title: Wild canids as sentinels of ecological health: a conservation medicine perspective

text: The extinction of species across the globe is accelerating, directly or indirectly due to human activities. Biological impoverishment, habitat fragmentation, climate change, increasing toxification, and the rapid global movement of people and other living organisms have worked synergistically to diminish ecosystem function. This has resulted in unprecedented levels of disease emergence, driven by human-induced environmental degradation, which poses a threat to the survival and health of biodiversity. The emerging discipline of conservation medicine addresses these concerns through the following entities: humans; global climate; habitat destruction and alteration; biodiversity, including wildlife populations; domestic animals; and pathogens, parasites and pollutants. Furthermore, conservation medicine focuses on explicit linkages between these entities. As a crisis discipline, the usefulness of conservation medicine ultimately will depend on its applicability to solving problems. The perspectives and scientific findings of conservation medicine provide input into biomedical education; and policy and management of ecosystems, habitats and imperiled species. A sentinel species is one that has presented itself, or has been selected, to provide insight into the state (health) of an ecosystem, based on user-defined (e.g., researchers, conservationists or policymakers) objectives (e.g., disease, parasites, toxics, climate change, habitat destruction), coupled with the utility and vulnerability of this species to the perceived stress. The scientific information generated by the sentinel species should empower stakeholders and decision-makers to take mitigative action or support predictive capabilities; the "utility" of the species selected should consider its value and relevance to conservationists and to society at large (e.g., education and outreach; social sciences). Wild canids may serve as excellent sentinel species of emerging canine vector-borne diseases. Several canine vector-borne diseases or antibodies to these pathogens have been identified in wild canids including visceral leishmaniosis, Lyme disease, heartworm, hepatozoonosis and anaplasmosis to name a few. These reports are relatively recent as they relate to wildlife-domestic animal interactions, globalisation, translocations, habitat fragmentation and climate change. These pathogens and their relationship to wild canids are described herein. Further research needs to be performed to elucidate the role of the 36 extant species of wild canids in the epidemiology of canine vector-borne diseases.


title: [Risk assessment of exported risk of novel coronavirus pneumonia from Hubei Province].

text: Objective: To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion: The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.


title: Human bocavirus in children with acute lymphoblastic leukemia

text: A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.


title: Aerosol containment box to the rescue: extra protection for the front line

text: As the COVID-19 pandemic has created shortages of vital personal protective equipment that threatens healthcare workers’ risk of exposure, a need for innovative new ways to protect healthcare workers has emerged. An aerosol containment box that covers the patient’s head and neck in bed provides a solution to protect clinicians during aerosol-generating procedures such as intubation. We collaborated with original designer HYL and modified the size to adapt to larger patients and operator mobility. We expand its applicability by allowing the use of different instruments. The container is outfitted with an ultra-low particulate air-equipped filtration vacuum device to create negative pressure within the chamber and actively remove floating droplet nuclei generated during a procedure. This barrier method will be a valuable and economical option to protect healthcare workers on the front line globally during this pandemic and beyond.


title: Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy

text: Recently Simmons et al. reported a new mechanism for SARS virus entry into target cells, where MDL28170 was identified as an efficient inhibitor of CTSL-meditated substrate cleavage with IC(50) of 2.5 nmol/l. Based on the molecule fingerprint searching method, 11 natural molecules were found in the Traditional Chinese Medicines Database (TCMD). Molecular simulation indicates that the MOL376 (a compound derived from a Chinese medicine herb with the therapeutic efficacy on the human body such as relieving cough, removing the phlegm, and relieving asthma) has not only the highest binding energy with the receptor but also the good match in geometric conformation. It was observed through docking studies that the van der Waals interactions made substantial contributions to the affinity, and that the receptor active pocket was too large for MDL21870 but more suitable for MOL736. Accordingly, MOL736 might possibly become a promising lead compound for CTSL inhibition for SARS therapy.


title: Structure and Cleavage Specificity of the Chymotrypsin-Like Serine Protease (3CLSP/nsp4) of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

text: Summary Biogenesis and replication of the porcine reproductive and respiratory syndrome virus (PRRSV) include the crucial step of replicative polyprotein processing by self-encoded proteases. Whole genome bioinformatics analysis suggests that nonstructural protein 4 (nsp4) is a 3C-like serine protease (3CLSP), responsible for most of the nonstructural protein processing. The gene encoding this protease was cloned and expressed in Escherichia coli in order to confirm this prediction. The purified protein was crystallized, and the structure was solved at 1.9 Å resolution. In addition, the crystal structure of the Ser118Ala mutant was determined at 2.0 Å resolution. The monomeric enzyme folds into three domains, similar to that of the homologous protease of equine arteritis virus, which, like PRRSV, is a member of the family Arteriviridae in the order of Nidovirales. The active site of the PRRSV 3CLSP is located between domains I and II and harbors a canonical catalytic triad comprising Ser118, His39, and Asp64. The structure also shows an atypical oxyanion hole and a partially collapsed S1 specificity pocket. The proteolytic activity of the purified protein was assessed in vitro. Three sites joining nonstructural protein domains in the PRRSV replicative polyprotein are confirmed to be processed by the enzyme. Two of them, the nsp3/nsp4 and nsp11/nsp12 junctions, are shown to be cleaved in trans, while cis cleavage is demonstrated for the nsp4/nsp5 linker. Thus, we provide structural evidence as well as enzymatic proof of the nsp4 protein being a functional 3CLSP. We also show that the enzyme has a strong preference for glutamic acid at the P1 position of the substrate.


title: Integrated Polymerase Chain Reaction Technologies (Sample-to-Answer Technologies)

text: The tools available for both infectious disease diagnostics and human identity testing have benefitted from major technological advances in the automation of nucleic acid purification, amplification, and detection methods. The seamless integration of these processes into a fully automated microscale format has led to the development of rapid, user-friendly sample-to-answer assay systems. The application of these systems for human identity testing allows for DNA profiles to be generated in a field-forward environment where they can be used to generate investigative leads in crimes or other actionable intelligence. When used for infectious disease diagnostics, the sensitivity and specificity of these assay systems meets or exceeds that of more conventional strategies for the detection of respiratory, gastrointestinal, nervous system, and sexually transmitted pathogens. The anticipated medical benefits of this technology include shorter hospital stays, the elimination of unnecessary or ineffectual treatment, improved patient outcomes, and an overall quantifiable reduction in healthcare costs.


title: A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis

text: [Image: see text] Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations.


title: HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2

text: To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 −174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.


title: Prioritising access to pandemic influenza vaccine: a review of the ethics literature

text: BACKGROUND: The world is threatened by future pandemics. Vaccines can play a key role in preventing harm, but there will inevitably be shortages because there is no possibility of advance stockpiling. We therefore need some method of prioritising access. MAIN TEXT: This paper reports a critical interpretative review of the published literature that discusses ethical arguments used to justify how we could prioritise vaccine during an influenza pandemic. We found that the focus of the literature was often on proposing different groups as priorities (e.g. those with pre-existing health conditions, the young, the old, health care workers etc.). Different reasons were often suggested as a means of justifying such priority groupings (e.g. appeal to best overall outcomes, fairness, belonging to a vulnerable or ‘at risk’ group etc.). We suggest that much of the literature, wrongly, assumes that we are able to plan priority groups prior to the time of a particular pandemic and development of a particular vaccine. We also point out the surprising absence of various issues from the literature (e.g. how vaccines fit within overall pandemic planning, a lack of specificity about place, issues of global justice etc.). CONCLUSIONS: The literature proposes a wide range of ways to prioritise vaccines, focusing on different groups and ‘principles’. Any plan to use pandemic vaccine must provide justifications for its prioritisation. The focus of this review was influenza pandemic vaccines, but lessons can be learnt for future allocations of coronavirus vaccine, if one becomes available.


title: Couverture vaccinale et mort inattendue du nourrisson. Étude prospective nationale

text: Introduction Alors que la France traverse une période de scepticisme vaccinal globalement préjudiciable à la couverture vaccinale, un observatoire national des morts inattendues du nourrisson (OMIN) collige de nouvelles données prospectives concernant la couverture vaccinale et le rôle potentiel d’agent infectieux dans ces décès, dans le but de mieux en comprendre la physiopathologie et de proposer des pistes de prévention adaptées. Matériels et méthodes Étude sur 2 ans (2015–2016), prospective, observationnelle, incluant toutes les MIN, admises dans l’un des 21 centres de référence de la mort inattendue du nourrisson (CRMIN). Le statut vaccinal des nourrissons est défini comme « à jour » ou avec un « retard vaccinal potentiellement dangereux » selon les délais définis par Dubos et al., ou « non vacciné », ou « non en âge d’être vacciné ». Les prélèvements bactériologiques et virologiques des voies respiratoires ont été réalisés lors de l’admission en CRMIN et caractérisés par le site du prélèvement (aspirations nasales, poumons, plèvres) et l’existence d’un germe potentiellement pathogène. Résultats Les 127 nourrissons inclus avaient un âge médian au jour du décès de 103jours (IC±22,5). Sex-ratio de 1,4 (H/F). Pour le vaccin pentavalent, le vaccin anti-hépatite B et le vaccin antipneumococcique, le statut vaccinal moyen est « à jour » pour 46 % (n =59±0), « non vacciné » pour 13 % (n =16±3), « retard potentiellement dangereux » pour 1,8 % (n =2,3±0,4), « non en âge d’être vacciné » pour 31 % (n =40±0) Les données sont inconnues pour 8,2 % (n =10±0,1) des cas. Les prélèvements respiratoires virologiques sont positifs chez 26 % (n =33) des cas. Les 48 prélèvements respiratoires positifs identifient 44 % (n =21) de rhinovirus, 15 % (n =7) de bocavirus, 8 % (n =4) de coronavirus et d’entérovirus, 6 % (n =3) de VRS. Les prélèvements respiratoires bactériologiques sont positifs dans 32 % (n =41) des cas. Les 58 prélèvements respiratoires positifs rapportent 43 % (n =25) d’entérobactéries, 14 % (n =8) d’Haemophilus spp., 12 % (n =7) de Staphylococcus aureus, 10 % (n =6) de Streptococcus pneumoniae, 7 % (n =4) de Bordetella spp. Conclusion Ces premiers résultats chez des enfants admis pour MIN montrent une couverture vaccinale insuffisante (46 %) comparable aux données déjà rapportées dans cette population mais inférieure à celle de la population générale (60 % selon Vennemann et al.). La notion de « retard vaccinal potentiellement dangereux » permet d’introduire une notion de délai dans l’analyse de la vaccination correspondant mieux au processus d’immunisation. La présence de bactérie ou virus dans les voies aérienne est fréquente (respectivement 32 % et 26 %), leur implication dans la survenue du décès mérite d’être investiguée car certains sont accessibles à une prévention vaccinale. Le rôle potentiel protecteur de la vaccination dans la MIN pourrait faire l’objet d’une étude cas-témoins.


title: Performing the nasopharyngeal and oropharyngeal swab for 2019‐novel coronavirus (SARS‐CoV‐2) safely: How to dress, undress, and technical notes

text: BACKGROUND: To show how to safely perform nasopharyngeal and/or oropharyngeal swabs for 2019‐novel coronavirus. METHODS: The video describes in detail the dressing and undressing procedures of health personnel, with the appropriate personal protective equipment. Technical notes for the execution of the nasopharyngeal and oropharyngeal swab are also provided to avoid sampling errors. RESULTS: The undressing phase is the procedure with the highest risk of self‐contamination for the health worker. Following the various steps as shown in the video, there were no cases of contagion among the otolaryngology team appointed to perform the swabs for SARS‐CoV‐2 testing. CONCLUSIONS: This study demonstrates the technical feasibility of safely performing nasopharyngeal and/or oropharyngeal swabs for identification of SARS‐CoV‐2 viral RNA.


“Care for patients with ventricular assist devices and suspected COVID‐19 infection”


Clinical role of respiratory virus infection in acute otitis media Arola M.; Ruuskanen O.; Ziegler T.; Mertsola J.; Nanto-Salonen K.; Putto-Laurila A.; Viljanen M.K.; Halonen P. Pediatrics (1990) 86/6 (848–855)


title: SARS-like cluster of circulating bat coronavirus pose threat for human emergence

text: The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARS-like CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations.


title: Presentation of pulmonary infection on CT in COVID-19: initial experience in Brazil.

text: The disease caused by the new coronavirus (SARS-CoV-2), designated COVID-19, emerged in late 2019 in China, in the city of Wuhan (Hubei province), and showed exponential growth in that country. It subsequently spread to all continents, and infection with SARS-CoV-2 is now classified as a pandemic. Given the magnitude achieved, scientific interest in COVID-19 has also grown in the international literature, including its manifestations on imaging studies, particularly on CT. To date, no case series have been published in Brazil. Therefore, our objective was to describe the CT findings in an initial series of 12 patients.


title: Dual detection of Legionella pneumophila and Legionella species by real-time PCR targeting the 23S-5S rRNA gene spacer region

text: Abstract Although the majority of cases of Legionnaires’ disease (LD) are caused by Legionella pneumophila, an increasing number of other Legionella species have been reported to cause human disease. There are no clinical presentations unique to LD and hence accurate laboratory tests are required for early diagnosis. Therefore, we designed a real-time PCR assay that targets the 23S-5S rRNA intergenic spacer region (23S-5S PCR) and allows for detection of all Legionella species and discrimination of L. pneumophila from other Legionella species. In total, 271 isolates representing 50 Legionella species were tested and the assay was validated using 39 culture-positive and 110 culture-negative patient specimens collected between 1989 and 2006. PCR-positive results were obtained with all 39 culture-positive samples (100% sensitivity). Specimens that tested positive according to 23S-5S PCR, but were culture-negative, were further analysed by DNA sequencing of the amplicon or the macrophage infectivity potentiator (mip) gene. In addition to L. pneumophila, Legionella longbeachae, Legionella cincinnatiensis and Legionella micdadei were identified in the specimens. The assay showed a 7-log dynamic range displaying a sensitivity of 7.5 CFU/mL or three genome equivalents per reaction. Sixty-one specimens containing viruses or bacteria other than Legionellae were negative according to 23S-5S PCR, demonstrating its specificity. Use of this assay should contribute to the earlier detection of respiratory disease caused by Legionella species, as well as to increased rates of detection.


title: COVID‐19 and psoriasis: Should we fear for patients treated with biologics?

text: The new coronavirus pandemic poses question and challenges for dermatologists. One of question is if psoriasis patients treated with immunomodulating and immunosuppressive drugs have to discontinue their treatment in the midst of fears for the infection and its consequences. One of the challenges is how can we support our patients in this critical time. Previous coronaviruses outbreaks reports, current published evidences on pathogenesis and on clinical reports of COVID infection in immunosuppressed patients are used to make a scientifically based decision.


title: An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus

text: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The virus that causes FIP (FIPV) is believed to occur sporadically and spread infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with typical signs of FIP were identified. Among them, seven cats were confirmed by necropsy and/or histopathological examinations. Despite the fact that more than one FCoV was identified in this multi-cat environment, the eight FIP cats were invariably found to be infected with a type II FCoV. Sequence analysis revealed that the type II FIPV detected from fecal samples, body effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene. Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene. Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death. Taken together, our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment.


title: Simultaneous detection of fourteen respiratory viruses in clinical specimens by two multiplex reverse transcription nested‐PCR assays

text: There is a need for rapid, sensitive, and accurate diagnosis of lower respiratory tract infections in children, elderly, and immunocompromised patients, who are susceptible to serious complications. The multiplex RT‐nested PCR assay has been used widely for simultaneous detection of non‐related viruses involved in infectious diseases because of its high specificity and sensitivity. A new multiplex RT‐PCR assay is described in this report. This approach includes nested primer sets targeted to conserve regions of human parainfluenza virus haemagglutinin, human coronavirus spike protein, and human enterovirus and rhinovirus polyprotein genes. It permits rapid, sensitive, and simultaneous detection and typing of the four types of parainfluenza viruses (1, 2, 3, 4AB), human coronavirus 229E and OC43, and the generic detection of enteroviruses and rhinoviruses. The testing of 201 clinical specimens with this multiplex assay along with other one formerly described by our group to simultaneously detect and type the influenza viruses, respiratory syncytial viruses, and a generic detection of all serotypes of adenovirus, covers the detection of most viruses causing respiratory infectious disease in humans. The results obtained were compared with conventional viral culture, immunofluorescence assay, and a third multiplex RT‐PCR assay for all human parainfluenza viruses types described previously. In conclusion, both multiplex RT‐PCR assays provide a system capable of detecting and identifying simultaneously 14 different respiratory viruses in clinical specimens with high sensitivity and specificity, being useful for routine diagnosis and survey of these viruses within the population. J. Med. Virol. 72:484–495, 2004. © 2004 Wiley‐Liss, Inc.


title: Trustworthy Health-Related Tweets on Social Media in Saudi Arabia: Tweet Metadata Analysis

text: BACKGROUND: Social media platforms play a vital role in the dissemination of health information. However, evidence suggests that a high proportion of Twitter posts (ie, tweets) are not necessarily accurate, and many studies suggest that tweets do not need to be accurate, or at least evidence based, to receive traction. This is a dangerous combination in the sphere of health information. OBJECTIVE: The first objective of this study is to examine health-related tweets originating from Saudi Arabia in terms of their accuracy. The second objective is to find factors that relate to the accuracy and dissemination of these tweets, thereby enabling the identification of ways to enhance the dissemination of accurate tweets. The initial findings from this study and methodological improvements will then be employed in a larger-scale study that will address these issues in more detail. METHODS: A health lexicon was used to extract health-related tweets using the Twitter application programming interface and the results were further filtered manually. A total of 300 tweets were each labeled by two medical doctors; the doctors agreed that 109 tweets were either accurate or inaccurate. Other measures were taken from these tweets’ metadata to see if there was any relationship between the measures and either the accuracy or the dissemination of the tweets. The entire range of this metadata was analyzed using Python, version 3.6.5 (Python Software Foundation), to answer the research questions posed. RESULTS: A total of 34 out of 109 tweets (31.2%) in the dataset used in this study were classified as untrustworthy health information. These came mainly from users with a non-health care background and social media accounts that had no corresponding physical (ie, organization) manifestation. Unsurprisingly, we found that traditionally trusted health sources were more likely to tweet accurate health information than other users. Likewise, these provisional results suggest that tweets posted in the morning are more trustworthy than tweets posted at night, possibly corresponding to official and casual posts, respectively. Our results also suggest that the crowd was quite good at identifying trustworthy information sources, as evidenced by the number of times a tweet’s author was tagged as favorited by the community. CONCLUSIONS: The results indicate some initially surprising factors that might correlate with the accuracy of tweets and their dissemination. For example, the time a tweet was posted correlated with its accuracy, which may reflect a difference between professional (ie, morning) and hobbyist (ie, evening) tweets. More surprisingly, tweets containing a kashida—a decorative element in Arabic writing used to justify the text within lines—were more likely to be disseminated through retweets. These findings will be further assessed using data analysis techniques on a much larger dataset in future work.


title: Domain-Swapped Structure of the Potent Antiviral Protein Griffithsin and Its Mode of Carbohydrate Binding

text: Summary The crystal structure of griffithsin, an antiviral lectin from the red alga Griffithsia sp., was solved and refined at 1.3 Å resolution for the free protein and 0.94 Å for a complex with mannose. Griffithsin molecules form a domain-swapped dimer, in which two β strands of one molecule complete a β prism consisting of three four-stranded sheets, with an approximate 3-fold axis, of another molecule. The structure of each monomer bears close resemblance to jacalin-related lectins, but its dimeric structure is unique. The structures of complexes of griffithsin with mannose and N-acetylglucosamine defined the locations of three almost identical carbohydrate binding sites on each monomer. We have also shown that griffithsin is a potent inhibitor of the coronavirus responsible for severe acute respiratory syndrome (SARS). Antiviral potency of griffithsin is likely due to the presence of multiple, similar sugar binding sites that provide redundant attachment points for complex carbohydrate molecules present on viral envelopes.


Abstract 35. Coronavirus infection in rats: induction of an autoimmune response against brain antigen


title: Severe Acute Respiratory Infection (SARI) sentinel surveillance in the country of Georgia, 2015-2017

text: BACKGROUND: Severe Acute Respiratory Infection (SARI) causes substantial mortality and morbidity worldwide. The country of Georgia conducts sentinel surveillance to monitor SARI activity and changes in its infectious etiology. This study characterizes the epidemiology of SARI in Georgia over the 2015/16 and 2016/17 influenza seasons, compares clinical presentations by etiology, and estimates influenza vaccine effectiveness using a test-negative design. METHODS: SARI cases were selected through alternate day systematic sampling between September 2015 and March 2017 at five sentinel surveillance inpatient sites. Nasopharyngeal swabs were tested for respiratory viruses and Mycoplasma pneumoniae using a multiplex diagnostic system. We present SARI case frequencies by demographic characteristics, co-morbidities, and clinical presentation, and used logistic regression to estimate influenza A vaccine effectiveness. RESULTS: 1,624 patients with SARI were identified. More cases occurred in February (28.7%; 466/1624) than other months. Influenza was the dominant pathogen in December-February, respiratory syncytial virus in March-May, and rhinovirus in June-November. Serious clinical symptoms including breathing difficulties, ICU hospitalization, and artificial ventilation were common among influenza A and human metapneumovirus cases. For influenza A/H3, a protective association between vaccination and disease status was observed when cases with unknown vaccination status were combined with those who were unvaccinated (OR: 0.53, 95% CI: 0.30, 0.97). CONCLUSIONS: Multi-pathogen diagnostic testing through Georgia’s sentinel surveillance provides useful information on etiology, seasonality, and demographic associations. Influenza A and B were associated with more severe outcomes, although the majority of the population studied was unvaccinated. Findings from sentinel surveillance can assist in prevention planning.


title: Exploration of trends in the incidence and prevalence of childhood maltreatment and domestic abuse recording in UK primary care: a retrospective cohort study using ‘the health improvement network’ database

text: OBJECTIVES: Describe the epidemiology of childhood maltreatment and domestic abuse (in women). DESIGN: Analysis of longitudinal records between 1 January 1995 to 31 December 2018. SETTING: UK primary care database: ‘The Health Improvement Network’ (THIN). PARTICIPANTS: 11 831 850 eligible patients from 787 contributing practices. Childhood maltreatment and domestic abuse (women only) were defined as the presence of a recorded Read code. OUTCOME MEASURES: The incidence rate (IR) and prevalence of childhood maltreatment (in children aged 0–18 years) and domestic abuse (in women aged over 18) between 1996 and 2017. An adjusted incidence rate ratio (aIRR) is given to examine the differences in IRs based on sex, ethnicity and deprivation. RESULTS: The age and gender breakdown of THIN has been previously reported to be representative of the UK population, however, there is substantial missing information on deprivation quintiles (<20%) and ethnicity (approximately 50%). The IR (IR 60.1; 95% CI 54.3 to 66.0 per 100 000 child years) and prevalence (416.1; 95% CI 401.3 to 430.9 per 100 000 child population) of childhood maltreatment rose until 2017. The aIRR was greater in patients from the most deprived backgrounds (aIRR 5.14; 95% CI 4.57 to 5.77 compared with least deprived) and from an ethnic minority community (eg, black aIRR 1.25; 1.04 to 1.49 compared with white). When examining domestic abuse in women, in 2017, the IR was 34.5 (31.4 to 37.7) per 100 000 adult years and prevalence 368.7 (358.7 to 378.7) per 100 000 adult population. Similarly, the IR was highest in the lowest socioeconomic class (aIRR 2.30; 2.71 to 3.30) and in ethnic minorities (South Asian aIRR 2.14; 1.92 to 2.39 and black aIRR 1.64; 1.42 to 1.89). CONCLUSION: Despite recent improvements in recording, there is still a substantial under-recording of maltreatment and abuse within UK primary care records, compared with currently existing sources of childhood maltreatment and domestic abuse data. Approaches must be implemented to improve recording and detection of childhood maltreatment and domestic abuse within medical records.


title: Pneumococcal superinfection in COVID-19 patients: a series of 5 cases

text: ABSTRACT Background: In the context of the COVID-19 pandemic the risk of misdiagnosis of other causes of respiratory infection is likely. In this work we aim to describe the clinical characteristics, treatment and outcome of pneumococcal infection in COVID-19 patients. Patients and methods: Every COVID-19 patient presenting with concomitant pneumococcal pneumonia during March 2020 in a tertiary teaching Hospital In Barcelona, Spain. Results: Five patients with PCR confirmed COVID19 or clinical and radiological suspicion were diagnosed of pneumococcal infection. In all cases chest x-ray were abnormal, with unilateral or bilateral infiltrates. Procalcitonin showed to be not sensitive enough to detect pneumococcal infection. Antibiotherapy was promptly started in all five cases with subsequent satisfactory evolution. Conclussion: International guidelines do not include the universal screening for bacterial co-infection. Radiological pattern of COVID-19 can be indistinguishable from that of pneumococcus pneumonia and frequency of co-infection is not well stablished, therefore clinicians should be aware of the possible SARS-CoV-2-pneumococcus association to avoid misdiagnosis and delay antibiotic therapy.


title: Primary health care policy and vision for community pharmacy and pharmacists in Lebanon

text: Within a crippling economic context and a rapidly evolving healthcare system, pharmacists in Lebanon are striving to promote their role in primary care. Community pharmacists, although held in high esteem by the population, are not recognised as primary health care providers by concerned authorities. They are perceived as medication sellers. The role of the pharmacist in primary health care networks, established by the Ministry of Public Health (MOPH) to serve most vulnerable populations, is limited to medication delivery. The practice of the pharmacy profession in Lebanon has been regulated in 1950 by the Lebanese Pharmacists Association [Order of Pharmacists of Lebanon] (OPL). In 2016, the OPL published its mission, vision, and objectives, aiming to protect the pharmacists’ rights by enforcing rules and procedures, raise the profession’s level through continuous education, and ensure patients’ appropriate access to medications and pharmacist’s counseling for safe medication use. Since then, based on the identified challenges, the OPL has suggested several programs, inspired by the World Health Organization and the International Pharmaceutical Federation guidelines, as part of a strategic plan to develop the pharmacy profession and support patient safety. These programs included the application of principles of good governance, the provision of paid services, developing pharmacists’ core and advanced competencies, generation of accreditation standards for both community pharmacy and pharmacy education, suggesting new laws and decrees, continuing education consolidation and professional development. There was an emphasis on all decisions to be evidence assessment-based. However, OPL faces a major internal political challenge: its governing body, which is reelected every three years, holds absolute powers in changing strategies for the three-year mandate, without program continuation beyond each mandate. Within this context, we recommend the implementation of a strategic plan to integrate pharmacy in primary health centers, promoting the public health aspect of the profession and taking into account of critical health issues and the changing demographics and epidemiological transition of the Lebanese population. Unless the proposed blueprint in this paper is adopted, the profession is unfortunately condemned to disappear in the current political, economic and health-related Lebanese context.


title: Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

text: The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.


title: COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

text: Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.


title: Porcine Innate and Adaptative Immune Responses to Influenza and Coronavirus Infections

text: abstract: Both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. Pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (SARS) virus. Studies on both innate and adaptative immune responses of pigs to influenza virus and coronaviruses contribute, therefore, to a better control of these infections in their natural hosts and will be briefly reviewed in this article. Pro‐inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6), were found in lung secretions of influenza virus infected pigs, and correlated with the intensity of clinical signs, whereas prior vaccination against influenza strongly reduced the production of infectious virus and cytokines in the lungs upon challenge, which was associated with clinical protection. An early type I IFN production was also found in coronavirus infected pigs, including at mucosal sites. IFN induction by coronavirus is shown to involve interaction between a viral glycoprotein and a leukocyte subset, likely equivalent to plasmacytoid dendritic cells, present in the mucosae and associated lymphoid tissues. Given the IFN mediated antiviral and immunomodulatory effects, the use of IFN or IFN inducers may prove an efficient strategy for a better control of influenza virus and coronavirus infections in pigs. Because influenza and coronaviruses target mucosal surfaces, adaptative immune responses have to be characterized at mucosal sites. Thus, nasal and pulmonary antibody responses were analyzed in influenza virus infected or vaccinated pigs showing short‐lived, but potentially protective local IgA and IgG antibody (Ab) responses. Interestingly, primary influenza virus infection induced long‐lived increase of lung CD8(+) T cells and local lymphoproliferative responses. Pigs infected by a respiratory coronavirus (PRCV) showed virus‐specific IgG Ab‐secreting cells in the bronchial lymph nodes, whereas the transmissible gastroenteritis coronavirus (TGEV) induced more IgA Ab‐secreting cells in gut tissues, which illustrates the importance of the route of antigen administration for inducing local immune effector mechanisms. Porcine viral infections provide, therefore, valuable models for evaluating the immune parameters that are important for controlling transmission of important viral zoonotic infections.


title: Stability of neurotropic mouse hepatitis virus (JHM strain) during chronic infection of neuroblastoma cells

text: A line of mouse neuroblastoma cells which was chronically infected with the neurotropic strain (JHM) of MHV, a member of the coronavirus group, was established. These cells, designated N(J), exhibited typical MHV cytopathic effects (CPE) at all passage levels along with the continual production of infectious virus. Most cells were positive for viral antigen by immunofluorescence. Viral particles consistent with the morphology of MHV were found by electron microscopy. The uninfected neuroblastoma cell line did not contain a detectable population of cells resistant to JHM, and persistence did not elicit the production of interferon. No plaque morphology or temperature sensitive mutants were selected for in the N(J) culture, and we were unable to detect the presence of either a defective or defective interfering virus population. The addition of low concentration antiviral antibody modulated the infection to a carrier culture with viral antigen in the cytoplasm of the cells, but no infectious virus was produced, and the cells lacked both surface viral antigen and CPE. Possible mechanisms of viral persistencein vitro are discussed.


title: Pathogenicity and immunogenicity of attenuated porcine epidemic diarrhea virus PC22A strain in conventional weaned pigs

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV) causes diarrhea in all ages of pigs with 50–100% mortality rates in neonatal piglets. In the United States, inactivated and subunit PEDV vaccines for pregnant sows are available, but fail to induce sufficient protection in neonatal piglets farrowed from PEDV naïve sows. A safe and efficacious live attenuated vaccine that can prime mucosal immune responses is urgently needed. In this study, we evaluated the safety and efficacy of two attenuated PEDV vaccine candidates, the emerging non-S INDEL PEDV strain PC22A at the 100th cell culture passage level - Clone no. 4 (P100C4) and at the 120th passage level (P120), in weaned pigs. RESULTS: Four groups of 40-day-old weaned pigs were inoculated orally with PEDV PC22A-P3 (virulent), -P100C4, -P120, and mock, respectively, and challenged with the P3 virus at 24 days post-inoculation (dpi). After inoculation, P3 caused diarrhea in all pigs with a high level of fecal viral RNA shedding. P100C4 and P120 did not cause diarrhea in pigs, although viral RNA was detected in feces of all pigs, except for one P100C4-inoculated pig. Compared with the P120 group, P3- and P100C4-inoculated pigs had higher serum PEDV-specific IgG and viral neutralizing (VN) antibody (Ab) titers at 14 dpi. After the challenge, no pigs in the P3 group but all pigs in the P100C4, P120, and mock groups had diarrhea. Compared with the P120 group, pigs in the P100C4 group had a more rapid decline in fecal PEDV RNA shedding titers, higher titers of serum PEDV-specific IgG, IgA, and VN Abs, and higher numbers of intestinal IgA Ab-secreting cells. CONCLUSIONS: PEDV PC22A P100C4 and P120 were fully attenuated in weaned pigs but failed to elicit protection against virulent P3 challenge. P100C4 induced higher PEDV-specific antibody responses than P120 post inoculation resulting in a greater anamnestic response post challenge. Therefore, P100C4 potentially could be tested as a priming vaccine or be further modified using reverse genetics. It also can be administered in multiple doses or be combined with inactivated or subunit vaccines and adjuvants as a PEDV vaccination regimen, whose efficacy can be tested in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1756-x) contains supplementary material, which is available to authorized users.


title: Reduced hospital admissions for ACS — more collateral damage from COVID-19

text: A decline in the number of hospital admissions for acute coronary syndrome was observed across Italy and USA during the peak of the COVID-19 pandemic.


title: Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections

text: Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.


title: Épidémiologie de l'infection virale et asthme

text: Summary The first epidemiological data concerning viruses and asthma were obtained in the 1970s and 1980s by viral isolation and serology. Viral infection can be identified in 24 % to 31.9 % of children, and in 13.3 % of adults. The three most frequent viruses are rhinovirus (RV), respiratory syncytial virus (RSV), and parainfluenza viruses (PIV), detected in 8.8 %, 6.4 % and 6 % of cases, respectively. Due to its amplifying properties, the use of PCR increases the frequency of viral detection, and appears particularly appropriate in asthma where the viral load can be reduced. In a study of bronchiolitis, RSV, PIV3, AdV and RV were identified in 39.3 %, 4.3 %, 1.4 % and 3.9 % of cases, respectively, by IF or culture, and in 62.4 %, 8.3 %, 10.8 % and 12.6 % of cases, respectively, by PCR. Two recent epidemiological surveys used molecular diagnosis in asthma attacks. In a series of 61 adults, 27 (44 %) infections were identified: 16 RV, 4 CV OC43, 3 PIV, 1 RSV, 1 VI, 1 Chlamydia psitacci. In children, viral infection was detected in 226 cases (77 %) : 84 RV, 38 CV, 21 IV, 21 PIV, 12 RSV. We have performed a short retrospective survey for 1997, using molecular biology, on 39 nasal aspirates from children consulting for asthma or wheezing bronchitis. Testing for respiratory viruses by conventional techniques identified 8 (20.5 %) viral infections: 3 RV, 3 RSV, 1 IBV and 1 VPI2. After nucleic acid extraction, PCR-hybridization techniques were applied to these samples to detect RSV, AdV, RV, CV 229E, CV OC43, CP and MP sequences. Twenty six aspirates (54 %) were positive only on molecular biology techniques: 11 RSV, 12 RV, 2 enterovirus, 1 CV OC43. Overall 34 (82 %) viral infections were detected in these children, and a mixed RSV-RV infection was identified in 6 cases. Compared to the studies reported in the literature, we observed the same predominance of RV infections, more RSV infections, probably related to the use of PCR, and a lower incidence of CV infections.


Recommendations Regarding COVID19 Infection in Rheumatic Patients in Greece


INNAMORA, a European Workshop focussed on the mechanisms of innate immunity in pathogen–host interaction and their exploitation in novel mucosal immunisation strategies


title: Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of yellow head virus in shrimp

text: Abstract A real-time reverse transcription loop-mediated isothermal amplification (real-time RT-LAMP) method was applied for detecting the replicase polyprotein-encoding gene of yellow head virus (YHV) in shrimp, Penaeus monodon. It is a novel, gene-specific assay that amplifies nucleic acid with high specificity, sensitivity and rapidity under isothermal conditions using a set of six specially designed primers that recognize eight distinct sequences of the target gene. This method works with even low copies of DNA and is based on magnesium pyrophosphate turbidity detection by an inexpensive photometer for quantitative analysis. A user-friendly protocol was developed with optimal conditions standardized at 63°C for 60min. With this protocol, the assay sensitivity was 10 times higher than the widely used YHV nested RT-PCR system. Cross-reactivity analysis using other shrimp virus DNA/cDNA and YHV-negative shrimp demonstrated high specificity of the assay. The real-time RT-LAMP method was performed also for an internal control gene, EF-1α, to compare with the expressions of the YHV gene in different organs of infected shrimp, and the resulting standard curves showed high correlation coefficient values. These results suggest that this assay is applicable widely as a new quantitative detection method in the pursuit of YHV-free shrimp culture.


title: Determinants of health literacy and health behavior regarding infectious respiratory diseases: a pathway model

text: BACKGROUND: Health literacy has been defined as the degree to which individuals have the capacity to obtain, process, and understand the basic health information and services needed to make appropriate health decisions. Currently, few studies have validated the causal pathways of determinants of health literacy through the use of statistical modeling. The purpose of the present study was to develop and validate a health literacy model at an individual level that could best explain the determinants of health literacy and the associations between health literacy and health behaviors even health status. METHODS: Skill-based health literacy test and a self-administrated questionnaire survey were conducted among 3222 Chinese adult residents. Path analysis was applied to validate the model. RESULTS: The model explained 38.6% of variance for health literacy, 11.7% for health behavior and 2.3% for health status: (GFI = 0.9990; RMR = 0.0521; χ(2) = 10.2151, P = 0.1159). Education has positive and direct effect on prior knowledge (β = 0.324) and health literacy (β = 0.346). Health literacy is also affected by prior knowledge (β = 0.245) and age (β = -0.361). Health literacy is a direct influencing factor of health behavior (β = 0.101). The most important factor of health status is age (β = 0.107). Health behavior and health status have a positive interaction effect. CONCLUSION: This model explains the determinants of health literacy and the associations between health literacy and health behaviors well. It could be applied to develop intervention strategies to increase individual health literacy, and then to promote health behavior and health status.


title: A novel semisynthesized small molecule icaritin reduces incidence of steroid-associated osteonecrosis with inhibition of both thrombosis and lipid-deposition in a dose-dependent manner

text: Abstract Background Intravascular-thrombosis and extravascular-lipid-deposition are the two key pathogenic events considered to interrupt intraosseous blood supply during steroid-associated osteonecrosis (ON) development. However, there are no reported candidate agents capable of simultaneously targeting these two key pathogenic events. The authors' published experimental studies have shown that Epimedium-derived flavonoids possess an anti-ON effect. Further, the authors have recently identified a small molecule Icaritin as an intestinal metabolite of Epimedium-derived flavonoids. Objective The present study was to evaluate the prevention effect of the available semisynthesized small molecule Icaritin on steroid-associated ON development in a rabbit model. Methods After receiving an established inductive protocol for inducing steroid-associated ON, eighty-four male 28-week-old New-Zealand white rabbits were divided into the following three daily oral administration groups, including low dose Icaritin group (L-ICT; n =28; 5 mg·kg−1·day−1), high dose Icaritin group (H-ICT; n =28; 10 mg·kg−1·day−1), and control vehicle group (CON; n =28). Before and after induction, dynamic contrast-enhanced MRI was performed on proximal femur for intra-osseous perfusion function index. Meanwhile, blood samples were examined for coagulation, fibrinolysis, lipid-transportation, endothelium injury, oxidative stress, and hepatocyte injury index, while marrow samples were quantified for adipogenic potential index of mesenchymal stem cell by in vitro culture and proliferator-activated receptor-gamma (PPARgamma) protein expression by western blot. At baseline, week 1 and 2 post-induction, 4, 8 and 16 rabbits in each group were sacrificed, respectively. After sacrifice, femora were dissected for micro-CT-based micro-angiography, followed by histological examination of ON lesion, intravascular thrombosis, extravascular fat-cell and vascular endothelial growth factor (VEGF) localized expression. Results The ON incidence in the L-ICT and H-ICT groups was both significantly lower than that in the CON group (p <0.05 for both). The ON incidence in the H-ICT group was significantly lower than that in the L-ICT group (p <0.05). A significant decrease in the vascularization index and a significant increase in the permeability index seen in the CON group was attenuated in the L-ICT group and almost prevented in the H-ICT group at week 1 post-induction. Reduced perfusion to vessel-like structural units was more rarely found in the H-ICT group than in the L-ICT group. Regarding intravascular thrombosis, a significant increase in the thrombotic vessel count, endothelium injury index, coagulation index, and a significant decrease in both the fibrinolysis and oxidative stress index in the CON group were attenuated in the L-ICT group and prevented in the H-ICT group. For extravascular lipid-deposition, a significant increase in the fat cell area fraction, adipogenic potential index, PPARgamma expression and lipid-transportation index in the CON group was attenuated in the L-ICT group and prevented in the H-ICT group. Increased immunoreactivity of VEGF in the CON group was attenuated in the L-ICT group and prevented in the H-ICT group. Regarding safety, the hepatocyte injury index did not show significant change from baseline in any group. Conclusion Icaritin, a novel semisynthesized small molecule with osteoprotective potential, exerts dose-dependent effect on reducing incidence of steroid-associated ON with inhibition of both intravascular thrombosis and extravascular lipid-deposition. Suppression of the up-regulated PPARgamma expression for extravascular adipogenesis of mesenchymal stem cells and protection from activated oxidative stress for intravascular endothelium injury were found to be involved in the underlying mechanisms.


title: Effectiveness of traveller screening for emerging pathogens is shaped by epidemiology and natural history of infection

text: During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We developed a mathematical model to understand how these factors combine to influence screening outcomes. We analyzed screening programs for six emerging pathogens in the early and late stages of an epidemic. We show that the effectiveness of different screening tools depends strongly on pathogen natural history and epidemiological features, as well as human factors in implementation and compliance. For pathogens with longer incubation periods, exposure risk detection dominates in growing epidemics, while fever becomes a better target in stable or declining epidemics. For pathogens with short incubation, fever screening drives detection in any epidemic stage. However, even in the most optimistic scenario arrival screening will miss the majority of cases. DOI: http://dx.doi.org/10.7554/eLife.05564.001


title: In-Hospital Telehealth Supports Care for Neonatal Patients in Strict Isolation

text: The aim of this study is to determine the feasibility of “in-hospital” inpatient telemedicine within a children's referral hospital to facilitate inpatient care activities such as interprofessional rounding and the provision of supportive services such as lactation consultations to pediatric patients in strict isolation. To test the feasibility of in-hospital video telemedicine, a dedicated telemedicine device was set up in the patient's room. This device and the accompanying Bluetooth stethoscope were used by the health care team located just outside the room for inpatient rounding and consultations from supportive services. Video telemedicine facilitated inpatient care and interactions with support services, reducing the number of health care providers with potential exposure to infection and decreasing personal protective equipment use. In the setting of strict isolation for highly infectious viral illness, telemedicine can be used for inpatient care activities such as interprofessional rounding and provision of supportive services. Key Points: Telehealth supports patient care in isolation. Telehealth reduced health care provider exposures. Telehealth conserves personal protective equipment.


title: Effects of COVID‐19 on Parkinson's disease clinical features: a community‐based case‐control study

text: The impact of Coronavirus disease 2019 (COVID‐19) on clinical features of Parkinson's disease (PD) has been poorly characterized so far. Out of 141 PD patients resident in Lombardy, we found twelve COVID‐19 cases (8.5%), whose mean age and disease duration (65.5 and 6.3 years, respectively) were similar to controls. Changes in clinical features in the period January‐April 2020 were compared with those of 36 PD control subjects, matched for sex, age, and disease‐duration, using the clinical impression of severity index for PD, the Movement Disorders Society Unified PD Rating Scale parts II and IV, and the non‐motor symptoms scale. Motor and nonmotor symptoms significantly worsened in the COVID‐19 group, requiring therapy adjustment in one‐third of cases. Clinical deterioration was explained by both infection‐related mechanisms and impaired pharmacokinetics of dopaminergic therapy. Urinary issues and fatigue were the most prominent nonmotor issues. Cognitive functions were marginally involved, while none experienced autonomic failure. This article is protected by copyright. All rights reserved.


title: Reference gene selection for normalization of PCR analysis in chicken embryo fibroblast infected with H5N1 AIV

text: Chicken embryo fibroblasts (CEFs) are among the most commonly used cells for the study of interactions between chicken hosts and H5N1 avian influenza virus (AIV). In this study, the expression of eleven housekeeping genes typically used for the normalization of quantitative real-time PCR (QPCR) analysis in mammals were compared in CEFs infected with H5N1 AIV to determine the most reliable reference genes in this system. CEFs cultured from 10-day-old SPF chicken embryos were infected with 100 TCID(50) of H5N1 AIV and harvested at 3, 12, 24 and 30 hours post-infection. The expression levels of the eleven reference genes in infected and uninfected CEFs were determined by real-time PCR. Based on expression stability and expression levels, our data suggest that the ribosomal protein L4 (RPL4) and tyrosine 3-monooxygenase tryptophan 5-monooxygenase activation protein zeta polypeptide (YWHAZ) are the best reference genes to use in the study of host cell response to H5N1 AIV infection. However, for the study of replication levels of H5N1 AIV in CEFs, the β-actin gene (ACTB) and the ribosomal protein L4 (RPL4) gene are the best references.


title: Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition

text: BACKGROUND: Lycorine, a natural alkaloid extracted from Amaryllidaceae, has shown various pharmacological effects. Recent studies have focused on the potential antitumor activity of lycorine. In our previous study, we found that lycorine decrease the cell viability of leukemia HL-60 cells and multiple myeloma KM3 cells and induces cell apoptosis. However, the effect and molecular mechanism of lycorine on human chronic myelocytic leukemia cells has yet to be determined. METHODS: Human chronic myelocytic leukemia cells K562 were treated with lycorine. Cell viability was monitored using the method of CCK-8. The histone deacetylase (HDAC) enzymatic activity was detected by HDAC colorimetric assay, and the cell cycle was analyzed by flow cytometry. The expression of cell-cycle related proteins were identified using Western blot. RESULTS: In the present study, we further revealed that lycorine can inhibit the proliferation of K562 cells. Analysis of HDAC activity showed that lycroine decreases HDAC enzymatic activities in K562 cells in a dose-dependent manner. Inhibition of HDAC activity has been associated with cell-cycle arrest and growth inhibition. We evaluated the cell cycle distribution after lycorine treatment and found that lycorine causes cell-cycle arrest in the G0/G1 phase. To investigate the mechanism behind this cell cycle arrest, G1-related proteins were assayed by Western blot. After lycorine treatment, cyclin D1 and cyclin-dependent kinase 4 expressions were inhibited and retinoblastoma protein phosphorylation was reduced. Lycorine treatment also significantly upregulated the expression of p53 and its target gene product, p21. CONCLUSIONS: These results suggest that inhibition of HDAC activity is responsible for at least part of the induction of cell-cycle arrest in the G0/G1 phase by lycorine and provide a mechanistic framework for further exploring the use of lycorine as a novel antitumor agent.


FACING DEMENTIA DURING THE COVID‐19 OUTBREAK


title: Inhibition of host protein synthesis by Sindbis virus: correlation with viral RNA replication and release of nuclear proteins to the cytoplasm

text: Infection of mammalian cells by Sindbis virus (SINV) profoundly blocks cellular mRNA translation. Experimental evidence points to viral non‐structural proteins (nsPs), in particular nsP2, as the mediator of this inhibition. However, individual expression of nsP1, nsP2, nsP3 or nsP1‐4 does not block cellular protein synthesis in BHK cells. Trans‐complementation of a defective SINV replicon lacking most of the coding region for nsPs by the co‐expression of nsP1‐4 propitiates viral RNA replication at low levels, and inhibition of cellular translation is not observed. Exit of nuclear proteins including T‐cell intracellular antigen and polypyrimidine tract‐binding protein is clearly detected in SINV‐infected cells, but not upon the expression of nsPs, even when the defective replicon was complemented. Analysis of a SINV variant with a point mutation in nsP2, exhibiting defects in the shut‐off of host protein synthesis, indicates that both viral RNA replication and the release of nuclear proteins to the cytoplasm are greatly inhibited. Furthermore, nucleoside analogues that inhibit cellular and viral RNA synthesis impede the blockade of host mRNA translation, in addition to the release of nuclear proteins. Prevention of the shut‐off of host mRNA translation by nucleoside analogues is not due to the inhibition of eIF2α phosphorylation, as this prevention is also observed in PKR (−/−) mouse embryonic fibroblasts that do not phosphorylate eIF2α after SINV infection. Collectively, our observations are consistent with the concept that for the inhibition of cellular protein synthesis to occur, viral RNA replication must take place at control levels, leading to the release of nuclear proteins to the cytoplasm.


COVID-19: thinking about further mental and neurological disorders


title: Cloning and expression of nucleocapsid protein gene of TGEV HB06 strain

text: The nucleocapsid protein gene of transmissible gastroenteritis virus, 1 149 bp in length, was amplified by RT-PCR from isolated strain HB06 and cloned into pMD18-T. Sequence comparison with other transmissible gastroenteritis virus (TGEV) strains selected from the Gene Bank revealed that the homology of N gene complete sequence shares more than 97% in nucleotide. N gene was cloned into BamHI and EcoRI multiple cloning sites of the prokaryotic expression vector pET 20 b, and named pETN. After being induced by isopropyl-β-D-thiogalactopyranoside (IPTG), the recombinant nucleocapsid protein was expressed. The result of SDS-PAGE and Western-blot showed that the recombinant nucleocapsid protein was 47 kDa and had strong positive reactions with TGEV-specific antibody.


title: Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 — National Poison Data System, United States, January 1, 2020–March 31, 2020

text: On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3). To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019. Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications. Call data from poison centers are uploaded in near real-time to NPDS. During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively. Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.


title: Impact of Digital Surge during Covid-19 Pandemic: A Viewpoint on Research and Practice

text: The Covid-19 pandemic has led to an inevitable surge in the use of digital technologies due to the social distancing norms and nationwide lockdowns. People and organizations all over the world have had to adjust to new ways of work and life. We explore possible scenarios of the digital surge and the research issues that arise. An increase in digitalization is leading firms and educational institutions to shift to work-from-home (WFH). Blockchain technology will become important and will entail research on design and regulations. Gig workers and the gig economy is likely to increase in scale, raising questions of work allocation, collaboration, motivation, and aspects of work overload and presenteeism. Workplace monitoring and technostress issues will become prominent with an increase in digital presence. Online fraud is likely to grow, along with research on managing security. The regulation of the internet, a key resource, will be crucial post-pandemic. Research may address the consequences and causes of the digital divide. Further, the issues of net neutrality and zero-rating plans will merit scrutiny. A key research issue will also be the impact and consequences of internet shutdowns, frequently resorted to by countries. Digital money, too, assumes importance in crisis situations and research will address their adoption, consequences, and mode. Aspects of surveillance and privacy gain importance with increase digital usage.


title: Plaque assay for human coronavirus NL63 using human colon carcinoma cells

text: BACKGROUND: Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV) NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. RESULTS: 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2) replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2). CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4(th )day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. CONCLUSION: CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.


title: Critical role of RIG‐I‐like receptors in inflammation in chronic obstructive pulmonary disease

text: INTRODUCTION: Viral infection is a significant cause of chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD. Retinoic acid inducible gene I (RIG‐I)‐like receptors (RLRs), including RIG‐I and melanoma differentiation associated gene 5 (MDA‐5), are important pattern recognition receptors for viral elimination. OBJECTIVE: The study aims to investigate the role of RIG‐I and MDA‐5 in COPD pathogenesis. METHODS: We examined the expression of RIG‐I and MDA‐5 by immunohistochemistry, real‐time PCR and Western blots in COPD patients and control subjects. RESULTS: Our results showed that MDA‐5 expression was upregulated in lung tissues and peripheral blood mononuclear cells of COPD patients and there was a negative correlation between MDA‐5 mRNA levels and forced expiratory volume in 1 s %pred. COPD patients had higher interleukin (IL)‐1 and IL‐8 mRNA expression levels, and these inflammatory cytokines positively correlate with MDA‐5 levels. However, there was no difference in the expression of RIG‐I between COPD patients and control subjects. CONCLUSION: Our results suggested that MDA‐5, but not RIG‐I, may play a critical role in airway inflammation in COPD.


Active cleaning


title: Prevalence of seropositivity to pathogens in small carnivores in adjacent areas of Lazovskii Reserve

text: The prevalence of infectious diseases in wild and feral carnivores is poorly known in Primorsky Krai, where rare species such as the Amur tiger and the Far East leopard roam. In this study we evaluated the prevalence of seropositivity in feral (cats, dogs) and wild (raccoon dog, badger, American mink, Far Eastern wild cat) carnivores to various pathogens: distemper virus, parvovirus, feline immunodeficiency and feline leukemia virus, feline coronavirus, Toxoplasma gondii, Mycoplasma sp., and Chlamydia sp. It was shown that seropositivity occurred significantly more frequent in feral animals than in wild ones. The highest percentage of seropositive animals was observed in feral dogs. It is these diseases that can be dangerous for the Amur tiger and the Far East leopard, thus affecting their populations.


title: A complication of coronavirus disease 2019: delirium

text: COVID-19 is predominantly a respiratory disease. However, some cases exhibit other features including Central Nervous System symptoms. In the older adult, COVID-19 may present with atypical symptoms, including delirium and its complications. The objective of this study is to describe the relationship between the new type of coronavirus infection and delirium. Systematic research (Cochrane Library and PubMed) was carried out (only upper time limit: April 2020). Publications found through this indexed search were reviewed and manually screened to identify relevant studies. Search terms used included “COVID-19, Delirium, Dementia, Intensive Care Unit”. We manually added articles identified through other sources (i.e., key journals). Older people are at the greatest risk from COVID-19. If infected, they may present delirium. Moreover, it is not exclusive to older people. Delirium is not inevitable; rather, it is preventable. Delirium prevention programs are even more crucial in the era of COVID-19 and cannot be allowed to wither despite the challenges of integrating delirium prevention with COVID-19 care. An acute change in condition, behaviour, or mental status should prompt a delirium screen. As regards the treatment, it is advisable to use non-pharmacological interventions first where possible. Medication may be needed for patients with agitation where there is intractable distress or high risk to self/others.


title: Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions

text: Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.


title: Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis

text: Sequence analyses of RNA virus genomes remain challenging due to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called ‘quasispecies’. Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (i) RNA virus genomes and (ii) subgenome-length (sg) RNAs comprised of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. Using DRS, we were able to map the longest (∼26 kb) contiguous read to the viral reference genome. By combining Illumina and nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV) 229E genome (27.3 kb). Furthermore, using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by demonstrating the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that direct RNA sequencing may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.


title: The SARS-CoV-2 seroprevalence is the key factor for deconfinement in France

text: Summary A new virus, SARS-CoV-2, has spread world-wide since December 2019, probably affecting millions of people and killing thousands. Failure to anticipate the spread of the virus now seriously threatens many health systems. We have designed a model for predicting the evolution of the SARS-CoV-2 epidemic in France, which is based on seroprevalence and makes it possible to anticipate the deconfinement strategy.


title: Pandemic Influenza A (H1N1) and Its Prevention: A Cross Sectional Study on Patients’ Knowledge, Attitude and Practice among Patients Attending Primary Health Care Clinic in Kuala Lumpur, Malaysia

text: The World Health Organization confirmed that the novel influenza A, H1N1 as a pandemic on 11 June 2009. After less than three months, 182 countries were affected by the pandemic accounting for about 150,000 infected cases and 3000 mortality. Successful H1N1 pandemic management strategies’ shaped by making changes in health behavior. The aim of this study was to document patients’ knowledge, attitudes and practices (KAP) regarding the pandemic influenza A (H1N1) and its prevention. We performed a cross-sectional study on knowledge, attitudes and practices (KAP) on preventive measures of Influenza A (H1N1) involving 322 patients attending Klinik Kesihatan Jinjang, a primary health care clinic in Kuala Lumpur, Malaysia from May 10 to 26, 2010 using a face to face interview with a structured pre-tested questionnaire. The majority of the respondents were females (56.8%), Malays (43.2%) aged between 18-27 years old (28.9%). There were significant association between knowledge on the complication of H1N1, effectiveness of the treatment, preventive measures of Influenza A (H1N1) and race (p<0.001) and educational level (p<0.001). There were also significant associations between attitude scores of these patients and their gender (p=0.03), and educational level (p=0.001). Practice scores related to H1N1 were found to be significantly associated with race (p<0.001) and educational level (p<0.001). The significant associations were observed between knowledge and attitude (p<0.001), knowledge and practices (p<0.001), as well as attitude and practices related to H1N1 (p<0.001). Knowledge has a crucial effect on patients’ attitude and practice particularly in a pandemic spread. So health policy makers should attempt to disseminate information about preventive measures to community in order to improve their preventive practices during pandemics.


Review of Slavoj Žižek (2020). Pandemic!: COVID-19 Shakes the World: New York and London: OR Books. 140 pp. ISBN 9781682193013 (Paperback)


title: Human Touch via Touchscreen: Rural nurses’ experiential perspectives on telehealth use in pediatric hospice care

text: CONTEXT: Telemedicine has the potential to extend care reach and access to home-based hospice services for children. Few studies have explored nurse perspectives regarding this communication modality for rural pediatric cohorts. OBJECTIVES: The objective of this qualitative study was to learn from the experiences of rural hospice nurses caring for children at the end of life using telehealth modalities to inform palliative communication. METHODS: Voice-recorded qualitative interviews with rural hospice nurse telehealth users inquiring on nurse experiences with telehealth. Semantic content analysis was used. RESULTS: Fifteen hospice nurses representing nine rural hospice agencies were interviewed. Nurses participated in an average of eight telehealth visits in the three-months prior. Nurses were female with mean age 38 years and average 7 years hospice nursing experience. Five themes about telehealth emerged: accessible support, participant inclusion, timely communication, informed and trusted planning, and familiarity fostered. Each theme had both benefits and cautions associated as well as telehealth suggestions. Nurses recommended individualizing communication, pacing content, fostering human connection, and developing relationships even with technology use. CONCLUSIONS: The experiences of nurses who utilize telehealth in their care for children receiving end of life care in rural regions may enable palliative care teams to understand both the benefits and challenges of telehealth use. Nurse insights on telehealth may help palliative care teams better honor the communication needs of patients and families while striving to improve care access.


title: The effects of personal protective equipment on airway management: An in-situ simulation

text: Abstract The novel coronavirus disease (COVID19) was declared a pandemic by the World Health Organisation on 11th March and has led to over 41,000 deaths in the UK. Public Health England guidance for aerosol generating procedures (AGP) requires the donning of personal protective equipment (PPE). We evaluated airway management skills using an in-situ emergency simulation. The scenarios were video recorded and scored by two independent assessors using a skill specific checklist. A total of 34 airway management procedures were evaluated. The checklist involved 13 steps with a maximum score of 26. The median (IQR [range]) checklist score was 25 (24-25 [20-26]). Four teams failed to intubate the trachea and proceeded to manage the airway using a supraglottic airway device. The mean (SD) intubation time was 47.9 (16.5) seconds and two anaesthetists (7%) required a second attempt. Our results show that airway management can be carried out successfully whilst donned in PPE. However, additional training in using newly introduced devices such as a McGrath® video laryngoscope is of paramount importance.


title: Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice

text: Cellular senescence, a persistent state of cell cycle arrest, accumulates in aged organisms, contributes to tissue dysfunction, and drives age-related phenotypes. The clearance of senescent cells is expected to decrease chronic, low-grade inflammation and improve tissue repair capacity, thus attenuating the decline of physical function in aged organisms. However, selective and effective clearance of senescent cells of different cell types has proven challenging. Herein, we developed a prodrug strategy to design a new compound based on the increased activity of lysosomal β-galactosidase (β-gal), a primary characteristic of senescent cells. Our prodrug SSK1 is specifically activated by β-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell types. In aged mice, our compound effectively cleared senescent cells in different tissues, decreased the senescence- and age-associated gene signatures, attenuated low-grade local and systemic inflammation, and restored physical function. Our results demonstrate that lysosomal β-gal can be effectively leveraged to selectively eliminate senescent cells, providing a novel strategy to develop anti-aging interventions.


title: Molecular cloning, expression, purification, and mass spectrometric characterization of 3C-like protease of SARS coronavirus

text: Abstract Severe acute respiratory syndrome (SARS) is an acute respiratory illness, which has broken out in China. It has been known that SARS coronavirus (SARS_CoV) is a novel human coronavirus and is responsible for SARS infection. Belonging to one of the major proteins associated with SARS_CoV, SARS 3C-like protease (SARS_3CLpro) functions as a cysteine protease engaging in the proteolytic cleavage of the viral precursor polyprotein to a series of functional proteins required for coronavirus replication and is considered as an appealing target for designing anti-SARS agents. To facilitate the studies regarding the functions and structures of SARS_3CLpro, in this report the synthetic genes encoding 3CLpro of SARS_CoV were assembled, and the plasmid was constructed using pQE30 as vector and expressed in Escherichia coli M15 cells. The highly yielded (∼15mg/L) expressed protease was purified by use of NTA-Ni2+ affinity chromatography and FPLC system, and its sequence was determined by LC/MS with the residue coverage of 46.4%.


title: Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient

text: The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures. Scientists have isolated virus from the first US COVID-19 patient. The isolation and reagents described here will serve as the US reference strain used in research, drug discovery and vaccine testing.


title: Upsurge of Enterovirus D68 and Circulation of the New Subclade D3 and Subclade B3 in Beijing, China, 2016

text: We conducted a surveillance among acute respiratory tract infection (ARTI) cases to define the epidemiology, clinical characteristics and genetic variations of enterovirus D68 (EV-D68) in Beijing, China from 2015 to 2017. Nasopharyngeal swabs and sputum were collected from 30 sentinel hospitals in Beijing and subjected to EV and EV-D68 detection by real-time PCR. The VP1 gene region and complete genome sequences of EV-D68 positive cases were analyzed. Of 21816 ARTI cases, 619 (2.84%) were EV positive and 42 cases were EV-D68 positive. The detection rates of EV-D68 were 0 (0/6644) in 2015, 0.53% (40/7522) in 2016 and 0.03% (2/7650) in 2017, respectively. Two peaks of EV-D68 infections occurred in late summer and early-winter. Ten cases (23.81%) with upper respiratory tract infection and 32 cases (76.19%) presented with pneumonia, including 3 cases with severe pneumonia. The phylogenetic analysis suggested 15 subclade D3 strains and 27 subclade B3 strains of EV-D68 were circulated in China from 2016 to 2017. A total of 52 amino acid polymorphisms were identified between subclades D1 and D3. These data suggest an upsurge of EV-D68 occurred in Beijing in 2016, the new subclade D3 emerged in 2016 and co-circulated with subclade B3 between 2016 and 2017.


title: Protocolo diagnóstico y tratamiento empírico de la bronquitis aguda

text: Acute bronchitis is an inflammatory disease of the highest caliber area that appears most frequently in cold months, affecting up to 5 % of the adult population. Clinically characterized by cough, may be associated with purulent sputum, and in some cases self-limiting existing bronchial hyperreactivity. Systemic antibiotics for treatment is not recommended.


title: Report of working group 1: Public health challenges

text: ABSTRACT There is a need to improve surveillance systems in order to recognise emerging threats, both in the community and in hospitals, in a timely manner. The laboratory arm of surveillance must be complemented by hospital and primary care components. We also need more training at all levels: undergraduate and postgraduate medical training, specialist training, as well as continuing professional development schemes. Core training programmes for infectious disease specialists and medical microbiologists must be established. The contribution of general practitioners, infection specialists, microbiology laboratories, and public health specialists/agencies to response systems should be defined as clearly as possible and should be either empirically based or derived from scenario-guided calamity models. The success of surveillance hinges on sufficient long-term resources and dedicated coordination. The European Centre for Disease Prevention and Control (ECDC) may assume this role. However, structural and administrative constraints of the diverse healthcare systems throughout Europe may represent an impediment to a harmonised response. Also, the funding of the ECDC cannot cover the operational demands. The ECDC may well work as a small coordinating unit; however, without a laboratory-based scientific status, it remains doubtful whether the ECDC will achieve the competence and authority needed for effective leadership in healthcare. The ESCMID, together with other national and international scientific societies, should put emphasis on the fact that infectious diseases have not received the necessary degree of attention from governments in the European region. The ESCMID should strengthen its role in harmonising and supporting the highest standards of training in the infection disciplines.


title: Government Intervention, Risk Perception, and the Adoption of Protective Action Recommendations: Evidence from the COVID-19 Prevention and Control Experience of China

text: This study examines the relationships between government interventions, risk perception, and the public’s adoption of protective action recommendations (PARs) during the COVID-19 coronavirus disease emergency in mainland China. We conducted quota sampling based on the proportion of the population in each province and gender ratios in the Sixth Census and obtained a sample size of 3837. Government intervention was divided into government communication, government prevention and control, and government rescue. We used multiple regression and a bootstrap mediation effect test to study the mechanism of these three forms of government intervention on the public’s adoption of PARs. The results show that government prevention and control and government rescue significantly increased the likelihood of the public adopting PARs. Risk perception was significantly associated with the public’s adoption of PARs. The effects of government interventions and risk perception on the public’s adoption of PARs was not found to vary by region. Risk perception is identified as an important mediating factor between government intervention and the public’s adoption of PARs. These results indicate that increasing the public’s risk perception is an effective strategy for governments seeking to encourage the public to adopt PARs during the COVID-19 pandemic.


A lesson learned from the MERS outbreak in South Korea in 2015