title: Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: a descriptive study

text: Abstract Background With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. Methods A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. Results Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2% were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, N = 301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; N = 216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p = 0.015). Although two consecutive negative results were confirmed in 70 patients, 30% of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. Conclusions This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years.


title: Twenty-five years of type I interferon-based treatment: A critical analysis of its therapeutic use

text: Abstract The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcome and mechanisms of refractoriness, new administration schedules, the combination of type I IFN with new drugs and the increased monitoring of patients’ susceptibility to type I IFN are expected to provide a new life to this valuable cytokine.


title: Development and Implementation of Evidence-Based Practice in Cancer Care: Challenges and Opportunities

text: The cancer burden is a global problem, and oncology nurses should be accountable for delivering safe and effective cancer care and providing the best possible experience for patients. The development and application of evidence-based practice in cancer care is an effective strategy in achieving this goal; however, the journey in which such practice involves may encounter various challenges. In this article, the author discusses her own experience, successful and unsuccessful of such a journey. Both challenges and opportunities are identified, and suggestions put forward for making collaborative efforts.


title: Coping flexibility in college students with depressive symptoms

text: BACKGROUND: The current study explored the prevalence of depressed mood among Chinese undergraduate students and examined the coping patterns and degree of flexibility of flexibility of such patterns associated with such mood. METHODS: A set of questionnaire assessing coping patterns, coping flexibility, and depressive symptoms were administered to 428 students (234 men and 194 women). RESULTS: A total of 266 participants both completed the entire set of questionnaires and reported a frequency of two or more stressful life events (the criterion needed to calculate variance in perceived controllability). Findings showed that higher levels of depressive symptoms were significantly associated with higher levels of both event frequency (r = .368, p < .001) and event impact (r = .245, p < .001) and lower levels of perceived controllability (r = -.261, p < .001), coping effectiveness (r = -.375, p < .001), and ratio of strategy to situation fit (r = -.108, p < .05). Depressive symptoms were not significantly associated with cognitive flexibility (variance of perceived controllability; r = .031, p = .527), Gender was not a significant moderator of any of the reported associations. CONCLUSIONS: Findings indicate that Chinese university students with depressive symptoms reported experiencing a greater number of negative events than did non-depressed university students. In addition, undergraduates with depressive symptoms were more likely than other undergraduates to utilize maladaptive coping methods. Such findings highlight the potential importance of interventions aimed at helping undergraduate students with a lower coping flexibility develop skills to cope with stressful life events.


20/20 foresight for 2020?


title: Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19

text: As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.


title: Viral mechanisms of immune evasion

text: Abstract During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus–host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.


title: Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

text: Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.


title: SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

text: Abstract Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated human alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 h and peaked at approximately 105 pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection.


Middle East respiratory syndrome: new disease, old lessons


title: Lessons from SARS: control of acute lung failure by the SARS receptor ACE2

text: Angiotensin-converting enzyme 2 (ACE2), a second angiotensin-converting enzyme (ACE), regulates the renin–angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular systems. Recently, it has been shown that severe acute respiratory syndrome (SARS) coronavirus, the cause of SARS, utilizes ACE2 as an essential receptor for cell fusion and in vivo infections in mice. Intriguingly, ACE2 acts as a protective factor in various experimental models of acute lung failure and, therefore, acts not only as a key determinant for SARS virus entry into cells but also contributes to SARS pathogenesis. Here we review the role of ACE2 in disease pathogenesis, including lung diseases and cardiovascular diseases.


title: Feline orofacial pain syndrome (FOPS): a retrospective study of 113 cases

text: Feline orofacial pain syndrome (FOPS) is a pain disorder of cats with behavioural signs of oral discomfort and tongue mutilation. This report describes the findings from a case series of 113 cats including 100 Burmese. FOPS is suspected to be a neuropathic pain disorder and the predominance within the Burmese cat breed suggests an inherited disorder, possibly involving central and/or ganglion processing of sensory trigeminal information. The disease is characterised by an episodic, typically unilateral, discomfort with pain-free intervals. The discomfort is triggered, in many cases, by mouth movements. The disease is often recurrent and with time may become unremitting – 12% of cases in this series were euthanased as a consequence of the condition. Sensitisation of trigeminal nerve endings as a consequence of oral disease or tooth eruption appears to be an important factor in the aetiology – 63% of cases had a history of oral lesions and at least 16% experienced their first sign of discomfort during eruption of permanent teeth. External factors can also influence the disease as FOPS events could be directly linked to a situation causing anxiety in 20% of cats. FOPS can be resistant to traditional analgesics and in some cases successful management required anti-convulsants with an analgesic effect.


title: Cathepsin B & L Are Not Required for Ebola Virus Replication

text: Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB(−/−) and catL(−/−) mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.


Imported Wuhan Coronavirus Infection: Is there any Correlation with Number of Immigrants from Endemic Area and Period after the First Outbreak?


title: Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development

text: The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.


title: Improving air quality in high-density cities by understanding the relationship between air pollutant dispersion and urban morphologies

text: Abstract In high-density megacities, air pollution has a higher impact on public health than cities of lower population density. Apart from higher pollution emissions due to human activities in densely populated street canyons, stagnated air flow due to closely packed tall buildings means lower dispersion potential. The coupled result leads to frequent reports of high air pollution indexes at street-side stations in Hong Kong. High-density urban morphologies need to be carefully designed to lessen the ill effects of high density urban living. This study addresses the knowledge-gap between planning and design principles and air pollution dispersion potentials in high density cities. The air ventilation assessment for projects in high-density Hong Kong is advanced to include air pollutant dispersion issues. The methods in this study are CFD simulation and parametric study. The SST κ–ω model is adopted after balancing the accuracy and computational cost in the comparative study. Urban-scale parametric studies are conducted to clarify the effects of urban permeability and building geometries on air pollution dispersion, for both the outdoor pedestrian environment and the indoor environment in the roadside buildings. Given the finite land resources in high-density cities and the numerous planning and design restrictions for development projects, the effectiveness of mitigation strategies is evaluated to optimize the benefits. A real urban case study is finally conducted to demonstrate that the suggested design principles from the parametric study are feasible in the practical high density urban design.


Co-infection of Influenza B Virus and SARS-CoV-2: A Case Report from Taiwan


COVID-19 : n’oublions pas l’Afrique !


title: Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past

text: Abstract Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients’ clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).


title: Optimal policies for control of the novel coronavirus disease (COVID-19) outbreak

text: Understanding the early transmission dynamics of diseases and estimating the effectiveness of control policies play inevitable roles in the prevention of epidemic diseases. To this end, this paper is concerned with the design of optimal control strategies for the novel coronavirus disease (COVID-19). A mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission based on Wuhan's data is considered. To solve the problem effectively and efficiently, a multi-objective genetic algorithm is proposed to achieve high-quality schedules for various factors including contact rate and transition rate of symptomatic infected individuals to the quarantined infected class. By changing these factors, two optimal policies are successfully designed. This study has two main scientific contributions that are: (1) This is pioneer research that proposes policies regarding COVID-19, (2) This is also the first research that addresses COVID-19 and considers its economic consequences through a multi-objective evolutionary algorithm. Numerical simulations conspicuously demonstrate that by applying the proposed optimal policies, governments could find useful and practical ways for control of the disease.


Tuberculous sarcoidosis: Is it a separate entity?


title: The occurrence of Chlamydia spp. in pigs with and without clinical disease

text: BACKGROUND: Within the genera Chlamydia, the development of refined diagnostic techniques has allowed the identification of four species that are capable of infecting pigs. The epidemiology, clinical, and zoonotic impacts of these species are however largely unknown. The study aimed to investigate the presence of Chlamydia spp. in the intestines of growing pigs and in conjunctival swabs from finisher pigs, and relate the findings to clinical signs. RESULTS: By histology, 20 of 48 pigs had intestinal lesions that may be consistent with chlamydial infection. By PCR, forty-six of the pigs were positive whereas two samples were inhibited. Sequencing of 19 DNA extracts identified these as Chlamydia suis. By immunohistochemistry, 32 of 44 samples were positive and a significant relationship was detected between macroscopically visible intestinal lesions and a high degree of infection. By real-time PCR, a significant difference was detected between pigs with and without conjunctivitis when a Ct value of 36 was employed but not when a Ct value of 38 was employed. CONCLUSIONS: Chlamydia suis was demonstrated in most samples and overall, no correlation to clinical signs was detected. However, a correlation was noted between samples with a high degree of infection and the presence of clinical signs. It is possible, that the intensive pig production systems studied might predispose for the transmission and maintenance of the infection thus increasing the infectious load and the risk for disease in the pig.


title: Global Uncertainties and Portfolio Flow Dynamics of the BRICS Countries

text: Abstract This paper investigates the dynamics of bond and stock market capital flows to BRICS countries under uncertainties such as global economic policy uncertainty and the US trade policy uncertainty. We use a time-varying Granger causality framework over the January 2008-November 2019 period to analyze the predictive power of uncertainties on capital flows in the form of bond and equity. The results show that the effects are heterogeneous across countries and stronger during the Global Financial Crisis period and post-2018 period while it lost its significance in the subsequent period. The negative influence of uncertainties on capital flows directed to BRICS countries is also evident in the results of non-parametric time-varying panel models. Overall, it is thought that the heterogeneous structure of the causality between uncertainty and portfolio flows into BRICS may present portfolio diversification benefits for global investors.


Covid-19 infection and mortality: a physiologist’s perspective enlightening clinical features and plausible interventional strategies


title: Innate Immune Priming by cGAS as a Preparatory Countermeasure Against RNA Virus Infection

text: The detection of nucleic acids by pattern recognition receptors is an ancient and conserved component of the innate immune system. Notably, RNA virus genomes are sensed by mammalian cytosolic RIG-I–like receptors, thereby activating interferon-stimulated gene (ISG) expression to restrict viral replication. However, recent evidence indicates that the cGAS-STING DNA sensing pathway also protects against RNA viruses. So far, the mechanisms responsible for DNA sensing of RNA viruses, which replicate without known DNA intermediates, remain unclear. By using cGAS gene knockout and reconstitution in human and mouse cell cultures, we discovered that DNA sensing and cGAMP synthase activities are required for cGAS-mediated restriction of vesicular stomatitis virus and Sindbis virus. The level of cGAMP produced in response to RNA virus infection was below the threshold of detection, suggesting that only transient and/or low levels of cGAMP are produced during RNA virus infections. To clarify the DNA ligands that activate cGAS activity, we confirmed that cGAS binds mitochondrial DNA in the cytosol of both uninfected and infected cells; however, the amount of cGAS-associated mitochondrial DNA did not change in response to virus infection. Rather, a variety of pre-existing cytosolic DNAs, including mitochondrial DNA and endogenous cDNAs, may serve as stimuli for basal cGAS activation. Importantly, cGAS knockout and reconstitution experiments demonstrated that cGAS drives low-level ISG expression at steady state. We propose that cGAS-STING restricts RNA viruses by promoting a preparatory immune activation state within cells, likely primed by endogenous cellular DNA ligands. Many medically important RNA viruses are restricted by the cGAS-STING DNA-sensing pathway of innate immune activation. Since these viruses replicate without DNA intermediates, it is unclear what DNA ligand(s) are responsible for triggering this pathway. We show here that cGAS’s DNA binding and signaling activities are required for RNA virus restriction, similar to the mechanisms by which it restricts DNA viruses. Furthermore, we confirmed that cGAS continuously binds host DNA, which was unaffected by RNA virus infection. Finally, cGAS expression correlated with the low-level expression of interferon-stimulated genes in uninfected cells, both in vitro and in vivo. We propose that cGAS-mediated sensing of endogenous DNA ligands contributes to RNA virus restriction by establishing a baseline of innate immune activation.


Effects of education on harm-reduction programmes


title: Addition of poly (propylene glycol) to multiblock copolymer to optimize siRNA delivery

text: Previous studies have examined different strategies for siRNA delivery with varying degrees of success. These include use of viral vectors, cationic liposomes, and polymers. Several copolymers were designed and synthesized based on blocks of poly(ethylene glycol) PEG, poly(propylene glycol) PPG, and poly(l-lysine). These were designated as P1, P2, and P3. We studied the copolymer self-assembly, siRNA binding, particle size, surface potential, architecture of the complexes, and siRNA delivery. Silencing of GFP using copolymer P3 to deliver GFP-specific siRNA to Neuro-2a cells expressing GFP was almost as effective as using Lipofectamine 2000, with minimal cytotoxicity. Thus, we have provided a new copolymer platform for siRNA delivery that we can continue to modify for improved delivery of siRNA in vitro and eventually in vivo.


title: Prenatal Versus Postnatal Tobacco Smoke Exposure and Intensive Care Use in Children Hospitalized With Bronchiolitis

text: Abstract Objective Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU). Methods We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used chi-square, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression. Results Among 2207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, and 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.14–2.00). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95, 95% CI 1.13–3.37) compared to children without postnatal tobacco smoke exposure (aOR 1.47, 95% CI 1.05–2.04). Conclusions Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages.


title: Towards a small animal model for hepatitis C

text: Hepatitis C virus (HCV) causes chronic liver disease and affects an estimated 3% of the world's population. Options for the prevention or therapy of HCV infection are limited; there is no vaccine and the nonspecific, interferon-based treatments now in use are frequently ineffective and have significant side effects. A small-animal model for HCV infection would significantly expedite antiviral compound development and preclinical testing, as well as open new avenues to decipher the mechanisms that underlie viral pathogenesis. The natural species tropism of HCV is, however, limited to humans and chimpanzees. Here, we discuss the prospects of developing a mouse model for HCV infection, taking into consideration recent results on HCV entry and replication, and new prospects in xenotransplantation biology. We highlight three independent, but possibly complementary, approaches towards overcoming current species barriers and generating a small-animal model for HCV pathogenesis.


title: Dynamic relationship between air transport demand and economic growth in the United States: A new look

text: Abstract This paper examines the short- and long-run effects of economic growth and market shocks (e.g., 9/11 terrorist attacks, Iraq war, SARS epidemic, and 2008 financial crisis) on air passenger and freight services using an autoregressive distributed lag (ARDL) approach to cointegration. Results show that, in the long-run, both air passenger and freight services tend to increase with economic growth. In the short-run, however, only air passenger service is responsive to economic growth. Finally, only the 9/11 terrorist attacks and the SARS have detrimental effects on air passenger demand both in the short- and long-run, and in the long-run, respectively. However, these market shocks are found to have little impact on air freight demand.


title: Systems vaccinology and big data in the vaccine development chain

text: Systems vaccinology has proven a fascinating development in the last decade. Where traditionally vaccine development has been dominated by trial and error, systems vaccinology is a tool that provides novel and comprehensive understanding if properly used. Data sets retrieved from systems‐based studies endorse rational design and effective development of safe and efficacious vaccines. In this review we first describe different omics‐techniques that form the pillars of systems vaccinology. In the second part, the application of systems vaccinology in the different stages of vaccine development is described. Overall, this review shows that systems vaccinology has become an important tool anywhere in the vaccine development chain.


title: Role of lipid rafts in porcine reproductive and respiratory syndrome virus infection in MARC-145 cells

text: Abstract Lipid rafts play an important role in the life cycle of many viruses. Cholesterol is a critical structural component of lipid rafts. Although the porcine reproductive and respiratory syndrome virus (PRRSV) has restricted cell tropism for cells of the monocyte/macrophage lineage, a non-macrophage cell MARC-145 was susceptible to PRRSV because of the expression of virus receptor CD163 on the cell surface, therefore MARC-145 cells is used as model cell for PRRSV studies. In order to determine if cholesterol is involved in PRRSV infection in MARC-145 cells, we used three pharmacological agents: methyl-β cyclodextrin (MβCD), mevinolin, and filipin complex to deplete cholesterol in MARC-145. Although these agents act by different mechanisms, they all significantly inhibited PRRSV infection. The inhibition could be prevented by addition of exogenous cholesterol. Cell membrane cholesterol depletion after virus infection had no effect on PRRSV production and cholesterol depletion pre-infection did not reduce the virus attachment, suggesting cholesterol is involved in virus entry. Further results showed that cholesterol depletion did not change expression levels of the PRRSV receptor CD163 in MARC-145, had no effect on clathrin-mediated endocytosis, but disturbed lipid-raft-dependent endocytosis. Collectively, these studies suggest that cholesterol is critical for PRRSV entry, which is likely to be mediated by a lipid-raft-dependent pathway.


title: Successful therapeutic management of canine Isosporosis in puppies

text: Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.


title: Recent trends in click chemistry as a promising technology for virus-related research

text: Abstract Click chemistry involves reactions that were originally introduced and used in organic chemistry to generate substances by joining small units together with heteroatom linkages (C-X-C). Over the last few decades, click chemistry has been widely used in virus-related research. Using click chemistry, the virus particle as well as viral protein and nucleic acids can be labeled. Subsequently, the labeled virions or molecules can be tracked in real time. Here, we reviewed the recent applications of click reactions in virus-related research, including viral tracking, the design of antiviral agents, the diagnosis of viral infection, and virus-based delivery systems. This review provides an overview of the general principles and applications of click chemistry in virus-related research.


title: Successful recovery from severe COVID‐19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab

text: Although immunosuppressed patients may be more prone to SARS‐CoV‐2 infection with atypical presentation, long‐term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID‐19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID‐19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID‐19 of a kidney‐transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.


title: Beyond Mfold: Recent advances in RNA bioinformatics

text: Abstract Computational analysis of RNA secondary structure is a classical field of biosequence analysis, which has recently gained momentum due to the manyfold regulatory functions of RNA that have become apparent. We present five recent computational approaches that address the problems of synoptic folding space analysis, pseudoknot prediction, structure alignment, comparative structure prediction, and miRNA target prediction. All these programs are in current use and are available via the Bielefeld Bioinformatics Server at http://bibiserv.techfak.uni-bielefeld.de.


title: Video for Active and Remote Learning

text: The outbreak of COVID-19 has caused the canceling of in-person lectures on a massive scale. Rapid movement of education to online platforms will eventually lead to innovations in remote education. At the moment, however, instructors lack guidance. This short article describes approaches for producing video for remote and active learning.


title: Emerging Influenza D Virus Threat: What We Know so Far!

text: Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the possibility of transmission among various hosts and potential to cause human disease.


title: Clinical ocular toxoplasmosis in neonatal kittens

text: ABSTRACT: OBJECTIVE: To describe ocular findings in kittens with congenital or early neonatal infection by Toxoplasma gondii and to determine if there are detectable differences in disease caused by three strains. ANIMALS STUDIED: Six adult female cats and the offspring from seven litters. METHODS: Four kittens from uninfected specific pathogen‐free (SPF) queens and 21 kittens from SPF queens inoculated at various times late in gestation with Mozart, Maggie, or ME‐49 strain of T. gondii were used. Ocular examinations were performed on queens prior to and after delivery, and on kittens weekly to bi‐weekly for up to 27 weeks. Whole blood for serology was collected from all kittens at 5½ to 8 weeks of age and again at 12 weeks of age or later. RESULTS: No kittens from noninfected queens developed ocular lesions or antibody to T. gondii. Three of the 24 kittens from infected queens died or were euthanized early in the study. Chorioretinitis was detected in 15 of 21 living kittens from infected queens. Two developed concurrent anterior uveitis that resolved within 1 week. Posterior segment lesions varied ophthalmoscopically between strains. Of 21 kittens from T. gondii‐infected queens, six developed positive antibody titers to T. gondii during the study. All seropositive kittens were born to queens infected with Mozart strain of T. gondii. CONCLUSION: Results of this study suggest that ocular toxoplasmosis can occur without other evidence of clinical illness in kittens infected in utero or in the neonatal period, and that T. gondii strains may have varying degrees of ocular pathogenicity in cats.


title: Pathogen genomic surveillance elucidates the origins, transmission and evolution of emerging viral agents in China

text: In the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in China, such as the severe acute respiratory syndrome (SARS) coronavirus and, more recently, the avian-origin influenza A/H7N9 virus, which have caused outbreaks among humans with high morbidity and mortality. In addition, several emerging and re-emerging viral pathogens have also been imported into China from travelers, e.g. the Middle East respiratory syndrome (MERS) coronavirus and Zika virus (ZIKV). Herein, we review these emerging viral pathogens in China and focus on how surveillance by pathogen genomics has been employed to discover and annotate novel pathogenic agents, identify natural reservoirs, monitor the transmission events and delineate their evolution and adaption to the human host. We also highlight the application of genomic sequencing in the recent Ebola epidemics in Western Africa. In summary, genomic sequencing has become a standard research tool in the field of emerging infectious diseases which has been proven invaluable in containing these viral infections and reducing burden of disease in humans and animals. Genomic surveillance of pathogenic agents will serve as a key epidemiological and research tool in the modern era of precision infectious diseases and in the future studies of virosphere.


title: A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses

text: Abstract Objective The re-emergence and spread of tropical viruses to new areas has raised a wave of concern worldwide. In order to treat patients at an early stage and prevent the diffusion of an outbreak, early diagnosis, and therefore fast and adequate detection, is needed. To this end, a multiplex reverse transcription real-time polymerase chain reaction TaqMan method was designed to detect Zika (ZIKV) and chikungunya (CHIKV) viruses simultaneously. Methods Two methods targeting different genome segments were selected from the literature for each virus. These were adapted for high genome coverage and combined in a four-plex assay that was thoroughly validated in-house. The SCREENED tool was used to evaluate the sequence coverage of the method. Results The full validation approach showed that the new four-plex method allows the specific and sensitive identification and discrimination of ZIKV and CHIKV in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes is shown for the first time. Conclusions PCR is a reliable user-friendly technique that can be applied in remote areas. Such multiplex methods enable early and efficient diagnosis, leading to rapid treatment and effective confinement in outbreak cases. They may also serve as an aid for surveillance, and the full validation permits easy method-transfer allowing worldwide harmonization.


title: Cancer is associated with severe disease in COVID-19 patients: a systematic review and meta-analysis

text: Cancer patients are vulnerable to complications of respiratory viruses. This systematic review and meta-analysis sought to examine the prevalence of cancer and its association with disease severity in patients with novel coronavirus disease 2019 (COVID-19). Searches were performed in MEDLINE, EMBASE and ScienceDirect from their inception until 28 April 2020. Severe disease was considered to encompass cases resulting in death or as defined by the primary study authors. Meta-analysis was performed using random-effect models. We included 20 studies involving 32,404 patients from China, the United Kingdom, the United States, Italy, Singapore, Thailand, France, India and South Korea. The pooled prevalence of cancer was 3.50% (95% confidence interval (CI) 1.70 to 5.80). The pooled prevalence was not moderated by study mean age, proportion of females or whether the study was conducted in/outside of China. Patients with cancer were more likely to experience severe COVID-19 disease compared to patients without cancer (pooled risk ratio 1.76, 95% CI 1.39 to 2.23). Our findings reiterate the need for additional precautionary measures to ensure that patients with cancer are not exposed to COVID-19, and if they become infected, extra attention should be provided to minimise their risk of adverse outcomes.


Emergency department lung ultrasound findings in novel coronavirus


title: CD8 memory T cells: cross-reactivity and heterologous immunity

text: Abstract Virus-specific memory T cell populations demonstrate plasticity in antigen recognition and in their ability to accommodate new memory T cell populations. The degeneracy of T cell antigen recognition and the flexibility of diverse antigen-specific repertoires allow the host to respond to a multitude of pathogens while accommodating these numerous large memory pools in a finite immune system. These cross-reactive memory T cells can be employed in immune responses and mediate protective immunity, but they can also induce life-threatening immunopathology or impede transplantation tolerance and graft survival. Here we discuss examples of altered viral pathogenesis occurring as a consequence of heterologous T cell immunity and propose models for the maintenance of a dynamic pool of memory cells.


SARS-CoV-2 in pregnancy: symptomatic pregnant women are only the tip of the iceberg


title: Treatment of Calf Diarrhea: Intravenous Fluid Therapy

text: Severely dehydrated calves that are unable to suckle need intravenous fluids for effective resuscitation. Intravenous fluid therapy is also indicated for sick calves without obvious dehydration, such as calves with strong ion acidosis, ruminal acidosis (rumen drinkers), severe pneumonia, septicemia, or hypothermia. This article presents an updated overview of intravenous fluid therapy for calves, recent insights into the development of metabolic acidosis in young calves resulting from accumulation of D-lactate, a simplified algorithm for intravenous fluid therapy, and a procedure for ear vein catheterization under field conditions.


title: Avian reovirus-triggered apoptosis enhances both virus spread and the processing of the viral nonstructural muNS protein

text: Abstract Avian reovirus non-structural protein muNS is partially cleaved in infected chicken embryo fibroblast cells to produce a 55-kDa carboxyterminal protein, termed muNSC, and a 17-kDa aminoterminal polypeptide, designated muNSN. In this study we demonstrate that muNS processing is catalyzed by a caspase 3-like protease activated during the course of avian reovirus infection. The cleavage site was mapped by site directed mutagenesis between residues Asp-154 and Ala-155 of the muNS sequence. Although muNS and muNSC, but not muNSN, are able to form inclusions when expressed individually in transfected cells, only muNS is able to recruit specific ARV proteins to these structures. Furthermore, muNSC associates with ARV factories more weakly than muNS, sigmaNS and lambdaA. Finally, the inhibition of caspase activity in ARV-infected cells does not diminish ARV gene expression and replication, but drastically reduces muNS processing and the release and dissemination of progeny viral particles.


title: Sonographic signs and patterns of COVID-19 pneumonia

text: The pandemic of COVID-19 is seriously challenging the medical organization in many parts of the world. This novel corona virus SARS-CoV-2 has a specific tropism for the low respiratory airways, but causes severe pneumonia in a low percentage of patients. However, the rapid spread of the infection during this pandemic is causing the need to hospitalize a high number of patients. Pneumonia in COVID-19 has peculiar features and can be studied by lung ultrasound in the early approach to suspected patients. The sonographic signs are non-specific when considered alone, but observation of some aspects of vertical artifacts can enhance the diagnostic power of the ultrasound examination. Also, the combination of sonographic signs in patterns and their correlation with blood exams in different phenotypes of the disease may allow for a reliable characterization and be of help in triaging and admitting patients.


title: Hypothalamic integration of immune function and metabolism

text: Abstract The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1β and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and dopamine (DA) and an increase in serotonin concentration in tumor-bearing rats, in first- and second-order hypothalamic nuclei, while tumor resection reverted these changes and normalized food intake, suggesting negative regulation of NPY and DA systems by cytokines during anorexia, probably mediated by serotonin that appears to play a pivotal role in the regulation of food intake in cancer. Among the different forms of therapy, nutritional manipulation of diet in tumor-bearing state has been investigated. Supplementation of tumor bearing rats with ω-3 fatty acid vs. control diet delayed the appearance of tumor, reduced tumor-growth rate and volume, negated onset of anorexia, increased body weight, decreased cytokines production and increased expression of NPY and decreased α-melanocyte-stimulating hormone (α-MSH) in hypothalamic nuclei. These data suggest that ω-3 fatty acid suppressed pro-inflammatory cytokines production and improved food intake by normalizing hypothalamic food intake-related peptides and point to the possibility of a therapeutic use of these fatty acids. The sum of these data support the concept that immune cell-derived cytokines are closely related with the regulation of metabolism and have both central and peripheral actions, inducing anorexia via hypothalamic anorectic factors, including serotonin and dopamine, and inhibiting NPY leading to a reduction in food intake and body weight, emphasizing the interconnection of the immune and neuroendocrine systems in regulating metabolism during infectious process, cachexia and obesity.


title: Preferences for scarce medical resource allocation: Differences between experts and the general public and implications for the COVID‐19 pandemic

text: This study concerns what lay people believe is the best way to allocate scarce medical resources. A sample of 515 individuals completed a short questionnaire asking them to rank‐order eight different ethical positions with respect to the allocation of scarce resources. They showed a strong preference for the ‘saves most lives’ and ‘sickest first’ options, with ‘reciprocity’ and a ‘lottery’ being least favoured. There was a reasonable degree of unanimity amongst respondents and comparatively few correlations with individual difference factors such as demography. The preference results are compared to expert recommendations (Emanuel et al., 2020, N. Engl. J. Med., 382, 2049) made in light of the current coronavirus pandemic, and differences are highlighted. Implications for scare medical resource allocations are discussed, and limitations of the study acknowledged.


title: Lack of SARS Transmission among Healthcare Workers, United States

text: Healthcare workers accounted for a large proportion of persons with severe acute respiratory syndrome (SARS) during the worldwide epidemic of early 2003. We conducted an investigation of healthcare workers exposed to laboratory-confirmed SARS patients in the United States to evaluate infection-control practices and possible SARS-associated coronavirus (SARS-CoV) transmission. We identified 110 healthcare workers with exposure within droplet range (i.e., 3 feet) to six SARS-CoV–positive patients. Forty-five healthcare workers had exposure without any mask use, 72 had exposure without eye protection, and 40 reported direct skin-to-skin contact. Potential droplet- and aerosol-generating procedures were infrequent: 5% of healthcare workers manipulated a patient’s airway, and 4% administered aerosolized medication. Despite numerous unprotected exposures, there was no serologic evidence of healthcare-related SARS-CoV transmission. Lack of transmission in the United States may be related to the relative absence of high-risk procedures or patients, factors that may place healthcare workers at higher risk for infection.


The never-ending ‘game’


title: COVID-19 epidemic in Brazil: where we at?

text: Abstract Objetive to analyze the trends of COVID-19 in Brazil in 2020 by Federal Units (FU). Method ecological time-series based on cumulative confirmed cases of COVID-19 from March 11 to May 12. Joinpoint regression models were applied to identify points of inflection in COVID-19 trends, considering the days since the 50th confirmed case as time unit. Results Brazil reached the 50th confirmed case of COVID-19 in 11 March 2020 and, 63 days after that, on May 12, 177,589 cases had been confirmed. The trends for all regions and FU are upward. In the last segment, from the 31st to the 63rd day, Brazil presented a DPC of 7.3% (95%CI= 7.2;7.5). For the country the ADPC was 14.2% (95%CI: 13.8;14.5). The highest ADPC values were found in the North, Northeast and Southeast regions. Conclusions In summary, our results show that all FUs in Brazil present upward trends of COVID-19. In some FUs, the slowdown in DPC in the last segment must be considered carefully. Each FUs is at a different stage of the pandemic and, therefore, non-pharmacological measures must be applied accordingly.


title: Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein

text: The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the “up” position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.


title: Case series of rash associated with influenza B in school children

text: This case series describes morbilliform and other rash presentations among schoolchildren during a March 2014 outbreak of influenza‐like illness (ILI) in British Columbia, Canada. Multiplex nucleic acid testing of nasopharyngeal specimens and paired serologic investigations identified that influenza B, characterized as B/Massachusetts/02/2012‐like (Yamagata‐lineage), was the only viral aetiology and most likely cause of ILI and rash. An association between influenza B and rash has been described infrequently elsewhere, and not previously in North America. Influenza B should be considered in the differential diagnosis of febrile exanthem. Evaluation of the nature, incidence and contributing agent–host–environment interactions, and immunologic mechanisms to possibly explain influenza‐associated rash is warranted.


title: The Crystal Structure of ORF-9b, a Lipid Binding Protein from the SARS Coronavirus

text: To achieve the greatest output from their limited genomes, viruses frequently make use of alternative open reading frames, in which translation is initiated from a start codon within an existing gene and, being out of frame, gives rise to a distinct protein product. These alternative protein products are, as yet, poorly characterized structurally. Here we report the crystal structure of ORF-9b, an alternative open reading frame within the nucleocapsid (N) gene from the SARS coronavirus. The protein has a novel fold, a dimeric tent-like β structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules. This cavity is likely to be involved in membrane attachment and, in mammalian cells, ORF-9b associates with intracellular vesicles, consistent with a role in the assembly of the virion. Analysis of ORF-9b and other overlapping genes suggests that they provide snapshots of the early evolution of novel protein folds.


title: Achieving Safe, Effective and Compassionate Quarantine or Isolation of Older Adults with Dementia in Nursing Homes.

text: Abstract Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.


title: A low density oligonucleotide microarray for the detection of viral and atypical bacterial respiratory pathogens

text: Abstract Acute respiratory tract infections are a major cause of morbidity and mortality worldwide and exert a considerable economic burden on healthcare systems. Acute respiratory tract infections of the upper and lower respiratory tract are caused by a wide variety of viral and bacterial pathogens, which require comprehensive laboratory investigations. Conventional serological and immunofluorescence-based diagnostic methods for acute respiratory tract infections lack sensitivity when compared to polymerase chain reaction (PCR)-based approaches and the development of new diagnostic methodologies is required, to provide accurate, sensitive and rapid diagnoses. In the present study, a PCR-based low density oligonucleotide microarray was developed for the detection of 16 viral and two atypical bacterial pathogens. The performance of this DNA microarray-based analysis exhibited comparable sensitivities and specificities to multiplex real-time reverse transcription polymerase chain reactions (rtPCRs) confirming the potential diagnostic utility of the method. In contrast to routine multiplex PCR, the microarray incorporates an intrinsic redundancy as multiple and non-identical probes per target on the array allow direct intra-assay confirmation of positives. This study demonstrates that microarray technology provides a viable alternative to conventional serological-based approaches and multiplex PCR for pathogen identification in acute respiratory tract infections.


title: Analysis of intermolecular RNA–RNA recombination by rubella virus

text: Abstract To investigate whether rubella virus (RUB) undergoes intermolecular RNA–RNA recombination, cells were cotransfected with pairs of in vitro transcripts from genomic cDNA plasmid vectors engineered to contain nonoverlapping deletions: the replicative transcript maintained the 5′-proximal nonstructural (NS) ORF (which contained the replicase, making it RNA replication competent), had a deletion in the 3′-proximal structural protein (SP) ORF, and maintained the 3′ end of the genome, including the putative 3′ cis-acting elements (CSE), while the nonreplicative transcript consisted of the 3′ half of the genome including the SP-ORF and 3′ CSE. Cotransfection yielded plaque-forming virus that synthesized the standard genomic and subgenomic RNAs and thus was generated by RNA–RNA recombination. Using transcripts tagged with a 3′-terminal deletion, it was found that recombinants contained the 3′ end derived from the replicative strand, indicating a cis-preference for initiation of negative-strand synthesis. In cotransfections in which the replicative transcript lacked the 3′ CSE, recombination occurred, albeit at lower efficiency, indicating that initiation in trans from the NS-ORF can occur. The 3′ CSE was sufficient as a nonreplicative transcript, showing that it can serve as a promoter for negative-strand RNA synthesis. While deletion mutagenesis showed that the presence of the junction untranslated region (J-UTR) between the ORFs appeared to be necessary on both transcripts for recombination in this region of the genome, analysis with transcripts tagged with restriction sites showed that the J-UTR was not a hot spot for recombination compared to neighboring regions in both ORFs. Sequence analysis of recombinants revealed that both precise (homologous) and imprecise recombination (aberrant, homologous resulting in duplications) occurred; however, imprecise recombination only involved the J-UTR or the 3′ end of the NS-ORF and the J-UTR (maintaining the NS-ORF), indicating selection pressure against duplications in other regions of the genome.


title: Continuing our work: transplant surgery and surgical oncology in a tertiary referral COVID-19 center

text: COVID-19 is rapidly spreading worldwide. Healthcare systems are struggling to properly allocate resources while ensuring cure for diseases outside of the infection. The aim of this study was to demonstrate how surgical activity was affected by the virus outbreak and show the changes in practice in a tertiary referral COVID-19 center. The official bulletins of the Italian National Institute for the Infectious Diseases “L. Spallanzani” were reviewed to retrieve the number of daily COVID-19 patients. Records of consecutive oncological and transplant procedures performed during the outbreak were reviewed. Patients with a high probability of postoperative intensive care unit (ICU) admission were considered as high risk and defined by an ASA score ≥ III and/or a Charlson Comorbidity Index (CCI) ≥ 6 and/or a Revised Cardiac Risk Index for Preoperative Risk (RCRI) ≥ 3. 72 patients were operated, including 12 (16.6%) liver and kidney transplantations. Patients had few comorbidities (26.3%), low ASA score (1.9 ± 0.5), CCI (3.7 ± 1.3), and RCRI (1.2 ± 0.6) and had overall a low risk of postoperative ICU admission. Few patients had liver cirrhosis (12.5%) or received preoperative systemic therapy (16.6%). 36 (50%) high-risk surgical procedures were performed, including major hepatectomies, pancreaticoduodenectomies, total gastrectomies, multivisceral resections, and transplantations. Despite this, only 15 patients (20.8%) were admitted to the ICU. Only oncologic cases and transplantations were performed during the COVID-19 outbreak. Careful selection of patients allowed to perform major cancer surgeries and transplantations without further stressing hospital resources, meanwhile minimizing collateral damage to patients.


Eosinophil count in severe coronavirus disease 2019 (COVID-19)


title: Open Skies in ASEAN

text: Abstract The countries of Association of South-East Asian Nations (ASEAN) have agreed to the formation of open skies within the region. Member countries differ widely in terms of their GDP per capita, their size, aviation policies and the strength of their aviation industries. Granted these differences, several possibilities for facilitating the move are examined. These include taking an economic approach to aviation negotiations, liberalising within sub-regional groupings, a staged framework of liberalisation, and increasing the scope for low-cost carriers to compete, possibly through development of secondary markets. Moves will also necessitate attention being given to complementary issues, such as competition and subsidy policies and ownership.


Welcome from the Editors-in-Chief


title: Age profile of susceptibility, mixing, and social distancing shape the dynamics of the novel coronavirus disease 2019 outbreak in China

text: Strict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.


title: Base Usage and Dinucleotide Frequency of Infectious Bursal Disease Virus

text: Base usage and dinucleotide frequency have been extensively studied in many eukaryotic organisms and bacteria, but not for viruses. In this paper, a comprehensive analysis of these aspects for infectious bursal disease virus (IBDV) was presented. The analysis of base usage indicated that all of the IBDV genes possess equivalent overall nucleotide distributions. However when the base usage at each codon positions was analysed by using cluster analysis, the VP5 open reading frame (ORF) formed a different cluster isolated from the other genes. The unusual base usage of VP5 ORF may indicate that the gene was originated by the virus “overprinting strategy”, a strategy in which virus may create novel gene by utilizing the unused reading frames of its existing genes. Meanwhile, the GC content of the IBDV genes and the chicken's coding sequences was comparable; suggesting the virus imitation of the host to increase its translational efficiency. The analysis of dinucleotide frequency indicated that IBDV genome had dinucleotide bias: the frequencies of CpG and TpA were lower and the TpG was higher than the expected. Classical methylation pathway, a process where CpG converted to TpG, may explain the significant correlation between the CpG deficiency and TpG abundance. “Principal component analysis of the dinucleotide frequencies” (DF-PCA) was used to analyse the overall dinucleotide frequencies of IBDV genome. DF-PCA on the hypervariable region and polyprotein (VPX-VP4-VP3) gene showed that the very virulent IBDV (vvIBDV) was segregated from other strains; which meant vvIBDV had a unique dinucleotide pattern. In summary, the study of base usage and dinucleotide frequency had unravelled many overlooked genomic properties of the virus.


title: Investigation of adverse reactions in healthcare personnel working in Level 3 barrier protection PPE to treat COVID-19

text: PURPOSE OF THE STUDY: The aim of our study was to investigate potential adverse reactions in healthcare professionals working in Level 3 barrier protection personal protective equipment (L3PPE) to treat patients with COVID-19. STUDY DESIGN: By using a convenience sampling approach, 129 out of 205 randomly selected healthcare professionals from the First Affiliated Hospital of Zhejiang University School of Medicine were invited to take part in a WeChat messaging app survey, Questionnaire Star, via a survey link. Healthcare personnel details were collected, including profession, years of professional experience and adverse reactions while wearing L3PPE. Survey results were divided by profession and years of professional experience; differences in adverse reactions were compared. RESULTS: Among the 129 healthcare professionals surveyed, 21 (16.28%) were doctors and 108 (83.72%) were nurses. A total of 122 (94.57%) healthcare professionals experienced discomfort while wearing L3PPE to treat patients with COVID-19. The main reasons for adverse reactions and discomfort include varying degrees of adverse skin reactions, respiratory difficulties, heat stress, dizziness and nausea. Doctors had a lower incidence of rashes (χ(2)=4.519, p=0.034) and dizziness (χ(2)=4.123, p=0.042) when compared with nurses. Junior (8.5 years of experience or fewer) healthcare personnel also experienced a higher rate of heat stress when compared with senior personnel (more than 8.5 years greater) (χ(2)=5.228, p=0.022). CONCLUSION: More attention should be offered to healthcare personnel wearing L3PPE to treat patients with COVID-19 because they are susceptible to developing adverse reactions.


title: Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia

text: Timely analysis of the laboratory characteristics associated with 2019 novel coronavirus pneumonia (COVID-19) can assist with clinical diagnosis and prognosis. This study is a collection of clinical data from 54 hospitalized adult patients diagnosed with COVID-19 in the Zhongfa Xincheng district of China at Tongji Hospital of Huazhong University of Science and Technology from January 28, 2020 to February 11, 2020. The average age of the patients was 61.8 ± 14.5 years, and the predominant age group was 50–79. The proportion of critical-type patients with comorbidities was higher than that of severe-type patients. Lymphocyte counts were significantly reduced in routine bloodwork for all patients, but significantly lower in critical-type patients than that in severe-type patients. Prolongation of prothrombin times (PT) and elevation of fibrinogen degradation products (FDPs) and D-dimers (D-Ds) were detected in coagulation function tests, and more significant changes were observed in critical-type patients compared to severe-type patients. Serum ferritin levels were sensitive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but could not be used for disease assessment. In addition, levels of two inflammatory factors, soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) were significantly increased in all patients, but higher in critical-type patients than in severe-type patients. Moreover, kidney injury was the second-most common organ affected by COVID-19 followed by heart and liver. Kidney and heart injury were more severe in critical-type patients than in severe-type patients. All of the 31 severe-type patients recovered. Of the critical-type patients, six died and 17 recovered. The length of hospital stay for critical-type patients was significantly longer for severe-type patients. In summary, increased lymphocyte counts, prolonged PT, secondary increases in fibrinolytic activity and increases in sIL-2R and IL-6 are typical features of COVID-19 and are associated with disease severity.


title: Cyber-Physical Systems Security: Limitations, Issues and Future Trends

text: Typically, Cyber-Physical Systems (CPS) involve various interconnected systems, which can monitor and manipulate real objects and processes. They are closely related to Internet of Things (IoT) systems, except that CPS focuses on the interaction between physical, networking and computation processes. Their integration with IoT led to a new CPS aspect, the Internet of Cyber-Physical Things (IoCPT). The fast and significant evolution of CPS affects various aspects in people’s way of life and enables a wider range of services and applications including e-Health, smart homes, e-Commerce, etc. However, interconnecting the cyber and physical worlds gives rise to new dangerous security challenges. Consequently, CPS security has attracted the attention of both researchers and industries. This paper surveys the main aspects of CPS and the corresponding applications, technologies, and standards. Moreover, CPS security vulnerabilities, threats and attacks are reviewed, while the key issues and challenges are identified. Additionally, the existing security measures are presented and analyzed while identifying their main limitations. Finally, several suggestions and recommendations are proposed benefiting from the lessons learned throughout this comprehensive review.


title: Rhinovirus Outbreaks in Long-term Care Facilities, Ontario, Canada

text: Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza.


title: Reconstructing propagation networks with natural diversity and identifying hidden sources

text: Our ability to uncover complex network structure and dynamics from data is fundamental to understanding and controlling collective dynamics in complex systems. Despite recent progress in this area, reconstructing networks with stochastic dynamical processes from limited time series remains to be an outstanding problem. Here we develop a framework based on compressed sensing to reconstruct complex networks on which stochastic spreading dynamics take place. We apply the methodology to a large number of model and real networks, finding that a full reconstruction of inhomogeneous interactions can be achieved from small amounts of polarized (binary) data, a virtue of compressed sensing. Further, we demonstrate that a hidden source that triggers the spreading process but is externally inaccessible can be ascertained and located with high confidence in the absence of direct routes of propagation from it. Our approach thus establishes a paradigm for tracing and controlling epidemic invasion and information diffusion in complex networked systems.


title: Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE: a quality improvement study

text: OBJECTIVE: The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including filtering facepiece respirators (FFRs) such as N95 masks. These masks are normally intended for single use, but their sterilization and subsequent reuse could substantially mitigate a world-wide shortage. DESIGN: Quality assurance. SETTING: A sealed environment chamber installed in the animal facility of an academic medical center. INTERVENTIONS: One to five sterilization cycles using ionized hydrogen peroxide (iHP), generated by SteraMist® equipment (TOMI; Frederick, MD). MAIN OUTCOME MEASURES: Personal protective equipment, including five N95 mask models from three manufacturers, were evaluated for efficacy of sterilization following iHP treatment (measured with bacterial spores in standard biological indicator assemblies). Additionally, N95 masks were assessed for their ability to efficiently filter particles down to 0.3μm and for their ability to form an airtight seal using a quantitative fit test. Filtration efficiency was measured using ambient particulate matter at a university lab and an aerosolized NaCl challenge at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. RESULTS: The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain function up to five cycles, the maximum number tested to date. Some but not all PPE could also be sterilized using an iHP environmental chamber, but pre-treatment with a handheld iHP generator was required for semi-enclosed surfaces such as respirator hoses. CONCLUSIONS: A typical iHP environment chamber with a volume of ~80 m(3) can treat ~7000 masks per day, as well as other items of PPE, making this an effective approach for a busy medical center.


title: Delayed Initiation of Remdesivir in a COVID‐19‐Positive Patient

text: We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40‐year‐old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID‐19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID‐19 polymerase chain reaction result. Supportive measures, in addition to a 5‐day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS‐CoV‐2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS‐CoV‐2 as well as to meet manufacturing demands.


title: The expression of SARS–CoV M gene in P. Pastoris and the diagnostic utility of the expression product

text: Abstract High-level protein expression is an important means of obtaining large amounts of viral proteins to investigate further their biological properties. To express the membrane (M) protein of SARS–CoV at high-level in vitro, the M gene fragment was amplified and cloned it into the Pichia Pastoris expression vector pPICZαA. SDS–PAGE and Western blotting analysis of the induced products of recombinant yeast transformant indicated that successful high-level expression of M protein was achieved, and that the expression product was similar antigenically to the natural protein. Purified recombinant M protein was used subsequently as an ELISA antigen for detection of eight serum samples screened previously by whole virus ELISA and immunofluorescence assay, and consistent results were obtained. These findings suggest that the recombinant M protein may be useful as a diagnostic reagent.


title: Attitudes to basic life support among medical students following the 2003 SARS outbreak in Hong Kong

text: Summary Background In 2003 severe acute respiratory syndrome (SARS) affected 1755 people in Hong Kong, including 386 health care professionals, some of whom were infected during resuscitation attempts of affected patients. This study seeks to explore whether this epidemic has altered the willingness of Hong Kong medical students to perform basic life support and mouth-to-mouth ventilation during an out-of-hospital cardiac arrest. Methods A questionnaire was used to survey Year 4 medical students at the end of their undergraduate anaesthesia attachment, during which basic life support (BLS) skills were taught. The survey was conducted during July and August 2003, approximately two months after Hong Kong was removed from the World Health Organisation SARS Infected Areas list, and was designed to examine student confidence in BLS skills, their perceptions of the risks associated with performing BLS and their willingness to perform BLS in varying situations. Results The response rate was over 60% (35 from a possible 54). Students were positive regarding the adequacy of their BLS training. They were concerned about disease transmission during resuscitation but were less positive regarding whether the risks had increased due to SARS. In all situations they were significantly more likely to perform mouth-to-mouth ventilation for a family member compared with a stranger (p <0.001) and to withhold mouth-to-mouth ventilation if either vomit or blood were present in the victim's mouth. Conclusions Hong Kong medical students feel able to perform BLS if required. They are concerned about the risk of disease transmission, including SARS, during resuscitation, but would be more likely to withhold mouth-to-mouth resuscitation in the presence of vomit or blood than due to a fear of contracting SARS.


title: [18F]FDG-PET/CT in different COVID-19 phases

text: PET/CT is an hybrid technique which allows both morfological and metabolical evalutaion. Three different morphometeabolical patterns are presented which reflect the evolutive phases of the COVID-19. This findings may help the clinician determine the correct treatment and security measure that need to be taken aaccording to the phase of the disease.


DIFFERENTIAL INDUCTION OF PROINFLAMMATORY CYTOKINES IN PRIMARY MOUSE ASTROCYTES AND MICROGLIA BY CORONAVIRUS INFECTION


title: Environmental survey to assess viral contamination of air and surfaces in hospital settings

text: Summary The presence of pathogenic viruses in healthcare settings represents a serious risk for both staff and patients. Direct viral detection in the environment poses significant technical problems and the indirect indicators currently in use suffer from serious limitations. The aim of this study was to monitor surfaces and air in hospital settings to reveal the presence of hepatitis C virus, human adenovirus, norovirus, human rotavirus and torque teno virus by nucleic acid assays, in parallel with measurements of total bacterial count and haemoglobin presence. In total, 114 surface and 62 air samples were collected. Bacterial contamination was very low (<1cfu/cm2) on surfaces, whereas the ‘medium’ detected value in air was 282cfu/m3. Overall, 19 (16.7%) surface samples tested positive for viral nucleic acids: one for norovirus, one for human adenovirus and 17 (14.9%) for torque teno virus (TTV). Only this latter virus was directly detected in 10 air samples (16.1%). Haemoglobin was found on two surfaces. No relationship was found between viral, biochemical or bacterial indicators. The data obtained confirm the difficulty of assessing viral contamination using bacterial indicators. The frequent detection of TTV suggests its possible use as an indicator for general viral contamination of the environment.


title: Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship

text: INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.


title: “SARS-CoV-2 in upper and lower airway samples of a laryngectomized patient: new insights and many lessons”

text: • Despite upper airways are functionally excluded, we are the first to report the presence of SARS-CoV-2 in the nasopharyngeal swab of a laryngectomized patient; • The primary nasal viral infection is not a mere anatomical constraint but it underlies an immunological priming that can condition the systemic inflammatory response; • Head and neck cancer patients have very often a significant history of smoking exposure and this makes them more susceptible to SARS-CoV-2 as well as to the development of multiple malignancies.


title: Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection

text: We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.


COVID-19 effects on Tuberculosis care in Sierra Leone


title: Phage Displayed Peptides to Avian H5N1 Virus Distinguished the Virus from Other Viruses

text: The purpose of the current study was to identify potential ligands and develop a novel diagnostic test to highly pathogenic avian influenza A virus (HPAI), subtype H5N1 viruses using phage display technology. The H5N1 viruses were used as an immobilized target in a biopanning process using a 12-mer phage display random peptide library. After five rounds of panning, three phages expressing peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses were identified by DNA sequencing. In terms of the minimum quantity of viruses, the phage-based ELISA was better than antiserum-based ELISA and a manual, semi-quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the selected phages bearing the specific peptides to H5N1 viruses were capable of differentiating this virus from other avian viruses in enzyme-linked immunosorbent assays.


title: Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

text: Hand–foot–mouth disease due to enterovirus 71 (EV71) and coxsackievirus A16 (CA16) has recently caused large outbreaks in mainland China in 2008. We performed complete genome sequencing on two EV71 (SZ/HK08-5 and SZ/HK08-6) and two CA16 (SZ/HK08-3 and SZ/HK08-7) strains from patients in Shenzhen, China. Phylogenetic, similarity plot and bootscan analyses revealed recombination between EV71 genotypes B and C at the 2A–2B junction, and between EV71 genotype B and CA16 strain G-10 in the 3C region for EV71 strains. A similar phenomenon was also found upon further gene sequencing with other EV71 strains. Recombination between CA16 strain G-10 and EV71 genotype A at the 2A–2B junction was also observed for CA16 strains. The present “double-recombinant” EV71 strains circulating in China and other EV71 subgenotype “C4” strains represent an additional genotype, D. CA16 strains should also be classified into two genotypes. This represents the first evidence for a combination of intratypic and intertypic recombination in EV71 strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-010-0722-0) contains supplementary material, which is available to authorized users.


title: Infectious diseases of the upper respiratory tract: implications for toxicology studies.

text: The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the assessment of chemically induced airway injury. In some instances the pathogenesis of infection with these agents has been relatively well studied in the lower respiratory tract. However, there are few well-controlled studies that have examined the upper respiratory region, which result in interpretive problems for toxicologic pathologists. The conduct and interpretation of both short-term and chronic rodent bioassays can be compromised by both the clinical and subclinical manifestations of infectious diseases. This paper reviews several important infectious diseases of the upper airway of rats and mice and discusses the potential influence of these conditions on the results of toxicology studies.


title: SARS-CoV-2: A New Song Recalls an Old Melody

text: The viruses causing the SARS outbreak of 2002–2003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation.


title: Impact of SARS on healthcare utilization by disease categories: Implications for delivery of healthcare services

text: Abstract Objective To assess the impact of the SARS epidemics in Taiwan on ambulatory care and inpatient utilization by disease categories and accreditation levels of hospital. Methods The National Health Insurance claims data of Taipei were analyzed. We calculated the changes in utilization between June 2002 and June 2003 to estimate the impact that SARS had on utilization. Results The top three disease categories with the most significant drop in utilization were gastroenteritis (−53%), acute bronchitis (−45%), and tonsillitis (−40%) in ambulatory care and acute bronchitis (−82%), gastroenteritis (−72%), and pneumonia (−64%) in inpatient care. On the other hand, the disease categories with the smallest reduction were allergic reactions (−4%), skin infections (−6%), and anxiety (−10%) in ambulatory care and respiratory failure (+40%), delivery (−2%), and fractures of lower limbs (−5%) in inpatient care. Conclusions Disease categories could be classified into three groups according to the extent of change in utilization during the SARS outbreaks. Diseases with a prominent reduction were respiratory diseases, minor problems, and elective procedures. Diseases with a moderate reduction were mainly chronic diseases. Diseases with a limited reduction were acute conditions, difficult mental disorders, or procedures that could not be postponed. The utilization of some diseases shifted significantly from medical centers to district hospitals or clinics.


Immunopathological aspects of coronavirus infections


“That which does not kill us, makes us stronger”: COVID-19 and Posttraumatic Growth


Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV


title: Heteronormativity, Disgust Sensitivity, and Hostile Attitudes toward Gay Men: Potential Mechanisms to Maintain Social Hierarchies

text: Within a social hierarchy based on sexual orientation, heteronormative ideology serves as a social force that maintains dominant group members’ status (e.g., heterosexual men). Disgust may be an emotional reaction to gay men’s violation of heteronormativity (i.e., same-sex sexual behavior) and motivate hostile attitudes toward gay men to promote interpersonal and intergroup boundaries. Based on this theoretical framework, we hypothesized that sexual disgust—compared to pathogen or moral disgust—would be most strongly associated with antigay hostility and would statistically mediate its relationship with heteronormativity. Heterosexual men in the United States (n = 409) completed an online questionnaire assessing heteronormative ideology, disgust sensitivity, and hostile attitudes toward gay men. Results support the hypotheses and suggest that gay men’s sexual behavior is the most likely elicitor of disgust and antigay hostility, as opposed to a perceived pathogen threat or moral transgression. The findings indicate that heteronormative attitudes and sexual disgust are likely contributors to antigay hostility. Thus, intervention efforts should seek to improve tolerance of same-sex sexual behavior among heterosexual men, which may mitigate emotional reactions and hostile attitudes toward gay men.


title: Reporting radiographers’ interpretation and use of the British Society of Thoracic Imaging’s coding system when reporting COVID-19 chest x-rays

text: Abstract Introduction The United Kingdom (UK) has experienced one of the worst initial waves of the COVID-19 pandemic. Clinical signs help guide initial diagnosis, though definitive diagnosis is made using the laboratory technique reverse transcription polymerase chain reaction (RT-PCR). The chest x-ray (CXR) is used as the primary imaging investigation in the United Kingdom (UK) for patients with suspected COVID-19. In some hospitals these CXRs may be reported by a radiographer. Methodology Retrospective review of CXR reports by radiographers for suspected COVID-19 patients attending the Emergency Department (ED) of a hospital in the UK. Interpretation and use of the British Society of Thoracic Imaging (BSTI) coding system was assessed. Report description and code use were cross-checked. Report and code usage were checked against the RT-PCR result to determine accuracy. Report availability was checked against the availability of the RT-PCR result. A confusion matrix was utilised to determine performance. The data were analysed manually using Excel. Results Sample size was 320 patients; 54.1% male patients (n = 173), 45.9% female patients (n = 147). The correct code matched report descriptions in 316 of the 320 cases (98.8%). In 299 of the 320 cases (93.4%), the reports were available before the RT-PCR swab result. CXR sensitivity for detecting COVID-19 was 85% compared to 93% for the initial RT-PCR. Conclusion Reporting radiographers can adequately utilise and apply the BSTI classification system when reporting COVID-19 CXRs. They can recognise the classic CXR appearances of COVID-19 and those with normal appearances. Future best practice includes checking laboratory results when reporting CXRs with ambiguous appearances. Implications for practice Utilisation of reporting radiographers to report CXRs in any future respiratory pandemic should be considered a service-enabling development.


title: Staying updated on COVID‐19: Social media to amplify science in thrombosis and hemostasis

text: Coronavirus disease 2019 is the most serious pandemic of the Internet era. The number of scientific manuscripts published on the subject daily has been overwhelming. The use of Twitter enables interested health professionals and the public to stay informed.


title: Sulfobutylether-β-Cyclodextrin

text: Abstract This review presents the early history, the motivation, the research and some of the backstories behind the discovery and development of sulfobutylether-β-cyclodextrin as a novel parenterally safe solubilizer and stabilizer. A specific sulfobutylether- β -cyclodextrin with an average degree of 6.5 sulfobutyl-groups variably substituted on the 2-, 3- and 6-hydroxyls of the seven glucopyranose (dextrose) units of β -cyclodextrin, is known by its commercial name, Captisol®. Today it is in 13 FDA approved injectables and numerous clinical candidates. It is also an example of a novel product discovered and initially preclinically developed at an academic institution.


Letter to the Editor: Can Sural Fasciocutaneous Flaps Be Effective in Patients Older Than 65?