title: Current progress in antiviral strategies

text: The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. Virus-targeting antivirals can function directly or indirectly to inhibit the biological functions of viral proteins, mostly enzymatic activities, or to block viral replication machinery. Host-targeting antivirals target the host proteins that are involved in the viral life cycle, regulating the function of the immune system or other cellular processes in host cells. Here we review key targets and considerations for the development of both antiviral strategies.


title: A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein

text: The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection.


title: COVID-19: FAQs—Congenital Heart Surgery Recovery and Defining a “New Normal”

text: As recovery of congenital heart surgery programs begins during this COVID-19 pandemic, we review key considerations such as screening, protection of patients and health care workers (HCWs), case prioritization, barriers to reactivation, redesign of patient care teams, contribution of telemedicine, modification of trainees’ experiences, preparation for potential resurgence, and strategies to maintain HCW wellness. COVID-19 has tested the resolve and grit of our specialty and we have an opportunity to emerge more refined.


title: Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus

text: Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.


title: Virocidal activity of Egyptian scorpion venoms against hepatitis C virus

text: BACKGROUND: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. METHODS: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. RESULTS: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC(50)) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. CONCLUSIONS: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.


Update on possible animal sources for COVID‐19 in humans


title: Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic – Rapid Review

text: Abstract The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.


COVID-19: Is Everything Appropriate to Create an Effective Vaccine?


title: Induction of Atypical Autophagy by Porcine Hemagglutinating Encephalomyelitis Virus Contributes to Viral Replication

text: Autophagy is a basic biological metabolic process involving in intracellular membrane transport pathways that recycle cellular components and eliminate intracellular microorganisms within the lysosome. Autophagy also plays an important part in virus infection and propagation. However, some pathogens, including viruses, have evolved unique trick to escape or exploit autophagy. This study explores the mechanism of autophagy induction by porcine hemagglutinating encephalomyelitis virus (PHEV) in Neuro-2a cells, and examines the role of autophagy in PHEV replication. PHEV triggered autophagy in Neuro-2a cells is dependent on the presence of bulk double- or single-membrane vacuoles, the accumulation of GFP-LC3 fluorescent dots, and the LC3 lipidation. In addition, PHEV induced an incomplete autophagic effect because the degradation level of p62 did not change in PHEV-infected cells. Further validation was captured using LysoTracker and lysosome-associated membrane protein by indirect immunofluorescence labeling in PHEV-infected cells. We also investigated the change in viral replication by pharmacological experiments with the autophagy inducer rapamycin or the autophagy inhibitor 3-MA, and the lysosomal inhibitor chloroquine (CQ). Suppression of autophagy by 3-MA increased viral replication, compared with the mock treatment, while promoting of autophagy by rapamycin reduced PHEV replication. CQ treatment enhanced the LC3 lipidation in PHEV-infected Neuro-2a cells but lowered PHEV replication. These results show that PHEV infection induces atypical autophagy and causes the appearance of autophagosomes but blocks the fusion with lysosomes, which is necessary for the replication of PHEV in nerve cells.


title: Inhalation delivery technology for genome-editing of respiratory diseases

text: The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system has significant therapeutic potentials for lung congenital diseases such as cystic fibrosis, as well as other pulmonary disorders like lung cancer and obstructive diseases. Local administration of CRISPR/Cas9 therapeutics through inhalation can achieve high drug concentration and minimise systemic exposure. While the field is advancing with better understanding on the biological functions achieved by CRISPR/Cas9 systems, the lack of progress in inhalation formulation and delivery of the molecule may impede their clinical translation efficiently. This forward-looking review discussed the current status of formulations and delivery for inhalation of relevant biologics such as genes (plasmids and mRNAs) and proteins, emphasising on their design strategies and preparation methods. By adapting and optimising formulation strategies used for genes and proteins, we envisage that development of inhalable CRISPR/Cas9 liquid or powder formulations for inhalation administration can potentially be fast-tracked in near future.


Reply to: Skin damage among healthcare workers managing coronavirus disease-2019


Q&A: Antibiotic resistance: where does it come from and what can we do about it?


title: Utilitarianism and the Pandemic

text: There are no egalitarians in a pandemic. The scale of the challenge for health systems and public policy means that there is an ineluctable need to prioritise the needs of the many. It is impossible to treat all citizens equally, and a failure to carefully consider the consequences of actions could lead to massive preventable loss of life. In a pandemic there is a strong ethical need to consider how to do most good overall. 1. Triage: which patients should receive access to a ventilator if there is overwhelming demand outstripping supply? 2. Lockdown: How should countries decide when to implement stringent social restrictions, balancing preventing deaths from COVID‐19 with causing deaths and reducing in wellbeing from other causes? Our aim is not to argue that utilitarianism is the only relevant ethical theory, or in favour of a purely utilitarian approach. However, clearly considering which options will do the most good overall will help societies identify and consider the necessary cost of other values. Societies may choose either to embrace or not to embrace the utilitarian course, but with a clear understanding of the values involved and the price they are willing to pay.


title: Severe Acute Respiratory Syndrome (SARS) in Singapore: Clinical Features of Index Patient and Initial Contacts

text: Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease. One of the largest outbreaks of SARS to date began in Singapore in March 2003. We describe the clinical, laboratory, and radiologic features of the index patient and the patient’s initial contacts affected with probable SARS.


title: Adult learning and education as a tool to contain pandemics: The COVID-19 experience

text: In combating pandemics, more can be gained by changing citizens’ behaviours than by relying solely on the medical route. In the current COVID-19 pandemic, the struggle to contain the outbreak and push back new infection figures will ultimately be won by training citizens how to avoid creating secondary transmission chains. The COVID-19 pandemic highlights the relationship between individual behaviour and group risk. Mass training of all social strata of a country’s entire population is therefore critical in mitigating the pandemic. The authors of this article argue that adult learning and education (ALE) can play a pivotal role particularly in countries where average literacy levels are low, as these are usually the same countries in which healthcare systems are more fragile. This article explains why ALE, especially the promotion of health literacy as part of ALE (which is itself part of lifelong learning), is necessary to enable individuals to make informed health-related decisions. Research has shown that low- or non-literate individuals are less responsive to health education, less likely to use disease prevention services, and less likely to successfully manage chronic disease than literate citizens. The authors refer to the evaluation of the health literacy aspect of a large-scale adult literacy campaign launched in South Africa in 2008 which has yielded measurable outcomes and proved that the intervention had enabled adults to better understand health messages. They stress the importance of populations having at least a basic level of literacy and numeracy skills to enable them to receive and act on vital information during a pandemic or disaster. They argue that ALE should in fact be understood as an inherent element of every national emergency strategy, both in terms of prior preparation for possible future emergencies (such as pandemics, earthquakes, tornados, flooding, bushfires etc.), and in terms of reaction to a given emergency such as the current COVID-19 pandemic.


title: Real-Time Polymerase Chain Reaction for Detecting SARS Coronavirus, Beijing, 2003

text: During the 2003 severe acute respiratory syndrome (SARS) outbreak, a real-time quantitative polymerase chain reaction, which targets the nucleocapsid gene at the 3′-end of the viral genome, was established to detect and identify the SARS-associated coronavirus. We describe the use of this assay to screen >700 clinical samples.


title: COVID-19: A Call for Physical Scientists and Engineers

text: [Image: see text] The COVID-19 pandemic is one of those global challenges that transcends territorial, political, ideological, religious, cultural, and certainly academic boundaries. Public health and healthcare workers are at the frontline, working to contain and to mitigate the spread of this disease. Although intervening biological and immunological responses against viral infection may seem far from the physical sciences and engineering that typically work with inanimate objects, there actually is much that can—and should—be done to help in this global crisis. In this Perspective, we convert the basics of infectious respiratory diseases and viruses into physical sciences and engineering intuitions, and through this exercise, we present examples of questions, hypotheses, and research needs identified based on clinicians’ experiences. We hope researchers in the physical sciences and engineering will proactively study these challenges, develop new hypotheses, define new research areas, and work with biological researchers, healthcare, and public health professionals to create user-centered solutions and to inform the general public, so that we can better address the many challenges associated with the transmission and spread of infectious respiratory diseases.


title: Identification of porcine circovirus type 2 in retrospective cases of pigs naturally infected with porcine epidemic diarrhoea virus

text: Abstract The identification of porcine circovirus type 2 (PCV2) was studied in fresh intestinal tissues by polymerase chain reaction (PCR) and in formalin-fixed, paraffin-wax-embedded intestinal tissues by in situ hybridisation. The tissues came from pigs naturally infected with porcine epidemic diarrhoea virus (PEDV). A total of 35 (32.7%) of 107 small intestinal samples from pigs naturally infected with PEDV were found to be positive using PCR. Positive signals for PCV2 were detected in 32 (29.9%) of 107 small intestinal samples from pigs naturally infected with PEDV by in situ hybridisation. The distribution of positive cells in the jejunum and ileum was multifocal or patchy. Distinct positive labelling was found throughout the lamina propria in the small intestines. The results of this study indicate that PCV2 is highly prevalent in pigs naturally infected with PEDV.


title: Prevalence of bovine viral diarrhea virus in dairy cattle herds in eastern China

text: Bovine viral diarrhea virus (BVDV) is a worldwide spreading pestivirus affecting cattle and other ruminants; however, there have been few reports on epidemiologic investigation of BVDV in eastern China. In this study, bulk tank milk from 36 herds of dairy cattle in eastern China was submitted to serological investigations, 77.8% of herds was BVDV antibody positive. Individual animal status in two herds was further investigated collecting blood samples, the positive ratio was 49.74% and 24.64%, and the average positive ratio of calves, heifers, and lactating cows was 15.94%, 40.16%, and 41.7%, respectively. Moreover, clinical survey was carried out among 8170 dairy cattle from 36 herds, for diarrhea syndrome, respiratory problems and reproductive failure, and pathogens of all clinical cattle were further investigated. The results showed that BVDV was one of the main pathogen, which infected animals combining with various other viruses. Then, nine BVDV strains were isolated; phylogenetic analysis showed that BVDV subtypes currently circulating in eastern China were BVDV 1a and BVDV 1c. In addition, out of 377 cows tested, the 1.86% detected positive to the BVDV antigen. This study provided the foundation of further study on vaccination and control strategies of BVDV in eastern China.


title: Evolutionary genetics of canine respiratory coronavirus and recent introduction into Swedish dogs

text: Abstract Canine respiratory coronavirus (CRCoV) has been identified as a causative agent of canine infectious respiratory disease, an upper respiratory infection affecting dogs. The epidemiology is currently opaque, with an unclear understanding of global prevalence, pathology, and genetic characteristics. In this study, Swedish privately-owned dogs with characteristic signs of canine infectious respiratory disease (n = 88) were screened for CRCoV and 13 positive samples (14.7%, 8.4–23.7% [95% confidence interval (CI)]) were further sequenced. Sequenced Swedish CRCoV isolates were highly similar despite being isolated from dogs living in geographically distant locations and sampled across 3 years (2013–2015). This is due to a single introduction into Swedish dogs in approximately 2010, as inferred by time structured phylogeny. Unlike other CRCoVs, there was no evidence of recombination in Swedish CRCoV isolates, further supporting a single introduction. Finally, there were low levels of polymorphisms, in the spike genes. Overall, we demonstrate that there is little diversity of CRCoV which is endemic in Swedish dogs.


title: Implementing Basic Infection Control Practices in Disaster Situations

text: Infections, troublesome in even optimal health care environments, can be a source of serious and persistent concern for local populations and health care workers during a disaster, and in austere environments such as those found in Iraq and Afghanistan. For these scenarios, it is vital to have standard infection control practices in place and to have them used consistently. Only then will healthcare workers be able to contain the potential spread of disease and improve conditions for those affected.


title: Clinical Manifestations, Laboratory Findings, and Treatment Outcomes of SARS Patients

text: Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.


title: Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays

text: Acute respiratory tract infection is a leading cause of hospital admission of children. This study used a broad capture, rapid and sensitive method (multiplex PCR assay) to detect 20 different respiratory pathogens including influenza A subtypes H1, H3, and H5; influenza B; parainfluenza types 1, 2, 3, and 4; respiratory syncytial virus (RSV) groups A and B; adenoviruses; human rhinoviruses; enteroviruses; human metapneumoviruses; human coronaviruses OC43, 229E, and SARS‐CoV; Chlamydophila pneumoniae; Legionella pneumophila; and Mycoplasma pneumoniae; from respiratory specimens of 475 children hospitalized over a 12‐month period for acute respiratory tract infections. The overall positive rate (47%) was about twice higher than previous reports based on conventional methods. Influenza A, parainfluenza and RSV accounted for 51%, and non‐cultivable viruses accounted for 30% of positive cases. Influenza A peaked at March and June. Influenza B was detected in January, February, and April. Parainfluenza was prevalent throughout the year except from April to June. Most RSV infections were found between February and September. Adenovirus had multiple peaks, whereas rhinovirus and coronavirus OC43 were detected mainly in winter and early spring. RSV infection was associated with bronchiolitis, and parainfluenza was associated with croup; otherwise the clinical manifestations were largely nonspecific. In general, children infected with influenza A, adenovirus and mixed viruses had higher temperatures. In view of the increasing concern about unexpected outbreaks of severe viral infections, a rapid multiplex PCR assay is a valuable tool to enhance the management of hospitalized patients, and for the surveillance for viral infections circulating in the community. J. Med. Virol. 81:153–159, 2009. © 2008 Wiley‐Liss, Inc.


title: Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population

text: Excessive immune response is believed to play a role in the development of severe acute respiratory syndrome (SARS). Inhomogeneous spread of SARS led one to think of an Asian genetic predisposition and contribution of human leukocyte antigen (HLA) to the disease susceptibility. However, past case-control studies showed inconsistent results. In Viet Nam, of 62 patients with SARS, 44 participated in the present study together with 103 individuals who had contact with SARS patients and 50 without contact history. HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.


title: Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus

text: To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In permissive cell lines, effects of SARS-CoV on cellular gene expression were analysed using high-density oligonucleotide arrays. Caco-2 and CL-14 cell lines were found to be highly permissive to SARS-CoV, due to the presence of angiotensin-converting enzyme 2 as a functional receptor. In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS.


Comment on “COVID-19 infection control protocol inside computed tomography suites”


title: Rapid implementation of mobile technology for real-time epidemiology of COVID-19

text: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.8 million users as of May 2, 2020. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.


title: Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways

text: BACKGROUND: Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects. METHODS: In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining. RESULTS: The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir. CONCLUSIONS: Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.


title: Transmissible gastroenteritis virus induced apoptosis in swine testes cell cultures

text: Transmissible gastroenteritis virus (TGEV) is a coronavirus which causes severe gastroenteritis and atrophy of intestinal villous epithelial cells in piglets. However, the mechanism of cell death caused by TGEV is not known. In this study, we report that TGEV induces cell death by apoptosis. TGEV-induced apoptosis was demonstrated by agarose gel electrophoresis, electron microscopy, and terminal deoxytransferase digoxigenin-dUTP nick end labeling (TUNEL). Double labeling experiment confirmed the result from electron microscopy and showed that most of the apoptotic cells were bystander cells as they were negative for TGEV nucleic acids. Results of this study indicate that TGEV induces apoptosis in vitro and that most of the cells undergoing apoptosis are bystander cells, thus amplifying the cytopathic effect of TGEV.


title: Critical care management of adults with community-acquired severe respiratory viral infection

text: With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05943-5) contains supplementary material, which is available to authorized users.


title: A protocol for the management of Maxillofacial Injuries in the wake of the COVID-19 Pandemic

text: The oral & maxillofacial region and by that virtue surgery of the same is correlated to an increased risk of the transfer of the SARS CoV-2. In times of a pandemic it is imperative to institute a protocol based management of maxillofacial injuries based on currently available literature which is suggestive, simplistic, executable and amenable to modifications should the rapidly changing situation demand the same. The author, in the present study conducted a review of literature to undertake the task of forming a simplistic protocol which is readily applicable for the management of maxillofacial injuries which would not only provide the clinician guidance on what to do now but caution towards the future implications of his/her present decision.


title: Epidemiology of Clostridium difficile infection in a large teaching hospital in Singapore

text: Summary Aims We undertook this study to define the incidence of toxigenic Clostridium difficile in our hospital and to characterise the isolates. Methods All unformed stool was tested for the presence of Toxin A (TcdA) and Toxin B (TcdB), and cultured for C. difficile. Culture filtrates were also tested for TcdA and TcdB. Detection of tcdA and tcdB genes was carried out for A2B+ strains by polymerase chain reaction (PCR).The minimum inhibitory concentrations (MICs) of metronidazole, vancomycin and clindamycin for all isolates were tested using the Etest. PCR ribotyping was carried out on all isolates. Results The incidence of Clostridium difficile associated disease (CDAD) was 3.2 cases per 1000 admissions or discharges and 53.8 cases per 100000 patient days. Most cases occurred in renal and haematology patients. CDAD was more common in patients aged over 50 years and of male gender. The Indian population was under-represented. Fourteen (11.8%) isolates were A-B+. All strains were susceptible to metronidazole but one strain showed intermediate resistance to vancomycin. Only 12.8% of the isolates were susceptible to clindamycin. Thirty-five isolates had PCR ribotype A, of which 29 (83%) had a clindamycin MIC >256mg/L. Thirty-three had PCR ribotype B, of which only one (3%) had a clindamycin MIC >256mg/L. The 14 A-B+ strains were all PCR ribotype C, and had a range of MICs for clindamycin from 2 to >256mg/L. Conclusions: The incidence of CDAD in our hospital is relatively low. Isolates remain susceptible to metronidazole and vancomycin.


title: Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State

text: BACKGROUND: Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. METHODS: We retrospectively analyzed a cohort of children who presented to Seattle Children’s Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. RESULTS: The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. CONCLUSIONS: The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.


title: Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens

text: Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and infectious bronchitis (IB) are two economically important avian diseases that affect poultry industry worldwide. Herein, we exploited a live attenuated SG mutant, JOL967, to deliver spike (S) protein 1 of IB virus (V) to elicit protective immunity against both FT and IB in chickens. The codon optimized S1 nucleotide sequence was cloned in-frame into a prokaryotic constitutive expression vector, pJHL65. Subsequently, empty pJHL65 or recombinant pJHL65-S1 plasmid was electroporated into JOL967 and the resultant clones were designated as JOL2068 and JOL2077, respectively. Our results demonstrated that the chickens vaccinated once orally with JOL2077 elicited significantly (p < 0.05) higher IBV-specific humoral and cell-mediated immunity compared to JOL2068 and PBS control groups. Consequently, on challenge with the virulent IBV strain at 28(th) day post-vaccination, JOL2077 vaccinated birds displayed significantly (p < 0.05) lower inflammatory lesions in virus-targeted tissues compared to control groups. Furthermore, 33.3% (2 of 6) of birds vaccinated with JOL2077 vaccine had shown virus recovery from tracheal tissues compared to 100% (6 of 6) recovery obtained in both the control groups. Against wild-type SG lethal challenge, both JOL2077 and JOL2068 vaccinated groups exhibited only 10% mortality compared to 80% mortality observed in PBS control group. In conclusion, we show that JOL2077 can induce efficient IBV- and carrier-specific protective immunity and can act as a bivalent vaccine against FT and IB. Further studies are warranted to investigate the potential of JOL2077 vaccine in broiler and young layer birds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0588-9) contains supplementary material, which is available to authorized users.


title: Event-Based Surveillance at Community and Healthcare Facilities, Vietnam, 2016–2017

text: Surveillance and outbreak reporting systems in Vietnam required improvements to function effectively as early warning and response systems. Accordingly, the Ministry of Health of Vietnam, in collaboration with the US Centers for Disease Control and Prevention, launched a pilot project in 2016 focusing on community and hospital event–based surveillance. The pilot was implemented in 4 of Vietnam’s 63 provinces. The pilot demonstrated that event-based surveillance resulted in early detection and reporting of outbreaks, improved collaboration between the healthcare facilities and preventive sectors of the ministry, and increased community participation in surveillance and reporting.


title: Implications of asymptomatic carriers for infectious disease transmission and control

text: For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae, some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.


title: Role of Immigrants and Migrants in Emerging Infectious Diseases

text: Population migration plays a critical role in the spread of disease by initiating outbreaks of acute diseases, changing the prevalence of infectious diseases at a given location, and changing the face of chronic disease resulting from previous infection. This article focuses on the recent demographic changes in North America that have facilitated the introduction and spread of new microbial threats, the role migrant populations play in changing the demographics of specific infectious diseases, and the potential responses of clinicians and public health officials in addressing the challenges posed by these infections. The emphasis of the article is on immigrant and migrant populations entering North America; the role of travelers in emerging infectious diseases is addressed in another article in this issue.


title: Effect of route of inoculation on innate and adaptive immune responses to porcine epidemic diarrhea virus infection in suckling pigs

text: Abstract The effects of route of administration on systemic and gut mucosal immune responses induced by porcine epidemic diarrhea virus (PEDV) infection in suckling pigs were investigated. Twenty-four conventional 5-day-old suckling piglets were randomly divided into four groups and were inoculated orally, intranasally (I.N.), intramuscularly (I.M.) with PEDV or DMEM (mock). Pigs were monitored daily for clinical signs and fecal viral load. Blood samples were collected at 7, 14, 21 days post infection (dpi) and subjected for the analyses of serum antibody production, T cell and natural killer (NK) cell frequencies, NK cytotoxicity and serum cytokine levels. Oral inoculation led to higher levels of PEDV-specific IgA antibodies in both serum and gut mucosal sites than did other routes of inoculation. Intranasal inoculation elicited significantly higher titers of virus-specific IgG antibodies in serum. PEDV-infected pigs regardless of inoculation routes had significantly lower NK cell frequencies than those of the control pigs at 14 dpi. The orally inoculated pigs had significantly higher CD3+CD8+ T cell frequencies as compared to I.N. or I.M. inoculated pigs at 14 dpi, while there was no significant difference among orally, I.N. or I.M. inoculated pigs and control pigs in CD3+CD4+ T cell frequencies in peripheral blood. PEDV-infected and control pigs had low, but detectable NK cell activities at 14 and 21 dpi, however, NK cell activities were barely detectable at 7 dpi whether the pigs were infected or not. Serum IL-10 levels were induced drastically in orally infected pigs at 7 dpi and then gradually declined. Serum IL-12 levels followed a similar pattern while the fold-change was much lower. In conclusion, oral inoculation may generate more comprehensive immune responses.


title: Risk factors for predicting mortality in elderly patients with COVID-19: a review of clinical data in China

text: Abstract While elderly patients are at high risk of fatality, research concerning COVID-19 has largely been done on clarifying the clinical features. As such, the present work aims to identify risk factors for mortality in elderly patients with COVID-19. Given that single-centre studies are less likely informative as elderly remains a minority in the total Chinese population, the present study reviewed the clinical data of geriatric COVID-19 patients gathered from different sources in the public domain. Based on the data of 154 individuals from 26 provinces, age remained a key mortality risk factor among geriatric patients of different ages. While dyspnoea and chest pain/discomfort were more commonly seen in deceased patients as they represented severe pneumonia, fever was more prominent in surviving patients. This was likely due to the lower baseline body temperature observed in elderly which translated to a lower maximum temperature of fever. However, lowering the threshold temperature for fever is not recommended in surveillance. Instead, baseline body temperature measured on a regular basis should be used to define the threshold temperature for fever. Against mixed results, more research should be done on identifying comorbidities associated with mortality in geriatric patients.


title: A preliminary assessment of the impact of COVID-19 on environment – A case study of China

text: Abstract The coronavirus disease (COVID-19) is seriously threatening world public health security. Currently, >200 countries and regions have been affected by the epidemic, with the number of infections and deaths still increasing. As an extreme event, the outbreak of COVID-19 has greatly damaged the global economic growth and caused a certain impact on the environment. This paper takes China as a case study, comprehensively evaluating the dynamic impact of COVID-19 on the environment. The analysis results indicate that the outbreak of COVID-19 improves China's air quality in the short term and significantly contributes to global carbon emission reduction. However, in the long run, there is no evidence that this improvement will continue. When China completely lifts the lockdown and resumes large-scale industrial production, its energy use and greenhouse gas (GHG) emissions are likely to exceed the level before the event. Moreover, COVID-19 significantly reduces the concentration of nitrogen dioxide (NO2) in the atmosphere. The decline initially occurred near Wuhan and eventually spread to the whole country. The above phenomenon shows that the decreasing economic activities and traffic restrictions directly lead to the changes of China's energy consumption and further prevent the environment from pollution. The results in this study support the fact that strict quarantine measures can not only protect the public from COVID-19, but also exert a positive impact on the environment. These findings can provide a reference for other countries to assess the influence of COVID-19 on the environment.


title: Chapter 7 Nanoparticles: synthesis and applications

text: Abstract This chapter focuses on the synthesis, functionalization, and applications of metallic, semiconductor, magnetic, and multifunctional nanoparticles. Synthesis methods such as chemical reduction, coprecipitation, seeding, microemulsion, hydrothermal synthesis, and sonoelectrodeposition are outlined. Functionalized nanoparticles are suitable for numerous applications. Several applications of nanoparticles in life sciences and the enviromment are discussed. Finally, some future trends are pointed out.


title: Complete Genome Sequences of Two Porcine Deltacoronavirus Strains, CHN-GD16-03 and CHN-GD16-05, Isolated in Southern China, 2016

text: We report here the amplification and sequence analysis of two complete genomes of newly emerged porcine deltacoronavirus (PDCoV) strains, isolated from diarrhea samples from piglets in Guangdong Province in southern China. These genomes provide further sequence data for evaluating the relationships among PDCoVs from different countries.


title: Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea

text: OBJECTIVES: The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14(th), 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. METHODS: The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. RESULTS: There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. CONCLUSION: COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.


On the use of chloroquine for chikungunya


To what extent do children transmit SARS‐CoV‐2 virus?


title: Effect of caffeine and reduced temperature (20 degrees C) on the organization of the pre-Golgi and the Golgi stack membranes

text: In the present study we have dissected the transport pathways between the ER and the Golgi complex using a recently introduced (Kuismanen, E., J. Jantti, V. Makiranta, and M. Sariola. 1992. J. Cell Sci. 102:505- 513) inhibition of transport by caffeine at 20 degrees C. Recovery of the Golgi complex from brefeldin A (BFA) treatment was inhibited by caffeine at reduced temperature (20 degrees C) suggesting that caffeine inhibits the membrane traffic between the ER and the Golgi complex. Caffeine at 20 degrees C did not inhibit the BFA-induced retrograde movement of the Golgi membranes. Further, incubation of the cells in 10 mM caffeine at 20 degrees C had profound effects on the distribution and the organization of the pre-Golgi and the Golgi stack membranes. Caffeine treatment at 20 degrees C resulted in a selective and reversible translocation of the pre- and cis-Golgi marker protein (p58) to the periphery of the cell. This caffeine-induced effect on the Golgi complex was different from that induced by BFA, since mannosidase II, a Golgi stack marker, remained perinuclearly located and the Golgi stack coat protein, beta-COP, was not detached from Golgi membranes in the presence of 10 mM caffeine at 20 degrees C. Electron microscopic analysis showed that, in the presence of caffeine at 20 degrees C, the morphology of the Golgi stack was altered and accumulation of numerous small vesicles in the Golgi region was observed. The results in the present study suggest that caffeine at reduced temperature (20 degrees C) reveals a functional interface between the pre-Golgi and the Golgi stack.


cGAS and STING: At the intersection of DNA and RNA virus-sensing networks


Elevated level of C‐reactive protein may be an early marker to predict risk for severity of COVID‐19


title: Identification and molecular characterization of a novel serotype infectious bronchitis virus (GI-28) in China

text: Abstract Avian infectious bronchitis coronavirus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which renders complete control of the disease by vaccination a challenging task due to the poor cross-protection between different serotypes. In this study, based on the results of S1 sequence analysis and virus cross-neutralization tests, IBV strain ck/CH/LGX/111119 was found to be genetically and antigenically different from other known IBV types, representing not only a novel genotype, but also a novel serotype (designated as GI-28). Viruses belonging to this novel serotype have been isolated from several regions in China in recent years, suggesting endemic circulation of the serotype in various geographic locations in China. Further studies by complete genomic analysis showed that strain ck/CH/LGX/111119 may have originated from recombination events involving LX4 genotype IBVs and an as-yet-unidentified IBV donating a S1 gene, or from the result of accumulation of mutations and selections, especially in the S1 gene, from a LX4 genotype virus. ck/CH/LGX/111119 is a nephropathogenic strain, although it had broader tissue tropism (respiratory, digestive, urinary, and reproductive tracts) among chickens challenged at one day old. Infection of the oviducts with ck/CH/LGX/111119 found in this study may have severe implications because the virus will likely induce the occurrence of false layers.


docid: swrsaqoc

title: Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies

text: BACKGROUND: Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad. METHODS: In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (n = 38, January to May) and rainy (n = 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus. RESULTS: Wheezing children had a higher [χ(2 )= 5.561, p = 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (n = 18, 25.7% vs. n = 7, 8.8%; p = 0.005), respiratory syncytial virus B (RSV B) (n = 2, 2.9% vs. n = 4, 5.0%), and enterovirus (n = 1, 1.4% vs. n = 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (p = 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, n = 6, 15.8%; Rainy, n = 19, 17.0%) and without seasonal association [χ(2 )= 0.028, p = 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons. CONCLUSION: Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.


title: Is gustatory impairment the first report of an oral manifestation in COVID‐19?

text: More recently, researchers Top of FormBottom of Formhave reported about the chemosensory alterations observed in patients with COVID-19 (Giacomelli et al., 2020). The findings on changes in olfactory and gustatory sensations are enlightening and probably one of the preliminary reports in this context and may have been overlooked earlier, since it is challenging to diagnose and also due to the gravity of the major symptoms, being dealt with.


title: Protocol for Metagenomic Virus Detection in Clinical Specimens

text: Sixty percent of emerging viruses have a zoonotic origin, making transmission from animals a major threat to public health. Prompt identification and analysis of these pathogens are indispensable to taking action toward prevention and protection of the affected population. We quantifiably compared classical and modern approaches of virus purification and enrichment in theory and experiments. Eventually, we established an unbiased protocol for detection of known and novel emerging viruses from organ tissues (tissue-based universal virus detection for viral metagenomics [TUViD-VM]). The final TUViD-VM protocol was extensively validated by using real-time PCR and next-generation sequencing. We could increase the amount of detectable virus nucleic acids and improved the detection of viruses <75,000-fold compared with other tested approaches. This TUViD-VM protocol can be used in metagenomic and virome studies to increase the likelihood of detecting viruses from any biological source.


docid: lcmkribq

title: Crime Rates in a Pandemic: the Largest Criminological Experiment in History

text: The COVID-19 pandemic of 2020 has impacted the world in ways not seen in generations. Initial evidence suggests one of the effects is crime rates, which appear to have fallen drastically in many communities around the world. We argue that the principal reason for the change is the government ordered stay-at-home orders, which impacted the routine activities of entire populations. Because these orders impacted countries, states, and communities at different times and in different ways, a naturally occurring, quasi-randomized control experiment has unfolded, allowing the testing of criminological theories as never before. Using new and traditional data sources made available as a result of the pandemic criminologists are equipped to study crime in society as never before. We encourage researchers to study specific types of crime, in a temporal fashion (following the stay-at-home orders), and placed-based. The results will reveal not only why, where, when, and to what extent crime changed, but also how to influence future crime reduction.


docid: ydmvugdw

title: Animal models for the study of influenza pathogenesis and therapy

text: Influenza A viruses causes a variety of illnesses in humans. The most common infection, seasonal influenza, is usually a mild, self-limited febrile syndrome, but it can be more severe in infants, the elderly, and immunodeficient persons, in whom it can progress to severe viral pneumonitis or be complicated by bacterial superinfection, leading to pneumonia and sepsis. Seasonal influenza also occasionally results in neurologic complications. Rarely, viruses that have spread from wild birds to domestic poultry can infect humans; such “avian influenza” can range in severity from mild conjunctivitis through the rapidly lethal disease seen in persons infected with the H5N1 virus that first emerged in Hong Kong in 1997. To develop effective therapies for this wide range of diseases, it is essential to have laboratory animal models that replicate the major features of illness in humans. This review describes models currently in use for elucidating influenza pathogenesis and evaluating new therapeutic agents.


title: Décision kinésithérapique: Alexandre L. 57 ans: Kinésithérapie et Covid-19 en réanimation, de la phase aiguë à la réhabilitation

text: Résumé Un homme de 57 ans est hospitalisé en réanimation pour un syndrome de détresse respiratoire aigüe (SDRA) lié à une infection à Covid-19. Après une première phase au cours de laquelle le patient est sédaté et curarisé, la kinésithérapie consiste à mobiliser passivement le patient, à participer au décubitus ventral; la kinésithérapie respiratoire n’étant pas forcément nécessaire. Dans un second temps, l’extubation est possible et plusieurs aspects sont développés : la kinésithérapie respiratoire, l’oxygénation, la déglutition et surtout la réhabilitation. Cependant, des atteintes du parenchyme pulmonaire abaissent de façon importante la saturation en oxygène au cours des exercices. L’oxygénation à haut débit et/ou la ventilation non-invasive (VNI) permettent d’optimiser la réhabilitation chez ce patient avec une réserve respiratoire encore précaire. Indice de factualité (i-FACT): 3.2 Abstract A 57-year-old man is hospitalized in intensive care for an acute respiratory distress syndrome related to a Covid-19 infection. After a first phase during which the patient is sedated and nerve-blocked, physiotherapy consists in passively mobilizing the patient, participating in the prone position, respiratory physiotherapy is not necessary. In a second step, extubation is possible and several aspects are developed: respiratory physiotherapy, oxygenation, swallowing and rehabilitation. However, damage to the lung significantly decreases oxygen saturation during exercise. High-flow nasal oxygenation and / or non-invasive ventilation (NIV) can optimize rehabilitation in this patient with a still precarious respiratory function. Evidence index (EVID-i): 3.2


docid: jrqhilgf

title: Attenuated live infectious bronchitis virus QX vaccine disseminates slowly to target organs distant from the site of inoculation

text: Abstract Infectious bronchitis (IB) is a highly contagious respiratory disease of poultry, caused by the avian coronavirus infectious bronchitis virus (IBV). Currently, one of the most relevant genotypes circulating worldwide is IBV-QX (GI-19), for which vaccines have been developed by passaging virulent QX strains in embryonated chicken eggs. Here we explored the attenuated phenotype of a commercially available QX live vaccine, IB Primo QX, in specific pathogens free broilers. At hatch, birds were inoculated with QX vaccine or its virulent progenitor IBV-D388, and postmortem swabs and tissues were collected each day up to eight days post infection to assess viral replication and morphological changes. In the trachea, viral RNA replication and protein expression were comparable in both groups. Both viruses induced morphologically comparable lesions in the trachea, albeit with a short delay in the vaccinated birds. In contrast, in the kidney, QX vaccine viral RNA was nearly absent, which coincided with the lack of any morphological changes in this organ. This was in contrast to high viral RNA titers and abundant lesions in the kidney after IBV D388 infection. Furthermore, QX vaccine showed reduced ability to reach and replicate in conjunctivae and intestines including cloaca, resulting in significantly lower titers and delayed protein expression, respectively. Nephropathogenic IBVs might reach the kidney also via an ascending route from the cloaca, based on our observation that viral RNA was detected in the cloaca one day before detection in the kidney. In the kidney distal tubular segments, collecting ducts and ureter were positive for viral antigen. Taken together, the attenuated phenotype of QX vaccine seems to rely on slower dissemination and lower replication in target tissues other than the site of inoculation.


Role of Multisector Partnerships in Controlling Emerging Zoonotic Diseases


title: Bleeding pneumonia: diffuse alveolar hemorrhage due to human metapneumovirus

text: Diffuse alveolar hemorrhage is a condition with high morbidity and mortality. The majority of cases are caused by pulmonary capillaritis associated with systemic vasculitis. Infection disease has also been associated with this condition. A 62-year-old woman with a history of chronic alcohol abuse presented with shortness of breath, hemoptysis, constipation, and icterus. Chest x-rays on admission showed diffuse patchy opacities concerning for diffuse alveolar hemorrhage. The patient quickly developed acute respiratory failure requiring intubation. PCR identified human metapneumovirus and bronchoalveolar lavage confirmed alveolar hemorrhage. Despite all efforts, the patient ultimately developed multi-organ failure and died. Human metapneumovirus is usually associated with mild upper and lower respiratory tract infections in young children. Nevertheless, clinicians should recognize that this virus has recently emerged as a significant pathogen, particularly in adult patients with underlying conditions and the elderly population.


title: In vitro methods for testing antiviral drugs

text: Abstract Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses.


title: Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time

text: The Bible describes the case of a woman with high fever cured by our Lord Jesus Christ. Based on the information provided by the gospels of Mark, Matthew and Luke, the diagnosis and the possible etiology of the febrile illness is discussed. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. We analysed a case of high fever that happened 2000 years ago in Biblical time and discussed possible etiologies.


title: Immunochromatographic test for detection of adenovirus from respiratory samples: Is it a real solution for pediatric emergency department?

text: Abstract Rapid diagnosis of adenoviral respiratory infections is required in order to decide optimal treatment strategies. The adenovirus antigen immunochromatography Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain), was evaluated versus the shell-vial culture and multiplex PCR (Clart Pneumovir Version 3.0, Genomica, Madrid, Spain), in nasopharyngeal washes and oropharyngeal swabs specimens from subjects with respiratory tract infections. Between April 2011 and November 2012, 224 patients were included. The IC Adeno Respiratory Card Letitest was positive for 77.9% (74 of 95) of patients diagnosed at bedside. Using multiplex-PCR as the reference standard, the overall sensitivity was 77.9% and the specificity was 73.6%. Taking shell-viral culture as the reference method, the Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain) sensitivity and specificity values were 80.0% and 60.9%, respectively. Using RT-PCR (Clart Pneumovir Version 3.0, Genomica, Madrid, Spain) as the reference standard, the viral culture sensitivity was 53.2% and the specificity was 100%. The Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain) assay could be a simple and rapid method for antigenic detection of adenovirus in pediatric respiratory samples although it would be necessary to improve the specificity and sensitivity of the test.


docid: qliuajut

title: Localized, Targeted, and Sustained siRNA Delivery

text: Short interfering RNA (siRNA) functions directly in the cytoplasm, where it is assembled into an RNA‐induced silencing complex (RISC). The localized delivery of siRNA to a specific site in vivo is highly challenging. There are many disease states in which a systemic effect of RNAi may be desirable; some examples include non‐localized cancers, HIV, neurodegenerative diseases, respiratory viruses, and heart and vascular disease. In this Concept, we will focus on the localized delivery of siRNA to a target site using various delivery modalities. In certain tissues, such as the eye, central nervous system and lung, it has been demonstrated that a simple injection of naked siRNA will silence gene expression specifically in that tissue. To achieve local gene silencing in other tissues, a variety of approaches have been pursued to help stabilize the siRNA and facilitate uptake; they include chemical modification of the siRNA or complexation within liposomes or polymers to form nanoparticles. Recently, the use of macroscopic biomaterial scaffolds for siRNA delivery has been reported, and although there is still significant work to be done in this area to optimize the delivery systems, it is an important area of research that offers the potential for having great impact on the field of siRNA delivery.


Eruption as a clinical manifestation of COVID-19: photographs of a patient


title: Successful establishment of a reverse genetic system for QX-type infectious bronchitis virus and technical improvement of the rescue procedure

text: Abstract In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. Ten fragments contiguously spanning the complete IBV genome were amplified and cloned into the vaccinia virus genome by homologous recombination. The full-length genomic cDNA was transcribed in vitro, and its transcript was transfected into BHK-21/N cells that could stably express IBV N protein. At 48 h post transfection, the culture medium was harvested and inoculated into 10-day-old specific-pathogen-free embryonated chicken eggs to replicate the rescued virus. This strategy was chosen to facilitate the rescue procedure and to ensure that the recombinant rYN virus will not require any cell culture adaptations. After only one in ovo passage, the recombinant YN virus (rYN) was successfully recovered and confirmed to possess the introduced silent marker mutation in its genome. Biological characteristics of rYN such as the EID50, TCID50, replication in ovo, and replication kinetcs in vitro were tested and all were similar to its parental strain YN. Our findings demonstrate the successful construction of highly-pathogenic QX-type IBV using a modified rescue procedure, allowing for future studies of the molecular biology and pathogenicity of IBV field strains.


Mapping illegal wildlife trade networks provides new opportunities for conservation actions


title: The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity

text: BACKGROUND: The outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction. METHODS: We have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro. RESULTS: Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. CONCLUSION: These results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis.


title: Airborne Infectious Microorganisms☆

text: Abstract Inhalation exposes the upper and lower respiratory tracts of humans to a variety of airborne particles and vapors. Airborne transmission of pathogenic microorganisms to humans from the environment, animals, or other humans can result in disease. Inhalation is an important route of exposure as the lung is more susceptible to infection than the gastrointestinal tract. Ingested microorganisms must pass through the acidic environment of the stomach before they can colonize tissue while inhaled microorganisms are deposited directly on the moist surfaces of the respiratory tract. Inhalation of microbial aerosols can elicit adverse human health effects including infection, allergic reaction, inflammation, and respiratory disease. Following inhalation, infectious viruses, bacteria, and fungi can establish in host cells of the respiratory tract. Some are translocated and infect the gastrointestinal tract and other tissues. This article discusses human viral, bacterial, and fungal diseases transmitted via aerosols. Viral diseases presented are influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), enteric viruses related infections, hantavirus disease, measles, and varicella. Bacterial diseases are Legionnaires’ disease, tuberculosis, and nontubercule mycobacterial disease. Exposure to some Gram-negative and Gram-positive bacteria, endotoxin, and actinomycetes when dispersed through the air can result in disease following inhalation. Fungal diseases included are histoplasmosis, coccidiomycosis, blastomycosis, cryptococcosis, and aspergillosis. The threat of bioterrorism with airborne infectious agents is also briefly presented.


title: Child protection in the time of COVID‐19

text: As the number of cases of coronavirus disease 2019 (COVID‐19) caused by the virus SARS‐CoV‐2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.


docid: epqgozkh

title: Molecular characterization of a porcine astrovirus strain in China

text: Pigs are increasingly recognized to harbor a wide range of viruses that apparently establish long-term persistence in these animals. They serve as reservoirs for a number of human zoonotic diseases. In this study, a porcine astrovirus (PAstV) strain, designated as PAstV JWH-1, is identified from a diarrheal pig in China, and it is partially characterized genetically. Sequence analysis shows that the PAstV JWH-1 strain contains divergent nucleotide sequences in both the open reading frame (ORF)1b/ORF2 consensus and the 3′-UTR regions (s2m motif), which are usually highly conserved among members of the family Astroviridae. Phylogenetic analysis indicates that the JWH-1 strain clusters closely with newly identified strains PAstV 12-4 and 14-4 and forms a group of mamastroviruses with the proposed novel deer astrovirus. Further recombination analysis shows that two possible interspecies recombination events between porcine and deer astroviruses occurred in the genome of the JWH-1 strain. This study further confirms that multiple lineages are present among PAstVs, and each lineage likely represents an independent origin. Additionally, the possibility of interspecies transmission among PAstVs is also suggested.


docid: zgqbfmzl

title: A Novel Coronavirus Outbreak from Wuhan City in China, Rapid Need for Emergency Departments Preparedness and Response; a Letter to Editor


title: Trending on Social Media: Integrating Social Media into Infectious Disease Dynamics

text: Social media plays an important role in alerting and educating the public during disease outbreaks. By increasing awareness of the disease and its prevention, it can lead to a modification of behaviour which then affects contact/incidence rates. Social media data may also be used when formulating, developing and parameterising models. As mobile technology continues to evolve and proliferate, social media is expected to occupy an increasingly prominent role in the field of infectious disease modelling to improve their predictive power. This article presents a review of existing models incorporating media in general and highlights opportunities for social media to enhance traditional compartmental models so as to make the best use of this resource in controlling the spread of disease.


title: Surfactants as Antimicrobials: A Brief Overview of Microbial Interfacial Chemistry and Surfactant Antimicrobial Activity

text: In this brief overview of a large and complex subject, as presented at the 2018 Surfactants in Solution conference, the need for, and impact of, hard surface antimicrobial products is demonstrated. The composition of the interfaces of three common classes of pathological microbes, bacteria, viruses, and fungi, is discussed so that surfactant and cleaning product development scientists better understand their interfacial characteristics. Studies of antimicrobial efficacy from the four major classes of surfactants (cationic, anionic, amphoteric, and nonionic) are shown. The need for preservatives in surfactants is elucidated. The regulatory aspects of antimicrobials in cleaning products to make antimicrobial claims are stressed.


title: Transplantation of glial-committed progenitor cells into a viral model of multiple sclerosis induces remyelination in the absence of an attenuated inflammatory response

text: Abstract Transplantation of remyelination-competent cells represents a promising strategy for the treatment of demyelinating diseases. As the environment dictates the success or failure of remyelination, it is critical to understand the role that the immune system plays in transplant-mediated remyelination. In this study, we evaluated the severity of neuroinflammation following transplantation of glial-committed progenitor cells into the spinal cords of mice chronically infected with mouse hepatitis virus (MHV), a model in which T cells and macrophages are critical in amplifying the severity of demyelination. Transplantation was performed following viral persistence in which inflammation and demyelination are established and clinical disease is evident. Mice were sacrificed 10 and 21 days following progenitor cell transplantation and the effect on neuroinflammation evaluated. Treatment did not alter accumulation of T cells or macrophages within the CNS as compared to control mice. Moreover, progenitor cell implantation did not affect local cytokine/chemokine gene expression in the CNS. Finally, remyelination associated with transplantation did not result in an imbalance of TH1-associated cytokine production by virus-specific T cells. These studies demonstrate that progenitor cell-mediated remyelination is not the result of modulating the composition of the cellular infiltrate nor cytokine expression by virus-specific T cells and suggest that remyelination may not depend on amelioration of the inflammatory response or alteration of cytokine secretion by virus-specific T cells.


title: Coronavirus infection, ER stress, apoptosis and innate immunity

text: The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER). Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR), a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However, under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus–host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP) kinase activation, autophagy, apoptosis, and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize the current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.


title: The state of gene therapy research in Africa, its significance and implications for the future

text: Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV-1, hepatitis B virus and Ebola virus, which are of significant public health importance in Africa. Although enthusiasm for gene therapy is justified, significant challenges to implementing the technology remain. These include ensuring efficient delivery of therapeutic nucleic acids to target cells, limiting unintended effects, cost and complexity of treatment regimens. In addition, implementation of effective legislation that will govern gene therapy research will be a challenge. Nevertheless, it is an exciting prospect that gene therapy should soon reach the mainstream of medical management. Participation of African researchers in the exciting developments is currently limited, but their involvement is important to address health problems, develop capacity and enhance economic progress of the continent.


title: Global Health: Governance and Policy Development

text: Global health policy is now being influenced by an ever-increasing number of nonstate and non-intergovernmental actors to include influential foundations, multinational corporations, multi-sectoral partnerships, and civil society organizations. This article reviews how globalization is a key driver for the ongoing evolution of global health governance. It describes the massive increases in bilateral and multilateral investments in global health and it highlights the current global and US architecture for performing global health programs. The article closes describing some of the challenges and prospects that characterize global health governance today.


title: Infection control influence of Middle East respiratory syndrome coronavirus: A hospital-based analysis

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) caused multiple outbreaks. Such outbreaks increase economic and infection control burdens. We studied the infection control influence of MERS-CoV using a hospital-based analysis. METHODS: Our hospital had 17 positive and 82 negative cases of MERS-CoV between April 1, 2013, and June 3, 2013. The study evaluated the impact of these cases on the use of gloves, surgical masks, N95 respirators, alcohol-based hand sanitizer, and soap, as well as hand hygiene compliance rates. RESULTS: During the study, the use of personal protective equipment during MERS-CoV compared with theperiod before MERS-CoV increased dramatically from 2,947.4 to 10,283.9 per 1,000 patient-days (P<.0000001) for surgical masks and from 22 to 232 per 1,000 patient-days (P <.0000001) for N95 masks. The use of alcohol-based hand sanitizer and soap showed a significant increase in utilized amount (P<.0000001). Hand hygiene compliance rates increased from 73% just before the occurrence of the first MERS case to 88% during MERS cases (P = .0001). The monthly added cost was $16,400 for included infection control items. CONCLUSIONS: There was a significant increase in the utilization of surgical masks, respirators, soap and alcohol-based hand sanitizers. Such an increase is a challenge and adds cost to the healthcare system.


title: Viral Vaccines in India: An Overview

text: Viruses cause a large number of diseases in humans, some of which are fatal, while others are highly debilitating. A majority of viral diseases attack infants and young children, while others strike people in their prime. Development of preventive measures against viral diseases is, therefore, of paramount importance. Vaccination is the most cost-effective medical intervention for preventing mortality and morbidity against infectious diseases. A number of effective and safe vaccines are currently available against several viral diseases of significant medical importance. Many of these manufactured in India, are at par with international standards and are affordable. For many other viral diseases, for which vaccines are currently not available, research is underway at various national laboratories, as well as in the private sector companies in India. The present overview highlights the various vaccine preventable viral diseases that are of special importance to India and aims to provide a glimpse of the various vaccines that are currently available, or are under development in India.


title: Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes'

text: About 60% of emerging infectious diseases in humans are of zoonotic origin. Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife. Here, we investigated whether blood meals from hematophagous flies could be used to identify the infectious agents circulating in wild vertebrates. To this aim, 1230 blood-engorged flies were caught in the forests of Gabon. Identified blood meals (30%) were from 20 vertebrate species including mammals, birds and reptiles. Among them, 9% were infected by different extant malaria parasites among which some belonged to known parasite species, others to new parasite species or to parasite lineages for which only the vector was known. This study demonstrates that using hematophagous flies as ‘flying syringes’ constitutes an interesting approach to investigate blood-borne pathogen diversity in wild vertebrates and could be used as an early detection tool of zoonotic pathogens. DOI: http://dx.doi.org/10.7554/eLife.22069.001


title: Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016

text: BACKGROUND: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. METHODS: The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases. RESULTS: From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. CONCLUSIONS: The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.


CHAPTER 7 Severe Acute Respiratory Syndrome (SARS)


title: Intranasal administration of oxytocin: Behavioral and clinical effects, a review

text: Abstract The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. ‘Direct-access-pathways’ from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology. Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral ‘prosocial’ effects: from social relations and ‘trust’ to treatment of ‘autism’. Only very recently in a microdialysis study in rats and mice, the ‘direct-nose-brain-pathways’ of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the ‘intrinsic’ OT-system in the hypothalamus as well needs further clarification. We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects.


title: Identification of C-geranylated flavonoids from Paulownia catalpifolia Gong Tong fruits by HPLC-DAD-ESI-MS/MS and their anti-aging effects on 2BS cells induced by H2O2

text: Abstract The fruits of Paulownia catalpifolia Gong Tong are used as a Chinese folk herbal medicine for the treatment of enteritis, tonsillitis, bronchitis, and dysentery, etc. Our previous study has identified new C-geranylated flavanones with obvious anti-proliferative effects in lung cancer A549 cells. In the present study, a new C-geranylated flavone, paucatalinone C (1) and five known C-geranylated flavanones (2–6) were isolated. In addition, a total of 34 C-geranylated flavonoids were detected by HPLC-DAD-ESI-MS/MS coupling techniques from the CH2Cl2 extract of P. catalpifolia. Futhermore, anti-aging effects of isolated compounds were evaluated in vitro with premature senescent 2BS cells induced by H2O2. Phytochemical results indicated that P. catalpifolia was a natural resource of abundant C-geranylated flavonoids. Diplacone (3) and paucatalinone A (5) were the potent anti-aging agents in the premature senescent 2BS cells induced by H2O2 and the C-geranyl substituent may be an important factor because of its lipophilic character.


title: Co‐infection with COVID‐19 and influenza A virus in two died patients with acute respiratory syndrome, Bojnurd, Iran

text: In some recently published papers researchers reported "Co-infection with SARS-CoV-2 and Influenza Virus"1-3 . They described the development of clinical symptoms of pneumoniae in patients and discussed about the importance of other respiratory viruses that cause symptoms similar to COVID-19. This article is protected by copyright. All rights reserved.


Virtual Assessment and Management in Foot and Ankle Surgery During the COVID-19 Pandemic: An Irish Experience


Tratamiento del catarro. Evidencia científica


Impact on colorectal cancer in COVID‐19 pandemic


title: Quantitative temporal‐spatial distribution of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) in post‐mortem tissues

text: Few post‐mortem studies have been performed on patients who have died from severe acute respiratory syndrome (SARS). No studies have examined how the SARS‐associated coronavirus (SARS‐CoV) loads in different organs with respect to time, post‐mortem. The aim of this study was to determine the quantitative temporal‐spatial distribution of SARS‐CoV in the post‐mortem tissue samples of seven patients. Quantitation of a house‐keeping gene, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was undertaken to standardize the amount of tissue tested. SARS‐CoV viral load and SARS‐CoV/GAPDH RNA ratio for each organ type were related to four time durations: onset of illness to death, death to post‐mortem tissue sampling, and total durations of treatment with ribavirin and hydrocortisone. The SARS‐CoV/GAPDH RNA ratio remained relatively stable in most organ tissue types for all these time durations. The ratio reached the highest value of equal to or greater than one for lung and small bowel, whereas those for heart, liver, spleen, and kidney were always less than one. It is concluded that SARS‐CoV viral loads in these organs remain relatively stable, post‐mortem. This quantitative assessment further supports SARS‐CoV has a specific tropism for the human respiratory and gastrointestinal tracts, which may be related to the density of SARS‐CoV receptors. J. Med. Virol. 79:1245–1253, 2007. © Wiley‐Liss, Inc.


docid: ldeylpne

title: Enzyme-linked immunosorbent assay for the detection of canine coronavirus and its antibody in dogs

text: Abstract Two methods of enzyme-linked immunosorbent assay (ELISA) were developed for the diagnosis of canine coronavirus (CCV) infection in dogs. One ELISA, in which CCV-infected CRFK cell lysate is used as antigen, is for the detection and titration of antibody against CCV, and the other ELISA uses the double antibody sandwich method for the detection of CCV antigen. The first ELISA procedure demonstrated antibody responses in dogs inoculated with CCV, as did the virus neutralization test; the second ELISA detected specific CCV antigen in feces and organ homogenates of inoculated dogs.


title: Evolution of Mouse Hepatitis Virus (MHV) during Chronic Infection: Quasispecies Nature of the Persisting MHV RNA

text: Abstract Coronavirus infection of mice has been used extensively as a model for the study of acute encephalitis and chronic demyelination. To examine the evolution of coronavirus RNA during chronic demyelinating infection, we isolated RNA from intracerebrally inoculated mice at 4, 6, 8, 13, 20, and 42 days postinfection and used reverse transcription-polymerase chain reaction amplification methods (RT-PCR) to detect viral sequences. RNA sequences from two viral structural genes, the spike gene and the nucleocapsid gene, were detected throughout the chronic infection. In contrast, infectious virus was not detectable from brain homongenates beyond 13 days postinfection. These results indicate that coronavirus RNA persists in the brain at times when infectious virus is not detected. To determine if genetic changes were occurring during viral replication in the host, we cloned and sequenced the RT-PCR products from the spike and nucleocapsid regions and analyzed the sequences for mutations. Sequencing of the cloned products revealed that a variety of mutant forms of viral RNA persisted in the CNS, including point mutants, deletion mutants, and termination mutants. The mutations accumulated during persistent infection in both the spike and the nucleocapsid sequences, with greater than 65% of the mutations encoding amino acid changes. These results show that a diverse population or quasispecies consisting of mutant and deletion variant viral RNAs (which may not be capable of producing infectious virus particles) persists in the central nervous system of mice during chronic demyelinating infection. The implications of these results for the role of persistent viral genetic information in the pathogenesis of chronic demyelination are discussed.


title: Chest radiograph screening for severe acute respiratory syndrome in the ED

text: Abstract The purpose of the study was to evaluate the use of chest radiography for the screening of severe acute respiratory syndrome (SARS). We retrospectively analyzed all patients who attended an Emergency Department SARS screening clinic during the outbreak in Hong Kong, from March 10 to June 5, 2003. Patients with clinical and epidemiologic suspicion of SARS were evaluated by serial chest radiography. All radiographs were reported by consensus from 2 radiologists, blinded to the clinical records. The prevalence of SARS was 13.3% among 1328 patients included. The initial radiograph had sensitivity 50.3%, specificity 95.0%, positive likelihood ratio 10.06, negative likelihood ratio 0.52, positive predictive value 61.5%, and negative predictive value 92.3% for diagnosing SARS. Serial chest radiography had sensitivity 94.4%, specificity 93.9%, positive likelihood ratio 15.48, negative likelihood ratio 0.06, positive predictive value 71.4%, and negative predictive value 99.0%. The initial chest radiograph has poor sensitivity, and serial radiographs are required to rule out SARS.