title: The Potential of Various Nanotechnologies for Coronavirus Diagnosis/Treatment Highlighted through a Literature Analysis

text: [Image: see text] With the current COVID-19 outbreak, it has become essential to develop efficient methods for the treatment and detection of this virus. Among the new approaches that could be tested, that relying on nanotechnology finds one of its main grounds in the similarity between nanoparticle (NP) and coronavirus (COV) sizes, which promotes NP–COV interactions. Since COVID-19 is very recent, most studies in this field have focused on other types of coronavirus than COVID-19, such as those involved in MERS or SARS diseases. Although their number is limited, they have led to promising results on various COV using a wide range of different types of nanosystems, e.g., nanoparticles, quantum dos, or nanoassemblies of polymers/proteins. Additional efforts deserve to be spent in this field to consolidate these findings. Here, I first summarize the different nanotechnology-based methods used for COV detection, i.e., optical, electrical, or PCR ones, whose sensitivity was improved by the presence of nanoparticles. Furthermore, I present vaccination methods, which comprise nanoparticles used either as adjuvants or as active principles. They often yield a better-controlled immune response, possibly due to an improved antigen presentation/processing than in non-nanoformulated vaccines. Certain antiviral approaches also took advantage of nanoparticle uses, leading to specific mechanisms such as the blocking of virus replication at the cellular level or the reduction of a COV induced apoptotic cellular death.


title: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

text: BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)


title: Letter to the Editor Re: Coronavirus disease 2019: The harms of exaggerated information and nonevidence‐based measures

text: Dr. Ioannidis may cause irreparable harm from recent publications. Novel coronavirus, by definition, arrives without precedence and therefore the reliable data Ioannidis craves. The unshakable facts regarding the Covid-19 consists of the number of deaths, country populations, and the dataset from the Diamond Princess cruise.


title: Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study

text: BACKGROUND: Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population. METHODS: We conducted a retrospective cohort study at the San Raffaele Hospital in Milan, Italy. We included consecutive patients (aged ≥18 years) with COVID-19, moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive protein ≥100 mg/L, ferritin ≥900 ng/mL, or both) who were managed with non-invasive ventilation outside of the ICU and who received standard treatment of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally. We compared survival, mechanical ventilation-free survival, changes in C-reactive protein, respiratory function, and clinical status in a cohort of patients who received additional treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) with a retrospective cohort of patients who did not receive anakinra (referred to as the standard treatment group). All outcomes were assessed at 21 days. This study is part of the COVID-19 Biobank study, which is registered with ClinicalTrials.gov, NCT04318366. FINDINGS: Between March 17 and March 27, 2020, 29 patients received high-dose intravenous anakinra, non-invasive ventilation, and standard treatment. Between March 10 and March 17, 2020, 16 patients received non-invasive ventilation and standard treatment only and comprised the comparison group for this study. A further seven patients received low-dose subcutaneous anakinra in addition to non-invasive ventilation and standard treatment; however, anakinra treatment was interrupted after 7 days because of a paucity of effects on serum C-reactive protein and clinical status. At 21 days, treatment with high-dose anakinra was associated with reductions in serum C-reactive protein and progressive improvements in respiratory function in 21 (72%) of 29 patients; five (17%) patients were on mechanical ventilation and three (10%) died. In the standard treatment group, eight (50%) of 16 patients showed respiratory improvement at 21 days; one (6%) patient was on mechanical ventilation and seven (44%) died. At 21 days, survival was 90% in the high-dose anakinra group and 56% in the standard treatment group (p=0·009). Mechanical ventilation-free survival was 72% in the anakinra group versus 50% in the standard treatment group (p=0·15). Bacteraemia occurred in four (14%) of 29 patients receiving high-dose anakinra and two (13%) of 16 patients receiving standard treatment. Discontinuation of anakinra was not followed by inflammatory relapses. INTERPRETATION: In this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients. Confirmation of efficacy will require controlled trials. FUNDING: None.


title: Impact of Hajj on Global Health Security

text: With the human society transfers from scattered pieces to a society as a whole and the advent of the aviation era, the occurrence of infectious diseases and their diffusion have led to international health security issues. As the world’s largest and irrevocable annual transnational religious movement, the Hajj and its connection with health security concerns have caught attention since the ancient times, because a huge population from all over the world gathers in the holy city of Mecca, which has tropical arid climate. Currently, the international community and international organizations are implementing multilevel governance with respect to the health security issues of the Hajj. Relevant agencies include the World Health Organization and its regional branches, International Red Cross and Red Crescent Movement (ICRC), the Ministry of Hajj as well as the Ministry of Health of Saudi Arabia, and the public health sectors/agencies in various countries that are involved with Hajj activities. The international community has successfully held the Hajj events, even when facing the challenges brought by some viral respiratory diseases such as SARS and MERS. The Hajj has become a rare opportunity for all stakeholders to improve their capabilities in international health security governance.


title: Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020

text: In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.


title: Large eddy simulation of wind‐induced interunit dispersion around multistory buildings

text: Previous studies regarding interunit dispersion used Reynolds‐averaged Navier–Stokes (RANS) models and thus obtained only mean dispersion routes and re‐entry ratios. Given that the envelope flow around a building is highly fluctuating, mean values could be insufficient to describe interunit dispersion. This study investigates the wind‐induced interunit dispersion around multistory buildings using the large eddy simulation (LES) method. This is the first time interunit dispersion has been investigated transiently using a LES model. The quality of the selected LES model is seriously assured through both experimental validation and sensitivity analyses. Two aspects are paid special attention: (i) comparison of dispersion routes with those provided by previous RANS simulations and (ii) comparison of timescales with those of natural ventilation and the survival times of pathogens. The LES results reveal larger dispersion scopes than the RANS results. Such larger scopes could be caused by the fluctuating and stochastic nature of envelope flows, which, however, is canceled out by the inherent Reynolds‐averaged treatment of RANS models. The timescales of interunit dispersion are comparable with those of natural ventilation. They are much shorter than the survival time of most pathogens under ordinary physical environments, indicating that interunit dispersion is a valid route for disease transmission.


title: COVID-19, chronic inflammatory rheumatic disease and anti-rheumatic treatments

text: Since December 2019, the pandemic caused by coronavirus disease 2019 (COVID-19) raises a real public health problem. COVID-19 appeared in Wuhan (Hubei province) in China. Drugs that have been used in rheumatology for decades seem to be effective in this infection and are for the most part being studied. The rational use of these anti-rheumatic drugs is based on the cytokinic storm (hyperproduction of IL1, IL6, TNF α) in the body by COVID-19 in its severe form. In this review, the authors make the difference between the infectious and auto-inflammatory part of COVID-19; the disease does not seem to be a risk factor for admission to the intensive care unit for patients suffering from inflammatory rheumatism; however, the poverty of studies on this subject should be noted. The authors also review anti-rheumatic drugs while studying COVID-19 treatment.


title: Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri

text: BACKGROUND: Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. RESULTS: The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. CONCLUSIONS: Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs.


title: Critical role of the lipid rafts in caprine herpesvirus type 1 infection in vitro

text: Abstract The fusion machinery for herpesvirus entry in the host cells involves the interactions of viral glycoproteins with cellular receptors, although additional viral and cellular domains are required. Extensive areas of the plasma membrane surface consist of lipid rafts organized into cholesterol-rich microdomains involved in signal transduction, protein sorting, membrane transport and in many processes of viruses infection. Because of the extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to the lipid rafts, we investigated the effect of cholesterol depletion by methyl-β-cyclodextrin (MβCD) on caprine herpesvirus 1 (CpHV.1) in three important phases of virus infection such as binding, entry and post-entry. MβCD treatment did not prejudice virus binding to cells, while a dose-dependent reduction of the virus yield was observed at the virus entry stage, and 30mM MβCD reduced infectivity evidently. Treatment of MDBK after virus entry revealed a moderate inhibitory effect suggesting that cholesterol is mainly required during virus entry rather than during the post-entry stage. Alteration of the envelope lipid composition affected virus entry and a noticeable reduction in virus infectivity was detected in the presence of 15mM MβCD. Considering that the recognition of a host cell receptor is a crucial step in the start-up phase of infection, these data are essential for the study of CpHV.1 pathogenesis. To date virus receptors for CpHV.1 have not yet been identified and further investigations are required to state that MβCD treatment affects the expression of the viral receptors.


title: Chapter 14 Diffusion, Strategic Interaction, and Social Structure

text: Abstract We provide an overview and synthesis of the literature on how social networks influence behaviors, with a focus on diffusion. We discuss some highlights from the empirical literature on the impact of networks on behaviors and diffusion. We also discuss some of the more prominent models of network interactions, including recent advances regarding interdependent behaviors, modeled via games on networks. JEL Classification Codes: D85, C72, L14, Z13


Etiology of acute respiratory infections in hospitalized children in Novosibirsk, Russia, in 2013–2017


title: Plasma Electrophoretogram in Feline Immunodeficiency Virus (FIV) and/or Feline Leukaemia Virus (FeLV) Infections

text: The electrophoretogram of 89 cats, including those infected by feline immunodeficiency virus (FIV+), feline leukaemia virus (FeLV+) and non‐infected, showed statistically significant differences in several of the fractions. FIV+ cats had very high protein values (mean, 8.10 g/dl), mostly because of hypergammaglobulinemia (mean, 2.81 g/dl) as compared with non‐infected animals and FeLV+. In addition, in these FIV+ animals, the albumin/globulins ratio (A/G) was very low (mean, 0.72). Statistically significant differences in A/G and α2‐globulin fraction were observed in FeLV+ group (A/G mean, 0.88 ± 0.08; α2‐globulin, mean, 0.84 ± 0.07 g/dl) when compared with non‐infected group (A/G mean, 1.06 ± 0.08; α2‐globulin mean, 0.68 ± 0.04 g/dl). The α1‐globulin fraction was higher in double infected animals (FIV and FeLV positive, F‐F) (3.55 g/dl), than in FeLV+ or FIV+ cats (3.10 and 3.07 g/dl respectively), but no statistical conclusions may be drawn from this fact because of the low number of F‐F animals. This technique may help to assess the initial clinical status of retrovirus‐infected cats, and the clinical course of these chronic diseases, specifically during and after suitable therapy.


Highly Attenuated Vaccinia Virus Dis as a Potential Sars Vaccine


Access to Care During a Global Health Crisis


title: Putative phage-display epitopes of the porcine epidemic diarrhea virus S1 protein and their anti-viral activity

text: Porcine epidemic diarrhea virus (PEDV) is a pathogen of swine that causes severe diarrhea and dehydration resulting in substantial morbidity and mortality in newborn piglets. Phage display is a technique with wide application, in particular, the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines. To identify antigen epitopes with specificity for PEDV, a monoclonal antibody (MAb-5E12) against the immunodominant region of the PEDV Spike protein (S1) was used as the target for biopanning a 12-mer phage display, random peptide library. After multiple rounds of biopanning and stringent washing, three phage-displayed peptides, designated L, W and H, were identified that recognize MAb-5E12. Sequence analysis showed that the one or more of the peptides exhibited partial sequence similarity to the native S1 sequence ‘MQYVYTPTYYML’ (designated peptide M) at position 201–212. In combination with software analysis for the prediction of B cell epitopes, aa 201–212 exhibited characteristics of a linear epitope on the PEDV S1 protein. In contrast to peptide M, a consensus motif ‘PxxY’ was identified on both peptides L and W, and on the S1 protein, but not on peptide H. Peptide M and the MAb-5E12-recognizing peptides L and W significantly inhibited the adsorption of PEDV on the cell surface as monitored through plaque-reduction assays. Furthermore, data from real-time PCR and indirect immunofluorescence assays were consistent with the ability of peptides M, L and W to block viral protein expression and thereby function as antiviral agents for PEDV.


title: Minimizing aerosol bone dust during autopsies

text: When sawing bone for medical or medico-legal procedures, fine, airborne dust is produced (aerosols) that can pose a health hazard when inhaled. The aim of this study was to determine the influence of saw blade frequency and contact load, bone condition, test environment, and saw blade type, on the production of aerosol particles. A custom test setup was designed, manufactured and used in 8 bone sawing experiments, using a particle counter to determine the production of aerosol particles while varying the 5 chosen parameters. The number of counted particles was highest with higher saw blade frequencies, lower saw blade contact loads, in dry completely skeletonized bone compared to fresh bone, and using an electrical oscillating saw compared to hand-sawing. Under all conditions, the high amount of aerosol counted posed potential health risks. The ventilation system that we tested was adequate in removing the produced particles, but these high-tech systems are not always available in developing countries or emergency situations. The production of aerosols can be reduced by optimizing the sawing parameters. However, even the lowest number of aerosol particles counted during the current study was high enough to cause potential health risks to practitioners. Safety precautions should be taken, such as external ventilation, proper breathing gear, and adequate protocols, to truly minimize the risk in all bone sawing scenarios.


ISUOG Consensus Statement on rationalization of gynecological ultrasound services in context of SARS‐CoV‐2


Presence of SARS-CoV-2 RNA in Isolation Ward Environment 28 Days after Exposure


title: Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: changes in treatment modalities related to the COVID-19 health crisis

text: Summary The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system. It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis. The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.


Letter to the editor on the outcomes in fracture patients infected with COVID-19.


An analytical study of behavioral risks and illness among camel keeper and non-camel keeper at zoo parks in Thailand 2014


title: Calculating virus spread

text: Getting a full picture of the coronavirus outbreak is extremely difficult. Maths can help plug some of the gaps, says Adam Kucharski


title: Strategies for risk management in urban–rural conflict: Two case studies of land acquisition in urbanising China

text: Urban and rural environments show clear differences in morphology, production mode and culture. With rapid urbanisation, these differences have become a major cause of urban–rural conflict. One of the most significant challenges arises from land acquisition, particularly in China, where cities have experienced substantial growth in the 21st century. Different types of risk are associated with land acquisition conflict in different Chinese cities. In this study, two types of cities are discussed: those with a historically low level of development but recent rapid economic growth, such as Yueqing; and cities that have maintained a relatively high level of development and experienced stable growth, such as Jiaxing. Land acquisition conflict in these two representative cities is then analysed in terms of property rights, access to resources and development. Analysis is performed at the institutional level to provide more accurate insights into the dynamics of conflict. The findings of the study suggest that different risk-management strategies are used in the two kinds of city, and that conflict is more likely to occur in cities with historically weaker development, such as Yueqing. To avoid such conflict, systematic risk-management strategies should be established in these cities.


First paediatric COVID‐19 associated death in Italy


title: Foodborne Diseases: Prevalence of Foodborne Diseases in Europe

text: Abstract Official estimates of the prevalence of foodborne disease are highly biased, failing to account for underdiagnosis and underreporting of laboratory-confirmed clinical disease in people. To overcome the biases inherent in routine surveillance there has been a burgeoning in methods used to assess the prevalence of foodborne disease in Europe. These show that prevalence of foodborne illness across Europe is very high no matter what method is used to measure it. Salmonella and Campylobacter are consistently found to be the leading foodborne pathogens in Europe.


Dépistage et diagnostic du cancer du sein à la fin de période de confinement COVID-19, aspects pratiques et hiérarchisation des priorités


title: The Impact of Schistosoma japonicum Infection and Treatment on Ultrasound-Detectable Morbidity: A Five-Year Cohort Study in Southwest China

text: BACKGROUND: Ultrasonography allows for non-invasive examination of the liver and spleen and can further our understanding of schistosomiasis morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We followed 578 people in Southwest China for up to five years. Participants were tested for Schistosoma japonicum infection in stool and seven standard measures of the liver and spleen were obtained using ultrasound to evaluate the relationship between schistosomiasis infection and ultrasound-detectable pathology, and the impact of targeted treatment on morbidity. Parenchymal fibrosis, a network pattern of the liver unique to S. japonicum, was associated with infection at the time of ultrasound (OR 1.40, 95% CI: 1.03–1.90) and infection intensity (test for trend, p = 0.002), adjusting for age, sex and year, and more strongly associated with prior infection status and intensity (adjusted OR 1.84, 95% CI: 1.30–2.60; test for trend: p<0.001 respectively), despite prompt treatment of infections. While declines in parenchymal fibrosis over time were statistically significant, only 28% of individuals with severe parenchymal fibrosis (grades 2 or 3) at enrollment reversed to normal or grade 1 within five years. Other liver abnormalities were less consistently associated with S. japonicum infection. CONCLUSIONS/SIGNIFICANCE: Parenchymal fibrosis is an appropriate measure of S. japonicum morbidity and can document reductions in disease following control efforts. Other ultrasound measures may have limited epidemiological value in regions with similar infection levels. Because severe fibrosis may not reverse quickly following treatment, efforts to reduce exposure to S. japonicum should be considered in combination with treatment to prevent schistosomiasis morbidity.


title: Transgenic milk as a method for the production of recombinant antibodies

text: Abstract Recombinant antibodies and their derivatives are increasingly being used as therapeutic agents. Clinical applications of antibodies often require large amounts of highly purified molecules, sometimes for multiple treatments. The development of very efficient expression systems is essential to the full exploitation of the antibody technology. Production of recombinant protein in the milk of transgenic dairy animals is currently being tested as an alternative to plasma fractionation for the manufacture of a number of blood factors (human antithrombin, human alpha-1-antitrypsin, human serum albumin, factor IX). The ability to routinely yield mg/ml levels of antibodies and the scale-up flexibility make transgenic production an attractive alternative to mammalian cell culture as a source of large quantities of biotherapeutics. The following review examines the potential of transgenic expression for the production of recombinant therapeutic antibodies.


title: The Risk of SARS-CoV-2 in Immunosuppressed IBD Patients

text: The SARS-CoV-19 virus and COVID-19 disease raise important questions about the risks to immunosuppressed IBD patients. We review the available data, including the SECURE IBD registry, and draw parallels to previous pandemics of influenza, SARs, and MERS.


title: Strength, Weakness, Opportunity, Threat (SWOT) Analysis of the Adaptations to Anatomical Education in the United Kingdom and Republic of Ireland in Response to the Covid‐19 Pandemic

text: The Covid‐19 pandemic has driven the fastest changes to higher education across the globe, necessitated by social distancing measures preventing face‐to‐face teaching. This has led to an almost immediate switch to distance learning by higher education institutions. Anatomy faces some unique challenges. Intrinsically, anatomy is a three‐dimensional subject that requires a sound understanding of the relationships between structures, often achieved by the study of human cadaveric material, models, and virtual resources. This study sought to identify the approaches taken in the United Kingdom and Republic of Ireland to deliver anatomical education through online means. Data were collected from 14 different universities in the United Kingdom and Republic of Ireland and compared adopting a thematic analysis approach. Once themes were generated, they were collectively brought together using a strength, weakness, opportunity, threat (SWOT) analysis. Key themes included the opportunity to develop new online resources and the chance to engage in new academic collaborations. Academics frequently mentioned the challenge that time constrains could place on the quality and effectiveness of these resources; especially as in many cases the aim of these resources was to compensate for a lack of exposure to cadaveric exposure. Comparisons of the actions taken by multiple higher education institutions reveal the ways that academics have tried to balance this demand. Discussions will facilitate decisions being made by higher education institutions regarding adapting the curriculum and assessment methods in anatomy.


title: COVID‐19 associated pulmonary aspergillosis (CAPA) in patients admitted with severe COVID‐19 pneumonia: An observational study from Pakistan

text: BACKGROUND: Invasive aspergillosis is a well‐known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID‐19 pneumonia, named as COVID‐19 associated aspergillosis (CAPA). METHODS: A retrospective observational study was conducted in patients with severe COVID‐19 pneumonia from February 2020‐ April 2020. Patients’ ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID‐19 by RT‐PCR for SARS‐Cov‐2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma and descriptive analysis was performed using Stata ver 12.1. RESULTS: A total of 147 patients with confirmed COVID‐19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients and of these five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonization. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51 – 85) and 3/5 patients were male. The most frequent co‐morbid was diabetes mellitus (4/5). The overall fatality rate of COVID‐19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all 3 patients with CAPA and the median length of stay was 16 days (IQR: 10; Range 6‐35 days). CONCLUSION: This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID‐19 and the need for screening for fungal infections in severe COVID‐19 patients with certain risk factors.


29 Viruses in faeces


title: STABILITY ANALYSIS OF THE HIV MODEL THROUGH INCOMMENSURATE FRACTIONAL-ORDER NONLINEAR SYSTEM

text: In this study, it is employed a new model of HIV infection in the form of incommensurate fractional differential equations systems involving the Caputo fractional derivative. Existence of the model's equilibrium points has been investigated. According to some special cases of the derivative-orders in the proposed model, the asymptotic stability of the infection-free equilibrium and endemic equilibrium has been proved under certain conditions. These stability conditions related to the derivative-orders depend on not only the basic reproduction rate frequently emphasized in the literature but also the newly obtained conditions in this study. Qualitative analysis results were complemented by numerical simulations in Matlab, illustrating the obtained stability result.


title: Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

text: INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.


title: Avian diseases which affect egg production and quality

text: This chapter addresses diseases and syndromes which have been shown, or are reported, to have adverse effects on egg production and quality. However, any disease of poultry can adversely affect egg production and quality indirectly, by affecting the health of the bird. The main topics are the effect on egg production and quality of bacteria (Salmonella, Mycoplasma, Escherichia coli, infectious coryza, Ornithobacterium, Gallibacterium, spirochaetosis), viruses (infectious bronchitis virus, egg drop syndrome, swollen head syndrome, avian encephalomyelitis, influenza, Newcastle disease, laryngotracheitis), syndromes (fatty liver haemorrhagic syndrome, cage layer osteoporosis) and toxic agents. A short section on clinical perspectives reports on information obtained from practising poultry veterinarians as such observations can provide valuable starting points for future research.


title: Development of multiplexed bead arrays for the simultaneous detection of nucleic acid from multiple viruses in bat samples

text: Abstract Virus surveillance of wildlife populations is important for identifying, monitoring, and predicting the emergence of pathogens that pose a potential threat to animal and human health. Bats are identified as important wildlife hosts of many viruses capable of causing fatal human disease, including members of the henipaviruses, coronaviruses, rhabdoviruses and filoviruses. As global warming and habitat change are thought to impact upon pathogen transmission dynamics and increase the risk of spillover, virus surveillance in bat populations remains a significant component of efforts to improve the prediction and control of potential future disease outbreaks caused by bat-borne viruses. In this study we have developed two fluid bead array assays containing customized panels that target multiple bat-borne viruses. These assays detect up to 11 viral RNA's simultaneously in urine samples collected from wild bat populations in Australia and Bangladesh. The assays developed show high specificity for the target viruses and the analytical sensitivity compares favorably to qRT-PCR. These assays enhance the ability to monitor multi-pathogen dynamics and identify patterns of virus shedding from bat populations, thus informing key approaches to outbreak response and control.


title: Estimation of the time-varying reproduction number of COVID-19 outbreak in China

text: BACKGROUND: The 2019 novel coronavirus (COVID-19) outbreak in Wuhan, China has attracted world-wide attention. As of March 31, 2020, a total of 82,631 cases of COVID-19 in China were confirmed by the National Health Commission (NHC) of China. METHODS: Three approaches, namely Poisson likelihood-based method (ML), exponential growth rate-based method (EGR) and stochastic Susceptible-Infected-Removed dynamic model-based method (SIR), were implemented to estimate the basic and controlled reproduction numbers. RESULTS: A total of 198 chains of transmission together with dates of symptoms onset and 139 dates of infections were identified among 14,829 confirmed cases outside Hubei Province as reported as of March 31, 2020. Based on this information, we found that the serial interval had an average of 4.60 days with a standard deviation of 5.55 days, the incubation period had an average of 8.00 days with a standard deviation of 4.75 days and the infectious period had an average of 13.96 days with a standard deviation of 5.20 days. The estimated controlled reproduction numbers, [Formula: see text] , produced by all three methods in all analyzed regions of China are significantly smaller compared with the basic reproduction numbers [Formula: see text]. CONCLUSIONS: The controlled reproduction number in China is much lower than one in all regions of China by now. It fell below one within 30 days from the implementations of unprecedent containment measures, which indicates that the strong measures taken by China government was effective to contain the epidemic. Nonetheless, efforts are still needed in order to end the current epidemic as imported cases from overseas pose a high risk of a second outbreak.


title: Chapter Four Social Influence in Liver Fluke Transmission Application of Social Network Analysis of Food Sharing in Thai Isaan Culture

text: Abstract In northeastern Thai (Isaan) culture traditional raw fish dishes and raw fish-eating habits are common. Eating and sharing meals together among the community's members, especially relatives and neighbours, are a common practice in both daily life and social gathering events. Fish are a significant protein source and are associated with variety of traditional recipes. Cyprinid fish are one of the most preferred fish by Isaan villagers for daily consumption because they are accessible and affordable. Consumption of these fish probably causes the persistence of high endemicity of human liver fluke infection, particularly with Opisthorchis viverrini, in northeast Thailand. Because the consumption of raw cyprinid fish is a well-documented risk factor for liver fluke infection, sharing of risky raw fish dishes may influence disease transmission through a community. Social network analysis was used to investigate fish and fish-based meal sharing among household members in Isaan villages in liver fluke endemic areas. The findings from three studies confirmed the persistence of traditional Isaan raw fish consumption and food-sharing practice. Social connections via food sharing among villagers played an important role in liver fluke infection and transmission dynamics as a risk factor. Thus these sociocultural factors should be taken into account in designing strategies for control of opisthorchiasis and other food-borne illnesses at the community level.


title: Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview

text: Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment.


Pathogen Discovery


title: What is for dinner? Viral metagenomics of US store bought beef, pork, and chicken

text: Abstract We describe here the metagenomics-derived viral sequences detected in beef, pork, and chicken purchased from stores in San Francisco. In beef we detected four previously reported viruses (two parvoviruses belonging to different genera, an anellovirus, and one circovirus-like virus) and one novel bovine polyomavirus species (BPyV2-SF) whose closest relatives infect primates. Detection of porcine hokovirus in beef indicated that this parvovirus can infect both ungulate species. In pork we detected four known parvoviruses from three genera, an anellovirus, and pig circovirus 2. Chicken meat contained numerous gyrovirus sequences including those of chicken anemia virus and of a novel gyrovirus species (GyV7-SF). Our results provide an initial characterization of some of the viruses commonly found in US store-bought meats which included a diverse group of parvoviruses and viral families with small circular DNA genomes. Whether any of these viruses can infect humans will require testing human sera for specific antibodies.


docid: vmllprex

title: Considerations for remote learning in pathology during COVID‐19 social distancing


title: Scorpion Venom–Toxins that Aid in Drug Development: A Review

text: Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K(+), Na(+), Cl(−), Ca(2+)) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development.


Will COVID-19 be evidence-based medicine’s nemesis?


COVID-19 and diabetes: No time to drag our feet during an untimely pandemic()


title: The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections

text: Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis.


title: Tourist arrivals in four major economies: another side of economic policy uncertainty and fear

text: In this paper, we examine the direction of causal relationships among migration-related fear, economic policy uncertainty, tourism, and economic growth in the panel economies of France, Germany, the UK, and the USA. To the best of our knowledge, this study is the first to examine the interaction and interrelationship between these variables in a multivariate causality study, using a quarterly data over the period 1985Q1–2017Q4 via time-series causality approach as advanced by Emirmahmutoglu and Kose (Econ Model 28:870–876, 2011) that produces country-specific causality statistic and also captures slope heterogeneity in panel data. Empirical results show that migration-related fear is linked with EPU, tourism arrivals, and real income. Thus, we suggest fear-induced economic policy uncertainty, fear-induced tourism, and economic policy uncertainty–induced growth hypotheses with credible policy suggestions for tourist destinations.


Fostering the common good in times of COVID-19: the Responsible Innovation in Health perspective


title: Recombinant measles AIK-C vaccine strain expressing heterologous virus antigens

text: Further attenuated measles vaccines were developed more than 50 years ago and have been used throughout the world. Recombinant measles vaccine candidates have been developed and express several heterologous virus protective antigens. Immunogenicity and protective actions were confirmed using experimental animals: transgenic mice, cotton rats, and primates. The recent development of measles vaccine-based vectored vaccine candidates has been reviewed and some information on recombinant measles vaccines expressing respiratory syncytial virus proteins has been shown and discussed.


title: Host–pathogen interactions during porcine reproductive and respiratory syndrome virus 1 infection of piglets

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is a major disease affecting pigs worldwide and resulting in considerable economic losses. While PRRS is a global phenomenon, the causative viruses PRRSV-1 (first detected in Europe) and PRRSV-2 (isolated in North America) are genetically and biologically distinct. In addition, the disease outcome is directly linked to co-infections associated with the porcine respiratory disease complex and the host response is variable between different breeds of pigs. It is therefore warranted when studying the pathogenesis of PRRS to consider each viral genotype separately and apply careful consideration to the disease model studied. We here review the respiratory pig model for PRRSV-1, with a focus on a recent set of studies conducted with carefully selected virus strains and pigs, which may serve as both a baseline and benchmark for future investigation.


“Is compulsive social media use amid COVID-19 pandemic addictive behavior or coping mechanism?


title: Aesthetıc dermatology procedures ın coronavırus‐days

text: Severe acute respiratory syndrome‐corona virus‐2 (SARS‐CoV‐2; COVID‐19), which causes coronavirus disease 2019, is highly contagious and a particularly popular problem in all around the World and also in all departments of every hospital. Protecting the well‐being of the aesthetic dermatologists while providing a sufficient workforce is vital for pandemic planning. In this article, we will discuss this problem from an aesthetic dermatology aspect and we will review whether these procedures are safe or not.


title: Infections respiratoires aiguës virales et asthme de l'enfant Aspects épidémiologiques, immunopathologiques et thérapeutiques

text: Summary Respiratory viral infections are very important triggers of asthma exacerbation. Recent epidemiologic studies support the hypothesis that they are associated with 80 to 85 % of acute attacks of asthma in children, both in mild exacerbations, and in more severe exacerbations leading to hospital admission. The respiratory syncytial and parainfluenza viruses are predominantly detected in infants, while rhinovirus and mycoplasma are the commonest viruses in children. The detailed mechanism of virus-induced exacerbations remains poorly understood, al though recent studies have provided evidence of increased activation of inflammatory cells in bronchial lavage. Allergic individuals, outside of periods of allergy, do not seem to have more virus-induced respiratory manifestations than nonallergic individuals. In contrast, rhinovirus infection may intensify both the immediate and late response to allergen challenge by increasing mast cell mediator release and recruitment of eosinophils in the lower airways. Human and animal studies suggest that local production of cytokines (IL4, IL8, RANTES, MIP-1a...) and the increased expression of intercellular adhesion molecule 1 (ICAM1) in asthmatic individuals, may play an important role for recruitment and activation of inflammatory cells in the airways. One hypothesis, that remains to be demonstrated, would be that in the presence of Th2 predominance, as occurs in asthma, an excess of IL4 could inhibit the development of cytotoxic CD8, NK and Th1 activity, thereby resulting in decreased IFN production, more severe allergic inflammation and less efficient viral clearance.


title: The virus-immunity ecosystem

text: The ecology of pathogenic viruses can be considered both in the context of survival in the macro-environments of nature, the theme pursued generally by epidemiologists, and in the micro-environments of the infected host. The long-lived, complex, higher vertebrates have evolved specialized, adaptive immune systems designed to minimise the consequences of such parasitism. Through evolutionary time, the differential selective pressures exerted variously by the need for virus and host survival have shaped both the “one-host” and vertebrate immunity. With the development of vaccines to protect us from many of our most familiar parasites, the most dangerous pathogens threatening us now tend to be those “emerging”, or adventitious, infectious age sporadically enter human populations from avian or other wild-life reservoirs. Such incursions must, of course, have been happening through the millenia, and are likely to have led to the extraordinary diversity of recognition molecules, the breadth in effector functions, and the persistent memory that distinguishes the vertebrate, adaptive immune system from the innate response mechanisms that operate more widely through animal biology. Both are important to contemporary humans and, particularly in the period immediately following infection, we still rely heavily on an immediate response capacity, elements of which are shared with much simpler, and more primitive organisms. Perhaps we will now move forward to develop useful therapies that exploit, or mimic, such responses. At this stage, however, most of our hopes for minimizing the threat posed by viruses still focus on the manipulation of the more precisely targeted, adaptive immune system.


docid: dpawfnhw

title: Mathematical modeling of the spread of the coronavirus disease 2019 (COVID-19) taking into account the undetected infections. The case of China

text: Abstract In this paper we develop a mathematical model for the spread of the coronavirus disease 2019 (COVID-19). It is a new θ-SEIHRD model (not a SIR, SEIR or other general purpose model), which takes into account the known special characteristics of this disease, as the existence of infectious undetected cases and the different sanitary and infectiousness conditions of hospitalized people. In particular, it includes a novel approach that considers the fraction θ of detected cases over the real total infected cases, which allows to study the importance of this ratio on the impact of COVID-19. The model is also able to estimate the needs of beds in hospitals. It is complex enough to capture the most important effects, but also simple enough to allow an affordable identification of its parameters, using the data that authorities report on this pandemic. We study the particular case of China (including Chinese Mainland, Macao, Hong-Kong and Taiwan, as done by the World Health Organization in its reports on COVID-19), the country spreading the disease, and use its reported data to identify the model parameters, which can be of interest for estimating the spread of COVID-19 in other countries. We show a good agreement between the reported data and the estimations given by our model. We also study the behavior of the outputs returned by our model when considering incomplete reported data (by truncating them at some dates before and after the peak of daily reported cases). By comparing those results, we can estimate the error produced by the model when identifying the parameters at early stages of the pandemic. Finally, taking into account the advantages of the novelties introduced by our model, we study different scenarios to show how different values of the percentage of detected cases would have changed the global magnitude of COVID-19 in China, which can be of interest for policy makers.


title: Early diagnosis of radiodermatitis using lactate dehydrogenase isozymes in hairless mice (SKH1-hr)

text: In this study, we evaluate a method for the early diagnosis of radiodermatitis for use in the prevention and therapy of this condition. Hairless mice (SKH1-hr) were used to study the early diagnosis of radiodermatitis. Lactate dehydrogenase (LDH, EC 1.1.1.27) isozymes were analyzed using native-polyacrylamide gel electrophoresis and western blotting of blood serum and tissues collected from SKH1-hr mice. Radiodermatitis developed 24 days after the first X-irradiation. Reduced spleen weight was observed after the last X-irradiation (P<0.05). Thereafter the weight increased until 24 days after the first irradiation, finally reaching levels comparable to those in the sham-irradiated control group. LDH activity was the highest in skeletal muscle and lowest in blood serum. LDH C(4), A(4), A(3)B, A(2)B(2), AB(3), and B(4) isozymes were detected, in the mentioned order, from the cathode. This result was similar in other mouse strains. In the irradiated group, LDH A(4) isozyme levels were reduced in the serum until inflammation occurred, whereas those of B(4) isozyme were elevated. The subunits A and B followed a similar trend to that of LDH A(4) and B(4) isozyme, respectively. Importantly, antibodies against LDH B(4) isozyme could prove useful in the early diagnosis of radiodermatitis.


title: Pulmonary and Cardiac Infections in Athletes

text: Pulmonary and cardiac infections in the athlete can have a wide range of presentations and complications. These infections may present few problems for the training athlete or become life threatening. The team physician must be able to make an accurate diagnosis, give the appropriate treatment, understand the potential complications, and ensure proper follow-up and return-to-play protocols.


title: Three-dimensional Culture of Human Airway Epithelium in Matrigel for Evaluation of Human Rhinovirus C and Bocavirus Infections

text: Abstract Objective Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses. Methods A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA. Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system. Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.


title: A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections

text: BACKGROUND: Immunofluorescence and virus culture are the main methods used to diagnose acute respiratory virus infections. Diagnosing these infections using nucleic acid amplification presents technical challenges, one of which is facilitating the different optimal annealing temperatures needed for each virus. To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses. RESULTS: Over an 18 month period a total of 222 specimens were tested by both immunofluorescence and the molecular strip. The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y) and 5 quality assurance scheme specimens. Viruses were recovered from a number of specimen types including broncho-alveolar lavage, nasopharyngeal secretions, sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses were detected in the study from 79 patients and 4 quality control specimens: 31 by immunofluorescence and 99 using the molecular strip. The strip consistently out-performed immunofluorescence with no loss of diagnostic specificity. CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. Results by immunofluorescence were available after an average of 4–12 hours while molecular strip results were available within 24 hours, considerably faster than viral culture. The combined strip and touchdown protocol proved to be a convenient and reliable method of testing for multiple viruses in a routine setting.


title: An optimized microarray platform for assaying genomic variation in Plasmodium falciparum field populations

text: We present an optimized probe design for copy number variation (CNV) and SNP genotyping in the Plasmodium falciparum genome. We demonstrate that variable length and isothermal probes are superior to static length probes. We show that sample preparation and hybridization conditions mitigate the effects of host DNA contamination in field samples. The microarray and workflow presented can be used to identify CNVs and SNPs with 95% accuracy in a single hybridization, in field samples containing up to 92% human DNA contamination.


title: An infectious RNA with a hepta-adenosine stretch responsible for programmed −1 ribosomal frameshift derived from a full-length cDNA clone of Hibiscus latent Singapore virus

text: Abstract Hibiscus latent Singapore virus (HLSV) is a member of Tobamovirus and its full-length cDNA clones were constructed. The in vitro transcripts from two HLSV full-length cDNA clones, which contain a hepta-adenosine stretch (pHLSV-7A) and an octo-adenosine stretch (pHLSV-8A), are both infectious. The replication level of HLSV-7A in Nicotiana benthamiana protoplasts was 5-fold lower, as compared to that of HLSV-8A. The replicase proteins of HLSV-7A were produced through programmed −1 ribosomal frameshift (−1 PRF) and the 7A stretch was a slippery sequence for −1 PRF. Mutations to the downstream pseudoknot of 7A stretch showed that the pseudoknot was not required for the frameshift in vitro. The stretch was found to be extended to 8A after subsequent replication cycles in vivo. It is envisaged that HLSV employs the monotonous runs of A and −1 PRF to convert its 7A to 8A to reach higher replication for its survival in plants.


title: Chapter 9 Respiratory System Diseases of Nonhuman Primates

text: Respiratory diseases are among the most important problems affecting nonhuman primate husbandry, especially among newly imported and outdoor-housed primates. Respiratory diseases are also a significant cause of morbidity and mortality in wild populations. Respiratory problems can affect the nasal passages and paranasal sinuses, the laryngeal air sacs, the larynx, trachea bronchi, and lung parenchyma (including vasculature and alveoli) and may be caused by direct infection with a variety of agents, including viruses, bacteria, fungi, and parasites, as well as by noninfectious, inflammatory stimuli such as particulates, allergens, pneuotoxins, and endogenous inflammatory mediators. Many of the respiratory pathogens reported in this chapter also affect humans or are of human origin (zoonotic or anthropozoonotic). This chapter reviews comparative respiratory anatomy and physiology as well as the diseases affecting all components of the respiratory system of nonhuman primates.


title: ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients

text: BACKGROUND: Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). METHODS: This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmH(2)O and ICU-acquired weakness was defined by Medical Research Council (MRC) score < 48. HRQOL was evaluated with the SF-36 questionnaire. RESULTS: Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p < 0.01)]. Health-related quality of life was not influenced by the presence of ICU-acquired weakness, diaphragm dysfunction or their coexistence. CONCLUSIONS: ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.


Can Colchicine as an Old Anti‐Inflammatory Agent Be Effective in COVID‐19?


title: Avian influenza viral nucleocapsid and hemagglutinin proteins induce chicken CD8+ memory T lymphocytes

text: Abstract The avian influenza viruses (AIVs) can be highly contagious to poultry and a zoonotic threat to humans. Since the memory CD8+ T lymphocyte responses in chickens to AIV proteins have not been defined, these responses to H5N9 AIV hemagglutinin (HA) and nucleocapsid (NP) proteins were evaluated by ex vivo stimulation with virus infected non-professional antigen presenting cells. Secretion of IFNγ by activated T lymphocytes was evaluated through macrophage induction of nitric oxide. AIV specific, MHC-I restricted memory CD8+ T lymphocyte responses to NP and HA were observed 3 to 9 weeks post-inoculation (p.i.). The responses specific to NP were greater than those to HA with maximum responses being observed at 5 weeks p.i. followed by a decline to weakly detectable levels by 9 weeks p.i. The cross-reaction of T lymphocytes to a heterologous H7N2 AIV strain demonstrated their ability to respond to a broader range of AIV.


title: Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

text: Summary Background We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). Methods We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. Findings Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. Interpretation The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf


title: Synthesis and Anti-HIV-1 Activity of Olean-9(11),12(13)-Dien-30-Oic Acid 3β-(2-O-β-D-Glucuronopyranosyl-β-D-Glucuronopyranoside)

text: The glycyrrhizic acid (GA) analog olean-9(11),12(13)-dien-30-oic acid 3β-(2-O-β-D-glucuronopyranosyl-β-D-glucuronopyranoside) (II) was synthesized via reduction of GA by NaBH(4) in refluxing 2-PrOH:H(2)O with subsequent work up with HCl (5%). The cytotoxicity and antiviral activity of this glycoside against HIV-1 was studied in MT-4 cell culture. It was found that II was practically non-toxic for MT-4 cells while inhibiting accumulation of virus-specific protein p24 and RNA-dependent DNA-polymerase activity of HIV-1 reverse transcriptase (RT) (IC(50) 3.1 ±1.0 μg/mL).


title: BCG vaccination strategy implemented to reduce the impact of COVID-19: Hype or Hope?

text: Abstract The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a adaptive immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.


title: Novel Coronavirus Pneumonia (COVID-19) Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section CT Features During Recovery

text: BACKGROUND: To retrospectively analyze the evolution of clinical features and thin-section CT imaging of novel coronavirus pneumonia (COVID-19) in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and CT pattern were documented in all patients during 4 weeks since admission. CT score was used to evaluate the extent of the disease. RESULTS: There was a marked improvement of fever, lymphocytes count, C-reactive protein and erythrocyte sedimentation rate within the first two weeks since admission. However, the mean CT score rapidly increased from the 1(st) to 3(rd) week, with a top score of 8.2 obtained in the 2(nd) week. During the 1(st) week, the main CT pattern was ground-glass opacities (GGO,76.5%). The frequency of GGO (52.9%) decreased in the 2(nd) week. Consolidation and mixed patterns (47.0%) were noted in the 2(nd) week. Thereafter, consolidations generally dissipated into GGO and the frequency of GGO increased in the 3(rd) week (76.5%) and 4(th) week (71.4%). Opacities were mainly located in the peripheral (76.5%), subpleural (47.1%) zones of the lungs, and presented as focal (35.3%) or multifocal (29.4%) in the 1(st) week and became more diffuse in the 2(nd) (47.1%) and 3(rd )week (58.8%), then showed reduced extent in 4(th )week (50%). CONCLUSIONS: The progression course of CT pattern was later than the clinical parameters within the first two weeks since admission; however, there was a synchronized improvement in both clinical and radiologic features in the 4(th) week.


Nasal colonization with coronavirus and apnea of the premature newborn


title: Replacing nebulizers by MDI-spacers for bronchodilator and inhaled corticosteroid administration: Impact on the utilization of hospital resources

text: Abstract Background and objectives Metered-dose inhalers plus spacers (MDI-spacer) are as effective as, or better than, nebulizers in aerosol delivery. The selection of aerosol delivery system for hospitalized children can have a significant impact on the utilization of healthcare resources. Design and setting A quality improvement project to evaluate the impact of conversion to MDI-spacer to administer bronchodilators (BDs) and inhaled corticosteroids (ICSs) to hospitalized children on the utilization of hospital resources. The project was conducted in a tertiary pediatric ward from April to May 2013. Materials and methods The project was conducted over a six-week period. In the first two weeks, data were gathered from all hospitalized children receiving BDs and/or ICSs by nebulizers. This data collection was followed by a two-week washout period during which training of healthcare providers and operational changes were implemented to enhance the conversion to MDI-spacer. In the last two weeks, data were gathered from hospitalized children after conversion to MDI-spacer. The primary outcomes included the mean time (in minutes) of medication preparation and delivery. Secondary outcomes included the following: need for respiratory therapy assistance, estimated cost of treatment sessions, and patient/caregiver satisfaction. Results Five hundred seventy-five treatment sessions were enrolled (288 on nebulizers, 287 on MDI-spacer). The nebulizer group had more male predominance and were slightly older compared to the MDI-spacer group (male: 59% vs. 53% and mean age: 52 vs. 40 months respectively). The duration of treatment preparation and delivery was significantly lower in the MDI-spacer group (2 min reduction in preparation time and 5 min reduction in delivery time; p < 0.01). Caregivers mastered MDI-spacer use after an average of two observed sessions, eliminating the need for respiratory therapy assistance during the hospital stay. Medication cost analysis showed savings in favor of MDI-spacer (cost reduction per 100 doses: 50% for albuterol, 30% for ipratropium bromide, and 87% for ICSs). The patient satisfaction survey showed “very good” to “excellent” levels in both groups. Conclusions Conversion to MDI-spacer for BDs and ICSs administration in hospitalized children improve hospital resource utilization.


title: Preparedness and Response to COVID-19 in Saudi Arabia: Building on MERS Experience

text: Abstract Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.


title: Immune system dysfunction during exposure to poult enteritis and mortality syndrome agents

text: Abstract Poult Enteritis and Mortality Syndrome (PEMS) is a condition of yet undefined etiology. Affected flocks may exhibit 100% morbidity with mortality up to 50% or more between 2 to 4 wk of age. The current study reports the immune status of poults experimentally infected with PEMS agent(s) in various trials. When compared with the unchallenged controls, PEMS-infected poults had significant atrophy of the bursa (up to 2-fold), thymus (up to 11-fold), and spleen (up to 2-fold) (P < or = 0.05). When challenged with SRBC, PEMS-infected poults had 1 to 2 log2 lower anti-SRBC antibody titers than the controls (P < or = 0.05). Responsiveness to a mitogenic lectin, phytohemagglutinin-P, was reduced significantly in PEMS poults (P < or = 0.05). These data show that the immune system of the poults is compromised significantly during PEMS infection in terms of lymphoid organ integrity and humoral and cell-mediated immunity. These findings imply, therefore, that immune dysfunction may contribute to the mortality observed during PEMS outbreaks.


title: Severe outbreak of bovine coronavirus infection in dairy cattle during the warmer season

text: Abstract A severe outbreak of enteric and respiratory disease associated with bovine coronavirus (BCoV) infection is described. The outbreak occurred in a dairy herd of southern Italy in the first decade of September 2006, when summer temperatures were still recorded, affecting calves, heifers and adult cows, with a marked decrease in milk production. By virus isolation and RT-PCR targeting the S gene, BCoV was identified as the etiological agent of the outbreak, whereas bacteriological, parasitological and toxicological investigations failed to detect other causes of disease. BCoV strains with 99–100% nucleotide identity in the S gene were isolated from nasal, ocular and rectal swabs, thus proving the absence of separate clusters of virus on the basis of tissue tropism. Sequence analysis of the haemagglutination-esterase and spike proteins of the strain detected in one rectal sample (339/06) showed a high genetic relatedness with recent BCoV isolates (98–99% amino acid identity), with several unique amino acid substitutions in the S protein. The BCoV outbreak described in this paper presents interesting aspects: (i) the occurrence of a severe form of disease in the warmer season; (ii) the simultaneous presence of respiratory and enteric disease; (iii) the involvement of young as well as adult cattle.


title: The immunomodulatory CEA cell adhesion molecule 6 (CEACAM6/CD66c) is a candidate receptor for the influenza A virus

text: To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoprotein as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (CEACAM6) as a glycoprotein receptor for Influenza A virus. Significance Statement Cells are enclosed by a semipermeable membrane that allows selective exchange of biomolecules between cells and their surroundings. A set of specialized proteins in this semipermeable membrane, work like gatekeepers to the cell and regulate entry of these biomolecules. One class of such surface proteins is termed as receptors. Viruses bind to one or more of these receptors and manipulate gatekeepers for their own successful entry into host-cells. A membrane protein that influenza A virus (Flu virus) uses for entry into the cells was not discovered till date. This study reports for the first time, a receptor for influenza A virus, that was sought after by researchers for decades. The viral receptor is a promising target that can be used to inhibit virus entry into host cells.


title: Profile analysis of circRNAs induced by porcine endemic diarrhea virus infection in porcine intestinal epithelial cells

text: Abstract The circRNA is a newly defined noncoding RNA and characterized by its unique splicing reactions to form circles. However, the function of circRNAs during viral infection remains largely unknown. In this study, the circRNA expression profile during porcine endemic diarrhea virus (PEDV) infection in IPEC-J2 cell line was investigated using the next-generation sequencing technology. A total of 26670 circRNA candidates were identified. The functional annotation analysis revealed that the parent genes of differentially expressed circRNAs might be associated with host response to PEDV infection. Further analysis verified the existence of eight selected circRNAs and confirmed that PEDV infection alerted the expression patterns of circRNAs and their linear parent genes in IPEC-J2 cell line. The circRNA-miRNA interaction network was also constructed to elucidate their potential targets. Our results provided not only the first large-scale profile analysis of circRNAs associated with PEDV infection but also a novel direction to elucidate host-PEDV interactions.


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title: Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells

text: Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there is growing evidence showing that autophagy can exert a lethal function via autophagic cell death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), there is a high medical need for identifying novel ACD-inducing drugs. Therefore, we screened a library containing 70 autophagy-inducing compounds to induce ATG5-dependent cell death in human MZ-54 GBM cells. Here, we identified three compounds, i.e. loperamide, pimozide, and STF-62247 that significantly induce cell death in several GBM cell lines compared to CRISPR/Cas9-generated ATG5- or ATG7-deficient cells, pointing to a death-promoting role of autophagy. Further cell death analyses conducted using pharmacological inhibitors revealed that apoptosis, ferroptosis, and necroptosis only play minor roles in loperamide-, pimozide- or STF-62247-induced cell death. Intriguingly, these three compounds induce massive lipidation of the autophagy marker protein LC3B as well as the formation of LC3B puncta, which are characteristic of autophagy. Furthermore, loperamide, pimozide, and STF-62247 enhance the autophagic flux in parental MZ-54 cells, but not in ATG5 or ATG7 knockout (KO) MZ-54 cells. In addition, loperamide- and pimozide-treated cells display a massive formation of autophagosomes and autolysosomes at the ultrastructural level. Finally, stimulation of autophagy by all three compounds is accompanied by dephosphorylation of mammalian target of rapamycin complex 1 (mTORC1), a well-known negative regulator of autophagy. In summary, our results indicate that loperamide, pimozide, and STF-62247 induce ATG5- and ATG7-dependent cell death in GBM cells, which is preceded by a massive induction of autophagy. These findings emphasize the lethal function and potential clinical relevance of hyperactivated autophagy in GBM.


title: Editorial: low population mortality from COVID‐19 in countries south of latitude 35 degrees North—supports vitamin D as a factor determining severity. Authors' reply

text: LINKED CONTENT This article is linked to Al‐Ani et al and Rhodes et al papers. To view these articles, visit https://doi.org/10.1111/apt.15779 and https://doi.org/10.1111/apt.15777.


title: Detection of swine transmissible gastroenteritis coronavirus using loop-mediated isothermal amplification

text: A conserved nucleic acid fragment of the nucleocapsid gene of Swine Transmissible Gastroenteritis Coronavirus (TGEV) was chosen as the target, six special primers were designed successfully. Loop-mediated isothermal amplification (LAMP) was developed to detect the TGEV by incubation at 60°C for 1 h and the product specificity was confirmed by HphI digestion. Standard curves with high accuracy for TGEV quantization was constructed by adding 1 × SYBR greenI in the LAMP reaction. The assay established in this study was found to detect only the TGEV and no cross-reaction with other viruses, demonstrating its high specificity. By using serial sample dilutions as templates, the detection limit of LAMP was about 10 pg RNA, 10 times more sensitive than that of PCR and could be comparable to the nest-PCR.


title: Influenza virus morphogenesis and budding

text: Influenza viruses are enveloped, negative stranded, segmented RNA viruses belonging to Orthomyxoviridae family. Each virion consists of three major subviral components, namely (i) a viral envelope decorated with three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and M2, (ii) an intermediate layer of matrix protein (M1), and (iii) an innermost helical viral ribonucleocapsid [vRNP] core formed by nucleoprotein (NP) and negative strand viral RNA (vRNA). Since complete virus particles are not found inside the cell, the processes of assembly, morphogenesis, budding and release of progeny virus particles at the plasma membrane of the infected cells are critically important for the production of infectious virions and pathogenesis of influenza viruses as well. Morphogenesis and budding require that all virus components must be brought to the budding site which is the apical plasma membrane in polarized epithelial cells whether in vitro cultured cells or in vivo infected animals. HA and NA forming the outer spikes on the viral envelope possess apical sorting signals and use exocytic pathways and lipid rafts for cell surface transport and apical sorting. NP also has apical determinant(s) and is probably transported to the apical budding site similarly via lipid rafts and/or through cortical actin microfilaments. M1 binds the NP and the exposed RNAs of vRNPs, as well as to the cytoplasmic tails (CT) and transmembrane (TM) domains of HA, NA and M2, and is likely brought to the budding site on the piggy-back of vRNP and transmembrane proteins. Budding processes involve bud initiation, bud growth and bud release. Presence of lipid rafts and assembly of viral components at the budding site can cause asymmetry of lipid bilayers and outward membrane bending leading to bud initiation and bud growth. Bud release requires fusion of the apposing viral and cellular membranes and scission of the virus buds from the infected cellular membrane. The processes involved in bud initiation, bud growth and bud scission/release require involvement both viral and host components and can affect bud closing and virus release in both positive and negative ways. Among the viral components, M1, M2 and NA play important roles in bud release and M1, M2 and NA mutations all affect the morphology of buds and released viruses. Disassembly of host cortical actin microfilaments at the pinching-off site appears to facilitate bud fission and release. Bud scission is energy dependent and only a small fraction of virus buds present on the cell surface is released. Discontinuity of M1 layer underneath the lipid bilayer, absence of outer membrane spikes, absence of lipid rafts in the lipid bilayer, as well as possible presence of M2 and disassembly of cortical actin microfilaments at the pinching off site appear to facilitate bud fission and bud release. We provide our current understanding of these important processes leading to the production of infectious influenza virus particles.


title: A Highly Pathogenic Strain of Porcine Deltacoronavirus Caused Watery Diarrhea in Newborn Piglets

text: Porcine deltacoronavirus (PDCoV) is a newly identified virus that causes watery diarrhea in newborn piglets and results in significant economic losses to the pig industry. Since first reported in Hong Kong in 2012, PDCoV has been subsequently detected in USA, South Korea, Thailand, and mainland China. Here we isolated a strain of PDCoV, named CHN-GD-2016, from the intestinal content of a diseased newborn piglet with severe diarrhea in a pig farm in Guangdong, China. PDCoV CHN-GD-2016 could be identified by immunofluorescence with PDCoV specific rabbit antisera, and typical crown-shaped particles with spiky surface projections of this PDCoV were observed with electron microscopy. Genomic analysis showed that the PDCoV CHN-GD-2016 was closely related to other Chinese PDCoV strains, with the highest sequence similarity with the strain CHN/Tianjin/2016. Importantly, inoculation of newborn piglets with 1 × 10(5) TCID(50) of CHN-GD-2016 by oral feeding successfully reproduced clear clinical symptoms, including vomiting, dehydration, and severe diarrhea in piglets. In addition, the virus RNA in rectal swabs from 1 to 7 days post inoculation was detected, macroscopic and microscopic lesions in small intestine were observed, and viral antigen was also detected in the small intestines with immunohistochemical staining. Collectively, the data show in this study confirms that PDCoV is present in Guangdong, China and is highly pathogenic in newborn piglets.


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title: Baculovirus Display: A Multifunctional Technology for Gene Delivery and Eukaryotic Library Development

text: Abstract For over a decade, phage display has proven to be of immense value, allowing selection of a large variety of genes with novel functions from diverse libraries. However, the folding and modification requirements of complex proteins place a severe constraint on the type of protein that can be successfully displayed using this strategy, a restriction that could be resolved by similarly engineering a eukaryotic virus for display purposes. The quite recently established eukaryotic molecular biology tool, the baculovirus display vector system (BDVS), allows combination of genotype with phenotype and thereby enables presentation of eukaryotic proteins on the viral envelope or capsid. Data have shown that the baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is a versatile tool for eukaryotic virus display. Insertion of heterologous peptides and/or proteins into the viral surface by utilizing the major envelope glycoprotein gp64, or foreign membrane‐derived counterparts, allows incorporation of the sequence of interest onto the surface of infected cells and virus particles. A number of strategies are being investigated in order to further develop the display capabilities of AcMNPV and improve the complexity of a library that may be accommodated. Numerous expression vectors for various approaches of surface display have already been developed. Further improvement of both insertion and selection strategies toward development of a refined tool for use in the creation of useful eukaryotic libraries is, however, needed. Here, the status of baculovirus display with respect to alteration of virus tropism, antigen presentation, transgene expression in mammalian cells, and development of eukaryotic libraries will be reviewed.


title: Telehealth Availability in US Hospitals in the Face of the COVID‐19 Pandemic

text: BACKGROUND: Telehealth is likely to play a crucial role in treating COVID‐19 patients. However, not all US hospitals possess telehealth capabilities. This brief report was designed to explore US hospitals’ readiness with respect to telehealth availability. We hope to gain deeper insight into the factors affecting possession of these valuable capabilities, and how this varies between rural and urban areas. METHODS: Based on 2017 data from the American Hospital Association survey, Area Health Resource Files and Medicare cost reports, we used logistic regression models to identify predictors of telehealth and eICU capabilities in US hospitals. RESULTS: We found that larger hospitals (OR(telehealth) = 1.013; P < .01) and system members (OR(telehealth) = 1.55; P < .01) (OR(eICU) = 1.65; P < .01) had higher odds of possessing telehealth and eICU capabilities. We also found evidence suggesting that telehealth and eICU capabilities are concentrated in particular regions; the West North Central region was the most likely to possess capabilities, given that these hospitals had higher odds of possessing telehealth (OR = 1.49; P < .10) and eICU capabilities (OR = 2.15; P < .05). Rural hospitals had higher odds of possessing telehealth capabilities as compared to their urban counterparts, although this relationship was marginally significant (OR = 1.34, P < .10). CONCLUSIONS: US hospitals vary in their preparation to use telehealth to aid in the COVID‐19 battle, among other issues. Hospitals’ odds of possessing the capability to provide such services vary largely by region; overall, rural hospitals have more widespread telehealth capabilities than urban hospitals. There is still great potential to expand these capabilities further, especially in areas that have been hard hit by COVID‐19.


Permettre aux médecins et aux soignants d’exercer leur mission en accord avec leur devoir d’humanité


title: Platelet-bound antibodies detected by a flow cytometric assay in cats with thrombocytopenia

text: Summary In cats, primary or secondary immune-mediated thrombocytopenia have rarely been described or characterised. The objective of this study was to determine platelet-bound antibodies (PBA) by a flow cytometric assay in both healthy and thrombocytopenic cats. Direct PBA testing was performed in 42 thrombocytopenic cats (platelet counts 6–179×109/l, median 56×109/l). Of these 42 cats, 19 had positive PBA test results, 17 of which were considered to have secondary immune-mediated thrombocytopenia (sITP). Underlying diseases included fat necroses (four cases), feline infectious peritonitis (three), feline leukaemia virus (two) or feline immunodeficiency virus (two) infections, lymphoma (two), leukaemia (one), hepatitis (one), pyelonephritis (one), or hyperthyroidism (one). In two cats, no underlying disease was found suggesting a primary immune-mediated thrombocytopenia (pITP). The PBA test was negative in 23 cats diagnosed with varying underlying diseases and in 47 healthy control cats with platelet values within the reference range. Only seven of the 42 cats with thrombocytopenia (platelet count 10–57×109/l, median 34×109/l) had spontaneous bleeding. This study suggests that immune-mediated destruction of platelets might be an important pathological mechanism for feline thrombocytopenia caused by various underlying diseases. In cats, pITP appears to be rarely diagnosed.