title: Collection, particle sizing and detection of airborne viruses

text: Viruses that affect humans, animals and plants are often dispersed and transmitted through airborne routes of infection. Due to current technological deficiencies, accurate determination of the presence of airborne viruses is challenging. This shortcoming limits our ability to evaluate the actual threat arising from inhalation or other relevant contact with aerosolized viruses. To improve our understanding of the mechanisms of airborne transmission of viruses, air sampling technologies that can detect the presence of aerosolized viruses, effectively collect them and maintain their viability, and determine their distribution in aerosol particles, are needed. The latest developments in sampling and detection methodologies for airborne viruses, their limitations, factors that can affect their performance and current research needs, are discussed in this review. Much more work is needed on the establishment of standard air sampling methods and their performance requirements. Sampling devices that can collect a wide size range of virus‐containing aerosols and maintain the viability of the collected viruses are needed. Ideally, the devices would be portable and technology‐enabled for on‐the‐spot detection and rapid identification of the viruses. Broad understanding of the airborne transmission of viruses is of seminal importance for the establishment of better infection control strategies.


title: Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic?

text: Abstract Context Coronavirus disease 2019 (COVID-19) pandemic has caused increased interest in the application of telehealth to provide care without exposing patients and physicians to the risk of contagion. The urological literature on the topic is sparse. Objective To perform a systematic review of the literature and evaluate all the available studies on urological applications of telehealth. Evidence acquisition After registration on PROSPERO, we searched PubMed and Scopus databases to collect any kind of studies evaluating any telehealth interventions in any urological conditions. The National Toxicology Program/Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies was used to estimate the risk of bias. A narrative synthesis was performed. Evidence synthesis We identified 45 studies (11 concerning prostate cancer [PCa], three hematuria management, six urinary stones, 14 urinary incontinence [UI], five urinary tract infections [UTIs], and six other conditions), including 12 randomized controlled trials. The available literature indicates that telemedicine has been implemented successfully in several common clinical scenarios, including the decision-making process following a diagnosis of nonmetastatic PCa, follow-up care of patients with localized PCa after curative treatments, initial diagnosis of hematuria, management diagnosis and follow-up care of uncomplicated urinary stones and uncomplicated UTIs, and initial evaluation, behavioral therapies, and pelvic floor muscle training in UI patients, as well as follow-up care after surgical treatments of stress urinary incontinence or pelvic organ prolapse. The methodological quality of most of the reports was good. Conclusions Telehealth has been implemented successfully in selected patients with PCa, UI, pelvic organ prolapse, uncomplicated urinary stones, and UTIs. Many urological conditions are suitable for telehealth, but more studies are needed on other highly prevalent urological malignant and benign conditions. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine. More robust data on long-term efficacy, safety, and health economics are necessary. Patient summary The diffusion of coronavirus disease 2019 (COVID-19) infections has recently increased the interest in telehealth, which is the adoption of telecommunication to deliver any health care activity. The available literature indicates that telemedicine has been adopted successfully in selected patients with several common clinical urological conditions, including prostate cancer, uncomplicated urinary stones, uncomplicated urinary infections, urinary incontinence, or pelvic organ prolapse. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine, but more robust data on long-term efficacy, safety, and costs are necessary.


title: A methodology for optimal placement of sensors in enclosed environments: A dynamical systems approach

text: Abstract Air quality has been an important issue in public health for many years. Sensing the level and distributions of impurities help in the control of building systems and mitigate long term health risks. Rapid detection of infectious diseases in large public areas like airports and train stations may help limit exposure and aid in reducing the spread of the disease. Complete coverage by sensors to account for any release scenario of chemical or biological warfare agents may provide the opportunity to develop isolation and evacuation plans that mitigate the impact of the attack. All these scenarios involve strategic placement of sensors to promptly detect and rapidly respond. This paper presents a data driven sensor placement algorithm based on a dynamical systems approach. The approach utilizes the finite dimensional Perron-Frobenius (PF) concept. The PF operator (or the Markov matrix) is used to construct an observability gramian that naturally incorporates sensor accuracy, location constraints, and sensing constraints. The algorithm determines the response times, sensor coverage maps, and the number of sensors needed. The utility of the procedure is illustrated using four examples: a literature example of the flow field inside an aircraft cabin and three air flow fields in different geometries. The effect of the constraints on the response times for different sensor placement scenarios is investigated. Knowledge of the response time and coverage of the multiple sensors aides in the design of mechanical systems and response mechanisms. The methodology provides a simple process for place sensors in a building, analyze the sensor coverage maps and response time necessary during extreme events, as well as evaluate indoor air quality. The theory established in this paper also allows for future work in topics related to construction of classical estimator problems for the sensors, real-time contaminant transport, and development of agent dispersion, contaminant isolation/removal, and evacuation strategies.


title: Using an integrated infection control strategy during outbreak control to minimize nosocomial infection of severe acute respiratory syndrome among healthcare workers

text: Summary Healthcare workers (HCWs) are at risk of acquiring severe acute respiratory syndrome (SARS) while caring for SARS patients. Personal protective equipment and negative pressure isolation rooms (NPIRs) have not been completely successful in protecting HCWs. We introduced an innovative, integrated infection control strategy involving triaging patients using barriers, zones of risk, and extensive installation of alcohol dispensers for glove-on hand rubbing. This integrated infection control approach was implemented at a SARS designated hospital (‘study hospital’) where NPIRs were not available. The number of HCWs who contracted SARS in the study hospital was compared with the number of HCWs who contracted SARS in 86 Taiwan hospitals that did not use the integrated infection control strategy. Two HCWs contracted SARS in the study hospital (0.03 cases/bed) compared with 93 HCWs in the other hospitals (0.13 cases/bed) during the same three-week period. Our strategy appeared to be effective in reducing the incidence of HCWs contracting SARS. The advantages included rapid implementation without NPIRs, flexibility to transfer patients, and re-inforcement for HCWs to comply with infection control procedures, especially handwashing. The efficacy and low cost are major advantages, especially in countries with large populations at risk and fewer economic resources.


title: Estimating finite-population reproductive numbers in heterogeneous populations

text: Abstract The basic reproductive number, R 0 , is one of the most important epidemiological quantities. R 0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R 0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R 0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate “finite-population reproductive numbers” with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R 0 is small relative to the size of the population and decreases the finite-population reproductive number when R 0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R 0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R 0 .


title: COVID-19 Lessons: The Alignment of Palliative Medicine and Trauma-Informed Care

text: As the COVID-19 pandemic wears on, its psychological, emotional, and existential toll continues to grow and indeed may now rival the physical suffering caused by the illness. Patients, caregivers, and healthcare workers are particularly at risk for trauma responses and would be well served by trauma-informed care (TIC) practices to minimize both immediate and long-term psychological distress. Given the significant overlap between the core tenets of TIC and accepted guidelines for the provision of quality palliative care (PC), PC teams are particularly well poised to both incorporate such practices into routine care and to argue for their integration across health systems. We outline this intersection in order to highlight the uniquely powerful role PC teams can play to reduce the long-term psychological impact of the COVID-19 pandemic.


title: An emergency department response to severe acute respiratory syndrome(): A prototype response to bioterrorism

text: STUDY OBJECTIVE: On March 13, 2003, Singapore physicians were alerted about an outbreak of atypical pneumonia that became known as severe acute respiratory syndrome (SARS). I describe the application of an emergency department (ED) disaster response plan to manage the SARS outbreak. METHODS: The ED implemented protection for staff, patients, and facility; infection control measures; and disaster-response workflow changes. The Ministry of Health, Singapore, centralized SARS cases in the hospital, and the ED became the national screening center. A screening questionnaire and a set of admission criteria were applied after assessment of clinical features and chest radiograph findings. RESULTS: For the duration of the outbreak that ended on May 31, 2003, the ED screened 11,461 persons for SARS, of whom 1,386 (12.9%) were admitted to rule out SARS and 235 (17%) were confirmed to have SARS. Among 10,075 persons discharged from the ED, there were 28 reattending patients who were admitted and diagnosed with SARS, giving an undertriage rate of 0.3% (95% confidence interval [CI] 0.1% to 0.4%). The sensitivity of an ED admission for SARS was 89.4% (95% CI 85.6% to 93.1%), and specificity was 89.7% (95% CI 89.2% to 90.3%). The positive predictive value was 17% (95% CI 15.7% to 18.4%), and the negative predictive value was 99.7% (95% CI 99.6% to 99.8%). No patient contracted SARS as a result of an ED visit. After full implementation of protective measures, 1 ED nurse with undiagnosed diabetes mellitus was treated for suspected SARS. CONCLUSION: Although the SARS outbreak was not a bioterrorism event, the ED disaster response was applicable in the outbreak's management. The use of a screening questionnaire and admission criteria enabled the ED to screen, treat, and safely discharge the majority of the patients.


docid: enyudvsr

title: Hendra virus in Queensland, Australia, during the winter of 2011: Veterinarians on the path to better management strategies

text: Abstract Following the emergence of Hendra virus (HeV), private veterinarians have had to adopt additional infection control strategies to manage this zoonosis. Between 1994 and 2010, seven people became infected with HeV, four fatally. All infected people were at a higher risk of exposure from contact with horses as they were either veterinary personnel, assisting veterinarians, or working in the horse industry. The management of emerging zoonoses is best approached from a One Health perspective as it benefits biosecurity as well as a public health, including the health of those most at risk, in this case private veterinarians. In 2011 we conducted a cross-sectional study of private veterinarians registered in Queensland and providing veterinary services to horses. The aim of this study was to gauge if participants had adopted recommendations for improved infection control, including the use of personal protective equipment (PPE), and the development of HeV specific management strategies during the winter of 2011. A majority of participants worked in practices that had a formal HeV management plan, mostly based on the perusal of official guidelines and an HeV field kit. The use of PPE increased as the health status of an equine patient decreased, demonstrating that many participants evaluated the risk of exposure to HeV appropriately; while others remained at risk of HeV infection by not using the appropriate PPE even when attending a sick horse. This study took place after Biosecurity Queensland had sent a comprehensive package about HeV management to all private veterinarians working in Queensland. However, those who had previous HeV experience through the management of suspected cases or had attended a HeV specific professional education programme in the previous 12 months were more likely to use PPE than those who had not. This may indicate that for private veterinarians in Queensland personal experience and face-to-face professional education sessions may be more effective in the improvement of HeV management than passive education via information packages. The role of different education pathways in the sustainable adoption of veterinary infection control measures should be further investigated.


Nosocomial or Hospital-acquired Infections: An Overview


title: Infection control practices in facilities for highly infectious diseases across Europe

text: Summary Background The management of patients with highly infectious diseases (HIDs) is a challenge for healthcare provision requiring a high level of care without compromising the safety of other patients and healthcare workers. Aim To study the infection control practice in isolation facilities participating in the European Network for Highly Infectious Diseases (EuroNHID) project. Methods A survey was conducted during 2009 of 48 isolation facilities caring for patients with HIDs in 16 European countries. Checklists and standard evaluation forms were used to collect and interpret data on hand hygiene, routine hygiene and disinfection, and waste management. Findings Forty percent of HIDs had no non-hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not have procedures for routine hygiene, final disinfection, or safe discarding of non-disposable objects or equipment. There was considerable variation in the management of waste and in the training of housekeeping personnel. EuroNHID has developed recommendations for hand hygiene, disinfection, routine hygiene, and waste management. Conclusions Most aspects of hand hygiene, routine hygiene and disinfection, and waste management were considered at least partially adequate in the majority of European isolation facilities dedicated for the care of patients with HIDs. But considerable variability was observed, with management of waste and training of housekeeping personnel being generally less satisfactory.


title: Disruption management in a constrained multi-product imperfect production system

text: Over several decades, production and inventory systems have been widely studied in different aspects, but only a few studies have considered the production disruption problem. In production systems, the production may be disrupted by priorly unknown disturbance and the entire manufacturing plan can be distorted. This research introduces a production-disruption model for a multi-product single-stage production-inventory system. First, a mathematical model for the multi-item production-inventory system is developed to maximize the total profit for a single-disruption recovery-time window. The main objective of the proposed model is to obtain the optimal manufacturing batch size for multi-item in the recovery time window so that the total profit is maximized. To maintain the matter of multi-product, budget and space constraints are used. A genetic algorithm and pattern search techniques are employed to solve this model and all randomly generated test results are compared. Some numerical examples and sensitivity analysis are given to explain the effectiveness and advantages of the proposed model. This proposed model offers a recovery plan for managers and decision-makers to make accurate and effective decisions in real time during the production disruption problems.


title: Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients

text: Abstract Background The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. Methods Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. Results There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. Conclusion SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.


title: Preschool wheeze prognosis: How do we predict outcome?

text: Summary Preschool wheezing is extremely common. Despite its prevalence, prognosis is often hard to determine. Preschool wheezing is not without significant associated morbidity which may result in increased utilization of medical resources. The child with preschool wheezing may represent one of at least three distinct phenotypes, each having different clinical significance and therapeutic implications. The challenge to the clinician is to correctly identify the operative phenotype as a basis for family education, effective therapy and ultimately a reasonable assertion regarding prognosis. The current article reviews clinical presentation, potential etiologies and triggers as well as historical, hereditary and laboratory markers that may aid in the diagnosis and management of this challenging presentation among preschool children.


title: Isolation of inhibitory RNA aptamers against severe acute respiratory syndrome (SARS) coronavirus NTPase/Helicase

text: Abstract Recent outbreak of Severe Acute Respiratory Syndrome (SARS) that caused almost 800 victims requires a development of efficient inhibitor against SARS coronavirus (SCV). In this study, RNA aptamers against SCV NTPase/Helicase (nsP10) were isolated from RNA library containing random sequences of 40 nts using in vitro selection technique. Nucleotide sequences of enriched RNA aptamer pool (ES15 RNA) contain AG-rich conserved sequence of 10–11 nucleotides [AAAGGR(G)GAAG; R, purine base] and/or additional sequence of 5 nucleotides [GAAAG], which mainly reside at the loop region in all the predicted secondary structures. Isolated RNAs were observed to efficiently inhibit double-stranded DNA unwinding activity of the helicase by up to ∼85% with an IC50 value of 1.2nM but show a slight effect on ATPase activity of the protein in the presence of cofactor, poly (rU). These results suggest that the pool of selected aptamers might be potentially useful as anti-SCV agents.


Immunosuppression in hematological cancer patients with Covid-19 – uncomplicated infections but delayed viral clearance?


title: DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

text: The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.


title: Analysis of synonymous codon usage in classical swine fever virus

text: Using the complete genome sequences of 35 classical swine fever viruses (CSFV) representing all three genotypes and all three kinds of virulence, we analyzed synonymous codon usage and the relative dinucleotide abundance in CSFV. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in CSFV. Furthermore, we observed that the relative abundance of dinucleotides in CSFV is independent of the overall base composition but is still the result of differential mutational pressure, which also shapes codon usage. In addition, other factors, such as the subgenotypes and aromaticity, also influence the codon usage variation among the genomes of CSFV. This study represents the most comprehensive analysis to date of CSFV codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-008-0296-z) contains supplementary material, which is available to authorized users.


docid: wnvhhrhy

title: Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus Suppresses Both MAVS and RIG-I Expression as One of the Mechanisms to Antagonize Type I Interferon Production

text: Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11. Since nsp11 is an endoribonuclease (EndoU), the structure function relationship was examined using a series of nsp11 EndoU mutant plasmids. The mutants that impaired the EndoU activity failed to suppress IFN and led to the normal expression of MAVS. Seven single amino acid substitutions (4 in subdomain A and 3 in subdomain B) plus one insertion (frame-shift in nsp11) were then introduced into PRRSV infectious cDNA clones to generate nsp11 mutant viruses. Unfortunately, all EndoU knock-out nsp11 mutant viruses appeared replication-defective and no progenies were produced. Three mutations in EndoU subdomain A expressed the N and nsp2/3 proteins but their infectivity diminished after 2 passages. Taken together, our data show that PRRSV nsp11 endoribonuclease activity is critical for both viral replication and IFN antagonism. More importantly, the endoribonuclease activity of nsp11 demonstrates the substrate specificity towards MAVS and RIG-I (transcripts and proteins) over p65 and IRF3 in the context of gene transfection and overexpression. This is likely a mechanism of nsp11 suppression of type I IFN production.


title: Developing Interactive Antimicrobial Stewardship and Infection Prevention Curricula for Diverse Learners: A Tailored Approach

text: BACKGROUND. To impart principles of antimicrobial stewardship (AS) and infection prevention and control (IPC), we developed a curriculum tailored to the diverse aptitudes of learners at our medical center. METHODS. We integrated case-based modules, group learning activities, smartphone applications (apps), decision support tools, and prescription audit and feedback into curricula of the medical school, medicine residency program, infectious diseases (ID) fellowship program, and hospital medicine program operations. Interventions were implemented in 2012–2016 using a quasi-experimental before-and-after study design, and this was assessed using pre- and postintervention surveys or audit of antibiotic prescriptions. RESULTS. Over 180 medical students participated in the AS and IPC seminars. After smartphone app introduction, 69% reported using the app as their preferred source of antibiotic information. Approximately 70% of students felt comfortable prescribing antibiotics for a known infection compared with 40% at baseline (P = .02), and approximately 83% were able to identify the appropriate personal protective equipment for specific scenarios. Approximately 99% agreed that they have a role in promoting patient safety and preventing healthcare-associated infections as medical students. At 20 months, appropriateness of trainee antibiotic prescriptions increased by 20% (P < .01). Almost all ID fellows indicated that the AS and IPC seminar was a vital training supplement. Uptake of internist antibiotic recommendations using AS decision support tools was approximately 70%. CONCLUSIONS. All 5 interventions addressed learning objectives and knowledge gaps and are applicable across a range of environments. Evaluating long-term impact of our curriculum is the focus of future study.


title: A guide for urogynecologic patient care utilizing telemedicine during the COVID-19 pandemic: review of existing evidence

text: INTRODUCTION AND HYPOTHESIS: The COVID-19 pandemic and the desire to “flatten the curve” of transmission have significantly affected the way providers care for patients. Female Pelvic Medicine and Reconstructive Surgeons (FPMRS) must provide high quality of care through remote access such as telemedicine. No clear guidelines exist on the use of telemedicine in FPMRS. Using expedited literature review methodology, we provide guidance regarding management of common outpatient urogynecology scenarios during the pandemic. METHODS: We grouped FPMRS conditions into those in which virtual management differs from direct in-person visits and conditions in which treatment would emphasize behavioral and conservative counseling but not deviate from current management paradigms. We conducted expedited literature review on four topics (telemedicine in FPMRS, pessary management, urinary tract infections, urinary retention) and addressed four other topics (urinary incontinence, prolapse, fecal incontinence, defecatory dysfunction) based on existing systematic reviews and guidelines. We further compiled expert consensus regarding management of FPMRS patients in the virtual setting, scenarios when in-person visits are necessary, symptoms that should alert providers, and specific considerations for FPMRS patients with suspected or confirmed COVID-19. RESULTS: Behavioral, medical, and conservative management will be valuable as first-line virtual treatments. Certain situations will require different treatments in the virtual setting while others will require an in-person visit despite the risks of COVID-19 transmission. CONCLUSIONS: We have presented guidance for treating FPMRS conditions via telemedicine based on rapid literature review and expert consensus and presented it in a format that can be actively referenced.


title: The use of simulation to prepare and improve responses to infectious disease outbreaks like COVID-19: practical tips and resources from Norway, Denmark, and the UK

text: In this paper, we describe the potential of simulation to improve hospital responses to the COVID-19 crisis. We provide tools which can be used to analyse the current needs of the situation, explain how simulation can help to improve responses to the crisis, what the key issues are with integrating simulation into organisations, and what to focus on when conducting simulations. We provide an overview of helpful resources and a collection of scenarios and support for centre-based and in situ simulations.


title: Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus

text: Dendritic cells (DCs) play a role in anti-viral immunity by providing early innate protection against viral replication and by presenting antigen to T cells for initiation of the adaptive immune response. Studies show the adaptive response to porcine reproductive and respiratory syndrome virus (PRRSV) is ineffective for complete viral elimination. Other studies describe the kinetics of the adaptive response to PRRSV, but have not investigated the early response by DCs. We hypothesize that there is an aberrant activation of DCs early in PRRSV infection; consequently, the adaptive response is triggered inadequately. The current study characterized a subtype of porcine lung DCs (L-DCs) and investigated the ability of PRRSV to infect and replicate in L-DCs and monocyte-derived DCs (MDDCs). Furthermore, the type I interferon anti-viral response to PRRSV with and without the addition of recombinant porcine IFN-α (rpIFN-α), an important cytokine that signals for anti-viral mediator activation, was analysed. Results show that PRRSV replicated in MDDCs but not L-DCs, providing evidence that these cells have followed distinct differentiation pathways. Although both cell types responded to PRRSV with an induction of IFN-β mRNA, the magnitude and duration of the response differed between cell types. The addition of rpIFN-α was protective in MDDCs, and mRNA synthesis of Mx (myxovirus resistant) and PKR (double-stranded RNA dependent protein kinase) was observed in both cell types after rpIFN-α addition. Overall, PRRSV replicated in MDDCs but not L-DCs, and rpIFN-α was required for the transcription of protective anti-viral mediators. DC response to PRRSV was limited to IFN-β transcription, which may be inadequate in triggering the adaptive immune response.


title: Rapid clinical diagnosis in fatal swine influenza (H1N1) pneumonia in an adult with negative rapid influenza diagnostic tests (RIDTs): Diagnostic swine influenza triad

text: Background The “herald wave” of the H1N1 pandemic spread from Mexico to the United States in spring 2009. Initially, the epicenter of H1N1 in the United States was in the New York area. Our hospital, like others, was inundated with large numbers of patients who presented at the Emergency Department (ED) with influenza-like illnesses (ILIs) for swine influenza testing and evaluation. Methods The Winthrop-University Hospital ED used rapid influenza (QuickVue A/B) tests to screen for H1N1 infection. Patients who were rapid influenza A test-positive were also reverse transcription-polymerase chain reaction (RT-PCR) positive for H1N1. In our ED, 30% of patients with ILIs and possible H1N1 pneumonia had negative rapid influenza A screening tests. Because H1N1 RT-PCR testing was restricted, there was no laboratory test to confirm or rule out H1N1. Other rapid influenza diagnostic tests (RIDTs), e.g., the respiratory fluorescent antibody (FA) viral panel test, were used to identify H1N1 patients with negative RIDTs. Results Unfortunately, there was not a good correlation between RIDT results and RT-PCR results. There was a critical need to develop a clinical syndromic approach for diagnosing hospitalized adults with probable H1N1 pneumonia with negative RIDTs. Early in the pandemic, the Winthrop-University Hospital Infectious Disease Division developed a diagnostic weighted point score system to diagnose H1N1 pneumonia clinically in RIDT-negative adults. The point score system worked well, but was time-consuming. As the “herald wave” of the pandemic progressed, our ED staff needed a rapid, simplified method to diagnose probable H1N1 pneumonia in hospitalized adults with negative RIDTs. A rapid and simplified diagnosis was based on the diagnostic weighted point score system, which we simplified into a triad of key, nonspecific laboratory indicators. In adults hospitalized with an ILI, a fever >102°F with severe myalgias, and a chest x-ray without focal segmental/lobar infiltrates, the presence of three indicators, i.e., otherwise unexplained relative lymphopenia, elevated serum transaminases, and an elevated creatinine phosphokinase, constituted the diagnostic swine influenza triad. The Infectious Disease Division's diagnostic swine flu triad was used effectively as the pandemic progressed, and was not only useful in correctly diagnosing probable H1N1 pneumonia in hospitalized adults with negative RIDTs, but was also in ruling out mimics of swine influenza, e.g., exacerbations of chronic bronchitis, asthma, or congestive heart failure, as well as bacterial community-acquired pneumonias (CAPs), e.g., legionnaire's disease. Conclusion Clinicians can use the Winthrop-University Hospital Infectious Disease Division's Diagnostic swine influenza triad to make a rapid clinical diagnosis of probable H1N1 pneumonia in hospitalized adult patients with negative RIDTs.


title: Validation of specific quantitative real-time RT-PCR assay panel for Infectious Bronchitis using synthetic DNA standards and clinical specimens

text: Abstract Infectious bronchitis (IB) is a highly contagious upper respiratory tract disease of chickens caused by infectious bronchitis virus (IBV), which has various serotypes that do not cross-protect. Vaccine control strategies for this virus are only effective when designed around the currently circulating serotypes. It is essential to not only rapidly detect IBV but also to identify the type of virus causing disease. Six TaqMan™-based quantitative real-time RT-PCR assays (Universal, Ark, Mass, DE/GA98, GA07, GA08) were developed and examined the sensitivity and specificity for each assay. Assays were developed targeting the hypervariable region in the S1 gene subunit. The analytical sensitivity of TaqMan™-based quantitative real-time RT-PCR assays (qRT-PCR) assays was evaluated using synthetic DNA standards that were identical with the target sequence and specificity was further validated using clinical and biological specimens. All developed assays performed equivalently when using synthetic DNA templates as standard material, as it achieved linearity over a 5 log10 dynamic range with a reproducible limit of detection of ≤10 target copies per reaction, with high calculated amplification efficiencies ranging between 90%–115%. Further validation of specificity using clinical and biological specimens was also successful.


The prevalence of patent interferences in gene technology


Potential Treatments for SARS‐CoV‐2 Infection


title: Problems of calf rearing in connection with their mortality and optimal growth: A review

text: Abstract Protection of calves against enteric and respiratory disorders is dependent on the passive immunity that the calf has received, its innate resistance to infection, the burden of infection in the environment and the nutrition of the calf. Superimposed on these, are the effects of management and physical environment. The plane of nutrition required for dairy heifers during rearing depends on the age at first calving, and for meat animals depends on the carcass weight and fat deposition required at a particular slaughter date in relation to time of birth.


title: Global Survey on Pancreatic Surgery During the COVID-19 Pandemic

text: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients’ and clinicians’ safety and safeguard health care capacity. SUMMARY BACKGROUND DATA: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. RESULTS: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2–5] to 1 (IQR 0–2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. CONCLUSIONS: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.


title: Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma?

text: Abstract Background: Although known as common causes of upper respiratory infections, rhinoviruses, enteroviruses, and corona-viruses are poorly studied as inducers of wheezing in infants, and their possible role in the development of childhood asthma has not been investigated. Objective: The purposes of this study were to assess the occurrence of RV, enterovirus, and coronavirus infections in wheezing infants and to evaluate the association of these viral findings with early school-age asthma. Methods: In 1999, outcome in relation to asthma was studied in 82 of 100 initially recruited children who had been hospitalized for wheezing in infancy during the period 1992-1993. In 2000, etiologic viral studies regarding the index episode of wheezing were supplemented by rhinovirus, enterovirus, and coronavirus detection by RT-PCR from frozen nasopharyngeal aspirates in 81 of the children for whom adequate samples were available. Of these children, 66 had participated in the follow-up in 1999. Results: Rhinoviruses were identified in 27 (33%) of the 81 children, enteroviruses in 10 (12%), and coronaviruses in none. Rhinoviruses were present as single viral findings in 22 (81%) of the 27 rhinovirus-positive cases, and rhinovirus infections were associated with the presence of atopic dermatitis in infancy. Enteroviruses were commonly encountered in mixed infections and had no association with atopy. As single viral findings, rhinoviruses were associated with the development of asthma (P = .047; odds ratio, 4.14; 95% CI, 1.02-16.77 versus rhinovirus-negative cases [by logistic regression adjusted for age, sex, and atopic dermatitis on entry)]. Conclusion: Our results present rhinoviruses as important inducers of wheezing even in infancy. The association with atopy and subsequent asthma calls for reevaluation of the role of rhinoviruses in the development of asthma. (J Allergy Clin Immunol 2003;111:66-71.)


title: Social media and outbreaks of emerging infectious diseases: A systematic review of literature

text: BACKGROUND: The public often turn to social media for information during emerging infectious diseases (EIDs) outbreaks. This study identified the major approaches and assessed the rigors in published research articles on EIDs and social media. METHODS: We searched 5 databases for published journal articles on EIDs and social media. We then evaluated these articles in terms of EIDs studied, social media examined, theoretical frameworks, methodologic approaches, and research findings. RESULTS: Thirty articles were included in the analysis (published between January 1, 2010, and March 1, 2016). EIDs that received most scholarly attention were H1N1 (or swine flu, n = 15), Ebola virus (n = 10), and H7N9 (or avian flu/bird flu, n = 2). Twitter was the most often studied social media (n = 17), followed by YouTube (n = 6), Facebook (n = 6), and blogs (n = 6). Three major approaches in this area of inquiry are identified: (1) assessment of the public's interest in and responses to EIDs, (2) examination of organizations' use of social media in communicating EIDs, and (3) evaluation of the accuracy of EID-related medical information on social media. CONCLUSIONS: Although academic studies of EID communication on social media are on the rise, they still suffer from a lack of theorization and a need for more methodologic rigor.


title: High Throughput Sequencing for Detection of Foodborne Pathogens

text: High-throughput sequencing (HTS) is becoming the state-of-the-art technology for typing of microbial isolates, especially in clinical samples. Yet, its application is still in its infancy for monitoring and outbreak investigations of foods. Here we review the published literature, covering not only bacterial but also viral and Eukaryote food pathogens, to assess the status and potential of HTS implementation to inform stakeholders, improve food safety and reduce outbreak impacts. The developments in sequencing technology and bioinformatics have outpaced the capacity to analyze and interpret the sequence data. The influence of sample processing, nucleic acid extraction and purification, harmonized protocols for generation and interpretation of data, and properly annotated and curated reference databases including non-pathogenic “natural” strains are other major obstacles to the realization of the full potential of HTS in analytical food surveillance, epidemiological and outbreak investigations, and in complementing preventive approaches for the control and management of foodborne pathogens. Despite significant obstacles, the achieved progress in capacity and broadening of the application range over the last decade is impressive and unprecedented, as illustrated with the chosen examples from the literature. Large consortia, often with broad international participation, are making coordinated efforts to cope with many of the mentioned obstacles. Further rapid progress can therefore be prospected for the next decade.


title: COVID-19 contagion and digital finance

text: Digital finance is going to be heavily affected by the COVID-19 outbreak. We present a statistical model which can be employed to understand the contagion dynamics of the COVID-19, so that its impact on finance can possibly be anticipated, and digitally monitored. The model is a Poisson autoregression of the daily new observed cases, and considers both short-term and long-term dependence in the infections counts. Model results are presented for the observed time series of China, the first affected country, but can be easily reproduced for all countries.


title: Corticosteroid-induced Osteonecrosis of the Femoral Head: Detection, Diagnosis, and Treatment in Earlier Stages

text: OBJECTIVE: This review aimed to provide a current recommendation to multidisciplinary physicians for early detection, diagnosis, and treatment of corticosteroid-induced osteonecrosis of the femoral head (ONFH) based on a comprehensive analysis of the clinical literature. DATA SOURCES: For the purpose of collecting potentially eligible articles, we searched for articles in the PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using the following key words: “corticosteroid”, “osteonecrosis of the femoral head”, “risk factors”, “diagnosis”, “prognosis”, and “treatment”. STUDY SELECTION: Articles on relationships between corticosteroid and ONFH were selected for this review. Articles on the diagnosis, prognosis, and intervention of earlier-stage ONFH were also reviewed. RESULTS: The incidence of corticosteroid-induced ONFH was associated with high doses of corticosteroids, and underlying diseases in certain predisposed individuals mainly occurred in the first 3 months of corticosteroid prescription. The enhanced awareness and minimized exposure to the established risk factors and earlier definitive diagnosis are essential for the success of joint preservation. When following up patients with ONFH, treatment should be started if necessary. Surgical treatment yielded better results than conservative therapy in earlier-stage ONFH. The ideal purpose of earlier intervention and treatment is permanent preservation of the femoral head without physical restrictions in daily living. CONCLUSIONS: Clinicians should enhance their precaution awareness of corticosteroid-induced ONFH. For high-risk patients, regular follow-up is very important in the 1(st) year after high-dose prescription of corticosteroids. Patients with suspected ONFH should be referred to orthopedists for diagnosis and treatment in its earlier stage to preserve the joint.


title: Barrier precautions, isolation protocols, and personal hygiene in veterinary hospitals

text: Because nosocomial and zoonotic diseases are inherent and ever-present risks in veterinary hospitals, proactive policies should be in place to reduce the risk of sporadic cases and outbreaks. Policies should ideally be put in place before disease issues arise, and policies should be effectively conveyed to all relevant personnel. Written policies are required for practical and liability reasons and should be reviewed regularly. Although no infection control program can eliminate disease concerns, proper implementation of barrier precautions and isolation can reduce the exposure of hospitalized animals and hospital personnel to infectious agents. Appropriate personal hygiene, particularly hand hygiene, can assist in the prevention of disease transmission when pathogens bypass barriers and are able to contact personnel. Veterinary hospitals have moral, professional, and legal requirements to provide a safe workplace and to reduce the risks to hospitalized patients. Based on experience in the human medical field and on the continual emergence of new infectious diseases, infection control challenges can only be expected to increase in the future. Regular reassessment of protocols based on ongoing research and clinical experiences is required.


title: The rise and fall of infectious disease in a warmer world

text: Now-outdated estimates proposed that climate change should have increased the number of people at risk of malaria, yet malaria and several other infectious diseases have declined. Although some diseases have increased as the climate has warmed, evidence for widespread climate-driven disease expansion has not materialized, despite increased research attention. Biological responses to warming depend on the non-linear relationships between physiological performance and temperature, called the thermal response curve. This leads performance to rise and fall with temperature. Under climate change, host species and their associated parasites face extinction if they cannot either thermoregulate or adapt by shifting phenology or geographic range. Climate change might also affect disease transmission through increases or decreases in host susceptibility and infective stage (and vector) production, longevity, and pathology. Many other factors drive disease transmission, especially economics, and some change in time along with temperature, making it hard to distinguish whether temperature drives disease or just correlates with disease drivers. Although it is difficult to predict how climate change will affect infectious disease, an ecological approach can help meet the challenge.


title: Bacillus subtilis and surfactin inhibit the transmissible gastroenteritis virus from entering the intestinal epithelial cells

text: Intestinal epithelial cells are the targets for transmissible gastroenteritis (TGE) virus (TGEV) infection. It is urgent to develop a novel candidate against TGEV entry. Bacillus subtilis is a probiotic with excellent anti-microorganism properties and one of its secretions, surfactin, has been regarded as a versatile weapon for most plant pathogens, especially for the enveloped virus. We demonstrate for the first time that B. subtilis OKB105 and its surfactin can effectively inhibit one animal coronavirus, TGEV, entering the intestinal porcine epithelial cell line (IPEC-J2). Then, several different experiments were performed to seek the might mechanisms. The plaque assays showed that surfactant could reduce the plaque generation of TGEV in a dose-dependent manner. Meanwhile, after incubation with TGEV for 1.5 h, B. subtilis could attach TGEV particles to their surface so that the number of virus to bind to the host cells was declined. Furthermore, our data showed that the inhibition of B. subtilis was closely related to the competition with TGEV for the viral entry receptors, including epidermal growth factor receptor (EGFR) and aminopeptidase N (APN) protein. In addition, Western blotting and apoptosis analysis indicated that B. subtilis could enhance the resistance of IPEC-J2 cells by up-regulating the expression of toll-like receptor (TLR)-6 and reducing the percentage of apoptotic cells. Taken together, our results suggest that B. subtilis OKB105 and its surfactin can antagonize TGEV entry in vitro and may serve as promising new candidates for TGEV prevention.


title: Effects of School Closures, 2008 Winter Influenza Season, Hong Kong

text: In winter 2008, kindergartens and primary schools in Hong Kong were closed for 2 weeks after media coverage indicated that 3 children had died, apparently from influenza. We examined prospective influenza surveillance data before, during, and after the closure. We did not find a substantial effect on community transmission.


title: Suppression of porcine reproductive and respiratory syndrome virus replication by morpholino antisense oligomers

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of a contagious disease characterized by reproductive failure in sows and respiratory disease in piglets. This infectious disease results in significant losses in the swine industry and specific anti-PRRSV drugs are needed. In this study, we evaluated a novel class of antisense compounds, peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMOs), for their ability to suppress PRRSV replication in cell culture. P-PMOs are analogs of single-stranded DNA and contain a modified backbone that confers highly specific binding to RNA and resistance to nucleases. Of six P-PMOs tested, one (‘5UP1’), with sequence complementary to the 5′-terminal 21 nucleotides of the PRRSV genome, was found to be highly effective at reducing PRRSV replication in a specific and dose-dependent manner in CRL11171 cells in culture. 5UP1 treatment generated up to a 4.5log reduction in infectious PRRSV yield, while a control P-PMO had no effect on viral titer. Immunofluorescence assay with an anti-PRRSV monoclonal antibody confirmed the titer observations. The sequence-specificity of 5UP1 effect was confirmed in part by a cell-free luciferase reporter assay system, which showed that 5UP1-mediated inhibition of translation decreased if the target-RNA contained mispairings in relation to the 5UP1 P-PMO. Real-time RT-PCR showed that the production of PRRSV negative-sense RNA was reduced if 5UP1 was added to cells at up to 6h post-virus inoculation. Cell viability assays detected no cytotoxicity of 5UP1 within the concentration-range of this study. These results indicate that P-PMO 5UP1 has potential as an anti-PRRSV agent.


docid: kbysppgb

title: Diagnostic performance of near-patient testing for influenza

text: Abstract Background Rapid diagnosis of influenza is important for controlling outbreaks and starting antiviral therapy. Direct antigen detection (DAD) is rapid, but lacks sensitivity, whereas nucleic acid amplification testing (NAT) is more sensitive, but also more time-consuming. Objectives To evaluate the performance of a rapid isothermal NAT and two DADs. Study design During February–May 2014, we tested 211 consecutive patients with influenza-like illness using a commercial isothermal NAT (Alere™ Influenza A&B) as well as the DAD Sofia® Influenza A+B and BinaxNOW® Influenza A&B for detection of influenza-A and -B virus. RespiFinder-22® a commercial multiplex NAT served as reference test. Serial 10-fold dilutions of influenza-A and -B cell culture supernatants were examined. Another 225 patient samples were tested during December 2014–February 2015. Results Compared to RespiFinder-22®, the isothermal NAT Alere™ Influenza A&B, and the DAD Sofia® Influenza A+B and BinaxNOW® Influenza A&B had sensitivities of 77.8%, 59.3% and 29.6%, and specificities of 99.5%, 98.9% and 100%, respectively, for the first 211 patient samples. Alere™ Influenza A&B showed 85.7% sensitivity and 100% specificity in the second cohort. Isothermal NAT was 10-100-fold more sensitive compared to DAD for influenza virus culture supernatants with a lower limit of detection of 5000–50,000 copies/mL. The average turn-around time (TAT) of isothermal NAT and DADs was 15min, but increased to 110min for Alere™ Influenza A&B, 30min for BinaxNOW® Influenza A&B, and 45min for Sofia® Influenza A+B, when analyzing batches of 6 samples. Conclusion Simple sample processing and a TAT of 15min render isothermal NAT Alere™ Influenza A&B suitable for sequential near-patient testing, but the TAT advantage is lost when testing of larger series.


title: Biogenesis and architecture of arterivirus replication organelles

text: Abstract All eukaryotic positive-stranded RNA (+RNA) viruses appropriate host cell membranes and transform them into replication organelles, specialized micro-environments that are thought to support viral RNA synthesis. Arteriviruses (order Nidovirales) belong to the subset of +RNA viruses that induce double-membrane vesicles (DMVs), similar to the structures induced by e.g. coronaviruses, picornaviruses and hepatitis C virus. In the last years, electron tomography has revealed substantial differences between the structures induced by these different virus groups. Arterivirus-induced DMVs appear to be closed compartments that are continuous with endoplasmic reticulum membranes, thus forming an extensive reticulovesicular network (RVN) of intriguing complexity. This RVN is remarkably similar to that described for the distantly related coronaviruses (also order Nidovirales) and sets them apart from other DMV-inducing viruses analysed to date. We review here the current knowledge and open questions on arterivirus replication organelles and discuss them in the light of the latest studies on other DMV-inducing viruses, particularly coronaviruses. Using the equine arteritis virus (EAV) model system and electron tomography, we present new data regarding the biogenesis of arterivirus-induced DMVs and uncover numerous putative intermediates in DMV formation. We generated cell lines that can be induced to express specific EAV replicase proteins and showed that DMVs induced by the transmembrane proteins nsp2 and nsp3 form an RVN and are comparable in topology and architecture to those formed during viral infection. Co-expression of the third EAV transmembrane protein (nsp5), expressed as part of a self-cleaving polypeptide that mimics viral polyprotein processing in infected cells, led to the formation of DMVs whose size was more homogenous and closer to what is observed upon EAV infection, suggesting a regulatory role for nsp5 in modulating membrane curvature and DMV formation.


title: Case report of chloroquine therapy and hypoglycaemia in type 1 diabetes: What should we have in mind during the COVID-19 pandemic?

text: Abstract A type 1 diabetes patient experienced remission associated with chloroquine therapy while travelling to a malaria-endemic area. Chloroquine has immunomodulatory and hypoglycaemic effects and may become more frequently used due to the COVID-19 pandemic. Patients with type 1 diabetes treated with chloroquine should be monitored for hypoglycaemia, even after recovery.


title: Exploring the Native Human Antibody Repertoire to Create Antiviral Therapeutics

text: Native human antibodies are defined as those that arise naturally as the result of the functioning of an intact human immune system. The utility of native antibodies for the treatment of human viral diseases has been established through experience with hyperimmune human globulins. Native antibodies, as a class, differ in some respects from those obtained by recombinant library methods (phage or transgenic mouse) and possess distinct properties that may make them ideal therapeutics for human viral diseases. Methods for cloning native human antibodies have been beset by technical problems, yet many antibodies specific for viral antigens have been cloned. In the present review, we discuss native human antibodies and ongoing improvements in cloning methods that should facilitate the creation of novel, potent antiviral therapeutics obtained from the native human antibody repertoire.


Maybe there is an alternative after all?


Covid-19 in Italy: lesson from the Veneto Region


title: Learning from Ebola Virus: How to Prevent Future Epidemics

text: The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases.


title: Antigenic variation among recent Japanese isolates of bovine coronaviruses belonging to phylogenetically distinct genetic groups

text: Bovine coronaviruses (BCoVs) isolated in Japan consist of four genetic groups, as determined by phylogenetic analysis using the polymorphic region (aa 456–592) of the S glycoprotein gene. Japanese field isolates of BCoV, reference Kakegawa strain, and vaccine strain 66/H were analyzed for their antigenic properties by indirect immunofluorescence and neutralization testing. There were no significant differences observed among these BCoVs in direct immunofluorescence tests. However, antigenic differences were observed between BCoVs in the neutralization tests, although there was no clear indication of a distinct serotype. A monoclonal antibody, 4H4, against the Kakegawa strain belonging to group 1 lacked significant neutralizing activity for viruses of groups 2, 3, and 4. Therefore, we speculate that the genetic differences between these groups may have altered their antigenicity. Analysis of mutant viruses resistant to neutralization by 4H4 revealed that the antigenic site of the Kakegawa strain maps to amino acid position 284 of the S glycoprotein. This site is not homologous to a known antigenic site (aa 528) of the Quebec strain belonging to group 1, and it is not located in the conformational domain comprising domain I (aa 351–403) and domain II (aa 517–621). This amino acid constitutes a neutralization epitope of BCoV, which is distinct from aa 528 of the Quebec strain. These results indicate antigenic evolution of BCoV between the genetic groups circulating in Japan.


title: COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

text: BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.


title: A wind tunnel study of effects of twisted wind flows on the pedestrian-level wind field in an urban environment

text: Abstract The influence of twisted wind flows on the pedestrian-level wind (PLW) field of an urban area was evaluated by testing a typical urban site (Tsuen Wan, Hong Kong) in a boundary layer wind tunnel. Four twisted wind profiles with different magnitudes and directions of yaw angles were employed to investigate variations in wind speed with the properties of the twisted wind flows at the pedestrian level. An additional conventional wind profile with similar wind speeds and turbulence intensities to the twisted winds but with zero yaw angles was simulated for comparisons. The mean wind speeds at 77 locations including the perimeter, roadsides, and groups of high-rise buildings were analysed for the conventional and the four twisted wind flows. The comparisons show a tendency of twisted winds to generate higher wind speeds at the pedestrian level than the conventional wind profile. The wind speeds of the twisted winds have a strong dependence on the magnitude and direction of the yaw angles, particularly at locations where the densities of buildings in the neighbourhood are low and hence local wind circulations are significantly modified by the twisted winds.


title: A case of cefditoren‐induced Acute Generalized Exanthematous Pustulosis during COVID‐19 pandemics. Severe Cutaneous Adverse Reactions (SCARs) are an issue

text: We read with interest the article by Recalcati et al. about the report of cutaneous manifestations in COVID‐19 patients. We would like to highlight that some potentially severe manifestations in these patients are not directly related to the coronavirus but to the medications administered.


title: Flexibility—Not just for yoga anymore!

text: Over the past few years, nucleosides have maintained a prominent role as one of the cornerstones of antiviral and anticancer therapeutics, and many approaches to nucleoside drug design have been pursued. One such approach involves flexibility in the sugar moiety of nucleosides, for example, in the highly successful anti-HIV and HBV drug tenofovir. In contrast, introduction of flexibility to the nucleobase scaffold has only more recently gained significance with the invention of our fleximers. The history, development, and some biological relevance for this innovative class of nucleosides are detailed herein.


Training Residents During the Covid-19 Pandemic


title: Digitally transforming work styles in an era of infectious disease

text: As a new perspective in this era of infectious disease confronting humanity (that cannot be avoided), and in light of research done to date, this article identifies the importance of exploratory research on the business and social impacts of “collaboration systems” which include video conferencing tools - important IT applications for companies. The article proposes analysis integrating four research streams on the digital transformation of work styles through collaboration systems.


title: Contact rate epidemic control of COVID-19: an equilibrium view

text: We consider the control of the COVID-19 pandemic through a standard SIR compartmental model. This control is induced by the aggregation of individuals' decisions to limit their social interactions: when the epidemic is ongoing, an individual can diminish his/her contact rate in order to avoid getting infected, but this effort comes at a social cost. If each individual lowers his/her contact rate, the epidemic vanishes faster, but the effort cost may be high. A Mean Field Nash equilibrium at the population level is formed, resulting in a lower effective transmission rate of the virus. We prove theoretically that equilibrium exists and compute it numerically. However, this equilibrium selects a sub-optimal solution in comparison to the societal optimum (a centralized decision respected fully by all individuals), meaning that the cost of anarchy is strictly positive. We provide numerical examples and a sensitivity analysis, as well as an extension to a SEIR compartmental model to account for the relatively long latent phase of the COVID-19 disease. In all the scenarii considered, the divergence between the individual and societal strategies happens both before the peak of the epidemic, due to individuals' fears, and after, when a significant propagation is still underway.


title: Expression of a coronavirus ribosomal frameshift signal in Escherichia coli: influence of tRNA anticodon modification on frameshifting 1 1 Edited by J. Karn

text: Abstract Eukaryotic ribosomal frameshift signals generally contain two elements, a heptanucleotide slippery sequence (XXXYYYN) and an RNA secondary structure, often an RNA pseudoknot, located downstream. Frameshifting takes place at the slippery sequence by simultaneous slippage of two ribosome-bound tRNAs. All of the tRNAs that are predicted to decode frameshift sites in the ribosomal A-site (XXXY YYN ) possess a hypermodified base in the anticodon-loop and it is conceivable that these modifications play a role in the frameshift process. To test this, we expressed slippery sequence variants of the coronavirus IBV frameshift signal in strains of Escherichia coli unable to modify fully either tRNALys or tRNAAsn. At the slippery sequences UUUA AAC and UUUA AAU (underlined codon decoded by tRNAAsn, anticodon 5′ QUU 3′), frameshifting was very inefficient (2 to 3%) and in strains deficient in the biosynthesis of Q base, was increased (AAU) or decreased (AAC) only two-fold. In E. coli, therefore, hypomodification of tRNAAsn had little effect on frameshifting. The situation with the efficient slippery sequences UUUA AAA (15%) and UUUA AAG (40%) (underlined codon decoded by tRNALys, anticodon 5′ mnm5s2UUU 3′) was more complex, since the wobble base of tRNALys is modified at two positions. Of four available mutants, only trmE (s2UUU) had a marked influence on frameshifting, increasing the efficiency of the process at the slippery sequence UUUA AAA . No effect on frameshifting was seen in trmC1 (cmnm5s2UUU) or trmC2 (nm5s2UUU) strains and only a very small reduction (at UUUA AAG ) was observed in an asuE (mnm5UUU) strain. The slipperiness of tRNALys, therefore, cannot be ascribed to a single modification site on the base. However, the data support a role for the amino group of the mnm5 substitution in shaping the anticodon structure. Whether these conclusions can be extended to eukaryotic translation systems is uncertain. Although E. coli ribosomes changed frame at the IBV signal (UUUAAAG) with an efficiency similar to that measured in reticulocyte lysates (40%), there were important qualitative differences. Frameshifting of prokaryotic ribosomes was pseudoknot-independent (although secondary structure dependent) and appeared to require slippage of only a single tRNA.


title: Homogeneous DNA sensing using enzyme-inhibiting DNA aptamers

text: Abstract A novel aptameric enzyme subunit (AES) which can detect target DNAs has been developed. AES is an enzyme-inhibiting aptamer bearing a target-molecule binding site which can allosterically control enzymatic activity. The thrombin-inhibiting aptamer bearing a G-quartet structure was chosen as the enzyme-inhibiting aptamer. The stem-and-loop structure, which contains a strand complementary to the target DNA, was inserted into the G-quartet structure of the thrombin-inhibiting aptamer to disrupt the G-quartet structure through the hybridization of the target DNA with the complementary strand in the AES. The disruption of the G-quartet structure led to a decrease of the inhibitory activity of the whole aptameric complex. Using this designed aptamer, we were able to detect target DNAs by measuring the thrombin activity in a homogeneous solution without bound/free separation, and the lower detection limit was 20nM.


title: Why hotel rooms were not full during a hallmark sporting event: The 2009 World Games experience

text: Hosting mega- and hallmark-events is perceived as an important vehicle for tourism development. However, in the case of the 2009 World Games, the first international hallmark sporting event in Taiwan, the volume of hotel occupancies and revenue fell short of expectations, despite 4 years of planning and an investment of US$218 million. This study set out to investigate this phenomenon by adopting semi-structured interviews to gather opinions from key stakeholders regarding their business operation and societal conditions. Factors contributing to the lower than expected revenue included inefficient collaboration among stakeholders, a substantial displacement effect to regional hotel competitors, and the unfriendly local atmosphere associated with the fear of H1N1, Typhoon Morakot, and controversial political events. To mitigate inefficiencies from stakeholder collaborations, the study results suggest greater equality in terms of responsibility, information distribution, and risk sharing is needed among the broader tourism industry, the event planning association, and the event supervising authority. In addition, business strategies should take into account Taiwan, an island destination, and current tourism characteristics to counter the displacement effects of loyal and potential customers.


title: Séance bi-académique de l’Académie nationale de médecine et de l’Académie des Sciences: « Confiance et défiance vis-à-vis des vaccins »

text: SUMMARY The explosion of vaccines during the 20th century allowed the control of numerous infectious plagues but multiple challenges oppose conservation and extension of these successes. The hesitation of modern societies in front of vaccinations requires researches in life, human and social sciences in order to reach a better understanding of vaccines mechanism of action and to improve the tolerance and acceptability of vaccines and additives. The ageing of the populations and the increase of subjects at risk also require to improve the immunogenicity and the efficiency of existing vaccines. The constant emergence of new epidemics or the development of the antibio-resistance imposes innovation and development of new vaccines. The recent difficulties faced by the development of vaccines against malaria, tuberculosis or AIDS illustrate the necessity of moving beyond classical recipes and of elaborating new vectors and new adjuvants, of better understanding the heterogeneity of vaccine immunity and of developing alternative routes of immunization. Multidisciplinary researches using the most recent advances in molecular, structural and cellular biology, in microbiology, immunology and of genetic engineering to answer these worldwide challenges.


title: Health Information–Seeking Patterns of the General Public and Indications for Disease Surveillance: Register-Based Study Using Lyme Disease

text: BACKGROUND: People using the Internet to find information on health issues, such as specific diseases, usually start their search from a general search engine, for example, Google. Internet searches such as these may yield results and data of questionable quality and reliability. Health Library is a free-of-charge medical portal on the Internet providing medical information for the general public. Physician’s Databases, an Internet evidence-based medicine source, provides medical information for health care professionals (HCPs) to support their clinical practice. Both databases are available throughout Finland, but the latter is used only by health professionals and pharmacies. Little is known about how the general public seeks medical information from medical sources on the Internet, how this behavior differs from HCPs’ queries, and what causes possible differences in behavior. OBJECTIVE: The aim of our study was to evaluate how the general public’s and HCPs’ information-seeking trends from Internet medical databases differ seasonally and temporally. In addition, we aimed to evaluate whether the general public’s information-seeking trends could be utilized for disease surveillance and whether media coverage could affect these seeking trends. METHODS: Lyme disease, serving as a well-defined disease model with distinct seasonal variation, was chosen as a case study. Two Internet medical databases, Health Library and Physician’s Databases, were used. We compared the general public’s article openings on Lyme disease from Health Library to HCPs’ article openings on Lyme disease from Physician’s Databases seasonally across Finland from 2011 to 2015. Additionally, media publications related to Lyme disease were searched from the largest and most popular media websites in Finland. RESULTS: Both databases, Health Library and Physician’s Databases, show visually similar patterns in temporal variations of article openings on Lyme disease in Finland from 2011 to 2015. However, Health Library openings show not only an increasing trend over time but also greater fluctuations, especially during peak opening seasons. Outside these seasons, publications in the media coincide with Health Library article openings only occasionally. CONCLUSIONS: Lyme disease–related information-seeking behaviors between the general public and HCPs from Internet medical portals share similar temporal variations, which is consistent with the trend seen in epidemiological data. Therefore, the general public’s article openings could be used as a supplementary source of information for disease surveillance. The fluctuations in article openings appeared stronger among the general public, thus, suggesting that different factors such as media coverage, affect the information-seeking behaviors of the public versus professionals. However, media coverage may also have an influence on HCPs. Not every publication was associated with an increase in openings, but the higher the media coverage by some publications, the higher the general public’s access to Health Library.


title: What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study

text: BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.


title: Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2

text: Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong Here, we dispute the conclusions of Xia (2020) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor We highlight major flaws in Xia’s inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited


title: The DEAD-box RNA helicase DDX5 acts as a positive regulator of Japanese encephalitis virus replication by binding to viral 3′ UTR

text: Abstract Japanese encephalitis virus (JEV), one of the causes for epidemic encephalitis, belongs to the family of Flaviviridae. In this study, we demonstrated that cellular DEAD-box RNA helicase DDX5 plays an important role in JEV replication. The knockdown of DDX5 was able to decrease JEV replication, and overexpression of DDX5 mutants lacking the helicase activity also reduced JEV replication, suggesting the helicase activity is essential for JEV replication. DDX5 knockdown did not affect virus assembly and release. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX5 could interact with JEV core protein, non-structural protein 3 (NS3) and 5 (NS5-MTase and NS5-RdRp domains). Meanwhile, we also confirmed that DDX5 interacts with these viral proteins during JEV infection. Confocal microscopy analysis showed that endogenous DDX5 is recruited to the cytoplasm and colocalizes with these viral proteins and viral RNA. RNA-pulldown experiment showed that DDX5 only binds to the JEV 3′ untranslated region (UTR). Finally, we confirmed the role of DDX5 in JEV RNA replication using JEV-replicon system. In conclusion, we identified DDX5 as a positive regulator for JEV replication.


title: Pandemics and Supply Chain Management Research: Toward a Theoretical Toolbox

text: The COVID‐19 pandemic paralyzed the world and revealed the critical importance of supply chain management – perhaps more so than any other event in modern history – in navigating crises. The extensive scope of disruption, massive spillover of effects across countries and industries, and extreme shifts in demand and supply that occurred during the COVID‐19 pandemic illustrate that pandemics are qualitatively different from typical disruptions. As such, pandemics require scholars to take a fresh look at what lenses offer understanding of supply chain phenomena in order to help supply chain managers better prepare for the next pandemic and foster transiliency (i.e., the ability to simultaneously restore some processes and change – often radically – others). To help scholars and managers achieve these aims, we offer an agenda for supply chain management research on pandemics by considering how the key tenets of well‐known and emergent theories can illuminate challenges and potential solutions. Specifically, we consider how resource dependence theory, institutional theory, resource orchestration theory, structural inertia, game theory, real options theory, event systems theory, awareness‐motivation‐capability framework, prospect theory, and tournament theory offer ideas that can help scholars build knowledge about pandemics’ effects on supply chains as well as help managers formulate responses. This article is protected by copyright. All rights reserved


title: Development of three multiplex RT-PCR assays for the detection of 12 respiratory RNA viruses

text: Abstract Three multiplex hemi-nested RT-PCR assays were developed to detect simultaneously 12 RNA respiratory viruses: influenza viruses A, B and C, human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), parainfluenza virus types 1–4 (PIV-1, -2, -3 and -4), human coronavirus OC43 and 229E (HCoV) and rhinovirus (hRV). An internal amplification control was included in one of the RT-PCR assays. The RT-PCR multiplex 1 and the hemi-nested multiplex 1 detected 1 and 0.1 TCID50 of RSV A, respectively, and 0.01 and 0.001 TCID50 of influenza virus A/H3N2, respectively. Two hundred and three nasal aspirates from hospitalised children were retrospectively tested in comparison with two conventional methods: direct immunofluorescence assay and viral isolation technique. Almost all samples (89/91) that were positive by immunofluorescence assay and/or viral isolation technique were detected by the multiplex assay. This method also detected an additional 85 viruses and 33 co-infections. The overall sensitivity (98%), rapidity and enhanced efficiency of these multiplex hemi-nested RT-PCR assays suggest that they would be a significant improvement over conventional methods for the detection of a broad spectrum of respiratory viruses.


title: Fatal Septicemic Melioidosis in a Young Military Person Possibly Co-Infected With Leptospira Interrogans and Orientia Tsutsugamushi

text: Concurrent melioidosis, leptospirosis, and scrub typhus after rural activities is rarely reported. A 19-year-old previously healthy man had fever onset after 2 weeks of military training. Pneumonia became evident on the fifth day of fever under intravenous penicillin and oral minocycline therapy. Acute respiratory failure developed the next day with shock and acute renal and liver function deterioration, which resulted in death. Blood cultures on the third and fifth days grew Burkholderia pseudomallei. Serology revealed leptospirosis and scrub typhus. The emergence of melioidosis in Taiwan and this death without antibiotic treatment for melioidosis alert us that B. pseudomallei should be included as a possible pathogen of pneumonia and sepsis, especially after rural activities.


title: Respiratory Viral Infections in Solid Organ and Hematopoietic Stem Cell Transplantation

text: Respiratory viruses are common in solid organ and hematopoietic stem cell transplant recipients and a recognized cause of significant morbidity and mortality. Epidemiology, risk factors, and attributable mortality in both populations are reviewed. In addition, virus-specific prevention and treatment options, including emerging investigational therapies, are discussed for respiratory syncytial virus, influenza, adenovirus, parainfluenza, and other respiratory viruses.


title: Infections à rhinovirus chez des enfants hospitalisés: étude sur une période de 3 ans

text: Summary Background. Rhinoviruses (RH) are responsible for acute respiratory illnesses, mainly in the upper respiratory tract. Population and methods. — 3,152 children aged under 16 years, admitted to the Paediatrics department of the University Hospital Centre of Poitiers from January 1, 1993 to December 31, 1995 with ear, nose and throat (ENT) and/or respiratory symptoms were systematically investigated. One hundred and forty-five RH strains were isolated from nasopharyngeal secretions of 87 boys and 58 girls (mean age: 20.3 months). Among these, 92 (63.4%) were less than 1 year of age. Bacteriological investigations were done for 29 patients when a concomitant bacterial infection was suspected. Results. RH infection rate was maximum before 1 year of age (median age: 6.5 months) and decreased with age. RH were isolated throughout the 3 years, with a first peak from February to April, and a second one in autumn. The main symptoms were sibilants (27.6%) and cough (24.1%). Sibilants were more frequently associated in children under 12 months of age (P = 0.01). Sometimes, ophthalmologic or digestive symptoms were present. Three children with respiratory distress were transferred to the reanimation ward. In addition, a RH strain was isolated from a child who died of sudden infant death. Thirty-four children (23.4%) were co-infected by one or several viruses; the most frequently detected were the respiratory syncytial virus (41.2%) and the adenoviruses (35.3%). Twenty-nine children were infected by two viruses and five by three. Associated bacterial infections were diagnosed in 23 children, especially conjunctivitis due to Haemophilus influenzae (21.7%). Among these children, eight had a multiple viral infection. Conclusion. RH have a limited pathogenicity but can be associated with serious illnesses among infants and childen.


Human cytomegalovirus-specific CD4+ and CD8+ T-cells in organ transplant recipients


title: Pathological evidence of pulmonary thrombotic phenomena in severe COVID‐19

text: Between February and March 2020, the Journal of Thrombosis and Hemosthasis has published four papers addressing the intricate, complex and still little understood relation between COVID‐19 and thrombogenesis (1‐4). ARS‐Cov‐2 induces in severe cases a cytokine storm that ultimately leads to the activation of the coagulation cascade, causing thrombotic phenomena (5). There is a further strong link between abnormal coagulation parameters (D‐dimer and fibrin degradation products) and mortality. Tang et al. described that 71.4% of nonsurvivors and 0.6% of survivors showed evidence of disseminated intravascular coagulation (DIC), suggesting that DIC is a frequent occurrence in severe COVID‐19 (4). The frequency of DIC in these patients is much higher than that reported for severe SARS (6).


title: An in vivo cell-based assay for investigating the specific interaction between the SARS-CoV N-protein and its viral RNA packaging sequence

text: Abstract The SARS-CoV nucleocapsid (N) protein serves multiple functions in viral replication, transcription, and assembly of the viral genome complex. Coronaviruses specifically package genomic RNA into assembled virions, and in SARS-CoV, it is reported that this process is driven by an interaction between the N-protein and a packaging signal encoded within the viral RNA. While recent studies have uncovered the sequence of this packaging signal, little is known about the specific interaction between the N-protein and the packaging signal sequence, and the mechanisms by which this interaction drives viral genome packaging. In this study, we developed a novel in vivo cell-based assay for examining this interaction between the N-protein and packaging signal RNA for SARS-CoV, as well as other viruses within the coronaviridae family. Our results demonstrate that the N-protein specifically recognizes the SARS-CoV packaging signal with greater affinity compared to signals from other coronaviruses or non-coronavirus species. We also use deletion mapping to identify a 151-nt region within the packaging signal sequence that is critical for N-protein-RNA binding, and conversely, we show that both the N-terminal and C-terminal domains of the N protein are necessary for recognizing the packaging RNA. These results describe, for the first time, in vivo evidence for an interaction between the SARS-CoV N-protein and its packaging signal RNA, and demonstrate the feasibility of using this cell-based assay to further probe viral RNA-protein interactions in future studies.


title: Improving the wind environment in high-density cities by understanding urban morphology and surface roughness: A study in Hong Kong

text: Abstract In this study, a high-resolution frontal area density (FAD) map that depicts the surface roughness of urban Hong Kong is produced using a mapping method that takes into account the dense urban morphology and the site wind availability of the territory. Using the MM5/CALMET model simulated wind data of Hong Kong, the FAD map of three urban zones are calculated: podium (0–15m), building (15–60m), and urban canopy (0–60m). The wind tunnel test data is used to correlate the FAD understanding of the three zones. The grid sensitivity test indicates that 200m×200m is the reasonable resolution for the FAD map; the test also establishes that the lower urban podium zone yields the best correlation with the experimental data. The study further establishes that the simpler two-dimensional ground coverage ratio (GCR), which is readily available in the planning circle, can be used to predict the area's average pedestrian level urban ventilation performance of the city. Working with their inhouse GIS team using available data, it allows the planners a way to understand the urban ventilation of the city for decisions related to air paths, urban permeability and site porosity.


title: Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and Respiratory Syndrome across Different Regions and Production Systems of the US

text: Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most impactful disease for the North American swine industry, due to its known considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors and reports weekly new PRRS cases in 766 sow herds across the US. The time-dependent reproduction number (TD-R) is a measure of a pathogen’s transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at the regional and system levels. The primary objective of the study here was to estimate the TD-R values for PRRSV using regional and system-level PRRS data, and to contrast it with commonly used metrics of disease, such as incidence estimates and space–time clusters. The second objective was to test whether the estimated TD-Rs were homogenous across four US regions. Retrospective monthly incidence data (2009–2016) were available from the SHMP. The dataset was divided into four regions based on location of participants, and demographic and environmental features, namely, South East (North Carolina), Upper Midwest East (UME, Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma panhandle). Generation time distributions were fit to incidence data for each region, and used to calculate the TD-Rs. The Kruskal–Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, we used a space–time permutation model to assess spatial–temporal patterns for the four regions. Results showed TD-Rs were right skewed with median values close to “1” across all regions, confirming that PRRS has an overall endemic nature. Variation in the TD-R patterns was noted across regions and production systems. Statistically significant periods of PRRSV spread (TD-R > 1) were identified for all regions except UME. A minimum of three space–time clusters were detected for all regions considering the time period examined herein; and their overlap with “spreader events” identified by the TD-R method varied according to region. TD-Rs may help to measure PRRS spread to understand, in quantitative terms, disease spread, and, ultimately, support the design, implementation, and monitoring of interventions aimed at mitigating the impact of PRRSV spread in the US.


title: Synchronized shift of oral, faecal and urinary microbiotas in bats and natural infection dynamics during seasonal reproduction

text: Seasonal reproduction is a period of extreme physiological and behavioural changes, yet we know little about how it may affect host microbial communities (i.e. microbiota) and pathogen transmission. Here, we investigated shifts of the bacterial microbiota in saliva, urine and faeces during the seasonal reproduction of bats in South Africa, and test for an interaction in shedding patterns of both bacterial (Leptospira) and viral (adeno- and herpesviruses) agents. Based on a comparative approach in two cave-dwelling bat species and high-throughput sequencing of the 16S rRNA gene, we demonstrated a clear signature in microbiota changes over the reproduction season, consistent across the multiple body habitats investigated, and associated with the sex, age and reproductive condition of bats. We observed in parallel highly dynamic shedding patterns for both bacteria and viruses, but did not find a significant association between viral shedding and bacterial microbiota composition. Indeed, only Leptospira shedding was associated with alterations in both the diversity and composition of the urinary microbiota. These results illustrate how seasonal reproduction in bats substantially affects microbiota composition and infection dynamics, and have broad implications for the understanding of disease ecology in important reservoir hosts, such as bats.