title: Comparing Twitter data to routine data sources in public health surveillance for the 2015 Pan/Parapan American Games: an ecological study

text: OBJECTIVES: This study examined Twitter for public health surveillance during a mass gathering in Canada with two objectives: to explore the feasibility of acquiring, categorizing and using geolocated Twitter data and to compare Twitter data against other data sources used for Pan Parapan American Games (P/PAG) surveillance. METHODS: Syndrome definitions were created using keyword categorization to extract posts from Twitter. Categories were developed iteratively for four relevant syndromes: respiratory, gastrointestinal, heat-related illness, and influenza-like illness (ILI). All data sources corresponded to the location of Toronto, Canada. Twitter data were acquired from a publicly available stream representing a 1% random sample of tweets from June 26 to September 10, 2015. Cross-correlation analyses of time series data were conducted between Twitter and comparator surveillance data sources: emergency department visits, telephone helpline calls, laboratory testing positivity rate, reportable disease data, and temperature. RESULTS: The frequency of daily tweets that were classified into syndromes was low, with the highest mean number of daily tweets being for ILI and respiratory syndromes (22.0 and 21.6, respectively) and the lowest, for the heat syndrome (4.1). Cross-correlation analyses of Twitter data demonstrated significant correlations for heat syndrome with two data sources: telephone helpline calls (r = 0.4) and temperature data (r = 0.5). CONCLUSION: Using simple syndromes based on keyword classification of geolocated tweets, we found a correlation between tweets and two routine data sources for heat alerts, the only public health event detected during P/PAG. Further research is needed to understand the role for Twitter in surveillance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-018-0059-0) contains supplementary material, which is available to authorized users.


title: Epidemiology of Respiratory Infections Caused by Atypical Bacteria in Two Kenyan Refugee Camps

text: Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella spp. are common causes of atypical pneumonia; however, data about these atypical pathogens are limited in the refugee setting. Paired nasopharyngeal and oropharyngeal specimens were collected from patients with respiratory illness presenting to healthcare centers in two refugee camps in Kenya. The specimens were tested for C. pneumoniae, M. pneumoniae, and Legionella spp. as well as eight respiratory viruses. Atypical pathogens were detected in 5.5% of the specimens of which 54% were co-infected with at least one of the eight viruses tested. Patients positive for atypical bacteria co-infected with virus were significantly more likely to have severe acute respiratory illness than patients infected with only atypical bacteria (P = 0.04). While the percentage of atypical pathogens identified was lower than expected, we found a significant relationship between atypical bacterial-viral co-infection and severity of disease in this refugee population.


title: Mating strategy is determinant of adenovirus prevalence in European bats

text: Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances for two of the three studied bat species (P. pygmaeus and P.kuhlii). These results increase our knowledge about the transmission mechanisms of adenoviruses.


title: Curating the innate immunity interactome

text: BACKGROUND: The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity. RESULTS: Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response. CONCLUSIONS: In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.


The role of ACE2 in pulmonary diseases—relevance for the nephrologist


title: Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement

text: Since the new coronavirus SARS (SARS-CoV2) has emerged from china, the infection (COVID-19) has affected many countries and led to many deaths worldwide. Like SARS-CoV, ACE2 as a functional receptor for SARS-CoV2 is essential for virus to entry to the cell. ACE2 is a part of RAS which is expressed in several organs that opposes the AngII functions by converting Ang II to Ang (1-7), the one with vasodilation effects. The death rate of COVID-19 is estimated about 3.4%, however, some comorbid conditions like underlying cardiovascular disease, hypertension, and diabetes increase the risk of mortality. In addition, cardiovascular involvement by SARS-CoV2 could be direct through either ACE2 receptors which are expressed tremendously in heart, or by the surge of different cytokines or by ARDS-induced hypoxia. Traditional risk factors could aggravate the process of COVID-19 infection that urges the triage of these high risk patients for SARS-CoV2. Currently, there is no effective, proven treatment or vaccination for COVID-19, but many investigators are struggling to find a treatment strategy as soon as possible. Some potential medications like chloroquine by itself or in combination with azithromycin, and some protease inhibitors used for the treatment of COVID-19 have cardiovascular adverse effects that should be kept in mind in order to close monitor of the patients receiving these medications.


33 Bronchiolitis


title: Detection of Group 2a Coronaviruses with Emphasis on Bovine and Wild Ruminant Strains: Virus Isolation and Detection of Antibody, Antigen, and Nucleic Acid

text: Group 2a of the Coronaviridae family contains human and animal pathogens that include mouse hepatitis virus, rat coronavirus, human respiratory coronaviruses OC43 and the recently identified HKU1 strain, a newly recognized canine respiratory coronavirus, porcine hemagglutinating encephalomyelitis virus, equine coronavirus, bovine coronavirus (BCoV), and wild-ruminant coronaviruses. The presence of a hemagglutinin-esterase (HE) surface glycoprotein in addition to the viral spike protein is a distinguishing characteristic of most group 2a coronaviruses. BCoV is ubiquitous in cattle worldwide and is an economically significant cause of calf diarrhea, winter dysentery of adult cattle, and respiratory disease in calves and feedlot cattle. We have developed and optimized laboratory diagnostic techniques, including virus isolation in HRT-18 cell cultures, antibody and antigen ELISA, and RT-PCR, for rapid, sensitive, and reliable diagnosis of BCoV and related wild ruminant coronaviruses.


title: Salvaging CNS Clinical Trials halted due to COVID‐19

text: The COVID‐19 pandemic has halted many ongoing CNS clinical trials, especially in Alzheimer’s disease. These long‐duration trials involve many stakeholders, especially the patients and their family members, who have demonstrated their commitment to developing new therapeutic interventions for this devastating disease. We certainly do not want to lose all the knowledge we have gained from these ongoing trials because of the pandemic. While some of these trials will need to restart, others can re‐start at different points along the trial protocol with substantial protocol amendments. However, there is an urgent need to combine useful information from the completers with those subjects undergoing complex protocols deviations and amendments after re‐start. We propose the concept of mechanistic modeling‐based virtual twin patients as a possible solution to harmonize the readouts from these complex and fragmented clinical datasets in a biologically relevant way.


title: Telemedicine: a Bridge Over Knowledge Gaps in Healthcare

text: PURPOSE OF THE REVIEW: The purpose of the review is to describe the Brazilian Telemedicine University Network RUTE concerning the Special Interest Group of Children and Adolescents, the new SIG-COVID19-BR activities for continuing medical education, and to update relevant information regarding diagnosis and treatment, using digital technologies. RECENT FINDINGS: A total of 145 sessions of video and webconferences were held with the participation of 6575 health professionals, including medical students, interns, and residents. Major topics involved the healthcare of children and adolescents were combined with the emergence of a new pandemic plus the need to decrease the professional knowledge gaps in geographically distant hospitals. SUMMARY: Telemedicine is a cost-effective tool and a bridge to decrease health disparities access for proper care and assistance for any population. RUTE is a Brazilian model of telemedicine which has a positive impact attracting the participation of health professionals, and even more so, during the Covid-19 virus pandemic outbreak.


title: Healthcare workers and health care-associated infections: knowledge, attitudes, and behavior in emergency departments in Italy

text: BACKGROUND: This survey assessed knowledge, attitudes, and compliance regarding standard precautions about health care-associated infections (HAIs) and the associated determinants among healthcare workers (HCWs) in emergency departments in Italy. METHODS: An anonymous questionnaire, self-administered by all HCWs in eight randomly selected non-academic acute general public hospitals, comprised questions on demographic and occupational characteristics; knowledge about the risks of acquiring and/or transmitting HAIs from/to a patient and standard precautions; attitudes toward guidelines and risk perceived of acquiring a HAI; practice of standard precautions; and sources of information. RESULTS: HCWs who know the risk of acquiring Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) from a patient were in practice from less years, worked fewer hours per week, knew that a HCW can transmit HCV and HIV to a patient, knew that HCV and HIV infections can be serious, and have received information from educational courses and scientific journals. Those who know that gloves, mask, protective eyewear, and hands hygiene after removing gloves are control measures were nurses, provided care to fewer patients, knew that HCWs' hands are vehicle for transmission of nosocomial pathogens, did not know that a HCW can transmit HCV and HIV to a patient, and have received information from educational courses and scientific journals. Being a nurse, knowing that HCWs' hands are vehicle for transmission of nosocomial pathogens, obtaining information from educational courses and scientific journals, and needing information were associated with a higher perceived risk of acquiring a HAI. HCWs who often or always used gloves and performed hands hygiene measures after removing gloves were nurses, provided care to fewer patients, and knew that hands hygiene after removing gloves was a control measure. CONCLUSIONS: HCWs have high knowledge, positive attitudes, but low compliance concerning standard precautions. Nurses had higher knowledge, perceived risk, and appropriate HAIs' control measures than physicians and HCWs answered correctly and used appropriately control measures if have received information from educational courses and scientific journals.


title: No more business as usual: agile and effective responses to emerging pathogen threats require open data and open analytics

text: The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.


title: Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons

text: BACKGROUND: The carcinoembryonic antigen (CEA)-related cell adhesion molecules CEACAM1 (BGP, CD66a), CEACAM5 (CEA, CD66e) and CEACAM6 (NCA, CD66c) are expressed in human lung. They play a role in innate and adaptive immunity and are targets for various bacterial and viral adhesins. Two pathogens that colonize the normally sterile lower respiratory tract in patients with chronic obstructive pulmonary disease (COPD) are non-typable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. Both pathogens bind to CEACAMs and elicit a variety of cellular reactions, including bacterial internalization, cell adhesion and apoptosis. METHODS: To analyze the (co-) expression of CEACAM1, CEACAM5 and CEACAM6 in different lung tissues with respect to COPD, smoking status and granulocyte infiltration, immunohistochemically stained paraffin sections of 19 donors were studied. To address short-term effects of cigarette smoke and acute inflammation, transcriptional regulation of CEACAM5, CEACAM6 and different CEACAM1 isoforms by cigarette smoke extract, interferons, Toll-like receptor agonists, and bacteria was tested in normal human bronchial epithelial (NHBE) cells by quantitative PCR. Corresponding CEACAM protein levels were determined by flow cytometry. RESULTS: Immunohistochemical analysis of lung sections showed the most frequent and intense staining for CEACAM1, CEACAM5 and CEACAM6 in bronchial and alveolar epithelium, but revealed no significant differences in connection with COPD, smoking status and granulocyte infiltration. In NHBE cells, mRNA expression of CEACAM1 isoforms CEACAM1-4L, CEACAM1-4S, CEACAM1-3L and CEACAM1-3S were up-regulated by interferons alpha, beta and gamma, as well as the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C). Interferon-gamma also increased CEACAM5 expression. These results were confirmed on protein level by FACS analysis. Importantly, also NTHI and M. catarrhalis increased CEACAM1 mRNA levels. This effect was independent of the ability to bind to CEACAM1. The expression of CEACAM6 was not affected by any treatment or bacterial infection. CONCLUSIONS: While we did not find a direct correlation between CEACAM1 expression and COPD, the COPD-associated bacteria NTHi and M. catarrhalis were able to increase the expression of their own receptor on host cells. Further, the data suggest a role for CEACAM1 and CEACAM5 in the phenomenon of increased host susceptibility to bacterial infection upon viral challenge in the human respiratory tract.


title: PNEUMONIA | Viral

text: Viral infection accounts for a substantial proportion of cases of acute pneumonia especially among young children and the elderly, the immunocompromised, and those with comorbidities. Influenza A and respiratory syncytial virus are by far the most common causes of viral pneumonia followed by adenovirus, parainfluenza virus types 1, 2 and 3, and influenza B. Other less common agents include picornaviruses, varicella-zoster virus, herpes simplex virus, cytomegalovirus, and hantavirus. The newly identified human metapneumovirus also plays a role. Zoonotic infections caused by severe acute respiratory syndrome-associated coronavirus and avian influenza A/H5N1 are examples of acute ‘atypical’ pneumonia with epidemic and pandemic potentials. In general, there are no reliable clinical or radiological features to distinguish viral from other causes of pneumonia. Respiratory viruses often show seasonality and a predilection for certain host groups. These epidemiological features are helpful in gauging the differential diagnoses. Confirmation of infection relies on laboratory investigations based on conventional approaches including direct viral antigen detection by specific monoclonal antibodies, virus isolation, and serology, as well as modern molecular approaches to amplify viral nucleic acid present in clinical specimens. The available spectrum of antiviral agents and the window for effective application are narrow. Treatment of viral pneumonia is primarily supportive. Vaccines for general use are only available for influenza A and B.


title: Estimating the Relative Probability of Direct Transmission between Infectious Disease Patients

text: Estimating infectious disease parameters such as the serial interval (time between symptom onset in primary and secondary cases) and reproductive number (average number of secondary cases produced by a primary case) are important to understand infectious disease dynamics. Many estimation methods require linking cases by direct transmission, a difficult task for most diseases. Using a subset of cases with detailed genetic or contact investigation data to develop a training set of probable transmission events, we build a model to estimate the relative transmission probability for all case pairs from demographic, spatial and clinical data. Our method is based on naive Bayes, a machine learning classification algorithm which uses the observed frequencies in the training dataset to estimate the probability that a pair is linked given a set of covariates. In simulations we find that the probabilities estimated using genetic distance between cases to define training transmission events are able to distinguish between truly linked and non-linked pairs with high accuracy (area under the receiver operating curve value of 95%). Additionally only a small subset of the cases, 10% - 40% depending on sample size, need to have detailed genetic data for our method to perform well. We show how these probabilities can be used to estimate the average effective reproductive number and apply our method to a tuberculosis outbreak in Hamburg, Germany. Our method is a novel way to infer transmission dynamics in any dataset when only a subset of cases have rich contact investigation and/or genetic data.


title: Gambling Before and During the COVID-19 Pandemic Among European Regular Sports Bettors: An Empirical Study Using Behavioral Tracking Data

text: The novel coronavirus-2019 (COVID-19) pandemic has had major impacts on most societies worldwide including the cancelation and postponement of sports events. This has had a major impact on the sports betting industry. The present study is first to investigate the behavior of a sample of online sports bettors before and after COVID-19 measures were put in place by European governments. The authors were given access to the player data by a large European online gambling operator comprising players from Sweden, Germany, Finland, and Norway. The behavioral change of the sports bettors before March 7 and after March 7 (2020) was computed. All sports bettors who placed at least one wager in at least 5 calendar weeks out of the 10 possible calendar weeks between January 1 and March 7 (n = 5396) were included in the analysis. Results showed statistically significant reductions among sports bettors wagering in online casinos. This indicates that there was no conversion of money spent from sports betting to online casino games, at least for this particular online gambling operator. The findings suggest that there was a significant decrease in the amount of money wagered by sports bettors during the COVID-19 pandemic (compared with before it) and that sports bettors did not switch to playing more online casino games and that there was also a significant reduction in playing online casino games among sports bettors.


title: Full-length characterization and phylogenetic analysis of hemagglutinin gene of H9N2 virus isolated from broilers in Iran during 1998–2007

text: H9N2 avian influenza A viruses (AIV) have become panzootic in Eurasia over the last decade and are endemic in Iran since 1998, and inactivated vaccine has been used in chickens to control the disease. The hemagglutinin (HA), one of eight protein-coding genes, plays an important role during the early stage of infection. To study their evolution and zoonotic potential, we conducted an in silico analysis of H9N2 viruses that have infected broiler in Tehran Province, Iran between 1998 and 2007. The complete coding region of HA genes from nine H9N2 subtypes isolated from chicken flocks in Tehran Province during 1998–2007 was amplified and sequenced. Sequence analysis and phylogenetic studies of H9N2 subtype viruses on the basis of data of 9 viruses in this study and 30 selected strains are available in the GenBank. Sequence and phylogenetic analyses revealed a large number of similar substitution mutations and close evolutionary relation among sequences of HA. The isolates possessed two types of amino acid motif –R–S-S-R/G-L- and -R-S-N-R/G-L- at the cleavage site of HA. The results showed that all nine representative H9N2 isolates belong to low pathogenic AIVs since none of the amino acid sequences at the cleavage site of the HA of the isolates possessed the basic motif required for highly pathogenic viruses (R-X-R/K-R). Six out of these nine isolates possessed leucine at position 226, which prevails in the sequences found in human strains. Phylogenetic analysis showed that all our isolates belonged to the G1-like sublineage. Also, these isolates showed some degree of homology with other H9N2 isolates, e.g., 89.46–93.93.39% with qu/HK/G1/97 and 93.39–98.39% with pa/Narita/92A/98. The available evidence indicates that HA genes of H9 influenza virus circulating in Iran during the past years were not well conserved. Our finding emphasizes the importance of reinforcing AIV surveillance, especially after the emergence of high pathogenicity in poultry in Iran.


title: A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

text: Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.


Coagulopathy and mesenteric ischaemia in severe SARS‐CoV‐2 infection


title: The effect of variant interference on de novo assembly for viral deep sequencing

text: Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approach has surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. Our results from >15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This “variant interference” (VI) is highly consistent and reproducible by ten most used de novo assemblers, and occurs independent of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the “rescue” of full viral genomes from fragmented contigs. These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.


title: Coronavirus-Pandemie – Erinnerungen an die Grippe-Epidemie von 1918 aus gynäkologisch-geburtshilflicher Sicht

text: From the medical reports on the flu epidemic in 1918, there is accordance with the present-day corona pandemic. The symptoms, course and outcome all seem to show parallels. Pregnant women in the last trimester are to be classified as being particularly vulnerable. Physicians in several disciplines, e.g. gynecology, general medicine and internal medicine are equally called upon to be particularly vigilant.


title: 13 Nanomaterial-based sensors

text: Abstract This chapter deals with the advancement of nanomaterial-based sensors in the last 10 years. The use of different types of nanomaterials, including graphene, carbon nanotubes, and metallic nanoparticles, was described, highlighting that graphene represents a rising star in the plethora of nanomaterials. Among the different transducers, the chapter describes the electrochemical and optical (bio)sensors, being the most promising devices. The use of materials at the nanodimension scale provides several improvements in terms of analytical features including sensitivity, rapidity of response, selectivity, and robustness, demonstrating the huge advantage of using the nanomaterials over the micromaterials in the development of smart and high-performant analytical tools.


title: Phylodynamic analysis and evaluation of the balance between anthropic and environmental factors affecting IBV spreading among Italian poultry farms

text: Infectious bronchitis virus (IBV) control is mainly based on wide vaccine administration. Although effective, its efficacy is not absolute, the viral circulation is not prevented and some side effects cannot be denied. Despite this, the determinants of IBV epidemiology and the factors affecting its circulation are still largely unknown and poorly investigated. In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Several biostatistical and bioinformatics approaches were used to reconstruct the history of the QX genotype in Italy and to assess the effect of different environmental, climatic and social factors on its spreading patterns. Moreover, two structured coalescent models were considered in order to investigate if an actual compartmentalization occurs between the two integrated poultry companies and the role of a third “ghost” deme, representative of minor industrial poultry companies and the rural sector. The obtained results suggest that the integration of the poultry companies is an effective barrier against IBV spreading, since the strains sampled from the two companies formed two essentially-independent clades. Remarkably, the only exceptions were represented by farms located in the high densely populated poultry area of Northern Italy. The inclusion of a third deme in the model revealed the likely role of other poultry companies and rural farms (particularly concentrated in Northern Italy) as sources of strain introduction into one of the major poultry companies, whose farms are mainly located in the high densely populated poultry area of Northern Italy. Accordingly, when the effect of different environmental and urban parameters on IBV geographic spreading was investigated, no factor seems to contribute to IBV dispersal velocity, being poultry population density the only exception. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Overall, the present study results stress the crucial relevance of human action rather than environmental factors, highlighting the direct benefits that could derive from improved management and organization of the poultry sector on a larger scale.


title: In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain)

text: The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on ‘docking score’. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class ‘bronchodilators’ and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma


title: COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland

text: BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6–2143 children infected with SARS-CoV‑2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18–45% were infants <1 year of age. The duration of hospital stay was 5–20 days. Most commonly reported symptoms were fever and cough; in 40–100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.


title: Microbial threat lists: obstacles in the quest for biosecurity?

text: Anxiety about threats from the microbial world and about the deliberate misuse of microorganisms has led to efforts to define and control these dangers using lists and regulations. One list with tremendous legal implications and a potentially huge impact on research is the Select Agents and Toxins List, which was created by the US Government to limit the possession of and access to particular microorganisms and toxins. In this article, in addition to highlighting general problems with taxonomy-based, microorganism-centric lists, we discuss our view that such lists may have the paradoxical effect of increasing the societal vulnerability to biological attack and natural epidemics by interfering with the sharing of microbial samples and hindering research on vaccines and therapeutics.


title: SARS-CoV-2 neutralizing antibody development strategies

text: In December 2019 a novel coronavirus was detected in Wuhan City of Hubei Province-China. Owing to a high rate of transmission from human to human, the new virus called SARS-CoV-2 differed from others by its unexpectedly rapid spread. The World Health Organization (WHO) described the most recent coronavirus epidemic as a global pandemic in March 2020. The virus spread triggered a health crisis (the COVID-19 disease) within three months, with socioeconomic implications. No approved targeted-therapies are available for COVID-19, yet. However, it is foreseen that antibody-based treatments may provide an immediate cure for patients. Current neutralizing antibody development studies primarily target the S protein among the structural elements of SARS-CoV-2, which mediates the cell entry of the virus through the angiotensin converting enzyme 2 (ACE2) receptor of host cells. This review aims to provide some of the neutralizing antibody development strategies for SARS-CoV-2 and in vitro and in vivo neutralization assays.


title: Immunosenescence and Influenza Vaccine Efficacy

text: A number of protective immune functions decline with age along with physiological and anatomical changes, contributing to the increased susceptibility of older adults to infectious diseases and suboptimal protective immune responses to vaccination. Influenza vaccination is the most cost-effective strategy to prevent complications from influenza viral infections; however, the immunogenicity and effectiveness of currently licensed vaccines in the United States is about 30–50% in preventing complications arising from influenza and preventing death from all causes during winter months in older adults. Hence, it is crucial to understand the molecular mechanisms that lead to immune dysfunction as a function of age so that appropriate strategies can be developed to enhance the disease resistance and immunogenicity of preventive vaccines, including influenza vaccines, for the older adult population.


docid: pehpclfe

title: Eagle Filters to produce respirators in Finland

text: Loudspring Oyj's subsidiary Eagle Filters Oy has decided to start manufacturing high-quality half-mask type FFP2 and FFP3 class respirators in Finland to meet strong Covid-19 demand for personal protective equipment.


title: Utility of flexible bronchoscopy with polymerase chain reaction in the diagnosis and management of pulmonary infiltrates in allogeneic HSCT patients

text: OBJECTIVES: Pulmonary infiltrates in allogeneic hematopoietic stem cell transplant (allo‐HSCT) patients are potentially life‐threatening and require early diagnosis and treatment. We aimed to retrospectively explore the clinical efficacy of polymerase chain reaction (PCR) in conjunction with flexible bronchoscopy (FB) in allo‐HSCT patients with pulmonary infiltrates. PATIENTS AND METHODS: We retrospectively reviewed all patients undergoing FB after allo‐HSCT at the Peking University Institute of Hematology from January 2013 to December 2016. We used PCR to detect various viruses in FB specimens, particularly for 27 viruses. RESULTS: One hundred forty‐nine diagnostic FBs were performed in 130 patients. The overall diagnostic yield was 58%. Eighty‐nine percent of the patients with a positive FB result were diagnosed with a pulmonary infection. Viruses were the most common infectious diagnosis (70%), followed by fungi (48%), bacteria (38%), and Pneumocystis jirovecii (12%). Multivariate analyses showed that a chest computed tomography (CT) finding of diffuse pulmonary infiltrates (P = .012) and positive results in assisted microbiological and serological analyses (P = .000) predicted a positive FB result. FB results prompted a treatment modification in 61% of cases. CONCLUSIONS: FB in conjunction with PCR is efficient in the rapid diagnosis and management of pulmonary infiltrates in allo‐HSCT patients.


title: pH-dependent aggregation and secretion of soluble monomeric influenza hemagglutinin

text: We previously reported the expression of soluble A/Victoria/3/75 (H3N2) hemagglutinin in insect cells and the molecular and immunological structure of an aggregated fraction, only observed in cell supernatant when expression was performed at low pH [23]. Here we report that besides this aggregated a monomeric and possibly a trimeric structure is detected in cell supernatant, irrespective of the pH of the medium. Evidence is presented that the aggregated fraction is generated out of monomeric HA0s molecules due to a low intracellular pH encountered during secretion.


title: Clinical trials for the prevention and treatment of COVID‐19: current state of play

text: Since coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID‐19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID‐19; treatment of hospitalised patients with moderate COVID‐19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir–ritonavir (seven trials) and remdesevir (five trials). There are many candidate drugs in pre‐clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.


docid: rcpfdygq

title: Enfermement carcéral, confinement socio-sanitaire et moyens d’évasion.Danser sa peine et au-delà…

text: Abstract Jail incarceration and social confinement due to a sanitary stay-at-home law against the ongoing covid-19 pandemic are compared through the introduction of dance workshops for imprisoned women charged with long sentences, then followed by an outside performance Soul Kitchen. The whole experience, organized by a famous contemporary choreographer Angelin Preljocaj, is filmed by Valérie Müller, producing Danser sa peine (To dance her sentence / her sorrow), nominated for an award. The sessions are planned: two hours and a half, 2 times a week, for four months, no technique required. A group of five women starts with ordinary easy functional movements, gaining in innovative and expressive qualities, spatial perceptions, feelings and interpersonal interactions, leaded by A. Preljocaj in a helpful and empathic mood. At the same time, he discovers the cooking authorization in their jail cell. The relevant results shift into a dynamic successful piece Soul Kitchen (2019) performed in town (Dance Festival in Montpellier, south of France) with dancing and cooking occurrences on stage. It makes sense, specially about self-esteem, body image and positive opinion from the audience. The women’s physical and psychological states linked with a long lack of space and sensitivity… move to a better self-balance and feelings of well-being. In a similar state of mind, the French confined population – youth to elderly–try to find different and imaginative strategies at home as moving in a restrictive area, enjoying family cooking… through trainings provided by Internet, looking for reducing anxiety, depressive disorders and other social problems. A panel of situations goes from deleterious conflictual relationships, dramatic isolation, to funny and positive ones using creativeness to escape, facing the disruption of daily life.


title: Cathepsin W Is Required for Escape of Influenza A Virus from Late Endosomes

text: Human cathepsin W (CtsW) is a cysteine protease, which was identified in a genome-wide RNA interference (RNAi) screen to be required for influenza A virus (IAV) replication. In this study, we show that reducing the levels of expression of CtsW reduces viral titers for different subtypes of IAV, and we map the target step of CtsW requirement to viral entry. Using a set of small interfering RNAs (siRNAs) targeting CtsW, we demonstrate that knockdown of CtsW results in a decrease of IAV nucleoprotein accumulation in the nuclei of infected cells at 3 h postinfection. Assays specific for the individual stages of IAV entry further show that attachment, internalization, and early endosomal trafficking are not affected by CtsW knockdown. However, we detected impaired escape of viral particles from late endosomes in CtsW knockdown cells. Moreover, fusion analysis with a dual-labeled influenza virus revealed a significant reduction in fusion events, with no detectable impact on endosomal pH, suggesting that CtsW is required at the stage of viral fusion. The defect in IAV entry upon CtsW knockdown could be rescued by ectopic expression of wild-type CtsW but not by the expression of a catalytically inactive mutant of CtsW, suggesting that the proteolytic activity of CtsW is required for successful entry of IAV. Our results establish CtsW as an important host factor for entry of IAV into target cells and suggest that CtsW could be a promising target for the development of future antiviral drugs.


title: Nitric oxide inhibits the replication cycle of porcine parvovirus in vitro

text: This study investigated the inhibitory effect and mechanism of nitric oxide (NO) on porcine parvovirus (PPV) replication in PK-15 cells. The results showed that two NO-generating compounds, S-nitroso-l-acetylpenicillamine (SNAP) and l-arginine (LA), at a noncytotoxic concentration could reduce PPV replication in a dose-dependent manner and that this anti-PPV effect could be reversed by the NO synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME). By assaying the steps of the PPV life cycle, we also show that NO inhibits viral DNA and protein synthesis. This experiment provides a frame of reference for the study of the anti-viral mechanism of NO.


title: Phylogenetic perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses

text: Abstract Severe Acute Respiratory Syndrome (SARS) is a respiratory disease caused by a zoonotic coronavirus (CoV) named SARS-CoV (SCoV), which rapidly swept the globe after its emergence in rural China during late 2002. The origins of SCoV have been mysterious and controversial, until the recent discovery of SARS-like CoV (SLCoV) in bats and the proposal of bats as the natural reservior of the Coronaviridae family. In this article, we focused on discussing how phylogenetics contributed to our understanding towards the emergence and transmission of SCoV. We first reviewed the epidemiology of SCoV from a phylogenetic perspective and discussed the controversies over its phylogenetic origins. Then, we summarized the phylogenetic findings in relation to its zoonotic origins and the proposed inter-species viral transmission events. Finally, we also discussed how the discoveries of SCoV and SLCoV expanded our knowledge on the evolution of the Coronaviridae family as well as its implications on the possible future re-emergence of SCoV.


Zoonoses: Infectious Diseases Transmissible From Animals to Humans, Fourth Edition


title: Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes

text: Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated for the first time that the mammalian reovirus strains Masked Palm Civet/China/2004 (MPC/04) and Bat/China/2003 (B/03) can induce transient activation of the PI3K/Akt pathway early in infection in vitro. When UV-treated, both viruses activated PI3K/Akt signaling, indicating that the virus/receptor interaction was sufficient to activate PI3K/Akt. Reovirus virions can use both clathrin- and caveolae-mediated endocytosis, but only chlorpromazine, a specific inhibitor of clathrin-mediated endocytosis, or siRNA targeting clathrin suppressed Akt phosphorylation. We also identified the upstream molecules of the PI3K pathway. Virus infection induced phosphorylation of focal adhesion kinase (FAK) but not Gab1, and blockage of FAK phosphorylation suppressed Akt phosphorylation. Blockage of PI3K/Akt activation increased virus RNA synthesis and viral yield. We also found that reovirus infection activated the IFN-stimulated response element (ISRE) in an interferon-independent manner and up-regulated IFN-stimulated genes (ISGs) via the PI3K/Akt/EMSY pathway. Suppression of PI3K/Akt activation impaired the induction of ISRE and down-regulated the expression of ISGs. Overexpression of ISG15 and Viperin inhibited virus replication, and knockdown of either enhanced virus replication. Collectively, these results demonstrate that PI3K/Akt activated by mammalian reovirus serves as a pathway for sensing and then inhibiting virus replication/infection.


title: Preparation for and organization during a major incident

text: Major incidents during the past 30 years have caused the NHS and other agencies to respond in a coordinated fashion and create the comprehensive Emergency Preparedness, Resilience and Response framework 2013. This along with supporting documents gives a detailed structure of the role of the NHS in any type of major incident from man-made disaster to pandemic flu. This has required preparation of communication, transport, security, military and healthcare systems. Included is also how the response is handled at a more local level and for different levels of response. The Royal Colleges have responded by including specialist training at the higher and advanced level for trainees so that victims are triaged at the scene and received by consultants with appropriate training in such work. Hospitals, ambulance services and intensive care units across the country are able to use networks to ensure not only logical and rapid access to major trauma centres but also to network highly sophisticated skills when advanced life support is required. The NHS is better able to cope with major incidents than ever before.


title: Extension Horses, Inc. experts act fast to create online resources to assist the horse industry during COVID-19

text: The COVID-19 pandemic and resulting stay-at-home directives, adopted out of necessity to protect human health, introduced significant challenges for horse owners and small equine businesses. Restricted access, and in many cases closure of barns, resulted in a multitude of questions and concerns within the equine community which needed to be addressed rapidly. Extension Horses, Inc. (EH) coordinated the development and delivery of a variety of educational resources utilizing a combination of online formats and dissemination through social media and EH member contact lists. A series of infographics, webinars, and podcasts (three in each category) were created to provide guidance on essential care of horses, emergency preparedness, financial assistance, legal concerns, and biosecurity during the crucial, initial weeks of the pandemic (March-April, 2020). Web conferencing technology (Zoom) was used to facilitate discussion and task delegation among EH members and to conduct and record webinars and podcasts. Podcasts were hosted on Buzzsprout and infographics were created using Adobe InDesign. Live webinar participants were invited to participate in several polls during the webinar and were sent a brief survey to complete at the end of the webinar series. Analytics for all educational resources combined demonstrated a 32-day total direct reach of 135,563. Most live webinar participants identified themselves as horse owners and small equine business owners (55%). The majority of live webinar participants indicated the information was useful (99%), and they would utilize the resources they had learned about (80%). Survey respondents said that Facebook, email, and word of mouth were key ways in which they learned about the webinars. The same survey found that the web-platform was an effective method to receive information (85% high satisfaction) and respondents were highly likely to recommend future EH webinars to others (88%). The three infographics had a total Facebook reach of 131,765, the webinars had 3,522 total views, and the three podcasts had 276 total downloads. The rapid response of EH and quick turnaround of products allowed a large online audience to receive vital information for coping with COVID-19. Having the established EH network, already familiar with virtual education, was a big asset in this effort. This can serve as a model for cooperative extension to utilize in future collaborative responses to industry issues.


title: Respiratory Picornaviruses and Respiratory Syncytial Virus as Causative Agents of Acute Expiratory Wheezing in Children

text: We studied the viral etiology of acute expiratory wheezing (bronchiolitis, acute asthma) in 293 hospitalized children in a 2-year prospective study in Finland. A potential causative viral agent was detected in 88% of the cases. Eleven different viruses were represented. Respiratory syncytial virus (RSV) (27%), enteroviruses (25%), rhinovirus (24%), and nontypable rhino/enterovirus (16%) were found most frequently. In infants, RSV was found in 54% and respiratory picornaviruses (rhinovirus and enteroviruses) in 42% of the cases. In older children, respiratory picornaviruses dominated (65% of children ages 1-2 years and 82% of children ages >3 years). Human metapneumovirus was detected in 4% of all children and in 11% of infants. To prevent and treat acute expiratory wheezing illnesses in children, efforts should be focused on RSV, enterovirus, and rhinovirus infections.


title: Transcriptomics in lung tissue upon respiratory syncytial virus infection reveals aging as important modulator of immune activation and matrix maintenance

text: Aging poses an increased risk of severe infection by respiratory syncytial virus (RSV). The many different biological pathways comprising the response to infection in lungs that are influenced by aging are complex and remain to be defined more thoroughly. Towards finding new directions in research on aging, we aimed to define biological pathways in the acute response to RSV that are affected in the lungs by aging. We therefore profiled the full transcriptome of lung tissue of mice prior to and during RSV infection both at young and old age. In the absence of RSV, we found aging to downregulate genes that are involved in constitution of the extracellular matrix. Moreover, uninfected old mice showed elevated expression of pathways that resemble injury, metabolic aberrations, and disorders mediated by functions of the immune system that were induced at young age only by an exogenous trigger like RSV. Furthermore, infection by RSV mounted stronger activation of anti-viral type-I interferon pathways at old age. Despite such exaggerated anti-viral responses, old mice showed reduced control of virus. Altogether, our findings emphasize important roles in aging-related susceptibility to respiratory disease for extracellular matrix dysfunctions and dysregulated immune activation in lungs.


title: Responding to Emerging Diseases Requires Multi-disciplinary and One Health Training, Egypt

text: BACKGROUND: In Egypt, several infectious diseases of zoonotic origin have emerged in recent years like H1N1, MERSCoV and H5N1, the latter now endemic. Responding to these diseases requires a workforce trained in multi-disciplinary approaches to zoonotic disease research and control. It is difficult to deliver multidisciplinary and one health training globally because of the limited number of higher education programs that support such training. In low and middle-income countries where the impacts of emerging zoonotic diseases are felt more directly there is enthusiasm for such training and the use of e-technology can foster international, long-term collaborations. OBJECTIVES: To provide health training for infectious diseases research and to foster multidisciplinary collaboration. METHODS: We designed and simultaneously held two training workshops, one focused on pediatric infectious diseases and another on emerging infectious diseases to meet the objective. Both workshops had pre- and post-workshop activities for multi-disciplinary methods with an emphasis on the use of mobile technologies to enhance emerging infectious diseases surveillance and research for public health professionals in Egypt. Faculty and scientists from all universities in Egypt and from the National Research Center were invited to participate. RESULTS: 85 participants attended, 31 abstracts were submitted, and over a 3 year period 3 international grant applications were submitted, and 4 abstracts were presented at international conferences. An online forum was developed to continue building collaboration. CONCLUSIONS: Interactive on-site workshops are suitable for providing multi-disciplinary training for disease surveillance, research and disease control. Participants shared the opinion that grant proposal and scientific manuscript writing were important skills that they felt they did not have. Long term investments in workshops of this nature are needed to build upon the excitement generated by these activities.


title: A Transgenic Flock House Virus Replicon Reveals an RNAi Independent Antiviral Mechanism Acting in Drosophila Follicular Somatic Cells

text: The small interfering RNA (siRNA) pathway is the main and best studied invertebrate antiviral response. Other poorly characterized protein based antiviral mechanisms also contribute to the control of viral replication in insects. In addition, it remains unclear whether tissue specific factors contribute to RNA and protein-based antiviral immunity mechanisms. In vivo screens to identify such factors are challenging and time consuming. In addition, the scored phenotype is usually limited to survival and/or viral load. Transgenic viral replicons are valuable tools to overcome these limitations and screen for novel antiviral factors. Here we describe transgenic Drosophila melanogaster lines encoding a Flock House Virus-derived replicon (FHV∆B2eGFP), expressing GFP as a reporter of viral replication. This replicon is efficiently controlled by the siRNA pathway in most somatic tissues, with GFP fluorescence providing a reliable marker for the activity of antiviral RNAi. Interestingly, in follicular somatic cells (FSC) of ovaries, this replicon is still partially repressed in an siRNA independent manner. We did not detect replicon derived Piwi-interacting RNAs in FSCs and identified 31 differentially expressed genes between restrictive and permissive FSCs. Altogether, our results uncovered a yet unidentified RNAi-independent mechanism controlling FHV replication in FSCs of ovaries and validate the FHV∆B2eGFP replicon as a tool to screen for novel tissue specific antiviral mechanisms.


title: COVID (Co-Operative Vascular Intervention Disease) Team of Greater Philadelphia

text: We established the COVID (Co-OperativeVascularInterventionDisease) Team of Greater Philadelphia because national guidelines may not apply to different geographic areas of the United States due to varying penetrance of the virus. On April 10, 2020, a ten-question survey regarding issues and strategies dealing with COVID-19 was e-mailed to 58 VSs in the Greater Philadelphia area. Fifty-four VSs in 18 surgical groups covering 28 hospitals responded. All groups accepted transfers due to continued ICU bed availability. Thirteen groups were asked to “re-deploy” if the need arose to function outside of the usual duties of a VS. None imposed age restrictions regarding older VSs continuing clinical hospital work. The majority restricted non-invasive vascular laboratory studies to those studies where findings might mandate intervention within 2-3 weeks, restricted dialysis access operations to urgent revisions of arteriovenous fistulas (AVFs)/ grafts that were failing or had ulcerations, converted from in-person to telemedicine clinic interactions, and experienced moderate/severe anxiety or fear about personal COVID-19 exposure in the hospital. The majority of VSs in the Philadelphia area have dramatically adjusted their clinical practices before the COVID-19 crisis reached peak levels experienced in other metropolitan areas.


title: Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent

text: Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.


docid: thobsldp

title: Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition

text: Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.


title: Smell and taste alterations in Covid‐19: a cross‐sectional analysis of different cohorts

text: BACKGROUND: : Olfactory (OD) and gustatory (GD) dysfunction have been proven to be a typical symptom of SARS‐CoV‐2 infection. However, their prevalence in different patient populations still needs to be clarified. METHODS: : A cross‐sectional study was performed from March 27 to April 1 2020 in Northern Italy. Physicians administered a survey‐based questionnaire to SARS‐CoV‐2 positive patients with the aim of assessing symptoms, focusing on OD and GD. Two groups were studied: patients hospitalized at ASST Spedali Civili University Hospital of Brescia (A); home‐quarantined subjects (B). RESULTS: : A total of 508 patients were enrolled: 295 in Group A and 213 in Group B. Mean age (±SD) was 55±15 years; 56% were men. Overall, OD and GD were present in 56% (95% CI 51‐60%) and 63% (59‐67%) of cases, respectively. In Group A, the prevalence of OD and GD was 44% (38‐50%) and 52% (46‐58%). In Group B, the prevalence of OD and GD was 72% (65‐79%) and 79% (73‐84%). In the entire cohort, total loss of olfaction and taste was reported in 64% and 60% of cases, respectively. OD and GD occurred as the first symptom in 10% and 11% of cases; in the remaining cases, they occurred after a mean of 4±3 days following the first symptom. At the time of the questionnaire, complete resolution of OD and GD was reported in 52% and 55% of cases (mean duration: 9±5 in both). CONCLUSIONS: : OD and GD are more prevalent in home‐quarantined subjects, and they are independently associated with younger age and female gender. This article is protected by copyright. All rights reserved


title: Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

text: BACKGROUND: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. METHODS: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10(6) (IQR 0.50 × 10(6)) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. FINDINGS: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. INTERPRETATION: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. FUNDING: None.


title: Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus replication at its physiologic concentration

text: This study was conducted to examine the effect of cystatin D, a newly discovered salivary cysteine protease inhibitor, on human coronavirus replication. When MRC‐5, human diploid lung cells, were incubated with dilutions of recombinant human cystatin D from 0.65–10 μM for 1 h prior to, during and after infection with coronavirus OC43 and 229e strains, a decrease in virus yield was observed resulting in an IC(50) of 0.8 μM for both virus strains. This dose is within the normal concentration range of cystatin D, 0.12–1.9 μM found in saliva. When a single dose, 2.5 μM, was applied, cystatin inhibition of release of virus progeny was not overcome until three days post infection whereas inhibition by leupeptin, a serine and cysteine protease inhibitor, was completely abrogated by two days. When cellular toxicity was measured by (3)H‐thymidine uptake, cystatin D did not markedly affect cell proliferation below a 10 μM dose. The results demonstrate that cystatin D is a potent inhibitor of coronavirus replication.


title: Chapter 21 Gnotobiotics and the Microbiome

text: Abstract This chapter provides an overview of germfree (GF), gnotobiotic (GN), and defined flora (DF) laboratory rats, relating their history, traditional and modern derivation procedures, the anatomy and physiology, and their use in the study of mammalian host–microbiome relationships. Extensive literature on the nutrition and physiology of GF rats and the expanding library of immunological reagents have increased the research utility of GF, GN, or DF rats. Such rats have been extensively used in metabolic experiments as nucleus seed stocks for the production of disease-free animals and as tools for infectious disease studies, among others. The chapter also presents research applications of GF rats that are particularly suitable for testing candidate viral carcinogens since they are uniquely free of all known viruses, for pathology studies in the distinguishing of primary mediation lesions from those associated with infections, and the study of the biological effects of radiation.


title: COVID and CopMich: comparing and contrasting COVID-19 experiences in the USA and Scandinavia

text: On 11 March 2020, the World Health Organization declared SARS-CoV-2 and its associated disease, COVID-19, a global pandemic. Across the world, governments took action to slow the spread and hospitals rushed to accommodate an influx of patients with this highly infectious and lethal disease. The urology departments in Ann Arbor, Michigan, USA, and Herlev and Gentofte, Copenhagen, Denmark — which are linked by the pre-existing CopMich Collaborative — had to respond with massive changes to the organization, staffing and workload of their teams. In this Viewpoint, authors from different urological subspecialties and at different career stages reflect on their experiences during the pandemic. Although their countries’ responses to the COVID-19 pandemic differed radically, the similarities between the responses in Copenhagen and Michigan demonstrate the universal characteristics of medicine and the value of teamwork, flexibility and collaboration.


title: Detection of Clostridium perfringens alpha toxin gene in lambs by loop mediated isothermal amplification

text: AIM: The loop mediated isothermal amplification (LAMP) was standardized for rapid detection of Clostridium perfringens. MATERIALS AND METHODS: A total of 120 fecal samples were collected from enterotoxemia suspected lambs were used for screening of C. perfringens cpa gene by LAMP. The specificity of the LAMP amplified products was tested by digesting with restriction enzyme XmnI for alpha toxin gene. RESULTS: Out of 120 samples screened 112 (93.3%) samples were positive by both LAMP and polymerase chain reaction (PCR) for detection of cpa gene which indicated the equal sensitivity of both the tests. The enzyme produced single cut in 162 base pair amplified product of alpha toxin gene at 81 base pair resulting in a single band in gel electrophoresis. CONCLUSION: Both LAMP and PCR for detection of cpa gene indicated the equal sensitivity of both the tests. Standardization of LAMP reaction for amplification of epsilon and beta toxin genes will help to identify the C. perfringens toxin types from the clinical samples. The test could be a suitable alternative to the PCR in detection of toxin types without the help of sophisticated machinery like thermal cycler. Considering its simplicity in operation and high sensitivity, there is the potential use of this technique in clinical diagnosis and surveillance of infectious diseases.


title: Aligning Student‐Led Initiatives and Incident Command System Resources in a Pandemic

text: Removed from classrooms and clinics amid the COVID‐19 pandemic, health professions students have answered the call to serve alternate roles by rapidly mobilizing to address health system and community‐identified needs in innovative ways. Many institutions, including the University of Nebraska Medical Center (UNMC), have formally recognized student roles by adding service learning requirements to adapted curricula. Although the crisis has spurred an explosion of student‐led volunteer initiatives, many risk operating beyond the protection of their academic institution and could bolster their efficacy by harnessing institutional resources.


title: A nation-wide epidemiological study of acute bovine respiratory disease in France

text: Abstract Acute bovine respiratory disease (ABRD) is a respiratory syndrome caused by various infectious agents, and represents a major economic and health problem in cattle herds worldwide. The aim of the study was to present how we can describe the epidemiological characteristics of ABRD in France, including risk factor analysis and spatio-temporal pattern investigation. The data were collected by specialized surveyors during the 2001 animal survey conducted by the French Ministry for Agriculture and Fisheries, from a representative sample of cattle herds. The health questionnaire concerned farm characteristics, practice of BRD vaccination, presence of ABRD, time of occurrence and number of affected animals for the period November 2000–October 2001. After a descriptive analysis of the syndrome, a space–time scan statistic was performed to detect potential clusters, and a logistic regression model was used for analysis of risk factors. The study sample included 16,581 cattle herds as representative of the 260,000 French herds. The ABRD cumulative incidence at farm level was 9.8%, the cumulative incidence at animal level was 2.1%, the cumulative mortality 0.1% and the lethality proportion 6.5%. ABRD occurred mainly during cold months with an epidemic peak in December. Spatial repartition of the syndrome showed that the whole territory was affected, with a higher number of cases in the north-east region, the main bovine production area in France. Three space–time clusters were identified in the period November 2000–February 2001. ABRD was significantly associated with production type, herd size, and BRD vaccination. Beef herds were less affected than dairy herds, and increased herd size increased the risk of ABRD. The outbreak was clustered in space and time, suggesting a common infectious agent for the epidemic in the detected areas. The influence of production type and herd size on syndrome occurrence highlighted the importance of management practices, human movement and animal density.


title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China

text: There is currently a global outbreak of coronavirus disease 2019 (COVID-19), and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported. Describe the epidemic characteristics of COVID-19 in Jingmen, Hubei, introduce the local prevention and control experience, and observe the impact of various prevention and control measures on the number of new cases. All the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29, 2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic. Of the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range, 2–88 years; IQR, 35–60). Thirty-three severe patients with a median age of 66 years (range, 33–82 years, IQR, 57–76) were treated in intensive care units; out of these patients, 66.7% (22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures. In conclusion, all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious, control measures have proven to be very effective, particularly wearing masks, which could prevent most infections.


title: How to deal with COVID-19 epidemic-related lockdown physical inactivity and sedentary increase in youth? Adaptation of Anses’ benchmarks

text: Faced with the spread of the SARS-CoV-2 virus, regulatory measures aiming to prevent interpersonal contaminations have been undertaken and among these, lockdown. Due to strong restrictions out-of-home movements, we hypothesize that overall physical activity will decrease and sedentary behavior increase. This could result in highest exposure to the well-known risk related to insufficient physical activity. To mitigate physical inactivity and sedentary behaviors health-related risks related to children and adolescents lockdown and school closure, Anses (French Agency for Food, Environmental and Occupational Health & Safety) has adapted, within the first days of the public authorities’ prescription, its former benchmarks. This paper supports and comments Anses’ Opinion by raising the questions of whether, why, and how to deal with short- or medium-term lockdown-related physical inactivity and sedentary behavior increases. Short-term and unknown long term-impacts on mental health and well-being, physical fitness and eating behaviors clearly appearing for children and adolescents as being the main issues of concern are highlighted. Targeting the compensations of the physical inactivity increase, the types, frequencies and durations of physical activity, are adapted to restricted environment. Sedentary behavior limitation and frequent interruptions becomes a priority. Overall, considering children and adolescents, the emerging risk justifies proposing specific adaptations and type of activities in order to ensure maintaining health underpinned, at least partly, by physiological equilibrium and physical fitness and avoid the installation of new unhealthy habits or routines that young people could keep after lockdown.


title: Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?

text: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro.


New Strategy for COVID-19: An Evolutionary Role for RGD Motif in SARS-CoV-2 and Potential Inhibitors for Virus Infection


title: COVID‐19: Face masks and human‐to‐human transmission

text: In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections，it may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.


GeneOne Life Science


title: Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers

text: BACKGROUND: We retrospectively analysed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers. METHODS: Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 RNA testing were obtained. RESULTS: Twenty-two patients (84.6%) correlated with clustering occurrence. The median period from contact to diagnosis and the last positive nucleic acid test was 19 (8–24 days) and 21.5 days (10–36 days), respectively. The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n=16, 61.5%; 7.5 days [2–20 days]) and patients with typical ground-glass or patchy opacities on CT(n=10, 38.5%; 12.5 days[8–22 days]; P<0.01). Seven patients (70.0%) with initial positive nucleic acid test results had a negative result simultaneously with improved CT findings. Obvious improvement in CT findings was observed in three patients (30.0%) despite positive nucleic acid test results. CONCLUSION: In asymptomatic patients, changes in biochemical and inflammatory variables are small and changes on chest CT can occur. It is worth noting the long existence of SARS-CoV-2 in some asymptomatic patients and false-negative results need to be considered in SARS-CoV-2nucleic acid test.


XI SOLANEP International Congress / XV Cystic Fibrosis Latinamerican Congress / XV Brazilian Congress of Pediatric Pulmonology


title: Experiences from the 2014 outbreak of bluetongue in Greece

text: Abstract Objective of this paper was to review relevant work and to present a general account of the bluetongue outbreak, which occurred in Greece in 2014. In total, 2895 outbreaks of the disease have been reported by the veterinary authorities of Greece; sheep, goats and cattle were affected with officially reported morbidity rates of 11.0%, 2.0% and 3.5%, respectively. No vaccinations were allowed and conservative measures were implemented to attempt to limit the disease, which at the end had expanded throughout the country. In field investigations, a significantly higher bluetongue morbidity rate (27.5%) in sheep has been reported. During that work, clinical anaemia was encountered, which was characterised as macrocytic, hypochromic, regenerative and non-haemolytic. Other investigations, which are reviewed in this paper, have described an outbreak of Citrobacter freundii-associated enteritis in newborn kids, offspring of goats subclinically infected with Bluetongue virus, increased rate of early embryonic deaths, reduced conception rates, increased incidence risk of mastitis and reduced milk yield in herds of subclinically-infected cattle and detection of the virus from hunter-harvested tissue samples of roe-deer. In 2015, vaccines against the disease have been licenced; vaccinations started in May 2015. Then, in 2015, only one outbreak of the disease was confirmed, which could have been the result of a combination of reasons acting concurrently to prevent further cases.


title: Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover

text: BACKGROUND: The recent SARS‐CoV‐2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease‐19 (COVID‐19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS‐CoV‐2. Therefore, we evaluated the outcome of SARS‐CoV‐2 infection in patients with inborn errors of immunity (IEI) such as X‐linked agammaglobulinemia (XLA). METHODS: When the SARS‐CoV‐2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS‐CoV‐2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID‐19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X‐linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID‐19, as diagnosed by SARS‐CoV‐2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS‐CoV‐2 infection, but can recover from infection, suggesting that B‐cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.


title: Influenza vaccination in patients with asthma: effect on peak expiratory flow, asthma symptoms and use of medication

text: Abstract This pilot study was undertaken to examine whether killed influenza vaccine causes exacerbations in asthmatic adults. Thirty-three stable asthmatics recorded peak expiratory flow (PEF), asthma symptoms, and use of asthma medication for 2 weeks, and then received killed influenza vaccine. Thereafter they recorded PEF, asthma symptoms and use of medication for a further 2 weeks. Comparison of recordings during the 2 weeks before and after vaccination revealed that influenza vaccine was not associated with reduction in PEF (P=0.76), increase in asthma symptoms (P=0.17) or use of asthma medication (P=0.58). Similar results for PEF (P=0.49), asthma symptoms (P=0.17), and asthma medication (P=0.16) were obtained when the analysis was restricted to the 2 days before and after vaccination.


title: A DEDICATED PATH TO EMERGENT THORACIC SURGERY IN COVID-19 PATIENTS: AN ITALIAN INSTITUTION PROTOCOL

text: Abstract The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic pointed out that the need to ensure emergent surgery in positive for infection patients is no longer hypothetical. Among emergency procedures, thoracic surgical operations are frequent. A standardized surgical pathway is mandatory in order to achieve effective and safe management of this subset of patients. We briefly present the protocol adopted by our thoracic surgery division.


title: Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania

text: OBJECTIVE: A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. METHODS: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. CONCLUSION: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.


title: Pandemic Influenza and Hospital Resources

text: Using estimates from the Centers for Disease Control and Prevention, the World Health Organization, and published models of the expected evolution of pandemic influenza, we modeled the surge capacity of healthcare facility and intensive care unit (ICU) requirements over time in northern Netherlands (≈1.7 million population). We compared the demands of various scenarios with estimates of maximum ICU capacity, factoring in healthcare worker absenteeism as well as reported and realistic estimates derived from semistructured telephone interviews with key management in ICUs in the study area. We show that even during the peak of the pandemic, most patients requiring ICU admission may be served, even those who have non–influenza-related conditions, provided that strong indications and decision-making rules are maintained for admission as well as for continuation (or discontinuation) of life support. Such a model should be integral to a preparedness plan for a pandemic with a new human-transmissible agent.


title: Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

text: Abstract Cholesterol 25-hydroxylase (CH25H) has been shown lately to be a host restriction factor that encodes an enzyme, which catalyzes the oxidized form of cholesterol to 25-hydroxycholesterol (25HC). A series of studies have shown that 25HC activity in hosts plays a vital role in inhibiting viral infection. In this study, we explored the antiviral effect of CH25H and 25HC on porcine epidemic diarrhea virus (PEDV), which causes high mortality rates in newborn piglets with severe diarrhea, and considerable financial loss in the swine industry worldwide. Our results showed that PEDV infection downregulated the expression of CH25H in Vero cells. An overexpression and knockdown assay indicated that CH25H has significant antiviral action against PEDV, and a CH25H mutant (CH25H-M) that lacks hydroxylase activity also retains antiviral activity to a lesser extent. Furthermore, 25HC had a broad-spectrum antiviral effect against different PEDV strains by blocking viral entry. In addition, CH25H and 25HC inhibited the replication of porcine transmissible gastroenteritis virus (TGEV). Taken together, CH25H as a natural host restriction factor could inhibit PEDV and TGEV infection.


title: Development of duplex real-time PCR for detection of two DNA respiratory viruses

text: Abstract A method was developed for the detection and quantitation of HAdV (human adenovirus) and HBoV (human bocavirus) based on a duplex real-time PCR, the AB PCR, using a Smartcycler instrument. A control real-time PCR was carried out on albumin DNA to standardise the non-homogenous respiratory samples. No cross-reactivity was observed with viruses or bacteria that could be found in the respiratory tract. The diagnosis rate using the AB PCR on clinical samples was 10.7%: 3.4% for HBoV detection, 6.9% for HAdV detection and 0.3% double detection HBoV–HAdV. The clinical and epidemiological characteristics of the HAdV- and HBoV-infected patients were evaluated. In the HAdV-positive group and the HBoV-positive group the samples were classified according to the severity of the disease. The HAdV viral load did not appear to be linked to the severity of the disease. Conversely, the difference between the two HBoV groups, severe and non-severe, was significant statistically when the comparison was based on the viral load (P =0.006) or after adjustment of the viral load to the number of cells in the samples (P =0.02).


title: Acute phase response to Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ infection in FIV-infected and non-FIV-infected cats

text: The pathogenicity of Haemoplasma spp. in cats varies with ‘Candidatus Mycoplasma haemominutum’ (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7–14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16–44 pi to half of the Mhf-infected cats, and on days 49–77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species.


title: 8 Sanitary and environmental aspects of sewage sludge management

text: Abstract Currently, sewage sludge management is a huge challenge in the field of environmental engineering. New effective solutions for the treatment of wastewater led to an improvement of the quality of the final effluent but considerably increased the volume of produced sewage sludge, which increases each year. Two points of view conflict regarding the recycling of those “wastes.” Primarily, dehydrated sewage sludge is considered a reservoir of nutrients and organic matter that can be used as a fertilizer in agriculture or as an organic amendment in the remediation of contaminated sites or to build “anthroposoils.” On the other hand, recycled sewage sludge is seen as a potential source of soil contamination by organic and inorganic pollutants and pathogens; potentially toxic elements (such as zinc, copper, cadmium, lead, silver, etc.); polycyclic aromatic hydrocarbons (PAH); polychlorobiphenyls (PCB); biocides and phytopharmaceuticals; pharmaceuticals, personal care products (PPCP), and residuals; synthetic hormones; microplastics; nanotechnology life cycle end products; and microorganisms such as Escherichia coli O157:H7 or Salmonella typhimurium. This chapter will focus on these aspects, highlighting the health and ecotoxicological risks associated with the presence of such contaminants in sludge. The environmental dangers of sludge spreading on soils will be presented as well as their possible treatment scenarios to propose an acceptable reuse of sewage sludge in a circular economy.


title: Clinical Characteristics of Asthmatic Patients With Influenza-Like Illness and Risk for Severe Exacerbations in Mexico

text: Abstract Background Patients with chronic inflammatory lung diseases, such as asthma, are at higher risk for influenza-like illness (ILI) complications. Viral infections are known to trigger asthma exacerbations, but a thorough description of the clinical characteristics of ILI-associated asthma exacerbations and the role of viruses as a risk factor for severe exacerbation (SE) in ILI has not been published yet. Objective To investigate risk factors for SE in patients with ILI and asthma. Methods Patients with ILI symptoms were recruited from 6 hospitals of Mexico (LaRed sites) during 2010 to 2014. Those with a previous asthma diagnosis and ILI symptoms and who were 5 years or older were included. Patients were assigned as cases or controls based on symptoms reported. SE was defined when participants presented with wheezing or dyspnea and required hospitalization. Results A total of 486 patients with ILI and a diagnosis of asthma were included. There were no differences in the proportion, number, or type of viral illness among those with and without SE. Those with SE were less likely to report ILI symptoms. Muscle pain and nasal drip were predictors for patients not progressing to SE. A delay in seeking medical care was associated with SE (odds ratio, 2.93; 95% CI, 1.46-5.88). Conclusion The presence of a particular virus did not predict SE. ILI symptoms in asthma patients are not associated with severe exacerbation. Patients with asthma should be encouraged to seek early medical care when ILI symptoms are first noticed to prevent serious complications.