title: An open label cluster randomized controlled trial of chloroquine, hydroxychloroquine or only supportive care in patients admitted with moderate to severe COVID‐19 (ARCHAIC) – Protocol publication

text: Chloroquine (CQ) and hydroxychloroquine (HCQ) were both employed in the treatment of COVID‐19 in China. Based on unpublished anecdotal positive results in China, CQ is now implemented in China and the Netherlands in moderate to severe COVID‐19.


title: COVID-19 Drug Treatment in China

text: PURPOSE OF REVIEW: An unprecedented outbreak of the novel coronavirus in China (COVID-19) occurred in December 2019, and then engulfed the entire world, presenting a significant and urgent threat to global health. Many research institutes have been involved in the development of drugs and vaccines against COVID-19. RECENT FINDINGS: At present, the strategy of new use of old drugs is mainly used to screen candidate drugs against the novel coronavirus (later termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and inhibit excessive immune response. Related research has made great progress. SUMMARY: In this review, we summarize the drugs used for COVID-19 treatment in China based on the emerging basic and clinical data. It is hoped that this review will be useful to provide guidance for the prevention, treatment, and control of COVID-19.


title: The Passing of Western Civilization

text: Modern western civilization reached a pinnacle in the last half of the 20(th) century, spending over 200 years evolving and spreading throughout the world. A robust social contract, technological advancement and pervasive economic success in the context of democracy and capitalism propelled the project. Unfortunately, two underlying pillars of past success developed intensifying negative consequences, hastening socioeconomic decline: insatiable collective wants and global population growth. The rise and decline of civilizations in history is well documented, yet oddly ignored in today’s dialogue. Contemporary civilization is assumed to be immune from forces that shaped cycles of past civilizations—that our age is somehow an exception. For the first time in human history planetary systems that seemed invisible until recently are sending us the message that our civilization is not exceptional, that there are finite limits to the thrust of humanity’s present trajectory. Viable solutions curbing the effects of habitat destruction, diminishing biodiversity and climate change along with rising inequality, debt, conflict and refugee flows are known but unimplementable. The current essay examines underlying causes of socioeconomic deterioration and entrapment, suggesting a comprehensive collective intelligence enterprise be launched to prepare for the global transition facing humanity.


title: EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction

text: Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.


title: Is influenza-like illness a useful concept and an appropriate test of influenza vaccine effectiveness?

text: PURPOSE: To assess the utility of “influenza-like illness” (ILI) and whether it appropriately tests influenza vaccine effectiveness. PRINCIPAL RESULTS: The WHO and CDC definitions of “influenza-like illness” are similar. However many studies use other definitions, some not specifying a temperature and requiring specific respiratory and/or systemic symptoms, making many samples non-comparable. Most ILI studies find less than 25% of cases are RT-PCR-positive, those which test for other viruses and bacteria usually find multiple other pathogens, and most identify no pathogen in about 50% of cases. ILI symptom and symptom combinations do not have high sensitivity or specificity in identifying PCR-positive influenza cases. Rapid influenza diagnostic tests are increasingly used to screen ILI cases and they have low sensitivity and high specificity when compared to RT-PCR in identifying influenza. MAIN CONCLUSIONS: The working diagnosis of ILI presumes influenza may be involved until proven otherwise. Health care workers would benefit by renaming the WHO and CDC ILI symptoms and signs as “acute respiratory illness” and also using the WHO acute severe respiratory illness definition if the illness is severe and meets this criterion. This renaming would shift attention to identify the viral and bacterial pathogens in cases and epidemics, identify new pathogens, implement vaccination plans appropriate to the identified pathogens, and estimate workload during the viral season. Randomised controlled trials testing the effectiveness of influenza vaccine require all participants to be assessed by a gold standard (RT-PCR). ILI has no role in measuring influenza vaccine effectiveness. ILI is well established in the literature and in the operational definition of many surveillance databases and its imprecise definition may be inhibiting progress in research and treatment. The current ILI definition could with benefit be renamed “acute respiratory illness,” with additional definitions for “severe acute respiratory illness” (SARI) with RT-PCR testing for pathogens to facilitate prevention and treatment.


title: Effect of shelter-in-place on emergency department radiology volumes during the COVID-19 pandemic

text: PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has led to significant disruptions in the healthcare system including surges of infected patients exceeding local capacity, closures of primary care offices, and delays of non-emergent medical care. Government-initiated measures to decrease healthcare utilization (i.e., “flattening the curve”) have included shelter-in-place mandates and social distancing, which have taken effect across most of the USA. We evaluate the immediate impact of the Public Health Messaging and shelter-in-place mandates on Emergency Department (ED) demand for radiology services. METHODS: We analyzed ED radiology volumes from the five University of California health systems during a 2-week time period following the shelter-in-place mandate and compared those volumes with March 2019 and early April 2019 volumes. RESULTS: ED radiology volumes declined from the 2019 baseline by 32 to 40% (p < 0.001) across the five health systems with a total decrease in volumes across all 5 systems by 35% (p < 0.001). Stratifying by subspecialty, the smallest declines were seen in non-trauma thoracic imaging, which decreased 18% (p value < 0.001), while all other non-trauma studies decreased by 48% (p < 0.001). CONCLUSION: Total ED radiology demand may be a marker for public adherence to shelter-in-place mandates, though ED chest radiology demand may increase with an increase in COVID-19 cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10140-020-01797-y) contains supplementary material, which is available to authorized users.


title: Digital health data-driven approaches to understand human behavior

text: Advances in digital technologies and data analytics have created unparalleled opportunities to assess and modify health behavior and thus accelerate the ability of science to understand and contribute to improved health behavior and health outcomes. Digital health data capture the richness and granularity of individuals’ behavior, the confluence of factors that impact behavior in the moment, and the within-individual evolution of behavior over time. These data may contribute to discovery science by revealing digital markers of health/risk behavior as well as translational science by informing personalized and timely models of intervention delivery. And they may help inform diagnostic classification of clinically problematic behavior and the clinical trajectories of diagnosable disorders over time. This manuscript provides a review of the state of the science of digital health data-driven approaches to understanding human behavior. It reviews methods of digital health assessment and sources of digital health data. It provides a synthesis of the scientific literature evaluating how digitally derived empirical data can inform our understanding of health behavior, with a particular focus on understanding the assessment, diagnosis and clinical trajectories of psychiatric disorders. And, it concludes with a discussion of future directions and timely opportunities in this line of research and its clinical application.


title: The geographic spread of infectious diseases Lisa Sattenspiel

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Chronic pain following COVID-19: implications for rehabilitation


title: Isolation and Characterization of Clinical RSV Isolates in Belgium during the Winters of 2016–2018

text: Respiratory Syncytial Virus (RSV) is a very important viral pathogen in children, immunocompromised and cardiopulmonary diseased patients and the elderly. Most of the published research with RSV was performed on RSV Long and RSV A2, isolated in 1956 and 1961, yet recent RSV isolates differ from these prototype strains. Additionally, these viruses have been serially passaged in cell culture, which may result in adaptations that affect virus–host interactions. We have isolated RSV from mucosal secretions of 12 patients in the winters 2016–2017 and 2017–2018, of which eight RSV-A subtypes and four RSV-B subtypes. Passage 3 of the isolates was assessed for viral replication kinetics and infectious virus production in HEp-2, A549 and BEAS-2B cells, thermal stability at 37 °C, 32 °C and 4 °C, syncytia formation, neutralization by palivizumab and mucin mRNA expression in infected A549 cells. We observed that viruses isolated in one RSV season show differences on the tested assays. Furthermore, comparison with RSV A2 and RSV B1 reveals for some RSV isolates differences in viral replication kinetics, thermal stability and fusion capacity. Major differences are, however, not observed and differences between the recent isolates and reference strains is, overall, similar to the observed variation in between the recent isolates. One clinical isolate (BE/ANT-A11/17) replicated very efficiently in all cell lines, and remarkably, even better than RSV A2 in the HEp-2 cell line.


title: Genomic Characterization and Phylogenetic Classification of Bovine Coronaviruses Through Whole Genome Sequence Analysis

text: Bovine coronavirus (BCoV) is zoonotically transmissible among species, since BCoV-like viruses have been detected in wild ruminants and humans. BCoV causing enteric and respiratory disease is widespread in cattle farms worldwide; however, limited information is available regarding the molecular characterization of BCoV because of its large genome size, despite its significant economic impact. This study aimed to better understand the genomic characterization and evolutionary dynamics of BCoV via comparative sequence and phylogenetic analyses through whole genome sequence analysis using 67 BCoV isolates collected throughout Japan from 2006 to 2017. On comparing the genomic sequences of the 67 BCoVs, genetic variations were detected in 5 of 10 open reading frames (ORFs) in the BCoV genome. Phylogenetic analysis using whole genomes from the 67 Japanese BCoV isolates in addition to those from 16 reference BCoV strains, revealed the existence of two major genotypes (classical and US wild ruminant genotypes). All Japanese BCoV isolates originated from the US wild ruminant genotype, and they tended to form the same clusters based on the year and farm of collection, not the disease type. Phylogenetic trees on hemagglutinin-esterase protein (HE), spike glycoprotein (S), nucleocapsid protein (N) genes and ORF1 revealed clusters similar to that on whole genome, suggesting that the evolution of BCoVs may be closely associated with variations in these genes. Furthermore, phylogenetic analysis of BCoV S genes including those of European and Asian BCoVs and human enteric coronavirus along with the Japanese BCoVs revealed that BCoVs differentiated into two major types (European and American types). Moreover, the European and American types were divided into eleven and three genotypes, respectively. Our analysis also demonstrated that BCoVs with different genotypes periodically emerged and predominantly circulated within the country. These findings provide useful information to elucidate the detailed molecular characterization of BCoVs, which have spread worldwide. Further genomic analyses of BCoV are essential to deepen the understanding of the evolution of this virus.


Face Masks and Containment of Coronavirus Disease 2019 (COVID-19): Experience from South Korea


title: Emerging Infectious Diseases and Blood Safety: Modeling the Transfusion-Transmission Risk

text: Abstract While the transfusion-transmission (TT) risk associated with the major transfusion-relevant viruses such as HIV is now very low, during the last 20 years there has been a growing awareness of the threat to blood safety from emerging infectious diseases, a number of which are known to be, or are potentially, transfusion transmissible. Two published models for estimating the transfusion-transmission risk from EIDs, referred to as the Biggerstaff-Petersen model and the European Upfront Risk Assessment Tool (EUFRAT), respectively, have been applied to several EIDs in outbreak situations. We describe and compare the methodological principles of both models, highlighting their similarities and differences. We also discuss the appropriateness of comparing results from the two models. Quantitating the TT risk of EIDs can inform decisions about risk mitigation strategies and their cost-effectiveness. Finally, we present a qualitative risk assessment for Zika virus (ZIKV), an EID agent that has caused several outbreaks since 2007. In the latest and largest ever outbreak, several probable cases of transfusion-transmission ZIKV have been reported, indicating that it is transfusion-transmissible and therefore a risk to blood safety. We discuss why quantitative modeling the TT risk of ZIKV is currently problematic.


title: Acute exacerbation of chronic bronchitis: disease-specific issues that influence the cost-effectiveness of antimicrobial therapy

text: Abstract Background: Acute exacerbation of chronic bronchitis (AECB) is a common condition, with substantial associated costs and morbidity. Research efforts have focused on innovations that will reduce the morbidity associated with AECB. Health care payers increasingly expect that the results of evidence-based economic evaluations will guide practitioners in their choice of cost-effective interventions. Objectives: To provide a framework on which to base effective and efficient antimicrobial therapy for AECB, we present a concise clinical review of AECB, followed by an assessment of the available data on the economic impact of this disease. We then address several AECB-specific issues that must be considered in cost-effectiveness analyses of AECB antimicrobial interventions. Methods: Published literature on the clinical and economic impact of AECB was identified using MEDLINE®, pre-MEDLINE®, HealthSTAR, CINAHL, Current Contents/All Editions, EMBASE, and International Pharmaceutical Abstracts databases. Other potential sources were identified by searching for references in retrieved articles, review articles, consensus statements, and articles written by selected authorities. Results: In evaluating cost-effectiveness analyses of AECB antimicrobial therapy it is critical to (1) use the disease-free interval as an outcome measure, (2) evaluate the sequence of multiple therapies, (3) address the impact of both current and future antibiotic resistance, and (4) measure all appropriate AECB-associated costs, both direct and indirect. Conclusions: Incorporating these approaches in economic analyses of AECB antimicrobial therapy can help health care organizations make evidence-based decisions regarding the cost-effective management of AECB.


title: The human rhinovirus: human‐pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery

text: As the major etiological agent of the common cold, human rhinoviruses (HRV) cause millions of lost working and school days annually. Moreover, clinical studies proved an association between harmless upper respiratory tract infections and more severe diseases e.g. sinusitis, asthma, and chronic obstructive pulmonary disease. Both the medicinal and socio‐economic impact of HRV infections and the lack of antiviral drugs substantiate the need for intensive antiviral research. A common structural feature of the approximately 100 HRV serotypes is the icosahedrally shaped capsid formed by 60 identical copies of viral capsid proteins VP1‐4. The capsid protects the single‐stranded, positive sense RNA genome of about 7,400 bases in length. Both structural as well as nonstructural proteins produced during the viral life cycle have been identified as potential targets for blocking viral replication at the step of attachment, entry, uncoating, RNA and protein synthesis by synthetic or natural compounds. Moreover, interferon and phytoceuticals were shown to protect host cells. Most of the known inhibitors of HRV replication were discovered as a result of empirical or semi‐empirical screening in cell culture. Structure–activity relationship studies are used for hit optimization and lead structure discovery. The increasing structural insight and molecular understanding of viral proteins on the one hand and the advent of innovative computer‐assisted technologies on the other hand have facilitated a rationalized access for the discovery of small chemical entities with antirhinoviral (anti‐HRV) activity. This review will (i) summarize existing structural knowledge about HRV, (ii) focus on mechanisms of anti‐HRV agents from synthetic and natural origin, and (iii) demonstrate strategies for efficient lead structure discovery. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 42–92, 2010


title: Indian Academy of Cytologists National Guidelines for Cytopathology Laboratories for Handling Suspected and Positive COVID-19 (SARS-CoV-2) Patient Samples

text: COVID-19, caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization. This scenario has impacted the way we practice cytopathology. Cytology laboratories receive fresh and potentially infectious biological samples including those from the respiratory tract, from COVID-19 positive or suspected patients. Hence, the Indian Academy of Cytologists thought it necessary and fit to bring forth appropriate guidelines starting from transportation, receipt, processing, and reporting of samples in the COVID-19 era. The guidelines are prepared with the aim of safeguarding and protecting the health care personnel including laboratory staff, trainees and cytopathologists by minimizing exposure to COVID-19 so that they remain safe, in order to able to provide a continuous service. We hope that these national guidelines will be implemented across all cytopathology laboratories effectively.


title: Exploring the influence of enforcing infection control directives on the risk of developing healthcare associated infections in the intensive care unit: A retrospective study

text: Summary Background Although strict adherence to infection control strategies is recognised as the simplest and most cost effective method to prevent the spread of healthcare associated infections (HAIs), measurement of the direct impact that such adherence may have on the risk of developing such infections has always been a challenge. Purpose The purpose of this study was to compare the risk of HAIs before and during the SARS outbreak. Such comparison is intended to provide a surrogate measure of the influence that strict enforcement of infection control strategies during the SARS outbreak may have had on the risk of HAIs. Methods A retrospective chart review was conducted on the medical records of 400 intensive care patients who were admitted to the ICU three months before and during the 2003 SARS outbreak. Results The rate of HAIs was higher in the pre-SARS period than the SARS period. Specifically, 61.7% of all reported infections were diagnosed in the pre-SARS period. The rate of HAIs in the pre-SARS period was 14.5% as opposed to 9% during the SARS period. Adjusted logistic regression analysis suggested that the odds of HAIs were 2.2 times higher in the pre-SARS period as compared to the SARS period (OR =2.2; 95%CI =1.08–4.49). Conclusion Our findings suggest that strict enforcement of infection control strategies may have a positive impact on the efforts to minimise the risk of HAIs. These findings carry a clinical significance that shall not be ignored with regard to our overall efforts to minimise the risk of developing HAIs in the ICU.


title: Acute Asthma in the Pediatric Emergency Department: Infections Are the Main Triggers of Exacerbations

text: BACKGROUND: Asthma exacerbations are a common reason for Emergency Department (ED) visits in children. AIM: To analyze differences among age groups in terms of triggering factors and seasonality and to identify those with higher risk of severe exacerbations. METHODS: We retrospectively revised the files of children admitted for acute asthma in 2016 in our Pediatric ED. RESULTS: Visits for acute asthma were 603/23197 (2.6%). 76% of the patients were <6 years old and 24% ≥6. Infections were the main trigger of exacerbations in both groups; 33% of the school-aged children had a triggering allergic condition (versus 3% in <6 years; p < .01). 191 patients had a previous history of asthma; among them, 95 were ≥6 years, 67% of whom were not using any controller medication, showing a higher risk of a moderate-to-severe exacerbation than those under long-term therapy (p < .01). Exacerbations peaked in autumn and winter in preschoolers and in spring and early autumn in the school-aged children. CONCLUSIONS: Infections are the main trigger of acute asthma in children of any age, followed by allergy in the school-aged children. Efforts for an improved management of patients affected by chronic asthma might go through individualized action plans and possibly vaccinations and allergen-avoidance measures.


title: Employee Adjustment and Well-Being in the Era of COVID-19: Implications for Human Resource Management

text: Today’s organizations have to remain alert and adaptive to unforeseen events, such as external crises, which create increased uncertainty among their workforce and pose immediate threats to the organizations’ performance and viability. However, with the recent COVID-19 pandemic, organizations suddenly have to navigate the unprecedented and thereby find new solutions to challenges arising across many areas of their operations. In this article, we discusses some of these challenges, focusing on the implications COVID-19 has for human resource management (HRM) as organizations help their workforce cope with and adjust to their newly altered work environment. In addition, we propose several avenues for future research and advocate for an integrated research agenda for tackling the challenges discussed.


title: 10 Infectious Disease Genomics

text: Abstract The history and development of infectious disease genomics have been closely associated with the Human Genome Project (HGP) during the past 20years. It has been emphasized since the beginning of the HGP that such effort must not be restricted to the human genome and should include other organisms including mouse, bacteria, yeast, fruit fly, and worm for comparative sequence analyses. A brief history is reviewed in this chapter. As of 2016, more than 7000 completed genome sequencing projects have been reported. One of the important motivations for these efforts is to develop preventative, diagnostic, and therapeutic strategies through the analysis of sequenced microorganisms, parasites, and vectors related to human health. A number of examples are discussed in this chapter.


COVID-19-Pandemie: Was wissen wir – was können wir empfehlen?: Ein Kommentar der Herausgeber


title: Molecular epidemiology of Porcine torovirus (PToV) in Sichuan Province, China: 2011–2013

text: BACKGROUND: Porcine torovirus (PToV) is a member of the genus Torovirus which is responsible for gastrointestinal disease in both human beings and animals with particular prevalence in youth. Torovirus infections are generally asymptomatic, however, their presence may worsen disease consequences in concurrent infections with other enteric pathogens. METHODS: A total of 872 diarrheic fecal samples from pigs of different ages were collected from 12 districts of Sichuan Province in the southwest of China. RT-PCR was done with PToV S gene specific primers to detect the presence of PToV positive samples. M gene specific primers were used with the PToV positive samples and the genes were sequenced. A phylogenetic tree was constructed based on the M gene nucleotide sequences from the 19 selected novel Sichuan strains and 21 PToV and BToV M gene sequences from GenBank. RESULTS: A total of 331 (37.96%, 331/872) samples were found to be positive for PToV and the highest prevalence was observed in piglets aged from 1 to 3 weeks old. Through phylogenetic inference the 40 PToV M gene containing sequences were placed into two genotypes (I & II). The 19 novel Sichuan strains of genotype I showed strong correlations to two Korean gene sequences (GU-07-56-11 and GU-07-56-22). Amino-acid sequence analysis of the 40 PToV M gene strains revealed that the M gene protein was highly conserved. CONCLUSIONS: This study uncovered the presence of PToV in Sichuan Province, and demonstrated the need for continuous surveillance PToV of epidemiology.


Physical activity during the COVID-19 global pandemic


title: Neonatal vaccine effectiveness and the role of adjuvants

text: Introduction: Neonates are less responsive to vaccines than adults, making it harder to protect newborns against infection. Neonatal differences in antigen-presenting cell, B and T cell function, all likely contribute. A key question is whether novel adjuvants might be able to make neonatal vaccines more effective. Areas covered: This review addresses the issues of how to improve neonatal vaccines, which we have defined as vaccines given in the first 4 weeks of life in a human infant or the first week of life in a mouse. A search was performed using keywords including ‘neonatal immunity’, ‘neonatal immunisation’, ‘vaccine’ and ‘adjuvant’ of PubMed articles published between 1960 and 2018. Expert opinion: Sugar-like structures have recently been shown to prime the infant adaptive immune system to respond to vaccines, being potentially more effective than traditional adjuvants. Sugar-based compounds with beneficial adjuvant effects in neonatal vaccine models include delta inulin (Advax), curdlan, and trehalose 6,6ʹ-dibehenate. Such compounds make interesting neonatal adjuvant candidates, either used alone or in combination with traditional innate immune adjuvants.


title: Viral Subversion of Nucleocytoplasmic Trafficking

text: Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Due to its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, while viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. Since viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. In addition, this review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens.


title: An efficient pattern growth approach for mining fault tolerant frequent itemsets

text: Abstract Mining fault tolerant (FT) frequent itemsets from transactional databases are computationally more expensive than mining exact matching frequent itemsets. Previous algorithms mine FT frequent itemsets using Apriori heuristic. Apriori-like algorithms generate exponential number of candidate itemsets including the itemsets that do not exist in the database. These algorithms require multiple scans of database for counting the support of candidate FT itemsets. In this paper we present a novel algorithm, which mines FT frequent itemsets using frequent pattern growth approach (FT-PatternGrowth). FT-PatternGrowth adopts a divide-and-conquer technique and recursively projects transactional database into a set of smaller projected transactional databases and mines FT frequent itemsets in each projected database by exploring only locally frequent items. This mines the complete set of FT frequent itemsets and substantially reduces those candidate itemsets that do not exist in the database. FT-PatternGrowth stores the transactional database in a highly condensed much smaller data structure called frequent pattern tree (FP-tree). The support of candidate itemsets are counted directly from the FP-tree without scanning the original database multiple times. This improves the processing speed of algorithm. Our experiments on benchmark databases indicates mining FT frequent itemsets using FT-PatternGrowth is highly efficient than Apriori-like algorithms.


title: Low transmission rate of 2009 H1N1 Influenza during a long-distance bus trip

text: BACKGROUND: Current data on the risk of transmission of 2009 H1N1 Influenza in public transportation systems (e.g., public trains, busses, airplanes) are conflicting. The main transmission route of this virus is thought to be via droplets, but airborne transmission has not been completely ruled out. METHODS: This is a contact tracing investigation of a young woman subsequently diagnosed with the 2009 H1N1 Influenza virus who was symptomatic during a long-distance bus trip from Spain to Switzerland. Fever and cough had begun 24 h earlier, 2 h before she stepped onto a bus for a long-distance trip. After the 2009 H1N1 virus had been confirmed in the patient, the other bus travellers were contacted by telephone on day 7 and 10 after the bus trip. RESULTS: Of the 72 individuals travelling on the bus with the H1N1-infected young woman, 52 (72%) could be contacted. Only one of these 52 developed fever, with onset of symptoms 3 days after the bus trip, and rRT-PCR analysis of the nasopharyngeal swab showed the infection to be caused by the 2009 H1N1 virus. One other person complained of coughing 1 day after the bus trip, but without fever, and no further investigation was carried out. All other passengers remained without fever, coughing, or arthralgia. The risk of transmission was calculated as 1.96% (95% confidence interval 0–5.76%). CONCLUSION: The transmission rate of 2009 H1N1 Influenza was low on a long-distance bus trip. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s15010-011-0084-x) contains supplementary material, which is available to authorized users.


title: Induction of systemic IFITM3 expression does not effectively control foot-and-mouth disease viral infection in transgenic pigs

text: Abstract Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and can cause severe economic loss. Interferon-induced transmembrane (IFITM) proteins constitute a family of viral restriction factors that can inhibit the replication of several types of viruses. Our previous study showed that overexpression of swine IFITM3 (sIFITM3) impeded replication of the FMD virus (FMDV) in BHK-21 cells and mice. In this study, sIFITM3-transgenic (TG) pigs were produced by handmade cloning. Results showed that sIFITM3 was highly overexpressed in many organs of sIFITM3-TG pigs compared to wild-type pigs. After a virulent FMDV strain (O/ES/2001) was intramuscularly inoculated, the sIFITM3-TG pigs showed slightly higher susceptibility to FMDV infection than wild-type pigs. Both groups displayed comparable degrees of clinical symptoms throughout the 14-day observation period. Therefore, the induction of systemic sIFITM3 expression does not protect pigs against FMDV infection. Based on these observations, we propose that a combination of interferons and vaccines be used to control FMDV infections and subsequent FMD outbreaks.


title: SARS-CoV-2 infection risk assessment in the endometrium: Viral infection-related gene expression across the menstrual cycle

text: STRUCTURED ABSTRACT Objective To determine susceptibility of the endometrium to infection by—and thereby potential damage from—SARS-CoV-2. Design Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic datasets. Setting Infertility research department affiliated with a public hospital. Patient(s) Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. Intervention(s) None. Main outcome measure(s) Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. Result(s) Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG and MX1 expression increased with age, especially in early phases of the cycle. Conclusion(s) Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments.


title: Knowledge, attitudes, and practices of Hong Kong population towards human A/H7N9 influenza pandemic preparedness, China, 2014

text: BACKGROUND: Since SARS epidemic in 2003, Hong Kong has experienced several major epidemic risks, but how general community might react to the repeated infectious diseases health risks have not been studied. In 2013, imported human H7N9 influenza infected cases from China were reported. Our study aims to assess the knowledge, attitude and practice (KAP) concerning A/H7N9 among Hong Kong general population regarding pandemic preparedness in early 2014. METHODS: A cross-sectional, population-based telephone survey study was conducted among the Cantonese-speaking population aged over 15 years in Hong Kong in February 2014. The study survey was composed of 78 KAP questions. Factors associated with individual and household pandemic preparedness were analyzed. RESULTS: Final study sample was 1,020 with a response rate of 45.9 %. Among the respondents, most of them believed personal hygiene and avoidance of avian contacts were effective in preventing H7N9 infections. The majority of respondents had satisfactory hand hygiene practices and avoided touching avian species but did not employ other preventive measures. Female, 25 years old or older, white collar workers, people with chronic diseases and people living in the city center tended to report better hygiene practices. The average State-Trait Anxiety Inventory score was 1.85, similar to that of the period during the first wave and at the start of the second wave of the H7N9 epidemic. Self-reported face masks wearing when having influenza-like illness in general population dropped from 92.4 % during H5N1 period in 2007 to 39.0 % in this study. CONCLUSION: Hong Kong citizens show a low level of anxiety, misconceptions regarding the novel strains as well as gaps between perceived usefulness and practice of preventive measures towards influenza outbreaks. Educational campaigns and framing the issue to increase public and media awareness are crucial in preventing the current public fatigue towards outbreaks.


title: Recent vaccine technology in industrial animals

text: Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with the PED virus spike gene. Recombinant vaccines can be produced by substitution of the target gene in the VEE vector. Both of these new vaccine technologies made it possible to control the infectious disease efficiently in a relatively short time.


title: Enhanced green fluorescent protein expression may be used to monitor murine coronavirus spread in vitro and in the mouse central nervous system

text: Targeted recombination was used to select mouse hepatitis virus isolates with stable and efficient expression of the gene encoding the enhanced green fluorescent protein (EGFP). The EGFP gene was inserted into the murine coronavirus genome in place of the nonessential gene 4. These viruses expressed the EGFP gene from an mRNA of slightly slower electrophoretic mobility than mRNA 4. EGFP protein was detected on a Western blot of infected cell lysates and EGFP activity (fluorescence) was visualized by microscopy in infected cells and in viral plaques. Expression of EGFP remained stable through at least six passages in tissue culture and during acute infection in the mouse central nervous system. These viruses replicated with similar kinetics and to similar final extents as wild-type virus both in tissue culture and in the mouse central nervous system (CNS). They caused encephalitis and demyelination in animals as wild-type virus; however, they were somewhat attenuated in virulence. Isogenic EGFP-expressing viruses that differ only in the spike gene and express either the spike gene of the highly neurovirulent MHV-4 strain or the more weakly neurovirulent MHV-A59 strain were compared; the difference in virulence and patterns of spread of viral antigen reflected the differences between parental viruses expressing each of these spike genes. Thus, EGFP-expressing viruses will be useful in the studies of murine coronavirus pathogenesis in mice.


title: Bottlenecks in the transmission of porcine reproductive and respiratory syndrome virus (PRRSV1) to naïve pigs and the quasi-species variation of the virus during infection in vaccinated pigs

text: This paper describes the results of two experiments regarding porcine reproductive and respiratory syndrome virus (PRRSV1): the first one studied the existence of bottlenecks in an experimental one-to-one model of transmission in pigs; while the second analysed the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viraemias after natural challenge. Serum samples, as well as the initial inoculum, were deep-sequenced and a viral quasi-species was constructed per sample. For the first experiment, the results consistently reported a reduction in the quasi-species diversity after a transmission event, pointing to the existence of bottlenecks during PRRSV1 transmission. However, despite the identified preferred and un-preferred transmitted variants not being randomly distributed along the virus genome, it was not possible to identify any variant producing a structural change in any viral protein. In contrast, the mutations identified in GP2, nsp9 and M of the second experiment pointed to changes in the amino acid charges and the viral RNA-dependent RNA polymerase structure. The fact that the affected proteins are known targets of the immunity against PRRSV, plus the differential level of neutralizing antibodies present in pigs developing short or long viraemias, suggests that the immune response selected those changes.


title: Molecular characterization of infectious bronchitis virus based on RNA‐dependent RNA polymerase gene

text: Extensive rate of variations in in spike glycoprotein subunit gene of infectious bronchitis virus (IBV) caused challenges for counting variants for differentiation of infected from vaccinated birds and addressing the variants of unknown significance. The study aimed at investigating the possibility use of RNA‐dependent RNA polymerase gene (RdRp) as a target for molecular characterization of IBV strains in Iran. Samples collected from commercial broiler flocks (n= 52) showing respiratory syndrome. Specific polymerase chain reaction (PCR) primers were designed for a variable region locates in RdRp gene, flanked by highly conserved regions. Reverse transcriptase PCR (RT‐PCR) followed by sequencing and sequence analysis could identified 8 IBV variants in an overall prevalence of 44.2%. Deduced nucleotide and amino acid sequences were compared with published sequences for IBV strains. Due to the long‐distance similarities, the field samples could be discriminated from vaccine strains. Phylogenetic analysis of RdRp gene sequences resulted in clustering the IBV strains related to each area. Using RdRp, as a genetic marker eliminates the challenges arise from the enormous variations that making difficult the discrimination between field and vaccine strains as well as affiliation of certain variants to various geographical areas. This article is protected by copyright. All rights reserved.


title: COVID-19: The Need for Immunoprevention at Industrial Scale

text: Novel Coronavirus Disease (COVID-19): The Need for Immunoprevention at Industrial Scale.


title: Normal and clinical haematology in the yak (Bos grunniens)

text: Haematological examinations have been carried out on 21 clinically normal male and female adult yaks (Bos grunniens). Animals sedated with xylazine had significantly lower red cell counts, haemoglobin levels and packed cell volumes, fewer lymphocytes and higher monocyte counts than those bled while manually restrained. There were few significant sex differences. Several animals had eosinophilia associated with asymptomatic intestinal nematode infection. Haematological reference values were calculated for clinically normal, xylazine sedated and manually restrained yaks. These were used to identify haematological changes in 10 animals with various abnormal clinical signs. It was concluded that blood counts can provide valuable diagnostic information in this species.


Priorities for Cath labs in the COVID-19 tsunami: Roberto Ferrari and co-authors present a procedure to follow subsequent to the outbreak in Italy


title: Developing animal models for polymicrobial diseases

text: Polymicrobial diseases involve two or more microorganisms that act synergistically, or in succession, to mediate complex disease processes. Although polymicrobial diseases in animals and humans can be caused by similar organisms, these diseases are often also caused by organisms from different kingdoms, genera, species, strains, substrains and even by phenotypic variants of a single species. Animal models are often required to understand the mechanisms of pathogenesis, and to develop therapies and prevention regimes. However, reproducing polymicrobial diseases of humans in animal hosts presents significant challenges.


title: Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection

text: SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.


title: IFITM3‐containing exosome as a novel mediator for anti‐viral response in dengue virus infection

text: Interferon‐inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV‐2 infection, we found that IFITM3 contributed to both the baseline and interferon‐induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM‐containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non‐infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome‐mediated anti‐viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species.


title: Italian recommendations for the diagnosis of gestational diabetes during COVID-19 pandemic: Position statement AMD-SID, Diabetes and Pregnancy Study Group

text: Abstract Aim In response to the COVID-19 pandemic, there is a need for substantial changes in the procedures for accessing healthcare services. Even in the current pandemic, we should not reduce our attention towards the diagnosis and treatment of GDM. The purpose of this document is to provide a temporary guide for GDM screening, replacing the current guidelines because of an unfavorable risk/benefit ratio for pregnant women or when usual laboratory facilities are not available. Data Synthesis At the first visit during pregnancy, in all women we must exclude the presence of an "Overt diabetes". The criteria for the diagnosis of overt diabetes are either one fasting plasma glucose ≥ 126 mg/dL, or one random plasma glucose ≥ 200 mg/dL, or one glycated hemoglobin ≥ 6.5% When the screening procedure (OGTT) cannot be safely performed, the diagnosis of GDM is acceptable, if fasting plasma glucose is ≥ 92 mg/dL. In order to consider the impaired fasting glucose an acceptable surrogate for the diagnosis of GDM, the fasting glucose measurement should be performed within the recommended time windows for the risk level (high or medium risk). Conclusions The changes to the screening procedure for GDM reported below are specifically produced in response to the health emergency of the COVID-19 pandemic. Therefore, these recommended changes should cease in effect and replaced by current national guidelines when the healthcare authorities declare the end of this emergency.


title: Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19

text: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.


title: Realigning science, society and policy in uncertain times

text: Against a backdrop of rapidly changing social, economic and geopolitical settings and ideologies, the world is facing a wide range of challenges, including in biodiversity, climate, energy, the environment, food, health and water. These can only be addressed by fully harnessing key capacities that science offers. However, there is a crisis of trust in science which affects some sections of society and some policy-makers, impairing the capacity of science to deliver its essential roles. This damaged relationship between science, society and policy has immense health, economic and social consequences and implications for sustainability of the entire planet. Scientists must strive collectively to re-establish trust by society and politicians where it is damaged, and reinforce conviction of science's central importance in underpinning policy. Science's roles must in turn be acknowledged by policies that sustain innovation and freedom to work without political interference or constraints. A well-functioning and trusting relationship between science, society and policy-makers offers a potent means to thwart and mitigate emergent global challenges.


title: Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection

text: Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.


title: Initial events in bovine coronavirus infection: analysis through immunogold probes and lysosomotropic inhibitors

text: The early events in the infection of human rectal tumor cells by bovine coronavirus were investigated by colloidal gold-mediated immunoelectron microscopy and by analysis of the effect of lysosomotropic weak bases on virus yield. Electron microscopic studies revealed sites of fusion between the virus envelope and the plasmalemma but fusion events along intracellular membranes were not observed despite extensive searches. Virion-antibody-colloidal gold complexes were, in fact, endocytosed by synchronously infected cells. These complexes were apparently non-infectious, and they accumulated in vacuoles that resembled secondary lysosomes. Exposure of cells to ammonium chloride or to methylamine during the first hour of infection had little inhibitory effect on the production of infectious virus. Chloroquine treatments were inhibitory but this effect depended on relatively late events in the infectious process. The chloroquine inhibitory step blocked infection of virus adsorbed to cells that were exposed to buffers in the pH range of 4.4 to 8.4. These findings indicate that BCV penetrates its host cell by direct fusion with the plasmalemma and does not require an acidic intracellular compartment for infectious entry.


The COVID‐19 pandemic and mental health impacts


title: Current status of rabies and prospects for elimination

text: Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60 000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.


title: Anticipating epidemic transitions with imperfect data

text: Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.


title: Nationalizing a global phenomenon: A study of how the press in 45 countries and territories portrays climate change

text: Abstract This study investigates the news coverage of climate change in 45 different countries and territories. Using the news framing approach, this study identifies the connections between several national socioeconomic, governance, and environmental traits and the portrayals of climate change. Although climate change is a global issue that affects every country in the world, how the news media frame it varies from country to country. Such a variation is related to each country’s economic development, climate severity, and governance. The findings of this study contribute to framing literature by assessing frame use in national contexts, filling in the gap in the application of this theoretical framework.


title: Potential Therapeutic Agents for Feline Calicivirus Infection

text: Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC(50) values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC(50) of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.


We Should Not Ignore What Scientific Articles are Telling US: A Lesson from the Italian COVID-19 Experience


title: Permissible peptide insertions surrounding the signal peptide-mature protein junction of the ClpG prepilin: CS31A fimbriae of Escherichia coli as carriers of foreign sequences

text: Abstract The clpG gene, expressing the Escherichia coli major CS31A fimbrial subunit ClpG, was subjected to random mutagenesis by insertion of an EcoRI linker and a kanamycin-resistance (KmR) cassette into the multiple newly generated EcoRI sites. The KmR gene was then excised by PstI, which left a 48-bp linker representing the heterologous sequence. The same procedure was followed to introduce a synthetic oligodeoxyribonucleotide (oligo) corresponding to epitope C from the spike protein S from the porcine transmissible gastroenteritis coronavirus (TGEV). Nine insertion/deletion mutants (indels) that contained long foreign peptides variously located around the ClpG signal peptide (SP) processing site were characterized. A striking feature of this study is the variety of amino acid (aa) insertions in the ClpG prepilin that have little or no effect on CS31A fimbria biogenesis. These ‘permissive’ sites tolerate inserts of 18 or 19 aa and accept sequences of different natures in view of their aa composition, charge and hydrophobicity. The results obtained here are also interesting in light of the high level of aa sequence conservation seen in the SP and N-terminal domains of the ClpG-related subunits. The structure-function relationship of the ClpG SP is discussed. The TGEV-C epitope fused to the N-terminal end of the mature ClpG protein was cell-surface exposed, as observed on immuno-electron microscopy. Therefore, the CS31A fimbria seems to be a potent tool for the presentation of foreign antigenic determinants or the production of heterologous polypeptides in E. coli.


Prevention of thrombosis in pregnant women with suspected SARS‐CoV‐2 infection: clinical management algorithm


title: Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

text: New treatments for multiple sclerosis (MS) focused on B cells have created an atmosphere of excitement in the MS community. B cells are now known to play a major role in disease, demonstrated by the highly impactful effect of a B cell-depleting antibody on controlling MS. The idea that a virus may play a role in the development of MS has a long history and is supported mostly by studies demonstrating a link between B cell-tropic Epstein–Barr virus (EBV) and disease onset. Efforts to develop antiviral strategies for treating MS are underway. Although gaps remain in our understanding of the etiology of MS, the role, if any, of viruses in propagating pathogenic immune responses deserves attention.


title: Pyogranulomatous panophthalmitis with systemic coronavirus disease in a domestic ferret (Mustela putorius furo)

text: A 15‐month‐old spayed female ferret (Mustela putorius furo) presented for lethargy and weight loss of 2 weeks duration. Upon physical examination, a 2‐mm‐diameter focal area of opacity was noted in the left cornea. In addition, the ferret was quiet, in poor body condition, and dehydrated. A complete blood count and plasma biochemistry revealed a severe nonregenerative anemia, azotemia, hyperproteinemia, hypoalbuminemia, and mild hyperphosphatemia and hyperchloremia. Urinalysis revealed hyposthenuria. Whole body radiographs showed multifocal thoracic nodular disease, splenomegaly, and renomegaly. Abdominal ultrasonography confirmed bilaterally enlarged kidneys, hypoechoic liver and spleen, and a caudal abdominal hypoechoic mobile nodule. The ferret was humanely euthanized, and a postmortem examination with subsequent histopathology showed multifocal necrotizing pyogranulomas in the lung, spleen, kidneys, mesenteric lymph nodes, and serosa of the duodenum. Pyogranulomatous panophthalmitis was diagnosed in the left eye. The multisystemic granulomatous lesions were suggestive of ferret systemic coronavirus (FRSCV). The presence of coronavirus in the left eye was confirmed by positive immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT‐PCR) on formalin fixed paraffin embedded tissue from the lung, spleen, and kidney was negative for FRSCV and positive for ferret enteric coronavirus (FRECV). Systemic coronavirus disease in ferrets closely resembles feline infectious peritonitis (FIP) in domestic cats, which can manifest with anterior uveitis, chorioretinitis, optic neuritis, and retinal detachment. To the authors’ knowledge, this is the first report of ocular lesions in a ferret with systemic coronavirus disease, suggesting that ferrets presented with similar ocular lesions should also be evaluated for evidence of coronavirus infection.


title: Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

text: INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.


title: Social determinants of COVID-19 mortality at the county level

text: The United States is currently the global epicenter of the COVID-19 pandemic. Emerging data suggests that social determinants of health may be key drivers of the epidemic, and that minorities, migrants, and essential workers may bear a disproportionate degree of risk. We used publicly accessible datasets to build a series of spatial autoregressive models assessing county level associations between COVID-19 mortality and (1) Percentage of Non-English speaking households, (2) percentage of individuals engaged in hired farm work, (3) percentage of uninsured individuals under the age of 65, and (3) percentage of individuals living at or below the poverty line. Across all counties (n=2940), counties with more farmworkers, more residents living in poverty, higher density, and more residents over the age of 65 had significantly higher levels of mortality. In urban counties (n=114), only county density was significantly associated with mortality. In non-urban counties (n=2826), counties with more non-English speaking households and more farm workers had significantly higher levels of mortality, as did counties with higher levels of poverty and more residents over the age of 65. More uninsured residents was significantly associated with decreased reported COVID-19 mortality. Individuals who do not speak English, individuals engaged in farm work, and individuals living in poverty may be at heightened risk for COVID-19 mortality in non-urban counties. Mortality among the uninsured may be being systematically undercounted in county and national level surveillance.


title: Do medical students receive training in correct use of personal protective equipment?

text: Background: Healthcare personnel often use incorrect technique for donning and doffing of personal protective equipment (PPE). Objective: We tested the hypothesis that medical students receive insufficient training on correct methods for donning and doffing PPE. Methods: We conducted a cross-sectional survey of medical students on clinical rotations at two teaching hospitals to determine the type of training they received in PPE technique. The students performed simulations of contaminated PPE removal with fluorescent lotion on gloves and were assessed for correct PPE technique and skin and/or clothing contamination. To obtain additional information on PPE training during medical education, residents, fellows, and attending physicians completed written questionnaires on PPE training received during medical school and on knowledge of PPE protocols recommended by the Centers for Disease Control and Prevention. Results: Of 27 medical students surveyed, only 11 (41%) reported receiving PPE training, and none had received training requiring demonstration of proficiency. During simulations, 25 of 27 (92.5%) students had one or more lapses in technique and 12 (44%) contaminated their skin with fluorescent lotion. For 100 residents, fellows and attending physicians representing 67 different medical schools, only 53% reported receiving training in use of PPE and only 39% selected correct donning and doffing sequence. Conclusions: Our findings suggest that there is a need for development of effective strategies to train medical students in correct use of PPE. Abbreviations: PPE: Personal protective equipment; MRSA: Methicillin-resistant Staphylococcus aureus; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; CDC: Centers for Disease Control and Prevention; OSCE: Objective structured clinical examination


title: Guidelines for balancing priorities in structural heart disease during the COVID-19 pandemic

text: During the novel coronavirus disease 2019 (COVID-19) pandemic, many hospitals have been asked to postpone elective and surgical cases. This begs the question, “What is elective in structural heart disease intervention?” The recently proposed Society for Cardiovascular Angiography and Interventions/American College of Cardiology consensus statement is, unfortunately, non-specific and insufficient in its scope and scale of response to the COVID-19 pandemic. We propose guidelines that are practical, multidisciplinary, implementable, and urgent. We believe that this will provide a helpful framework for our colleagues to manage their practice during the surge and peak phases of the pandemic. General principles that apply across structural heart disease interventions include tracking and reporting cardiovascular outcomes, “healthcare distancing,” preserving vital resources and personnel, shared decision-making between the heart team and hospital administration on resource-intensive cases, and considering delaying research cases. Specific guidance for transcatheter aortic valve replacement and MitraClip procedures varies according to pandemic phase. During the surge phase, treatment should broadly be limited to those at increased risk of complications in the near term. During the peak phase, treatment should be limited to inpatients for whom it may facilitate discharge. Keeping our patients and ourselves safe is paramount, as well as justly rationing resources.


title: Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model

text: Abstract Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103+ dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines.


title: Finding an Accurate Early Forecasting Model from Small Dataset: A Case of 2019-nCoV Novel Coronavirus Outbreak

text: Epidemic is a rapid and wide spread of infectious disease threatening many lives and economy damages. It is important to fore-tell the epidemic lifetime so to decide on timely and remedic actions. These measures include closing borders, schools, suspending community services and commuters. Resuming such curfews depends on the momentum of the outbreak and its rate of decay. Being able to accurately forecast the fate of an epidemic is an extremely important but difficult task. Due to limited knowledge of the novel disease, the high uncertainty involved and the complex societal-political factors that influence the widespread of the new virus, any forecast is anything but reliable. Another factor is the insufficient amount of available data. Data samples are often scarce when an epidemic just started. With only few training samples on hand, finding a forecasting model which offers forecast at the best efforts is a big challenge in machine learning. In the past, three popular methods have been proposed, they include 1) augmenting the existing little data, 2) using a panel selection to pick the best forecasting model from several models, and 3) fine-tuning the parameters of an individual forecastingmodel for the highest possible accuracy. In this paper, a methodology that embraces these three virtues of data mining from a small dataset is proposed...


title: Characterisation of cyclin D1 down-regulation in coronavirus infected cells

text: The positive strand RNA coronavirus, infectious bronchitis virus (IBV), induces a G2/M phase arrest and reduction in the G1 and G1/S phase transition regulator cyclin D1. Quantitative real-time RT-PCR and Western blot analysis demonstrated that cyclin D1 was reduced post-transcriptionally within infected cells independently of the cell-cycle stage at the time of infection. Confocal microscopy revealed that cyclin D1 decreased in IBV-infected cells as infection progressed and inhibition studies indicated that a population of cyclin D1 could be targeted for degradation by a virus mediated pathway. In contrast to the SARS-coronavirus, IBV nucleocapsid protein did not interact with cyclin D1.


title: The importance of contact network topology for the success of vaccination strategies

text: Abstract The effects of a number of vaccination strategies on the spread of an SIR type disease are numerically investigated for several common network topologies including random, scale-free, small world, and meta-random networks. These strategies, namely, prioritized, random, follow links and contact tracing, are compared across networks using extensive simulations with disease parameters relevant for viruses such as pandemic influenza H1N1/09. Two scenarios for a network SIR model are considered. First, a model with a given transmission rate is studied. Second, a model with a given initial growth rate is considered, because the initial growth rate is commonly used to impute the transmission rate from incidence curves and to predict the course of an epidemic. Since a vaccine may not be readily available for a new virus, the case of a delay in the start of vaccination is also considered in addition to the case of no delay. It is found that network topology can have a larger impact on the spread of the disease than the choice of vaccination strategy. Simulations also show that the network structure has a large effect on both the course of an epidemic and the determination of the transmission rate from the initial growth rate. The effect of delay in the vaccination start time varies tremendously with network topology. Results show that, without the knowledge of network topology, predictions on the peak and the final size of an epidemic cannot be made solely based on the initial exponential growth rate or transmission rate. This demonstrates the importance of understanding the topology of realistic contact networks when evaluating vaccination strategies.


title: Detection of coronavirus-like particles in homosexual men with acquired immunodeficiency and related lymphadenopathy syndrome

text: Coronavirus-like particles were identified by electronmicroscopy in the feces of homosexual men. The particles banded at a density of 1.21 g/ml after cesium chloride density gradient centrifugation. To determine whether the presence of this virus might be related to clinical symptoms, several patient groups were studied prospectively. In 8 of 16 (50%) homosexual males with acquired immunodeficiency syndrome (AIDS) or unexplained lymphadenopathy syndrome (LAS), coronavirus particles were found. In contrast, such particles were found in none of 18 heterosexual controls and in only 3 of 20 homosexual males without AIDS or LAS. Thus, coronavirus excretion correlated significantly (2α<0.01) with the clinical diagnosis of AIDS or with syndromes belonging to the AIDS-related complex. In addition, such particles identified in the serum of one patient with LAS and diarrhea suggest invasion and systemic spread of the agent and underline that this virus behaves differently from “common cold” human coronaviruses.


title: Shedding of “virus-like” particles in canine faeces

text: Abstract Diarrhoeic faeces from about 500 dogs were examined by negative stain electron microscopy. As well as parvovirus, and some of the other recognised viral causes of gastroenteritis, unusual “virus-like” particles were observed in about 8% of the samples. The particles were spherical, 100 nm to 300 nm in diameter, and surrounded by a thick wall penetrated by numerous pores. An additional 74 samples of normal faeces yielded no “virus-like” particles. We do not know the nature of these particles.


Covid-19 in Brazil: Learning How to Walk in the Dark Without Leaving Anything Behind


title: Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

text: Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NF{kappa}B, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.


title: Differential Effects of Intervention Timing on COVID-19 Spread in the United States

text: Assessing the effects of early non-pharmaceutical interventions(1–5) on COVID-19 spread in the United States is crucial for understanding and planning future control measures to combat the ongoing pandemic(6–10). Here we use county-level observations of reported infections and deaths(11), in conjunction with human mobility data(12) and a metapopulation transmission model(13,14), to quantify changes of disease transmission rates in US counties from March 15, 2020 to May 3, 2020. We find significant reductions of the basic reproductive numbers in major metropolitan areas in association with social distancing and other control measures. Counterfactual simulations indicate that, had these same control measures been implemented just 1–2 weeks earlier, a substantial number of cases and deaths could have been averted. Specifically, nationwide, 56.5% [95% Cl: 48.1%−65.9%] of reported infections and 54.0% [95% Cl: 43.6%−63.8%] of reported deaths as of May 3, 2020 could have been avoided if the same control measures had been implemented just one week earlier. We also examine the effects of delays in re-implementing social distancing following a relaxation of control measures. A longer response time results in a stronger rebound of infections and death. Our findings underscore the importance of early intervention and aggressive response in controlling the COVID-19 pandemic.


title: Viruses in Horses with Neurologic and Respiratory Diseases

text: Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and a novel parvovirus) were detected in plasma from neurological cases. Plasma from horses with respiratory signs contained the same two copiparvoviruses plus equine pegivirus D and respiratory swabs contained equine herpes virus 2 and 5. Based on genetic distances the novel copiparvovirus qualified as a member of a new parvovirus species we named Eqcopivirus. These samples plus another 41 plasma samples from healthy horses were tested by real-time PCRs for multiple equine parvoviruses and hepacivirus. Over half the samples tested were positive for one to three viruses with eqcopivirus DNA detected in 20.5%, equine hepacivirus RNA and equine parvovirus-H DNA in 16% each, and horse parvovirus-CSF DNA in 12% of horses. Comparing viral prevalence in plasma none of the now three genetically characterized equine parvoviruses (all in the copiparvovirus genus) was significantly associated with neurological and respiratory signs in this limited sampling.


title: Recovery of pulmonary functions, exercise capacity, and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis

text: BACKGROUND: Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge. OBJECTIVES: The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011. PATIENTS AND METHODS: Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL(CO)), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ). RESULTS: Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV (1)), DL(CO), and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge. CONCLUSION: The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.


title: Transmission of Influenza Virus via Aerosols and Fomites in the Guinea Pig Model

text: Limited data on the relative contributions of different routes of transmission for influenza virus are available. Person-to-person transmission is central to seasonal and pandemic spread; nevertheless, the modes of spread are a matter of ongoing debate. Resolution of this discussion is paramount to the development of effective control measures in health care and community settings. Using the guinea pig model, we demonstrated that transmission of influenza A/Panama/2007/1999 (H3N2) virus through the air is efficient, compared with spread through contaminated environmental surfaces (fomites). We also examined the aerosol transmission efficiencies of 2 human influenza virus A strains and found that A/Panama/2007/1999 influenza virus transmitted more efficiently than A/Texas/36/1991 (H1N1) virus in our model. The data provide new and much-needed insights into the modes of influenza virus spread and strain-specific differences in the efficiency of transmission.


title: Detection of respiratory viruses and Bordetella bronchiseptica in dogs with acute respiratory tract infections

text: Abstract Canine infectious respiratory disease (CIRD) is an acute, highly contagious disease complex caused by a variety of infectious agents. At present, the role of viral and bacterial components as primary or secondary pathogens in CIRD is not fully understood. The aim of this study was to investigate the prevalence of canine parainfluenza virus (CPIV), canine adenovirus type 2 (CAV-2), canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine herpes virus-1 (CHV-1), canine distemper virus (CDV) and Bordetella bronchiseptica in dogs with CIRD and to compare the data with findings in healthy dogs. Sixty-one dogs with CIRD and 90 clinically healthy dogs from Southern Germany were prospectively enrolled in this study. Nasal and pharyngeal swabs were collected from all dogs and were analysed for CPIV, CAV-2, CIV, CRCoV, CHV-1, CDV, and B. bronchiseptica by real-time PCR. In dogs with acute respiratory signs, 37.7% tested positive for CPIV, 9.8% for CRCoV and 78.7% for B. bronchiseptica. Co-infections with more than one agent were detected in 47.9% of B. bronchiseptica-positive, 82.6% of CPIV-positive, and 100% of CRCoV-positive dogs. In clinically healthy dogs, 1.1% tested positive for CAV-2, 7.8% for CPIV and 45.6% for B. bronchiseptica. CPIV and B. bronchiseptica were detected significantly more often in dogs with CIRD than in clinically healthy dogs (P < 0.001 for each pathogen) and were the most common infectious agents in dogs with CIRD in Southern Germany. Mixed infections with several pathogens were common. In conclusion, clinically healthy dogs can carry respiratory pathogens and could act as sources of infection for susceptible dogs.


title: Access to smart devices and utilization of online health resources among older cardiac rehabilitation participants

text: BACKGROUND: Newer models of cardiac rehabilitation (CR) delivery are promising but depend upon patient participation and ability to use technological media including Internet and smart devices. AIM: To explore the availability of smart devices, current utilization and proficiency of use among older CR program attendees. METHODS: Study participants were enrolled from four CR programs in Omaha, Nebraska United States and completed a questionnaire of 28 items. RESULTS: Of 376 participants approached, 169 responded (45%). Mean age was 71.1 (SD ± 10) years. Demographics were 73.5% males, 89.7% Caucasians, 52% with college degree and 56.9%, with income of 40K$ or more. Smart device ownership was 84.5%; desktop computer was the most preferred device. Average Internet use was 1.9 h/d (SD ± 1.7); 54.3% of participants indicating for general usage but only 18.4% pursued health-related purposes. Utilization of other health information modalities was low, 29.8% used mobile health applications and 12.5% used wearable devices. Of all participants, 72% reported no barriers to using Internet. Education and income were associated positively with measures of utilization and with less perceived barriers. CONCLUSION: Among an older group of subjects attending CR, most have access to smart devices and do not perceive significant barriers to Internet use. Nonetheless, there was low utilization of health-related resources suggesting a need for targeted education in this patient population.


title: Isolation and characterization of feline panleukopenia virus from a diarrheic monkey

text: Abstract A feline panleukopenia virus (FPV) mutant, monkey/BJ-22/2008/CHN, was isolated from intestinal contents of a diarrheic monkey in Beijing, China. The virus was identified by morphology and physicochemical characteristics, and specific fragments were obtained by PCR using consensus primers of parvovirus and specific primers of FPV. Sequence of the full-length VP2 gene of the isolated FPV was determined and analyzed by comparison with reference FPV and canine parvovirus (CPV) isolates, showing high homology with FPV (98.75%) and CPV (98.15%). Phylogenetic analysis indicated that the isolated FPV formed a monophyletic branch in FPV cluster which differed from the other 11 FPV isolates from China and other countries. The isolated virus caused typical clinical symptoms of FPV in cats. This is the first report on isolation of FPV from a monkey.


title: Identification of a New Antizyme mRNA +1 Frameshifting Stimulatory Pseudoknot in a Subset of Diverse Invertebrates and its Apparent Absence in Intermediate Species

text: Abstract The expression of eukaryotic antizyme genes requires +1 translational frameshifting. The frameshift in decoding most vertebrate antizyme mRNAs is stimulated by an RNA pseudoknot 3′ of the frameshift site. Although the frameshifting event itself is conserved in a wide variety of organisms from yeast to mammals, until recently no corresponding 3′ RNA pseudoknot was known in invertebrate antizyme mRNAs. A pseudoknot, different in structure and origin from its vertebrate counterparts, is now shown to be encoded by the antizyme genes of distantly related invertebrates. Identification of the 3′ frameshifting stimulator in intermediate species or other invertebrates remains unresolved.


title: Experimental infection of peridomestic mammals with emergent H7N9 (A/Anhui/1/2013) influenza A virus: Implications for biosecurity and wet markets

text: Abstract During 2013, a novel avian-origin H7N9 influenza A virus (IAV) emerged in China and subsequently caused large economic and public health burdens. We experimentally infected three common peridomestic wild mammals with H7N9 (A/Anhui/1/2013) IAV. Striped skunks exhibited the highest burden of disease followed by raccoons and cottontail rabbits. Striped skunks also produced the highest levels of viral shedding (up to 106.4 PFU/mL nasal flush) followed by cottontail rabbits (up to 105.8 PFU/mL nasal flush) and raccoons (up to 105.2 PFU/mL nasal flush). Thus, various mammalian species, especially those that are peridomestic, could play a role in the epidemiology of emergent H7N9 IAV. Mammals should be accounted for in biosecurity plans associated with H7N9 and their presence in wet markets, dependent on species, could lead to increased transmission among interspecific species aggregations and may also pose an elevated zoonotic disease risk to visitors and workers of such markets.


title: Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children

text: INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.


title: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

text: The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.