak in Hong Kong

text: Severe acute respiratory syndrome (SARS) is now a global public health threat with many medical, ethical, social, economic, political, and legal implications. The nonspecific signs and symptoms of this disease, coupled with a relatively long incubation period and the initial absence of a reliable diagnostic test, limited the understanding of the magnitude of the outbreak. This paper outlines our experience with public health issues that have arisen during this outbreak of SARS in Hong Kong. We confirmed that case detection, reporting, clear and timely dissemination of information, and strict infection control measures are essential in handling such an infectious disease outbreak. The need for an outbreak response unit is crucial to combat any future outbreak.


Difficulties faced by sexual and gender minorities during Covid 19 crisis


title: Guidance on the management of Diabetic Ketoacidosis in the exceptional circumstances of the COVID‐19 pandemic

text: During the early stages of the COVID‐19 pandemic, hospitals in London, the UK epicentre, reported an unusually high number of people presenting with COVID‐19 disease developing diabetic ketoacidosis, hyperosmolar hyperglycaemic state, or a combination of both. Very high doses of insulin were often needed to manage the hyperglycaemia. It has been proposed that these metabolic disturbances may result from severe insulin resistance combined with decreased insulin secretion due to beta cell dysfunction.


title: Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission

text: BACKGROUND AND OBJECTIVE: Infection is as an important trigger for acute asthma and chronic obstructive pulmonary disease (COPD). The aim of this article was to determine the prevalence and impact of virus and bacterial infections in acute asthma and COPD. METHODS: Subjects were recruited, within 24 h of hospital admission for acute exacerbations of asthma and COPD. Nose/throat swabs and sputum samples were collected and examined by multiplex polymerase chain reaction for respiratory viruses and cultured for bacteria. The primary outcomes were length of stay (LOS) and readmission to hospital within 60 days. RESULTS: A total of 199 subjects were recruited (96 had asthma and 103 COPD) for 235 events (36 re‐presented). A virus was detected in 79 subjects (40%), bacteria in 41 (21%), and of these, 18 had both. Rhinovirus A was the most frequently isolated virus. A multivariate analysis was performed to control for confounders. It found that detection of a virus, a virus and bacteria, forced expiratory volume in 1 s (FEV(1)) and a diagnosis of COPD were all independent predictors of prolonged LOS, while risk of readmission within 60 days was increased with virus infection alone, virus and bacterial infection, lower FEV(1) and current smoking. CONCLUSIONS: Virus infection, especially in the presence of chronic bacterial infection, is an important determinant of more severe acute exacerbations in both asthma and COPD, and patients with co‐infections are more likely to be readmitted to hospital following their exacerbation.


title: Spatio-Temporal Analysis of Infectious Diseases

text: Epidemiological research on the pathogenesis, diagnosis, and treatment of infectious diseases is a broad field of study with renewed validity in the face of social changes and new threats [...].


title: Molecular cloning and sequence determination of the peplomer protein gene of feline infectious peritonitis virus type I

text: cDNA clones spanning the entire region of the peplomer (S) gene of feline infectious peritonitis virus (FIPV) type I strain KU-2 were obtained and their complete nucleotide sequences were determined. A long open reading frame (ORF) encoding 1464 amino acid residues was found in the gene, which was 12 residues longer than the ORF of the FIPV type II strain 79–1146. The sequences of FIPV type I and mainly FIPV type II were compared. The homologies at the N- (amino acid residues 1–693) and C- (residues 694–1464) terminal halves were 29.8 and 60.7%, respectively. This was much lower than that between FIPV type II and other antigenically related coronaviruses, such as transmissible gastroenteritis virus of swine and canine coronavirus. This supported the serological relatedness of the viruses and confirmed that the peplomer protein of FIPV type I has distinct structural features that differ from those of antigenically related viruses.


title: Dispatches from the Frontlines: A Critical Care Nurse's Response to COVID19

text: Abstract The emergency alert that appeared on my phone read “SCDU Activation,” indicating Emory University Hospital's Serious Communicable Diseases Unit had just been pulled into the battle against COVID-19. As part of this unit,I've donned PPE and participated in countless training exercises, and prepared other clinicians to safely care for people with highly pathogenic infectious diseases.What followed the activation alert, however, was a dynamic interplay between deliberate biosafety methodologies and rapid, reflexive critical care interventions as my teammates and I navigated a novel, burgeoning health threat that called for a whole-system response.As this pandemic continues to exact a grave toll on healthcare workers, our families and our communities, politicians have asked, “How could we have seen this coming?” “As a pandemic preparedness researcher, my question to them is, “How could you not have seen this coming?” This perspective piece argues that despite the many missed opportunities to prepare for this crisis, the greatest opportunities lie ahead of us if we choose today to invest in pandemic preparedness for tomorrow.


title: Phylogeny and prevalence of kobuviruses in dogs and cats in the UK

text: Abstract The kobuviruses represent an emerging genus in the Picornaviridae. Here we have used next generation sequencing and conventional approaches to identify the first canine kobuvirus (CaKoV) from outside the USA. Phylogenetic analysis suggests that a single lineage genotype of CaKoV now exists in Europe and the USA with 94% nucleotide similarity in the coding region. CaKoV was only identified in a single case from a case–control study of canine diarrhoea, suggesting this virus was not a frequent cause of disease in this population. Attempts to grow CaKoV in cell culture failed. Sequence analysis suggested CaKoV was distinct from human Aichi virus (AiV), and unlikely to pose a significant zoonotic risk. Serosurveys by ELISA, immunofluorescence and neutralisation tests, using AiV as antigen, suggested kobuvirus infection is prevalent in dogs. In addition, IgG antibody to AiV was also detected in cat sera, indicating for the first time that cats may also be susceptible to kobuvirus infection.


title: Effect of the Fat Eaten at Breakfast on Lipid Metabolism: A Crossover Trial in Women with Cardiovascular Risk

text: Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased β-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.


title: Sequence analysis of infectious bronchitis virus isolates from the 1960s in the United States

text: To better understand the molecular epidemiology of infectious bronchitis virus (IBV) in the United States following the introduction of commercial IBV vaccines, we sequenced the S1 and N structural protein genes of thirteen IBV field isolates collected in the 1960s. Analysis of the S1 sequence showed that seven isolates were of the Massachusetts (Mass) genotype, five were SE17, and one was of the Connecticut (Conn) genotype, suggesting that these three IBVs were circulating in commercial poultry raised in different regions in the United States during the 1960s. The S1 genes of Mass-type isolates had high levels of sequence variation, representing 81.3-81.9 % nucleotide (nt) and 77.3-78.7 % amino acid (aa) identity when compared to those of the SE17-type isolates. In contrast, the N genes from the same isolates were less variable (>92 % nt and >93 % aa identity) when compared to those of the SE17-type isolates. Phylogenetic analysis based on the S1 gene indicated that one isolate (L748) was more closely related to the Mass type. In contrast, phylogenetic analysis based on the N gene showed that L748 was more closely related to the SE17 type, indicating that there had been exchange of S1 genetic materials between Mass- and SE17-like viruses. In addition, the Mass-type isolates had high levels of sequence identity in the S1 gene compared with widely used modified live vaccines (Mass41, Ma5 and H120) and modern field strains from the USA and other countries, suggesting a common ancestor. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-012-1500-y) contains supplementary material, which is available to authorized users.