title: Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system

text: Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R(−/−) (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat’s remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.


title: Optimal Strategies for Reducing Number of People in the Social Security System

text: Providing social security to the population in need has become a major expenditure for many governments. Reducing the number of dependents in the social security system and maintaining a dynamic economically active population is a high priority concern for policymakers. A good understanding of the dynamics of the social security system—specifically, who enters and who exits the system—would be helpful for formulating effective interventions. Here, we made use of the data of Hong Kong’s Comprehensive Social Security Assistance (CSSA), which is currently a basic welfare scheme in Hong Kong that provides supplementary payments to households that cannot support themselves financially. We proposed a stochastic model to examine the in- and out- movement in the CSSA scheme and conducted elasticity analyses. The elasticity analyses allowed us to identify the potential target groups of people that would lead to the largest reduction in the number of the CSSA recipients in the system. This analytical method can also reveal whether policies would be more effective in preventing people from entering the CSSA system or helping them leave the CSSA scheme. Our analyses suggest that targeting those aged 30–49 with children would have the largest impact. Additionally, we found that policies that aim to prevent this group from entering the CSSA system would be more effective in reducing the number of CSSA recipients compared with policies that aim to help them exit. In contrast, for the younger age group of 10–29, policies that help them leave CSSA would be more effective than policies that prevent them from entering CSSA. Providing employment for those unemployed in this younger group would be more effective. The results indicate that by tailoring measures to specific subgroups, the overall number of CSSA recipients would be reduced, thereby improving the efficiency of Hong Kong’s social security system, which has accounted for more than 16.5% of Hong Kong government expenditure in 2018, amounting to more than HKD 92 billion.


title: Systems biology: a tool for charting the antiviral landscape

text: The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as “the antiviral landscape”. Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral responses. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.


title: Novel amodiaquine derivatives potently inhibit Ebola virus infection

text: Ebola virus disease is a severe disease caused by highly pathogenic Ebolaviruses. Although it shows a high mortality rate in humans, currently there is no licensed therapeutic. During the recent epidemic in West Africa, it was demonstrated that administration of antimalarial medication containing amodiaquine significantly lowered mortality rate of patients infected with the virus. Here, in order to improve its antiviral activity, a series of amodiaquine derivatives were synthesized and tested for Ebola virus infection. We found that multiple compounds were more potent than amodiaquine. The structure-activity relationship analysis revealed that the two independent parts, which are the alkyl chains extending from the aminomethyl group and a halogen bonded to the quinoline ring, were keys for enhancing antiviral potency without increasing toxicity. When these modifications were combined, the antiviral efficacy could be further improved with the selectivity indexes being over 10-times higher than amodiaquine. Mechanistic evaluation demonstrated that the potent derivatives blocked host cell entry of Ebola virus, like the parental amodiaquine. Taken together, our work identified novel potent amodiaquine derivatives, which will aid in further development of effective antiviral therapeutics.


title: Viral diseases of the respiratory system

text: Abstract Infectious bronchitis, Newcastle disease, infectious laryngotracheitis, avian influenza, and pneumovirus are the viruses that more frequently affect the respiratory tract of chickens. Because of the tendency to change its antigenic properties, infectious bronchitis is currently the viral disease present in most poultry producing areas of the world. New serotypes and variant strains are reported in several countries. Current commercially available vaccines do not always provide protection against new field isolates. Vaccination programs are constantly adjusted in an attempt to improve protection against this disease. Infectious laryngotracheitis has appeared in the broiler industry as a serious disease. Improved vaccines are needed to control the disease in broilers. In the U.S., the control of the highly pathogenic forms of avian influenza and the velogenic forms of Newcastle disease have been achieved by eradication. In other countries, effective vaccines have been used to control Newcastle and avian influenza. Avian pneumovirus infection is also an emerging disease of chickens and turkeys.


title: Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection

text: Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable.


title: Structural and functional analysis of the S proteins of two human coronavirus OC43 strains adapted to growth in different cells

text: The receptor-binding activity of strain CU (grown in MDCK I cells) and of strain VA (adapted to Vero cells) of human coronavirus OC43 was analyzed and compared with the binding activity of bovine coronavirus (BCV) and of the OC43 strain provided by the American Type Culture Collection (AT). Results obtained with resialylated erythrocytes indicated that the ability of the viruses to recognize 9-O-acetylated sialic acid in an α2,6-linkage decreased in the following order: AT>CU>BCV>VA. Only minor differences were observed with respect to the α2,3-linkage. The amino acid sequence of the S protein of strain CU and VA was derived from the nucleotide sequence of the cloned gene. Strain VA differed from strain CU in 34 positions, 18 in the S1 and 16 in the S2 subunit.


title: A model-based tool to predict the propagation of infectious disease via airports

text: Summary Epidemics of novel or re-emerging infectious diseases have quickly spread globally via air travel, as highlighted by pandemic H1N1 influenza in 2009 (pH1N1). Federal, state, and local public health responders must be able to plan for and respond to these events at aviation points of entry. The emergence of a novel influenza virus and its spread to the United States were simulated for February 2009 from 55 international metropolitan areas using three basic reproduction numbers (R 0): 1.53, 1.70, and 1.90. Empirical data from the pH1N1 virus were used to validate our SEIR model. Time to entry to the U.S. during the early stages of a prototypical novel communicable disease was predicted based on the aviation network patterns and the epidemiology of the disease. For example, approximately 96% of origins (R 0 of 1.53) propagated a disease into the U.S. in under 75 days, 90% of these origins propagated a disease in under 50 days. An R 0 of 1.53 reproduced the pH1NI observations. The ability to anticipate the rate and location of disease introduction into the U.S. provides greater opportunity to plan responses based on the scenario as it is unfolding. This simulation tool can aid public health officials to assess risk and leverage resources efficiently.


title: The signal peptide as a new target for drug design

text: Abstract Many current and potential drug targets are membrane-bound or secreted proteins that are expressed and transported via the Sec61 secretory pathway. They are targeted to translocon channels across the membrane of the endoplasmic reticulum (ER) by signal peptides (SPs), which are temporary structures on the N-termini of their nascent chains. During translation, such proteins enter the lumen and membrane of the ER by a process known as co-translational translocation. Small molecules have been found that interfere with this process, decreasing protein expression by recognizing the unique structures of the SPs of particular proteins. The SP may thus become a validated target for designing drugs for numerous disorders, including certain hereditary diseases.


title: Association between renin–angiotensin system inhibitors and COVID-19 complications

text: AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.


Physical activity: Benefits and challenges during the COVID‐19 pandemic


title: The Global Phylogeography of Lyssaviruses - Challenging the 'Out of Africa' Hypothesis

text: Rabies virus kills tens of thousands of people globally each year, especially in resource-limited countries. Yet, there are genetically- and antigenically-related lyssaviruses, all capable of causing the disease rabies, circulating globally among bats without causing conspicuous disease outbreaks. The species richness and greater genetic diversity of African lyssaviruses, along with the lack of antibody cross-reactivity among them, has led to the hypothesis that Africa is the origin of lyssaviruses. This hypothesis was tested using a probabilistic phylogeographical approach. The nucleoprotein gene sequences from 153 representatives of 16 lyssavirus species, collected between 1956 and 2015, were used to develop a phylogenetic tree which incorporated relevant geographic and temporal data relating to the viruses. In addition, complete genome sequences from all 16 (putative) species were analysed. The most probable ancestral distribution for the internal nodes was inferred using three different approaches and was confirmed by analysis of complete genomes. These results support a Palearctic origin for lyssaviruses (posterior probability = 0.85), challenging the ‘out of Africa’ hypothesis, and suggest three independent transmission events to the Afrotropical region, representing the three phylogroups that form the three major lyssavirus clades.


title: Could melatonin be used in COVID‐19 patients with laryngopharyngeal reflux disease?

text: The study by Jiang et al. [1] to determine the impact of laryngopharyngeal reflux disease (LPRD) on the clinical outcomes in hospitalized patients with novel coronavirus disease 2019 (COVID‐19) is first of its kind study in the literature. While available studies have mostly focused on the effect of cardiovascular comorbidities, the authors' work raises the concurrent gastrointestinal related issues in patients with COVID‐19. This article is protected by copyright. All rights reserved.


title: A facile Q-RT-PCR assay for monitoring SARS-CoV-2 growth in cell culture

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the ongoing COVID-19 pandemic, has infected millions within just a few months and is continuing to spread around the globe causing immense respiratory disease and mortality. Assays to monitor SARS-CoV-2 growth depend on time-consuming and costly RNA extraction steps, hampering progress in basic research and drug development efforts. Here we developed a facile Q-RT-PCR assay that bypasses viral RNA extraction steps and can monitor SARS-CoV-2 replication kinetics from a small amount of cell culture supernatants. Using this assay, we screened the activities of a number of entry, SARS-CoV-2- and HIV-1-specific inhibitors in a proof of concept study. In line with previous studies which has shown that processing of the viral Spike protein by cellular proteases and endosomal fusion are required for entry, we found that E64D and apilimod potently decreased the amount of SARS-CoV-2 RNA in cell culture supernatants with minimal cytotoxicity. Surprisingly, we found that macropinocytosis inhibitor EIPA similarly decreased viral RNA in supernatants suggesting that entry may additionally be mediated by an alternative pathway. HIV-1-specific inhibitors nevirapine (an NNRTI), amprenavir (a protease inhibitor), and ALLINI-2 (an allosteric integrase inhibitor) modestly inhibited SARS-CoV-2 replication, albeit the IC(50) values were much higher than that required for HIV-1. Taken together, this facile assay will undoubtedly expedite basic SARS-CoV-2 research, be amenable to mid-throughput screens to identify chemical inhibitors of SARS-CoV-2, and be applicable to a broad number of RNA and DNA viruses.


title: Impact of pandemic control over airport economics: Reconciling public health with airport business through a streamlined approach in pandemic control

text: Abstract Rapid aviation commercialisation and upsurge in worldwide affluence created a new avenue for disease proliferation across countries at an unprecedented rate. Epidemic and pandemic occurrences over the last decade demonstrate airports' role in disease transmission; while also exhibiting their importance as containment nodes. Tremendous amount of resources and effort are necessary to achieve the latter but inevitably, disrupt normal operations. The contrasting objectives between public health authorities and airport authorities result in compromising measures for both parties. Broadly similar controlling measures were adopted by various airports during outbreaks in the last decade. Their effectiveness have been analysed in terms of disease control; economic impact to airports were, however, not quantified. This paper concludes that more efficient airport pandemic control plans cause less severe economic impact on airports during pandemic and recommends a streamlined approach that improves overall effect of pandemic control while minimising economic impacts to airport businesses.


title: A Preliminary Evaluation of the Public Risk Perception Related to the COVID-19 Health Emergency in Italy

text: Governments faced with the spread of COVID-19 pandemic are adopting strict and severe mitigation measures to influence people’s behaviors. Public perception of health risk plays a key role in the adoption of these actions, in people’s feelings, and in their daily habits. To support decision makers from international to local levels to face with future sanitary emergencies, this study aims at investigating Italian public perceptions of health risk. To this purpose, a questionnaire was designed and administered within the period of Italian COVID-19 lockdown and quarantine to almost 9000 citizens in Italy and abroad. The obtained results highlight a significative influence that mass media play on both the level of knowledge and the feelings of the respondents. The findings also point out future variations of some perceived behaviors consequent to the COVID-19 outbreak.


title: Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference

text: The severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV.


Specific Considerations for Pediatric, Fetal, and Congenital Heart Disease Patients and Echocardiography Service Providers During the 2019 Novel Coronavirus Outbreak: Council on Pediatric and Congenital Heart Disease Supplement to the Statement of the American Society of Echocardiography Endorsed by


A Letter to the Editor on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)”


COVID‐19 and implications for eating disorders


title: Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

text: Viruses from the Filoviridae family, as many other virus families, require an acidic pH for successful infection and are therefore susceptible to the actions of 4‐aminoquinolines, such as chloroquine. Although the mechanisms of action of chloroquine clearly indicate that it might inhibit filoviral infections, several clinical trials that attempted to use chloroquine in the treatment of other acute viral infections – including dengue and influenza A and B – caused by low pH‐dependent viruses, have reported that chloroquine had no clinical efficacy, and these results demoted chloroquine from the potential treatments for other virus families requiring low pH for infectivity. The present review is aimed at investigating whether chloroquine could combat the present Ebola virus epidemic, and also at exploring the main reasons for the reported lack of efficacy. Literature was sourced from PubMed, Scopus, Google Scholar, reference list of articles and textbooks – Fields Virology (Volumes 1and 2), the cytokine handbook, Pharmacology in Medicine: Principles and Practice, and hydroxychloroquine and chloroquine retinopathy. The present analysis concludes that (1) chloroquine might find a place in the treatment of Ebola, either as a monotherapy or in combination therapies; (2) the ineffectiveness of chloroquine, or its analogue, hydroxychloroquine, at treating infections from low pH‐dependent viruses is a result of the failure to attain and sustain a steady state concentration sufficient to increase and keep the pH of the acidic organelles to approximately neutral levels; (3) to successfully treat filoviral infections – or other viral infections that emerge or emerged from low pH‐dependent viruses – a steady state chloroquine plasma concentration of at least 1 µg/mL(~3.125 μM/L) or a whole blood concentration of 16 μM/L must be achieved and be sustained until the patients' viraemia becomes undetectable. These concentrations, however, do not rule out the efficacy of other, higher, steady state concentrations – although such concentrations might be accompanied by severe adverse effects or toxicities. The feasibility of the conclusion in the preceding texts has recently been supported by a subsequent study that shows that amodiaquine, a derivative of CQ, is able to protect humans infected with Ebola from death.


title: Neumopatías hospitalarias en pacientes con ventilación mecánica

text: Las neumopatías son la primera causa de infección hospitalaria en reanimación. Las neumopatías hospitalarias en los pacientes con ventilación mecánica (NHPVM) ocurren después de al menos 48 horas de ventilación mecánica invasiva. Su mecanismo es multifactorial, pero la opinión predominante es que obedecen a una inhalación posterior a la colonización orofaríngea, gástrica o traqueal. El retraso en la manifestación permite clasificar las NHPVM en precoces o tardías según se desarrollen antes o después del 5.° día de ventilación mecánica. La clínica puede ayudar al diagnóstico, sobre todo mediante la CPIS (Clinical Pulmonary Infection Score) y también es útil el lavado broncoalveolar (LBA), que parece la mejor prueba para el diagnóstico microbiológico. El diagnóstico diferencial se plantea con una neumopatía no bacteriana o incluso no infecciosa (neoplásica, inflamatoria, fibrosante) en la que siempre debe plantearse la búsqueda de otro foco infeccioso en función de la orientación clínica inicial o del fracaso de la antibioticoterapia. El uso preferente de la ventilación no invasiva, cuando es posible, parece que ayuda a prevenir el desarrollo de la neumopatía hospitalaria. La posición inclinada 30-45° del paciente es la única medida preventiva verdaderamente validada en las NHPVM. El tratamiento curativo de las neumopatías bacterianas descansa por lo general en un tratamiento antibiótico doble, que puede orientarse por los datos de muestras obtenidas con métodos no invasivos como las aspiraciones traqueales efectuadas de forma periódica y sistemática. La duración del tratamiento es discutible, pero los últimos datos apoyan un tratamiento con antibióticos relativamente corto, de 8 días.


title: Transcriptional profiling reveals TRPM5-expressing cells involved in viral infection in the olfactory epithelium

text: Background Understanding viral infection of the olfactory epithelium is essential because smell loss can occur with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), and because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Results Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of fluorescent protein markers for olfactory sensory neurons and TRPM5 in the mouse (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells and olfactory sensory neurons. These cells express the Tmprss2 transcript that encodes for a serine protease that primes the SARS-CoV-2 spike protein before entry into host cells. Intranasal infection with herpes simplex virus type 1 (HSV-1) elicited a decrease in olfactory sensory neurons. Conclusion Our study provides new insights into a potential role for TRPM5-expressing cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells and olfactory sensory neurons indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.


title: SARS — beginning to understand a new virus

text: The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.


title: Ethical Principles—Emergency Medicine

text: Neither law nor religion, bioethics absorbs and applies elements of both. Its theories, principles, and methods stem from various philosophical schools. Practitioners use case-based reasoning to apply bioethics to clinical situations, usually giving most weight to patients' autonomy and values, but also incorporating other relevant bioethical principles, including those encompassed in professional oaths and codes. Emergency clinicians must be able to recognize bioethical dilemmas, have action plans based on their readings and discussions, and have a method through which to apply ethical principles in clinical settings. This article provides an overview of ethical considerations and guidelines for emergency clinicians.


title: Understanding face mask use to prevent coronavirus and other illnesses: Development of a multidimensional face mask perceptions scale

text: Face masks are an avenue to curb the spread of coronavirus, but few people in Western societies wear face masks. Social scientists have rarely studied face mask wearing, leaving little guidance for methods to encourage these behaviours. In the current article, we provide an approach to address this issue by developing the 32‐item and 8‐dimension Face Mask Perceptions Scale (FMPS). We begin by developing an over‐representative item list in a qualitative study, wherein participants’ responses are used to develop items to ensure content relevance. This item list is then reduced via exploratory factor analysis in a second study, and the eight dimensions of the scale are supported. We also support the validity of the FMPS, as the scale significantly relates to both face mask wearing and health perceptions. We lastly confirm the factor structure of the FMPS in a third study via confirmatory factor analysis. From these efforts, we identify an avenue that social scientists can aid in preventing coronavirus and illness more broadly – by studying face mask perceptions and behaviours.


title: Synthesis of novel N-acyl-β-d-glucopyranosylamines and ureas as potential lead cytostatic agents

text: Novel classes of acetylated and fully deprotected N-acyl-β-d-glucopyranosylamines and ureas have been synthesized and biologically evaluated. Acylation of the per-O-acetylated β-d-glucopyranosylurea (5), easily prepared via its corresponding phosphinimine derivative, by zinc chloride catalyzed reaction of the corresponding acyl chlorides RCOCl (a–f) gave the protected N-acyl-β-d-glucopyranosylureas (6a–f), in acceptable-to-moderate yields. Subsequent deacetylation of analogues 6a–f under Zemplén conditions afforded the fully deprotected derivatives 7a,b,d,e,f, while the desired urea 7c was formed after treatment of 6c with dibutyltin oxide. All protected and unprotected compounds were examined for their cytotoxic activity in different L1210, CEM and HeLa tumor cell lines and were also evaluated against a broad panel of DΝΑ and RNA viruses. Derivative 7c exhibited cytostatic activity against the three evaluated tumor cell lines (IC(50) 9–24 μΜ) and might be the basis for the synthesis of structure-related derivatives with improved cytostatic potential. Only analogue 6f weakly but significantly inhibited the replication of parainfluenza-3 virus, Sindbis virus and Coxsackie virus B4 in cell cultures at concentrations of 45–58 μM.


title: Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation

text: The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract (polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.


title: PLANT-Dx: A Molecular Diagnostic for Point-of-Use Detection of Plant Pathogens

text: [Image: see text] Synthetic biology based diagnostic technologies have improved upon gold standard diagnostic methodologies by decreasing cost, increasing accuracy, and enhancing portability. However, there has been little effort in adapting these technologies toward applications related to point-of-use monitoring of plant and crop health. Here, we take a step toward this vision by developing an approach that couples isothermal amplification of specific plant pathogen genomic sequences with customizable synthetic RNA regulators that are designed to trigger the production of a colorimetric output in cell-free gene expression reactions. We demonstrate our system can sense viral derived sequences with high sensitivity and specificity, and can be utilized to directly detect viruses from infected plant material. Furthermore, we demonstrate that the entire system can operate using only body heat and naked-eye visual analysis of outputs. We anticipate these strategies to be important components of user-friendly and deployable diagnostic systems that can be configured to detect a range of important plant pathogens.


title: Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis

text: Abstract The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.


docid: jooqvyoz

title: Molecular investigation of a full-length genome of a Q1-like IBV strain isolated in Italy in 2013

text: Abstract Since 1996 a new Infectious Bronchitis virus (IBV) genotype, referred to as Q1, circulated in China and was reported for the first time in Italy in 2011, associated with an increase of mortality, kidney lesions and proventriculitis. During northern Italian outbreak of respiratory disease in a broiler flock in 2013, an IBV strain was detected by RT-PCR and characterized as Q1-like based on partial S1 sequence. The virus was isolated and named γCoV/Ck/Italy/I2022/13. All coding regions of the isolate were sequenced and compared with 130 complete genome sequences of IBV and TCoV, downloaded from ViPR. This showed the highest identity with a Chinese strain CK/CH/LDL/97I (p-distance=0.044). To identify potential recombination events a complete genome SimPlot analysis was carried out which revealed the presence of possible multiple recombination events, but the minor parent strains remained unknown. A phylogenetic analysis of the complete S1 gene was performed using all complete S1 sequences available on ViPR and showed the isolate clustered with an Q1-like strain isolated in Italy in 2011 (p-distance=0.004) and a group of Chinese Q1-like strains isolated from the mid 90's (p-distance equal or higher than 0.001). It could be hypothesized that the isolate descended from the Italian 2011 Q1-like strain or was the result of a separate introduction from China through commercial trade or migratory birds; but the data currently available does not distinguish between these possibilities.


title: Hierarchical virtual screening approaches in small molecule drug discovery

text: Abstract Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery.


title: Virus — cell interactions in the nervous system and the role of the immune response

text: Abstract The outcome of a viral infection within the nervous system depends on a complex interplay between the virus, its target cell and the immune system. Recent research has elucidated a variety of mechanisms involved in these interactions and their role in the production of disease.


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

text: Abstract 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. Specifically, 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, NFκB, 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: Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action

text: The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a “Public Health Emergency of International Concern” (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level.


title: COVID‐19 and Older People in Asia: AWGS Calls to Actions

text: The coronavirus disease 2019 (COVID‐19) pandemic has casted a huge impact on global public health and economy. In this challenging situation, older people are vulnerable to the infection and the secondary effects of the pandemic and need special attentions. To evaluate the impacts of COVID‐19 on older people, it is important to balance the successful pandemic control and active management of secondary consequences. These considerations are especially salient in the Asian context, with its diversity among countries in terms of sociocultural heritage, healthcare setup and availability of resources. Thus, the Asian Working Group for Sarcopenia summarized the considerations of Asian countries focusing on responses and difficulties in each country, impacts of health inequity related to COVID‐19 pandemic and proposed recommendations for older people which are germane to the Asian context. More innovative services should be developed to address the increasing demands for new approaches to deliver health care in the difficult times and to establish resilient health care systems for older people. This article is protected by copyright. All rights reserved.


title: Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid

text: Abstract We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection.


title: Use of face masks in a primary care outpatient setting in Hong Kong: Knowledge, attitudes and practices

text: Summary Objectives To assess if a knowledge gap exists in the correct use of face masks, and to explore the correlations between knowledge, attitudes and practices regarding the use of face masks among outpatients and their caregivers in an outpatient clinic in Hong Kong. Study design Cross-sectional study. Methods Outpatients and their caregivers who were present at an outpatient setting in Hong Kong were invited to participate in this survey. All participants were asked to complete a self-administered closed-ended questionnaire about their knowledge, attitudes and practices regarding the use of face masks. Data were described using descriptive statistics and correlation coefficients. Results Among the 399 respondents, 52% knew the correct steps in wearing a face mask, and their attitudes toward face masks were generally positive. Further analyses showed that respondents were more likely to wear a face mask at a clinic than in a public place or at home. Moreover, respondents were more likely to wear a face mask to protect others against influenza-like illness (ILI) than for self-protection. There was low to moderate correlation between attitudes and practices (correlation coefficient 0.26, P < 0.05). Conclusions This study identified a knowledge gap in the correct use of face masks among outpatients and their caregivers; attitudes and practices regarding the use of face masks were generally positive, but correlation was not high. It is recommended that public health education campaigns should tailor efficient programmes to combat ILI transmission among outpatient clinic populations by improving knowledge about the correct use of face masks.


docid: mejtndwz

title: A test of syndromic surveillance using a severe acute respiratory syndrome model

text: Abstract Objectives We describe a field simulation that was conducted using volunteers to assess the ability of 3 hospitals in a network to manage a large influx of patients with a potentially communicable disease. This drill provided the opportunity to evaluate the ability of the New York City Department of Health and Mental Hygiene's (NYC-DOHMH) emergency department chief complaint syndromic surveillance system to detect a cluster of patients with febrile respiratory illness. Methods The evaluation was a prospective simulation. The clinical picture was modeled on severe acute respiratory syndrome symptoms. Forty-four volunteers participated in the drill as mock patients. Results Records from 42 patients (95%) were successfully transmitted to the NYC-DOHMH. The electronic chief complaint for 24 (57%) of these patients indicated febrile or respiratory illness. The drill did not generate a statistical signal in the NYC-DOHMH SaTScan analysis. The 42 drill patients were classified in 8 hierarchical categories based on chief complaints: sepsis (2), cold (3), diarrhea (2), respiratory (20), fever/flu (4), vomit (3), and other (8). The number of respiratory visits, while elevated on the day of the drill, did not appear particularly unusual when compared with the 14-day baseline period used for spatial analyses. Conclusions This drill with a cluster of patients with febrile respiratory illness failed to trigger a signal from the NYC-DOHMH emergency department chief complaint syndromic surveillance system. This highlighted several limitations and challenges to syndromic surveillance monitoring.


The next SARS?


title: Should we be concerned about COVID‐19 with nonhuman primates?

text: The coronavirus disease 2019 pandemic has radically changed the human activities worldwide. Although we are still learning about the disease, it is necessary that primatologists, veterinarians, and all that are living with nonhuman primates (NHP) be concerned about the probable health impacts as these animals face this new pandemic. We want to increase discussion with the scientific community that is directly involved with these animals, because preliminary studies report that NHP may become infected and develop symptoms similar to those in human beings.


title: Grundfos produces face shields for health services

text: Up to 5000 visors or face shields are being produced each day by Grundfos to help employees in the Danish health and care sector fight Covid-19.


The well-known and less well-known benefits of vaccines


title: Random-peptide libraries and antigen-fragment libraries for epitope mapping and the development of vaccines and diagnostics

text: Abstract Random peptide libraries and antigen-fragment libraries (also known as gene-fragment libraries) have been used to identify epitopes on protein antigens. These technologies promise to make significant contributions to diagnostic and vaccine development. Researchers in a number of labs have shown that phage selected from libraries with protective antibodies, raised against whole antigen, can be used as immunogens to stimulate antibody responses that bind native antigen and provide protection in vivo. Others have used the sera of patients with idiopathic diseases to screen libraries, and by this approach have identified candidate antigens involved in immune disease. These may prove useful for diagnosis and, possibly, in determining disease etiology.


title: The impact of COVID-19 pandemic on IBD endoscopic procedures in a high-volume IBD Center

text: Background and study aims The COVID-19 pandemic is having a major clinical and also organizational impact on national health care systems, particularly in high-volume hospitals that are utilized for several essential clinical needs. We aimed to analyze the short-term impact of the SARS-CoV-2 pandemic on management of endoscopic procedures in patients with inflammatory bowel disease (IBD). Patients and methods This was an observational prospective study exploring major clinical and organizational changes in endoscopic management at the IBD Center – CEMAD of the Fondazione Policlinico Gemelli IRCCS, Rome, Italy since the beginning of SARS-CoV-2 pandemic. Results Our IBD Unit, with up to 1,500 IBD patients receiving biotechnological or experimental therapy, represents a high-volume Italian and European IBD center. Since the beginning of the outbreak, our hospital has been extremely impacted by care related to COVID-19 cases, with a consequent need to dramatically reorganize management of endoscopic procedures for IBD. Conclusions Outbreak restrictions have significantly impacted the volume of endoscopic activities for IBD. Specific strategies have been designed to guarantee a high level of safety for both patients with IBD and healthcare personnel dedicated to their treatment.


title: Biosecurity and bovine respiratory disease

text: Although biosecurity practices play a role in minimizing respiratory disease in cattle, they must be used in combination with other management strategies that address the many other risk factors. Because the pathogens involved in bovine respiratory disease are enzootic in the general cattle population, biosecurity practices aimed at the complete elimination of exposure are currently impractical. Several animal husbandry and production management practices can be used to minimize pathogen shedding, exposure, and transmission within a given population, however. Various combinations of these control measures can be applied to individual farms to help decrease the morbidity and mortality attributed to respiratory disease.


title: Excellent antimicrobial properties of silver‐loaded mesoporous silica SBA‐15

text: AIMS: To synthesize silver‐loaded mesoporous silica SBA‐15 (Ag/SBA‐15) materials and examine their antimicrobial action and antimicrobial mechanism. METHODS AND RESULTS: Ag/SBA‐15 materials were prepared by means of incipient wetness impregnation, impregnation and direct hydrothermal synthesis methods. The antimicrobial activity of Ag/SBA‐15 was investigated using Escherichia coli as an indicator bacterium, and the antimicrobial mechanism was explored. The properties and Ag(+) release behaviour of Ag/SBA‐15 materials were compared. Experimental results showed that Ag/SBA‐15 materials resulted in 7·5 log inactivation of E. coli for only 60 min, which exhibited very high antimicrobial activities at room temperature without using any light or electrical power input. The cell wall and cell membrane were destroyed in the antimicrobial process, leading to leakage of intracellular components. The formation of extracellular reactive oxygen species (ROS) involved in the bactericidal process was confirmed. Production of intracellular ROS was also discovered. CONCLUSIONS: Ag/SBA‐15 exhibited high antimicrobial activity against E. coli. This antimicrobial effect was a synergistic action between extracellular ROS and the toxicity of Ag(+), which induced intracellular ROS production and subsequent cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed for the first time the antimicrobial activities and mechanisms of Ag/SBA‐15 materials prepared with different methods.


title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms

text: At the end of 2019, the entire world has witnessed the birth of a new member of coronavirus family in Wuhan, China. Ever since, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has swiftly invaded every corner on the planet. By the end of April 2020, almost 3.5 million cases have been reported worldwide, with a death toll of about 250000 deaths. It is currently well-recognized that patient’s immune response plays a pivotal role in the pathogenesis of Coronavirus Disease 2019 (COVID-19). This inflammatory element was evidenced by its elevated mediators that, in severe cases, reach their peak in a cytokine storm. Together with the reported markers of liver injury, such hyperinflammatory state may trigger significant derangements in hepatic cytochrome P450 metabolic machinery, and subsequent modulation of drug clearance that may result in unexpected therapeutic/toxic response. We hypothesize that COVID-19 patients are potentially vulnerable to a significant disease-drug interaction, and therefore, suitable dosing guidelines with therapeutic drug monitoring should be implemented to assure optimal clinical outcomes.


title: A Retrospective Study of 17 Cases of Mycobacteriosis in Domestic Ferrets (Mustela Putorius furo) between 2005 and 2013

text: Abstract From 2005 to 2013, 17 ferrets were diagnosed with mycobacteriosis at the authors’ practices. Clinical findings included ocular, respiratory, and digestive abnormalities. Diagnosis was based on histopathology, specific histochemical stains, and/or on polymerase chain reaction. All bacteria identified belonged to the nontuberculous Mycobacterium complex. Several treatment protocols were attempted, frequently based on the use of enrofloxacin. In all, 3 ferrets were considered cured. Mycobacteriosis in ferrets is a polymorphous disease with diverse clinical presentations. It is also likely an underdiagnosed disease in pet ferrets, which appear to be particularly susceptible to environmental sources. Mycobacteriosis should be included in the differential diagnosis for ocular, respiratory, and gastrointestinal diseases; in particular, it should be differentiated from systemic coronavirus infection.


Atypical Presentation of COVID‐19 in an Older Adult: Lethargy and Vomiting from Severe Hypovolemic Hyponatremia


Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States


Peptide-mediated Cell and In Vivo Delivery of Antisense Oligonucleotides and siRNA


title: Pros and cons of corticosteroid therapy for COVID-19 patients

text: In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.


docid: tcgnnggb

title: Experimental infection of dogs (Canis familiaris) with sporulated oocysts of Neospora caninum

text: Abstract Neospora caninum is widely distributed in the world and this parasite is one of the major causes of abortion in cattle. Dogs and coyotes are definitive hosts of N. caninum and several species of domestic and wild animals are intermediate hosts. Dogs can become infected by the ingestion of tissues containing cysts and then excrete oocysts. It is not yet known whether sporulated oocysts are able to induce a patent infection in dogs, i.e. a shedding of N. caninum oocysts in feces. The objective of this study was to experimentally examine the infection of dogs by sporulated oocysts. The oocysts used in the experiment were obtained by feeding dogs with brain of buffaloes (Bubalus bubalis) positive for anti-N. caninum antibodies by indirect fluorescent antibody test (IFAT ≥200). Oocysts shed by these dogs were confirmed to be N. caninum by molecular methods and by bioassay in gerbils, and sporulated N. caninum oocysts were used for the oral infection of four dogs. The dogs were 8 weeks old and negative for antibodies to N. caninum and Toxoplasma gondii. Dogs 1 and 4 received an inoculum of 10,000 sporulated oocysts each; dog 2 an inoculum of 5000 sporulated oocysts and dog 3 received 1000 sporulated oocysts of N. caninum. The total feces excreted by these dogs were collected and examined daily for a period of 30 days. No oocysts were found in their feces. The dogs were monitored monthly for a 6-month period to observe a possible seroconversion and when this occurred the animals were eliminated from the experiment. Dogs 1 and 4 seroconverted 1 month after the infection with titer, in the IFAT, of 1600 and 800, respectively; the other two dogs presented no seroconvertion during the 6-month period. Dogs 1 and 2 were euthanized 180 days after infection and were examined for the detection of N. caninum in tissues (brain, muscle, lymph node, liver, lung, heart and bone marrow) by immunohistochemistry and PCR with negative results in both techniques. Bioassay in gerbils with brain of these dogs was also performed and again the results were negative. In conclusion, dogs infected with sporulated oocysts of N. caninum were not able to shed oocysts in feces. However, a higher dose of infection stimulated the production of antibodies against N. caninum in the dogs.


title: Clinical care for severe influenza and other severe illness in resource‐limited settings: the need for evidence and guidelines

text: The 2009 influenza A (H1N1) pandemic highlighted the importance of quality hospital care of the severely ill, yet there is evidence that the impact of the 2009 pandemic was highest in low‐ and middle‐income countries with fewer resources. Recent data indicate that death and suffering from seasonal influenza and severe illness in general are increased in resource‐limited settings. However, there are limited clinical data and guidelines for the management of influenza and other severe illness in these settings. Life‐saving supportive care through syndromic case management is used successfully in high‐resource intensive care units and in global programs such as the Integrated Management of Childhood Illness (IMCI). While there are a variety of challenges to the management of the severely ill in resource‐limited settings, several new international initiatives have begun to develop syndromic management strategies for these environments, including the World Health Organization's Integrated Management of Adult and Adolescent Illness Program. These standardized clinical guidelines emphasize syndromic case management and do not require high‐resource intensive care units. These efforts must be enhanced by quality clinical research to provide missing evidence and to refine recommendations, which must be carefully integrated into existing healthcare systems. Realizing a sustainable, global impact on death and suffering due to severe influenza and other severe illness necessitates an ongoing and concerted international effort to iteratively generate, implement, and evaluate best‐practice management guidelines for use in resource‐limited settings.


“Regarding ‘Understanding the "Scope" of the Problem: Why Laparoscopy is Considered Safe During the COVID-19 Pandemic.’”


title: A Patient Self-collection Method for Longitudinal Monitoring of Respiratory Virus Infection in Solid Organ Transplant Recipients

text: BACKGROUND: Methods for the longitudinal study of respiratory virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (SOT) recipients. OBJECTIVES: To assess the feasibility and patient acceptability of self-collected foam nasal swabs for detection of respiratory viruses in SOT recipients and to define the virologic and clinical course. STUDY DESIGN: We prospectively monitored the course of symptomatic respiratory virus infection in 18 SOT patients (14 lung, 3 liver, and 1 kidney) using patient self-collected swabs. RESULTS: The initial study sample was positive in 15 patients with the following respiratory viruses: rhinovirus (6), metapneumovirus (1), coronavirus (2), respiratory syncytial virus (2), parainfluenza virus (2), and influenza A virus (2). One hundred four weekly self-collected nasal swabs were obtained, with a median of 4 samples per patient (range 1–17). Median duration of viral detection was 21 days (range 4–77 days). Additional new respiratory viruses detected during follow-up of these 15 patients included rhinovirus (3), metapneumovirus (2), coronavirus (1), respiratory syncytial virus (1), parainfluenza virus (1), and adenovirus (1). Specimen collection compliance was good; 16/18 (89%) patients collected all required specimens and 79/86 (92%) follow-up specimens were obtained within the 7±3 day protocol-defined window. All participants agreed or strongly agreed that the procedure was comfortable, simple, and 13/14 (93%) were willing to participate in future studies using this procedure. CONCLUSION: Self-collected nasal swabs provide a convenient, feasible, and patient-acceptable methodology for longitudinal monitoring of upper respiratory virus infection in SOT recipients.


Spectrum of histopathological findings in coronavirus disease-19, Middle East respiratory syndrome and severe acute respiratory syndrome


Self-risk assessment for patients with rheumatic disease during the COVID-19 pandemic


docid: jcsfbxgu

title: 1 The nature of airports

text: Abstract This chapter presents the historic development of global air transportation. As it is the main function to accommodate this traffic growth, airports have advanced in response to it. First, their role within the air transport system will be described. A picture of their social, environmental, economic and political impact will be given next. This chapter’s feature is on airport products and services.


title: Optimal design of non-equilibrium experiments for genetic network interrogation

text: Abstract Many experimental systems in biology, especially synthetic gene networks, are amenable to perturbations that are controlled by the experimenter. We developed an optimal design algorithm that calculates optimal observation times in conjunction with optimal experimental perturbations in order to maximize the amount of information gained from longitudinal data derived from such experiments. We applied the algorithm to a validated model of a synthetic Brome Mosaic Virus (BMV) gene network and found that optimizing experimental perturbations may substantially decrease uncertainty in estimating BMV model parameters.


title: Persistent Value of the Stethoscope in the Age of COVID-19

text: The stethoscope has long been at the center of patient care as well as a symbol of the physician-patient relationship. While advancements in other diagnostic modalities have allowed for more efficient and accurate diagnosis, the stethoscope has evolved in parallel to address the needs of the modern era of medicine. These advancements include sound visualization, ambient noise reduction/cancellation, Bluetooth™ transmission, and computer algorithm diagnostic support. However, despite these advancements, the ever-changing climate of infection prevention, especially in the wake of the COVID-19 pandemic, has led many to question the stethoscope as a vector for infectious diseases. Stethoscopes have been reported to harbor bacteria with contamination levels comparable to a physician's hand. Although disinfection is recommended, stethoscope hygiene compliance remains low. In addition, disinfectants may not be completely effective in eliminating microorganisms. Despite these risks, the growing technological integration with the stethoscope continues to make it a highly valuable tool. Rather than casting our valuable tool and symbol of medicine aside, we must create and implement an effective method of stethoscope hygiene to keep patients safe. • Stethoscopes are clinically valuable and integral to the doctor-patient connection; • Technological advancement will augment the utility of the stethoscope; • The stethoscope has high utility for assessment of COVID-19 patients; • Pathogen contamination in light of COVID-19 is a concern for the stethoscope; • Innovations in stethoscope hygiene will allow safe auscultation.


title: Protein folding liquid chromatography and its recent developments

text: Abstract The ultimate goal of proteomics is to identify biologically active proteins and to produce them using biotechnology tools such as bacterial hosts. However, proteins produced by Escherichia coli must be refolded to their native state. Protein folding liquid chromatography (PFLC) is a new method developed in recent years, and it is widely used in molecular biology and biotechnology. In this paper, the new method, PFLC is introduced and its recent development is reviewed. In addition the paper includes definitions, advantages, principles, applications for both laboratory and large scales, apparatus, and effecting factors of PFLC. In addition, the role of this method in the future is examined.


title: Recuperando las coberturas vacunales perdidas en la pandemia COVID-19

text: RESUMEN La pandemia de la enfermedad por coronavirus 2019 puede tener un impacto alarmante en las coberturas de vacunación. La OMS, la UNICEF y la Gavi advierten de que al menos 80 millones de niños menores de 1 año corren el riesgo de contraer enfermedades como la difteria, el sarampión y la poliomielitis por la interrupción de la inmunización sistemática y la suspensión temporal de 93 campañas de vacunación a gran escala. En España, un nuevo escenario asistencial, que prioriza lo telemático sobre lo presencial, el miedo al contagio por acudir a los centros sanitarios y las recomendaciones de distanciamiento físico y de movilidad restringida, reducen la asistencia a los centros de atención primaria. A pesar de las recomendaciones establecidas por las autoridades sanitarias, las coberturas vacunales han descendido en todas las comunidades autónomas entre un 5% y un 60%, dependiendo de la edad y del tipo de vacuna. Las vacunaciones en las escuelas se han suspendido y solo se ha mantenido, en general, la cobertura de la vacuna frente al tétanos, la difteria y la tosferina en las embarazadas. La disminución ha sido más manifiesta para las vacunas no financiadas: la primera dosis de vacuna antimeningocócica B disminuyó un 68,4% en la Comunidad Valenciana, y en Andalucía se observó un descenso de las dosis totales de esta vacuna (39%) y de la del rotavirus (18%). La reanudación de las vacunaciones debe ser planificada, organizaday realizada en el menor tiempo posible. En este artículo se comentan algunos aspectos de la recuperación de las coberturas vacunales para diferentes grupos: niños, adolescentes y adultos, y pacientes de riesgo y en situaciones especiales. Abstract The 2019 coronavirus disease pandemic can have an alarming impact on vaccination coverage. WHO, UNICEF and Gavi warn that at least 80 million children under the age of 1 are at risk of contracting diseases such as diphtheria, measles and polio due to the interruption of routine immunization and the temporary suspension of 93 campaigns of large-scale vaccination. In Spain, a new healthcare scenario, which prioritizes telematics over in person, fear of contagion by going to health centers, and recommendations for physical distance and restricted mobility, reduce attendance at primary care centers. Despite recommendations established by the health authorities, vaccination coverage has decreased in all Autonomous Communities between 5% and 60%, depending on the age and type of vaccine. School vaccinations have been suspended and only vaccination of pregnant women against tetanus, diphtheria and pertussis has been maintained. The decrease has been more evident for non gratuity vaccines: the first dose of meningococcal vaccine B has decreased by 68.4% in the Valencian Community, and Andalusia has observed a 39% decrease in the total doses of this vaccine and of 18% for that of rotavirus. The recovering of vaccinations should be planned, organized and carried out in the shortest possible time. This article discusses some aspects of the recovery of vaccination coverage for different groups: children, adolescents and adults, and patients at risk and in special situations.


title: Dorsal spinous process impingement syndrome (‘kissing spine’) in a cat: imaging appearance and surgical management

text: Spinal pain is an important clinical presentation in feline patients, but the underlying causes can often be difficult to elucidate. Dorsal spinous process impingement syndrome (‘kissing spine’ or in human patients ‘Baastrup syndrome’) is a significant cause of spinal pain in equine and human patients and radiographically is characterised by a close approximation of adjacent spinous processes with reactive bone sclerosis affecting these spinous processes. In this report we describe the first reported case of dorsal spinous process impingement syndrome in a cat causing spinal pain, and successful surgical management of the syndrome. The affected cat presented at 5 years of age for evaluation of a 7-month history of progressive thoracolumbar pain. Radiographs revealed close approximation of the dorsal spinous processes of the seventh, eighth and ninth thoracic vertebrae (T7, T8 and T9), with associated reactive bone sclerosis. Surgical resection of the T8 dorsal spinous process resulted in complete resolution of the clinical signs with no evidence of recurrence 9 months after surgery.


title: A health concern regarding the protein corona, aggregation and disaggregation

text: Abstract Nanoparticle (NP)–protein complexes exhibit the “correct identity” of NP in biological media. Therefore, protein–NP interactions should be closely explored to understand and modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, morphology of NPs, and influence of pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of techniques. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH, and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP–protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in vivo.


title: Induction and control of the type I interferon pathway by Bluetongue virus

text: Abstract The innate immune response is the first line of defence against viruses, involving the production of type I IFN (IFN-α/β) and other pro-inflammatory cytokines that control the infection. It also shapes the adaptive immune response generated by both T and B cells. Production of type I IFN occurs both in vivo and in vitro in response to Bluetongue virus (BTV), an arthropod-borne virus. However, the mechanisms responsible for the production of IFN-β in response to BTV remained unknown until recently and are still not completely understood. In this review, we describe the recent advances in the identification of cellular sensors and signalling pathways involved in this process. The RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) were shown to be involved in the expression of IFN-β as well as in the control of BTV infection in non-haematopoietic cells. In contrast, induction of IFN-α/β synthesis in sheep primary plasmacytoid dendritic cells (pDCs) required the MyD88 adaptor independently of the Toll-like receptor 7 (TLR7), as well as the kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK). As type I IFN is essential for the establishment of an antiviral cellular response, most of viruses have elaborated counteracting mechanisms to hinder its action. This review also addresses the ability of BTV to interfere with IFN-β synthesis and the recent findings describing the non-structural viral protein NS3 as a powerful antagonist of the host cellular response.


title: NK cells: A double edge sword against SARS-CoV-2

text: Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).


docid: gwnfcfvk

title: Virus–host interaction in feline immunodeficiency virus (FIV) infection

text: Abstract Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus–host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections.


docid: imtttzvr

title: Glycosylation and oligomerization of the spike protein of marburg virus

text: Abstract The oligosaccharide side chains of the glycoprotein of Marburg virus (MW 170,000) have been analyzed by determining their sensitivity to enzymatic degradation and their reactivity with lectins. It was found that they consist of N- and O-glycans. Studies employing chemical cross-linking showed that the glycoprotein is present as a homotrimer in the viral envelope.


title: Surveillance strategy for early detection of unusual infectious disease events

text: New pathogens continue to emerge, and the increased connectedness of populations across the globe through international travel and trade favors rapid dispersal of any new disease. The ability to respond to such events has increased but the question is what ‘preparedness’ means at the level of the clinician. Clinicians deal with patients with unexplained illness on a daily basis, and even with syndromes highly indicative of infectious diseases, the cause of illness is often not detected, unless extensive and costly diagnostic work-ups are done. This review discusses innovations in diagnostics and surveillance aimed at early detection of unusual disease. Risk based approaches are promising, but optimal preparedness planning requires multidisciplinary partnerships across domains, and a global translational research agenda to develop tools, systems, and evidence for interventions.


title: Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins

text: The crystal structure of the reovirus attachment protein, σ1, reveals a fibre‐like structure that is remarkably similar to that of the adenovirus attachment protein, fibre. Both proteins are trimers with head‐and‐tail morphology. They share unique domain structures and functional properties including defined regions of flexibility within the tail and an unusual symmetry mismatch with the pentameric viral capsid protein into which they are inserted. Moreover, the receptors for reoviruses and adenoviruses, junctional adhesion molecule 1 and coxsackievirus and adenovirus receptor, respectively, also share key structural and functional properties. Although reoviruses and adenoviruses belong to different virus families and have few properties in common, the observed similarities between σ1 and fibre point to a conserved mechanism of attachment and an ancient evolutionary relationship. Copyright © 2003 John Wiley & Sons, Ltd.


title: Early Cytokine mRNA Expression Profiles Predict Morbillivirus Disease Outcome in Ferrets

text: Severe immunosuppression is a hallmark of Morbillivirus infections. To study the underlying mechanisms, we have developed a ferret model of canine distemper virus infection. The model reproduces all clinical signs of measles, but the lack of ferret-specific reagents has limited the characterization of the cellular immune response. Towards this, we cloned ferret cytokines and established semi-quantitative real-time PCR assays. To demonstrate the utility of these assays we compared the cytokine profiles elicited by lethal and non-lethal strains during the prodromal phase. We observed a general lack of cytokine induction in animals that later succumbed to the disease, whereas survivors mounted a robust and sustained response. The newly developed cytokine assays strengthen and expand the ferret model not only for Morbillivirus pathogenesis studies but also for several other human respiratory viruses including influenza and SARS.


title: Aerosol emission and superemission during human speech increase with voice loudness

text: Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm(3)) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as “speech superemitters,” consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.


title: Role of Telecom Network to Manage COVID-19 in India: Aarogya Setu

text: Concerted Research, Development and Innovation have enabled telecom and Internet reach most of the 1.3 billion people in India at a price-point that they can afford. This telecom network is being used for a whole lot of application today providing a large variety of services like education, health care, financial inclusion and disaster management. In almost all crisis situation like that created by coronavirus, one finds that telecom network can be leveraged to offer help to the needy, administration and coordinators to better manage the disaster. Aarogya Setu for smartphones and Aarogya Setu for feature phones are two such efforts, which are potentially going to help in this difficult situation.


docid: izxhiusf

title: In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis

text: BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician. We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 10(4) colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.


title: Potential Triggers of MS

text: MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. The primary cause of this CNS disease remains elusive. Here we will address our current understanding of the role of viruses as potential environmental triggers for MS. Virus infections can act peripherally (outside the CNS) or within the CNS. The association of viral infections with demyelinating disease, in both animals and humans, will be discussed, as will the potential contributions of peripheral infection with Torque Teno virus, infection outside of and/or within the CNS with Epstein-Barr virus and infection within the CNS with Human Herpesvirus 6 to MS. An experimental animal model, Theiler’s murine encephalomyelitis virus infection of susceptible strains of mice is an example of viral infections of the CNS as a prerequisite for demyelination. Finally, the proposition that multiple virus infections, which first prime the immune system and then trigger the disease, as a model where infections outside of the CNS lead to inflammatory changes within the CNS, are required for the development of a MS-like disease is explored.


title: Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

text: Abstract Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CLpro of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R1 or R4 destabilizes the oxyanion hole in the 3CLpro. Interestingly, 3f, 3g and 3m could inhibit both NA and 3CLpro and serve as a starting point to develop broad-spectrum antiviral agents.


title: Dengue research: a bibliometric analysis of worldwide and Arab publications during 1872–2015

text: BACKGROUND: Dengue is an important emerging and re-emerging arboviral infection globally as a rapidly growing and widespread public health problem, with transmission occurring in more than 128 countries in Asia, Americas, southeast Africa, western Pacific, and eastern Mediterranean regions. Therefore, the aim of this study was to characterize and quantify the scientific output of dengue research in Arab countries relative to that worldwide by using a bibliometric analysis. METHODS: The standardized search approach based on the use of the the keyword “dengue” in the title, abstract, and keyword field was used to get research output related to dengue at a global level. All data related to dengue were collected from the past to December 31, 2015. RESULTS: A total of 19,581 dengue-related documents identified in the Scopus database. The results show that the study of dengue exhibits an overall upward trend from 1872 to 2015 with peak publications in 2014. The leading countries in dengue research were the USA (4,709; 24.05 %), India (1,942; 9.92 %), Brazil (1,530; 7.81 %), Thailand (1,260; 6.43 %), the UK (1,129; 5.77 %), and France (1,087; 5.55 %). Only 226 (1.16 % of the overall global research effort in the dengue field) articles were published from the Arab region. The total number of citations for all publications was 352,710, with an average of 18.0 citations per publication. Furthermore, the h-index for all extracted data related to dengue research was 186. Kingdom of Saudi Arabia (KSA) was the most productive country in Arab region with 102 documents representing 45.1 %. Furthermore, the h-index for all extracted data related to dengue research was 27. The USA was Arab’s most main cooperative partner (46, 20.4 %), followed by India (36, 15.9 %). CONCLUSIONS: The amount of literature related to dengue research has considerably increased over the last decade. This bibliometric analysis has demonstrated the leading role that the USA, India, Brazil, Thailand, the UK, and France play in dengue research. The Arab world produced fewer publications related to dengue with lower quality than other world countries.


title: Reaction Cycles of Halogen Species in the Immune Defense: Implications for Human Health and Diseases and the Pathology and Treatment of COVID-19

text: There is no vaccine or specific antiviral treatment for COVID-19. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. It is therefore challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.


COVID-19 - Journal de Bord – 11/04/2020: Masque chirurgical et autres protections


title: Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma

text: Background Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. Objective To study whether RSV or RV types are differentially associated with the future use of asthma control medication. Methods Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. Results A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03). Conclusions Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.


title: Generation and characterisation of monoclonal antibodies against influenza virus A, subtype H5N1

text: Abstract The emergence of highly pathogenic avian influenza A virus (HPAIV) subtype H5N1 in 1997 has since resulted in large outbreaks in poultry and in transmission from poultry to humans, mostly in southeast Asia, but also in several European countries. Effective diagnosis and control measures are essential for the management of HPAIV infections. To develop a rapid diagnostic test, a panel of murine monoclonal antibodies (mAbs) against influenza virus A subtype H5 was generated. Eleven mAbs were produced and characterised according to their reactivity by indirect and sandwich ELISA and western blotting against different H5 subtypes representing past and viruses currently circulating. Ten out of 11 mAbs reacted strongly with the haemagglutinin (HA) protein of H5 viruses, whereas one mAb reacted with the M1 protein. Targeted HA protein epitopes seemed to be conformational. One hybridoma clone binds to a linear epitope of the M1 protein. One specific mAb reacts with HPAIV H5 in the immunofluorescence test, and two antibodies neutralised H5 viruses. On the basis of the results, the set of seven mAbs is appropriate for developing diagnostic tests. With the generated mAbs, a sandwich ELISA was developed recognising all H5N1 strains tested but no other influenza viruses. With this ELISA, as little as 0.005 HA units or 0.1ng/ml H5N1 was detected, surpassing other ELISA tests. The novel reagents have the potential to improve significantly available rapid antigen detection systems.


title: The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

text: Abstract The physiological and pharmacological role of nucleic acids structures folded into the non canonical G-quadruplex conformation have recently emerged. Their activities are targeted at vital cellular processes including telomere maintenance, regulation of transcription and processing of the pre-messenger or telomeric RNA. In addition, severe conditions like cancer, fragile X syndrome, Bloom syndrome, Werner syndrome and Fanconi anemia J are related to genomic defects that involve G-quadruplex forming sequences. In this connection G-quadruplex recognition and processing by nucleic acid directed proteins and enzymes represents a key event to activate or deactivate physiological or pathological pathways. In this review we examine protein-G-quadruplex recognition in physiologically significant conditions and discuss how to possibly exploit the interactions’ selectivity for targeted therapeutic intervention.


title: Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan

text: BACKGROUND: Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. METHODS: Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. RESULTS: The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. CONCLUSIONS: The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.


title: Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

text: BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can cause acute inflammation. Long noncoding RNAs (lncRNAs) play important roles in a number of biological process including inflammation response. However, whether lncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells (IPECs) is largely unknown. RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of lncRNAs in Mock and TGEV-infected porcine intestinal epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 106 lncRNAs were differentially expressed. Many differentially expressed lncRNAs act as elements to competitively attach microRNAs (miRNAs) which target to messenger RNA (mRNAs) to mediate expression of genes that related to toll-like receptors (TLRs), NOD-like receptors (NLRs), tumor necrosis factor (TNF), and RIG-I-like receptors (RLRs) pathways. Functional analysis of the binding proteins and the up/down-stream genes of the differentially expressed lncRNAs revealed that lncRNAs were principally related to inflammatory response. Meanwhile, we found that the differentially expressed lncRNA TCONS_00058367 might lead to a reduction of phosphorylation of transcription factor p65 (p-p65) in TGEV-infected IPEC-J2 cells by negatively regulating its antisense gene promyelocytic leukemia (PML). CONCLUSIONS: The data showed that differentially expressed lncRNAs might be involved in inflammatory response induced by TGEV through acting as miRNA sponges, regulating their up/down-stream genes, or directly binding proteins.


Isolation of a Coronavirus from Urinary Tract Tumours of Endemic Balkan Nephropathy Patients