title: Fighting COVID-19: Integrated Micro- and Nanosystems for Viral Infection Diagnostics

text: The pandemic of coronavirus disease 2019 (COVID-19) highlights the importance of rapid and sensitive diagnostics of viral infection that enables the efficient tracing of cases and the implementation of public health measures for disease containment. The immediate actions from both academia and industry have led to the development of many COVID-19 diagnostic systems that have secured fast-track regulatory approvals and have been serving our healthcare frontlines since the early stage of the pandemic. On diagnostic technologies, many of these clinically validated systems have significantly benefited from the recent advances in micro- and nanotechnologies in terms of platform design, analytical method, and system integration and miniaturization. The continued development of new diagnostic platforms integrating micro- and nanocomponents will address some of the shortcomings we have witnessed in the existing COVID-19 diagnostic systems. This Perspective reviews the previous and ongoing research efforts on developing integrated micro- and nanosystems for nucleic acid-based virus detection, and highlights promising technologies that could provide better solutions for the diagnosis of COVID-19 and other viral infectious diseases. With the summary and outlook of this rapidly evolving research field, we hope to inspire more research and development activities to better prepare our society for future public health crises.


title: Bioinformatics and evolutionary insight on the spike glycoprotein gene of QX-like and Massachusetts strains of infectious bronchitis virus

text: BACKGROUND: Infectious bronchitis virus (IBV) is a Gammacoronavirus of the family Coronaviridae and is a causative agent of an economically important disease in poultry. The spike glycoprotein of IBV is essential for host cell attachment, neutralization, and is involved in the induction of protective immunity. Previously obtained sequence data of the spike gene of IBV QX-like and Massachusetts strains were subjected to bioinformatics analysis. FINDINGS: On analysis of potential phosphorylation sites, the Ser542 and Ser563 sites were not present in Massachusetts strains, while QX-like isolates did not have the Ser534 site. Massachusetts and QX-like strains showed different cleavage site motifs. The N-glycosylation sites ASN-XAA-SER/THR-55, 147, 200 and 545 were additionally present in QX-like strains. The leucine-rich repeat regions in Massachusetts strains consisted of stretches of 63 to 69 amino acids, while in the QX-like strains they contained 59 amino acids in length. An additional palmitoylation site was observed in CK/SWE/082066/2010 a QX-like strain. Primary structure data showed difference in the physical properties and hydrophobic nature of both genotypes. The comparison of secondary structures revealed no new structural domains in the genotypic variants. The phylogenetic analyses based on avian and mammalian coronaviruses showed the analysed IBV as closely related to turkey coronaviruses and distantly related to thrush and munia coronaviruses. CONCLUSION: The study demonstrated that spike glycoprotein of the Massachusetts and the QX-like variants of IBV are molecularly distinct and that this may reflect in differences in the behavior of these viruses in vivo.


title: Community acquired respiratory virus infections in adult patients undergoing umbilical cord blood transplantation

text: Characteristics and risk factors (RFs) of community-acquired respiratory virus (CARV) infections after umbilical cord blood transplantation (UCBT) are lacking. We retrospectively analyzed CARV infections in 216 single-unit myeloablative UCBT recipients. One-hundred and fourteen episodes of CARV infections were diagnosed in 62 (29%) patients. Upper respiratory tract disease (URTD) occurred in 61 (54%) whereas lower respiratory tract disease (LRTD) in 53 (46%). The 5-year cumulative incidence of CARV infection was 29%. RFs for developing CARV infections were: prednisone-based graft-versus-host disease (GVHD) prophylaxis and grade II–IV acute GVHD. RFs analysis of CARV progression to LRTD identified 2007–2009 period and absolute lymphocyte count (ALC) < 0.5 × 10(9)/L. ALC < 0.5 × 10(9)/L had a negative impact on day 60 mortality in both overall CARV and those with LRTD, whereas proven LRTD was associated with higher day 60 mortality. CARV infections had a negative effect on non-relapse mortality. Overall survival at day 60 after CARV detection was significantly lower in recipients with LRTD compared with URTD (74% vs. 93%, respectively). In conclusion, CARV infections after UCBT are frequent and may have a negative effect in the outcomes, in particular in the context of lymphocytopenia.


Peaceful Goodbyes: Providing End‐of‐Life Care to Patients with COVID‐19


title: Time required to initiate outbreak and pandemic observational research

text: Abstract Purpose Observational research focused upon emerging infectious diseases such as Ebola virus, Middle East respiratory syndrome, and Zika virus has been challenging to quickly initiate. We aimed to determine the duration of start-up procedures and barriers encountered for an observational study focused upon such infectious outbreaks. Materials and methods At 1 pediatric and 5 adult intensive care units, we measured durations from protocol receipt to a variety of outbreak research milestones, including research ethics board (REB) approval, data sharing agreement (DSA) execution, and patient study screening initiation. Results The median (interquartile range) time from site receipt of the protocol to REB submission was 73 (30-126) days; to REB approval, 158 (42-188) days; to DSA completion, 276 (186-312) days; and to study screening initiation, 293 (269-391) days. The median time from REB submission to REB approval was 43 (13-85) days. The median time for all start-up procedures was 335 (188-335) days. Conclusions There is a lengthy start-up period required for outbreak-focused research. Completing DSAs was the most time-consuming step. A reactive approach to newly emerging threats such as Ebola virus, Middle East respiratory syndrome, and Zika virus will likely not allow sufficient time to initiate research before most outbreaks are advanced.


title: What have we learned from worldwide experiences on the management and treatment of hospital effluent? — An overview and a discussion on perspectives

text: Abstract This study overviews lessons learned from experimental investigations on dedicated treatment systems of hospital effluent carried out worldwide in the last twenty years. It includes 48 peer reviewed papers from 1995 to 2015 assessing the efficacy of different treatment levels (preliminary, primary, secondary and polishing) of hospital wastewater in removing a wide spectrum of pharmaceutical compounds as well as conventional contaminants. Moreover, it highlights the rationale and the reasons for each study: reducing the discharge of micropollutants in surface water, improving existing wastewater treatment technologies and reducing the risk of spread of pathogens causing endemic diseases and finally, it offers a critical analysis of the conclusions and suggestions of each study. The most investigated technologies are membrane bioreactors equipped with ultrafiltration membranes in the secondary step, ozonation followed by activated carbon filtration (in powder and in granules) in the polishing step. Interesting research projects deal with photo-Fenton processes acting as primary treatments to enhance biodegradation before biological treatment, and as a polishing step, thus further reducing micro-contaminant occurrence. Investment and operational costs are also presented and discussed for the different treatment technologies tested worldwide, in particular membrane bioreactors and various advanced oxidation processes. This study also discusses the need for further research to evaluate toxicity resulting from advanced oxidation processes as well as the need to develop an accurate feasibility study that encompasses technical, ecotoxicological and economic aspects to identify the best available treatment in the different situations from a global view point.


title: Observed and projected drivers of emerging infectious diseases in Europe

text: Emerging infectious diseases are of international concern because of the potential for, and impact of, pandemics; however, they are difficult to predict. To identify the drivers of disease emergence, we analyzed infectious disease threat events (IDTEs) detected through epidemic intelligence collected at the European Centre for Disease Prevention and Control (ECDC) between 2008 and 2013, and compared the observed results with a 2008 ECDC foresight study of projected drivers of future IDTEs in Europe. Among 10 categories of IDTEs, foodborne and waterborne IDTEs were the most common, vaccine‐preventable IDTEs caused the highest number of cases, and airborne IDTEs caused the most deaths. Observed drivers for each IDTE were sorted into three main groups: globalization and environmental drivers contributed to 61% of all IDTEs, public health system drivers contributed to 21%, and social and demographic drivers to 18%. A multiple logistic regression analysis showed that four of the top five drivers for observed IDTEs were in the globalization and environment group. In the observational study, the globalization and environment group was related to all IDTE categories, but only to five of eight categories in the foresight study. Directly targeting these drivers with public health interventions may diminish the chances of IDTE occurrence from the outset.


title: Assessing changes in US public trust in science amid the Covid-19 pandemic

text: Abstract Introduction The emergence of the Covid-19 and subsequent pandemic has led to the most substantive large-scale, open, and public social discussion of epidemiology and science in recent history. In the United States, extensive debate has ensued as to the risk posed by the disease, whether the health system is prepared to manage a high volume of critical cases, whether any number of public health responses are necessary and appropriate, and the appropriate ways to prevent, manage, and treat the pandemic. We hypothesized that the interplay between scientists, policymakers, and the public in an open forum was associated with increased overall public trust in science and scientists, but that this was moderated by political orientation and/or religious commitment. In the context of a public health emergency, it is important to understand the degree to which science and scientists are trusted to produce information that can provide reassurance and also can explain the details of a highly complex event like a viral pandemic while providing actionable recommendations. Methods Data were obtained on March 17-18, 2020, from a sample of 242 US-based Amazon Mechanical Turk users. Respondents completed a 49-question survey consisting of key socidemographic variables, political affiliation, religious commitment, and two iterations of the Trust in Science and Scientist Inventory (one for March 2020, and one for December 2019 using retrospective recall). Changes in mean level of trust and interaction with political affiliation and/or religious commitment were assessed using mixed ANOVA via the general linear model. Results On a scale from 1 (low trust) to 5 (high trust), the mean level of trust in science and scientists was static; 3.82 in December 2019, and 3.81 in March 2020. Conservative political orientation and high religious commitment were associated with significantly less overall trust in science; the interaction effect suggested that liberal trust in science decreased slightly from December 2019 to March 2020, while conservative trust increased slightly. Discussion Counter to our expectations, the overall level of trust in science remained static after the first several months of Covid-19 in the United States, though there is some evidence that political orientation was associated with magnitude and directionality of change in trust. Continued examination of these trends is important for understanding public response to epidemiologic recommendations.


COVID-19 and STEMI: A snapshot analysis of presentation patterns during a pandemic


title: Picornavirus Subversion of the Autophagy Pathway

text: While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates that some picornaviruses hijack autophagy in order to induce autophagosome-like membrane structures for genomic RNA replication. Expression of picornavirus proteins can specifically induce the machinery of autophagy, although the mechanisms by which the viruses employ autophagy appear to differ. Many picornaviruses up-regulate autophagy in order to promote viral replication while some members of the family also inhibit degradation by autolysosomes. Here we explore the unusual relationship of this medically important family of viruses with a degradative mechanism of innate immunity.


title: Electron microscope observations on the entry of avian infectious bronchitis virus into susceptible cells

text: Infectious bronchitis virus was observed to enter cells of chicken chorioallantoic membrane by viropexis. There was no support for the suggestion that entry took place by fusion of viral and plasma membranes. The results of electron microscopy showed that virus attachment occurred both at 4° and at 37° C. Viropexis was not observed until the preparations were warmed. Similar results were obtained using chicken kidney cells. Quantitative data obtained from a plaque counting system employing chicken kidney cells indicated that attachment was the same at both temperatures and that some virus particles were taken up at 4° C. Virus uptake was triggered by attachment of the virus to the cell membrane and the subsequent process of virus entry visualised by E. M. appeared to proceed without the involvement of lysosomal enzymes. No intracellular virus was located by electron microscopy in warmed preparations when virus was treated with specific antiserum, either before or after adsorption to the cells.


title: Central Hypoventilation: A Case Study of Issues Associated with Travel Medicine and Respiratory Infection

text: Aim. We presented the case of a child with central hypoventilation syndrome (CHS) to highlight issues that need to be considered in planning long-haul flight and problems that may arise during the flight. Case. The pediatric intensive care unit (PICU) received a child with central hypoventilation syndrome (Ondine's curse) on nocturnal ventilatory support who travelled to Hong Kong on a make-a-wish journey. He was diagnosed with central hypoventilation and had been well managed in Canada. During a long-haul aviation travel, he developed respiratory symptoms and desaturations. The child arrived in Hong Kong and his respiratory symptoms persisted. He was taken to a PICU for management. The child remained well and investigations revealed no pathogen to account for his respiratory infection. He went on with his make-a-wish journey. Conclusions. Various issues of travel medicine such as equipment, airline arrangement, in-flight ventilatory support, travel insurance, and respiratory infection are explored and discussed. This case illustrates that long-haul air travel is possible for children with respiratory compromise if anticipatory preparation is timely arranged.


A Celebration of the Life and Work of Caroline Breese Hall, MD


title: In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses

text: BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO(2)% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization. CONCLUSION: This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.


title: Detection of 793/B serotype of infectious bronchitis virus in tissue sample by indirect immunoperoxidase assay

text: The indirect immunoperoxidase (IIP) assay was compared with the reverse transcription–polymerase chain reaction (RT-PCR) for detection of 793/B serotype of infectious bronchitis virus in tissues samples collected from experimentally infected chickens. This technique was optimized in specific pathogen-free (SPF)-embryonated chicken eggs and broiler chickens inoculated with the Iranian IR/773/2001 strain of 793/B serotype The trachea, lung, kidney, and cecal tonsil tissue samples from experimentally infected chicken embryos and chickens were collected in order to prepare tissue sections in IIP assay and to detect in RT-PCR. The sensitivity and specificity values of IIP assay were, respectively, 83 and 84 %, and the positive and negative prediction values were 71 and 91 % when compared with RT-PCR.


Getting Back to Work: Risk Assessing Personal Vulnerabilities to COVID-19


title: Coronavirus Outbreak in Nigeria: Burden and Socio-Medical Response during the First 100 Days

text: Abstract Background The coronavirus disease of 2019 (COVID-19) pandemic shocked the world, overwhelming the health systems of even high-income countries. Expectedly, the situation has elicited social and medical responses from the public and governments respectively. Nigeria recorded an imported case from Italy on February 27, 2020. Hence, this paper assesses the early socio-medical response to COVID-19 in Nigeria within the first 100 days after the index case. The paper employs analytical methods and collates data from various media reports and official sources. Findings The incidence of COVID-19 grows steadily in Nigeria, moving from an imported case and elitist pattern to community transmission. The case fatality stood at 2.8%. The country recorded an upsurge (52% of total cases) in the transmission of COVID-19 during the short period the lockdown was relaxed. The paper presents a concise response framework to highlight some specific multisectoral responses to the pandemic. A combination of social and medical responses help Nigeria to curtail the spread of the virus to a large extent. Conclusion The potential of overwhelming COVID-19 is still imminent in Nigeria as the country is attempting to hurriedly open the economy, which could sacrifice public health gains for temporary economic gains.


title: Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold

text: INTRODUCTION: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy. METHODS AND ANALYSIS: This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days. ETHICS AND DISSEMINATION: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants. TRIAL REGISTRATION NUMBER: U1111-1194-4345 and ACTRN12617001340325; Pre-results.


title: ACE2 as a Therapeutic Target for COVID-19;its Role in Infectious Processes and Regulation by Modulators of the RAAS System

text: Angiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsiblefor mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ACE2bound to tissue facilitates infectivity of SARS-CoV-2;thus, one could argue that decreasing ACE2tissue expression would be beneficial However, ACE2 catalytic activity towards angiotensin I (AngI) and II (Ang II) mitigates deleterious effects associated with activation of the renin-angiotensinaldosteronesystem (RAAS) on several organs, including a pro-inflammatory status At the tissuelevel, SARS-CoV-2 (a) binds to ACE2, leading to its internalization, and (b) favors ACE2 cleavage toform soluble ACE2: these actions result in decreased ACE2 tissue levels Preserving tissue ACE2activity while preventing ACE2 shredding is expected to circumvent unrestrained inflammatoryresponse Concerns have been raised around RAAS modulators and their effects on ACE2expression or catalytic activity Various cellular and animal models report conflicting results invarious tissues However, recent data from observational and meta-analysis studies in SARS-CoV-2-infected patients have concluded that RAAS modulators do not increase plasma ACE2 levels orsusceptibility to infection and are not associated with more severe diseases This review presentsour current but evolving knowledge of the complex interplay between SARS-CoV-2 infection, ACE2levels, modulators of RAAS activity and the effects of RAAS modulators on ACE2 expression


title: Acute lower respiratory infections in hospitalized children over a 6 year period in Tokyo

text: Abstract Background: Acute lower respiratory infections are major causes of hospitalization in children and are mainly caused by respiratory viruses. In the present study, we investigated the etiologic agents responsible for acute lower respiratory infections from the period November 1986 to October 1992 in order to determine the seasonal pattern and different characteristics of age distribution of respiratory infectious agents, mainly virus infections. Methods: A total of 1521 patients with lower respiratory infections was hospitalized in Saiseikai Central Hospital, Tokyo, Japan. Nasopharyngeal secretions were obtained for virus isolation and paired sera in the acute and convalescent phases were obtained for serological examination. Results: Etiological agents were identified in 668 of 1521 patients (43.9%) by serological antibody responses, virus isolation and/or detection of virus antigen: 240 (15.8%) with respiratory syncytial (RS) virus; 62 (4.1%) with influenza virus type A; 26 (1.7%) with influenza virus type B; 86 (5.7%) with adenovirus; 81 (5.3%) with parainfluenza virus; 32 (2.1%) with measles virus; 20 (1.3%) with enteroviruses or Herpes virus other than respiratory viruses; 75 (4.9%) with Mycoplasma pneumoniae; 10 (0.7%) with pertussis; and 36 (2.4%) with mixed infections. In the remaining 853 patients (56.1%), etiologic agents were not identified. Respiratory syncytial (RS) virus was a main causative agent of respiratory infections in patients younger than 3 years of age. Influenza virus and M. pneumoniae were two main causative agents in patients with acute respiratory illness over 5 years of age. Parainfluenza virus type 3 was frequently observed in infants from 9 to 12 months of age. A distinct seasonal pattern of viral infections was consistently observed in each year during the study period; RS and influenza viruses were prevalent in winter, parainfluenza virus was prevalent in spring and M. pneumoniae was prevalent in summer and autumn. However, adenovirus infections were observed in all seasons. Serological responses were poor in patients younger than 1 year of age and they were mainly diagnosed by virus isolation or detection of virus antigen. Conclusions: Virological epidemiology provides useful information in daily clinical practice for the prediction of etiological agents based on patient age and the seasonal distribution of agents. We should examine virus isolation and the detection of virus antigen, along with serological examinations in patients with respiratory infections, especially in infants younger than 1 year of age because of poor serological responses.


title: Coronavirus concerns: What do women with gynecologic cancer need to know during the COVID-19 crisis?

text: • COVID-19 is likely uniquely unsettling to gynecologic oncology patients. • Resources addressing the questions of patients with cancer during the COVID-19 crises remain scarce. • Women with gynecologic cancer were invited to participate in a webinar on COVID-19 and cancer concerns. • We share participant questions to understand concerns and utilize this knowledge to improve patient education and support.


title: Understanding the alphaviruses: Recent research on important emerging pathogens and progress towards their control

text: Abstract The alphaviruses were amongst the first arboviruses to be isolated, characterized and assigned a taxonomic status. They are globally very widespread, infecting a large variety of terrestrial animals, insects and even fish, and circulate both in the sylvatic and urban/peri-urban environment, causing considerable human morbidity and mortality. Nevertheless, despite their obvious importance as pathogens, there are currently no effective antiviral drugs with which to treat humans or animals infected by any of these viruses. The EU-supported project—VIZIER (Comparative Structural Genomics of Viral Enzymes Involved in Replication, FP6 Project: 2004-511960) was instigated with an ultimate view of contributing to the development of antiviral therapies for RNA viruses, including the alphaviruses [Coutard, B., Gorbalenya, A.E., Snijder, E.J., Leontovich, A.M., Poupon, A., De Lamballerie, X., Charrel, R., Gould, E.A., Gunther, S., Norder, H., Klempa, B., Bourhy, H., Rohayemj, J., L’hermite, E., Nordlund, P., Stuart, D.I., Owens, R.J., Grimes, J.M., Tuckerm, P.A., Bolognesi, M., Mattevi, A., Coll, M., Jones, T.A., Åqvist, J., Unger, T., Hilgenfeld, R., Bricogne, G., Neyts, J., La Colla, P., Puerstinger, G., Gonzalez, J.P., Leroy, E., Cambillau, C., Romette, J.L., Canard, B., 2008. The VIZIER project: preparedness against pathogenic RNA viruses. Antiviral Res. 78, 37–46]. This review highlights some of the major features of alphaviruses that have been investigated during recent years. After describing their classification, epidemiology and evolutionary history and the expanding geographic distribution of Chikungunya virus, we review progress in understanding the structure and function of alphavirus replicative enzymes achieved under the VIZIER programme and the development of new disease control strategies.


title: Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009–2016

text: Previous studies indicated that fruit bats carry two betacoronaviruses, BatCoV HKU9 and BatCoV GCCDC1. To investigate the epidemiology and genetic diversity of these coronaviruses, we conducted a longitudinal surveillance in fruit bats in Yunnan province, China during 2009–2016. A total of 59 (10.63%) bat samples were positive for the two betacorona-viruses, 46 (8.29%) for HKU9 and 13 (2.34%) for GCCDC1, or closely related viruses. We identified a novel HKU9 strain, tentatively designated as BatCoV HKU9-2202, by sequencing the full-length genome. The BatCoV HKU9-2202 shared 83% nucleotide identity with other BatCoV HKU9 stains based on whole genome sequences. The most divergent region is in the spike protein, which only shares 68% amino acid identity with BatCoV HKU9. Quantitative PCR revealed that the intestine was the primary infection organ of BatCoV HKU9 and GCCDC1, but some HKU9 was also detected in the heart, kidney, and lung tissues of bats. This study highlights the importance of virus surveillance in natural reservoirs and emphasizes the need for preparedness against the potential spill-over of these viruses to local residents living near bat caves. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0017-2) contains supplementary material, which is available to authorized users.


title: Active implications for dermatologists in “SARS‐CoV‐2 era”: Personal experience and review of literature

text: On December 31, 2019, from the Chinese city of Wuhan, Hubei, comes the first case of "atypical ARDS/ interstitial pneumonia". On February 11, 2020 the WHO officially announced the name of the emergent disease associated with new coronavirus identified as SARS‐CoV‐2 (Severe Acute Respiratory Syndrome Coronavirus ‐2): COVID‐19 (Coronavirus Disease 2019) (1). On February 13, 72000 cases have been officially recorded in China, among which 15000 were registered in Hubei province only, with 242 deaths in a single day. After that, Chinese republic has ordered drastic containment measures for fighting SARS‐CoV‐2 virus spreading (1).


title: One cannot rule them all: Are bacterial toxins-antitoxins druggable?

text: Type II (proteic) toxin–antitoxin (TA) operons are widely spread in bacteria and archaea. They are organized as operons in which, usually, the antitoxin gene precedes the cognate toxin gene. The antitoxin generally acts as a transcriptional self-repressor, whereas the toxin acts as a co-repressor, both proteins constituting a harmless complex. When bacteria encounter a stressful environment, TAs are triggered. The antitoxin protein is unstable and will be degraded by host proteases, releasing the free toxin to halt essential processes. The result is a cessation of cell growth or even death. Because of their ubiquity and the essential processes targeted, TAs have been proposed as good candidates for development of novel antimicrobials. We discuss here the possible druggability of TAs as antivirals and antibacterials, with focus on the potentials and the challenges that their use may find in the ‘real’ world. We present strategies to develop TAs as antibacterials in view of novel technologies, such as the use of very small molecules (fragments) as inhibitors of protein–protein interactions. Appropriate fragments could disrupt the T:A interfaces leading to the release of the targeted TA pair. Possible ways of delivery and formulation of Tas are also discussed.


title: Interferon-Inducible Myxovirus Resistance Proteins: Potential Biomarkers for Differentiating Viral from Bacterial Infections

text: BACKGROUND: In 2015, the 68th World Health Assembly declared that effective, rapid, low-cost diagnostic tools were needed for guiding optimal use of antibiotics in medicine. This review is devoted to interferon-inducible myxovirus resistance proteins as potential biomarkers for differentiating viral from bacterial infections. CONTENT: After viral infection, a branch of the interferon (IFN)-induced molecular reactions is triggered by the binding of IFNs with their receptors, a process leading to the activation of mx1 and mx2, which produce antiviral Mx proteins (MxA and MxB). We summarize current knowledge of the structures and functions of type I and III IFNs. Antiviral mechanisms of Mx proteins are discussed in reference to their structural and functional data to provide an in-depth picture of protection against viral attacks. Knowing such a mechanism may allow the development of countermeasures and the specific detection of any viral infection. Clinical research data indicate that Mx proteins are biomarkers for many virus infections, with some exceptions, whereas C-reactive protein (CRP) and procalcitonin have established positions as general biomarkers for bacterial infections. SUMMARY: Mx genes are not directly induced by viruses and are not expressed constitutively; their expression strictly depends on IFN signaling. MxA protein production in peripheral blood cells has been shown to be a clinically sensitive and specific marker for viral infection. Viral infections specifically increase MxA concentrations, whereas viruses have only a modest increase in CRP or procalcitonin concentrations. Therefore, comparison of MxA and CRP and/or procalcitonin values can be used for the differentiation of infectious etiology.


title: Beware of asymptomatic transmission: Study on 2019-nCoV prevention and control measures based on extended SEIR model

text: The 2019 new coronavirus, “2019-nCoV”, was discovered from Wuhan Viral Pneumonia cases in December 2019, and was named by the World Health Organization on January 12, 2020. In the early stage, people knows little about the 2019-nCoV virus was not clear, and the spread period was encountering China’s annual spring migration, which made the epidemic spread rapidly from Wuhan to almost all provinces in China. This study builds a SEIRD model that considers the movement of people across regions, revealing the effects of three measures on controlling the spread of the epidemic.Based on MATLAB R2017a, computational experiments were performed to simulate the epidemic prevention and control measures. The research results show that current prevention and control measures in China are very necessary. This study further validates the concerns of international and domestic experts regarding asymptomatic transmission (E-status). The results of this study are applicable to explore the impact of the implementation of relevant measures on the prevention and control of epidemic spread, and to identify key individuals that may exist during the spread of the epidemic.


title: Isolation of MERS Coronavirus from a Dromedary Camel, Qatar, 2014

text: We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS-CoV) from a camel in Qatar. This virus is highly similar to the human England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently replicated in human cells, providing further evidence for the zoonotic potential of MERS-CoV from camels.


title: Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-β in Porcine Intestinal Epithelial Cells

text: Transmissible gastroenteritis virus (TGEV) is a porcine intestinal coronavirus that causes fatal severe watery diarrhea in piglets. The neonatal Fc receptor (FcRn) is the only IgG transport receptor, its expression on mucosal surfaces is triggered upon viral stimulation, which significantly enhances mucosal immunity. We utilized TGEV as a model pathogen to explore the role of FcRn in resisting viral invasion in overall intestinal mucosal immunity. TGEV induced FcRn expression by activating NF-κB signaling in porcine small intestinal epithelial (IPEC-J2) cells, however, the underlying mechanisms are unclear. First, using small interfering RNAs, we found that TGEV up-regulated FcRn expression via TLR3, TLR9 and RIG-I. Moreover, TGEV induced IL-1β, IL-6, IL-8, TGF-β, and TNF-α production. TGF-β-stimulated IPEC-J2 cells highly up-regulated FcRn expression, while treatment with a JNK-specific inhibitor down-regulated the expression. TGEV nucleocapsid (N) protein also enhanced FcRn promoter activity via the NF-κB signaling pathway and its central region (aa 128–252) was essential for FcRn activation. Additionally, N protein-mediated FcRn up-regulation promotes IgG transcytosis. Thus, TGEV N protein and TGF-β up-regulated FcRn expression, further clarifying the molecular mechanism of up-regulation of FcRn expression by TGEV.


title: Regulation of signaling mediated by nucleic acid sensors for innate interferon-mediated responses during viral infection

text: Type I and type III interferons are important anti-viral cytokines that are massively induced during viral infection. This dynamic process is regulated by many executors and regulators for efficient eradication of invading viruses and protection from harmful, excessive responses. An array of innate sensors recognizes virus-derived nucleic acids to activate their downstream signaling to evoke cytokine responses including interferons. In particular, a cytoplasmic RNA sensor RIG-I (retinoic acid-inducible gene I) is involved in the detection of multiple types of not only RNA viruses but also DNA viruses. Accumulating findings have revealed that activation of nucleic acid sensors and the related signaling mediators is regulated on the basis of post-translational modification such as ubiquitination, phosphorylation and ADP-ribosylation. In addition, long non-coding RNAs (lncRNAs) have been implicated as a new class of regulators in innate signaling. A comprehensive understanding of the regulatory mechanisms of innate sensor activation and its signaling in host–virus interaction will provide a better therapeutic strategy to efficiently control viral infection and maintain immune homeostasis.


title: 23 Response to SARS as a prototype for bioterrorism Lessons in a Regional Hospital in Hong Kong

text: Publisher Summary This chapter reviews the response to severe acute respiratory syndrome (SARS), which can serve as a prototype for combating acts of bioterrorism, in the setting of a Hong Kong acute-care hospital. After overcoming the onslaught of SARS, the Hong Kong community has become aware that emerging infections can occur at any time. This is reinforced by the recent avian influenza outbreaks, which act as a reminder of this looming threat. Hospitals have to evaluate their levels of preparedness against bioterrorism, which can simulate infectious disease outbreaks. The priority areas for improvement include community involvement, staff education, improved information technology, disease surveillance, and additional equipment and staff. Multidimensional and flexible-response plans require strong leadership and clear directions to be effective, and such plans must also consider human frailties during great stress, when every resource is stretched to its utmost limit. The chapter concludes by discussing the various infection-control measures implemented in Hong Kong.


title: Data on corona-virus readiness strategies influencing customer satisfaction and customer behavioural intentions in South African retail stores

text: This article presents raw inferential statistical data that determined the coronavirus readiness strategies at retail stores in South Africa and their consequences for consumer behavioural intentions. The data was collected from customers within the metropolitan area of Bloemfontein. The data were analysed using a quantitative approach. Structured questionnaires were provided to customers throughout South Africa's Bloemfontein metropolitan area. Reliability and validity were confirmed. The data was presented using Structural Equation Modeling (SEM) using the Smart PLS program. The analysis of the SEM path shows estimates of the interconnectivity of the major constructs in the data. The findings from this dataset show that sanitised retail entrances, sanitised retail counters and sanitised retail shelves had a statistically significant effect on customer satisfaction with covid-19 readiness in retail stores. Furthermore, the data reveals that retail social distancing and senior citizens shopping hours had a statistically insignificant effect on customer satisfaction with covid-19 readiness. Moreover, the data reveals that customer satisfaction with covid-19 readiness strategies of retail stores also had a positive and statistically significant effect on customer behavioural intentions.


title: Cloning whole bacterial genomes in yeast

text: Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation.


title: COVID-19: An Update about the Discovery Clinical Trial

text: Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.


title: Touch in the Era of COVID‐19

text: I moved out of our shared bedroom of nearly 10 years on 3/22/2020. It was not a difficult decision as we have two young children and wondered what would happen if both of us became ill at the same time. As a Maternal‐Fetal medicine physician in New York City, I was acutely aware of the coming COVID‐19 crisis, and its potential ramifications on the health of my family, friends, patients and community. I am trained to function well in emergencies, and in this case, it was a quick and seemingly logical next‐step to sleep separately.


title: The influence of temperature on wettability alteration during CO2 storage in saline aquifers

text: Abstract The wettability of a formation is defined as the tendency of one fluid to spread on a surface in competition with other fluids which are also in contact with it. However, the impact of temperature on wettability in an aquifer and the modification of relative permeability curves based on the temperature variation in aquifers is not well covered in the literature. This study redresses this dearth of information by investigating the impact of temperature on wettability distribution in a reservoir and updating the relative permeability curves based on its temperature propagation. The impact of the latter is studied in relation to the solubility of CO2 injected into an aquifer using the numerical methods (i.e. ECLIPSE). If the CO2 injected has a temperature higher than the formation geothermal temperature, it can change the wettability of the formation further to a more CO2 wet condition. This increases the risk of leakage and also changes the relative permeability curves as the CO2 moves through the reservoir, a situation that needs to be considered in reservoir simulations. The results show that updating and modifying the relative permeability curves with temperature variation in an aquifer can increase the amount of CO2 dissolution there.


title: Assessment and management of the risk of SARS-CoV-2 infection in an IVF laboratory: a failure mode and effect analysis (FMEA)

text: RESEARCH QUESTION: To identify corrective measures aimed at reducing the risk of aerosol-mediated viral infection within an IVF laboratory. DESIGN: A Failure Modes and Effect Analysis (FMEA) was conducted by a multidisciplinary IVF team. A schematic representation of new protocols and procedures adopted during COVID-19 emergency has been defined, including directives about the behavior to adopt when entering the clinic and the laboratory, in case of face-to-face contact with patients and between staff members. Lastly, the risk of cross-contamination between samples belonging to different patients during cell handling and manipulation has been also evaluated. Potential failure modes for each phase have been analyzed, focusing on possible sources of error. Risk priority numbers have been calculated as products of Occurrence x Severity x Detection scores. RESULTS: Except for cell-cell contamination, which has been considered highly unlikely, failure modes during Patient-Staff, Staff-Staff and Staff-Cell interactions were estimated at moderate-high risk of infection. The main corrective measures entailed precautionary logistic measures, the implementation of additional personal protective equipment (PPE), and changes in setting the IVF laboratory and scheduling the daily routine. Some IVF procedures were also revised mainly aiming at increasing staff's awareness and caution during pandemic. CONCLUSIONS: Standard IVF laboratory protocols are insufficient to face a virus whose transmission is aerosol-mediated. The measures outlined in this FMEA should thus be considered not only facing this pandemic but also for the future to be able to manage promptly any aerosol-mediated virus infection, whose impact on the management of an IVF laboratory might be less severe than COVID-19 although not completely negligible (i.e. staff reduction and patient health at the time of IVF procedure).


title: Serum IgG Concentrations in Adult Patients Experiencing Virus-Induced Severe Asthma Exacerbations

text: Background Patients experiencing severe asthma exacerbations have a poorer quality of life and an increase in morbidity and mortality. Viruses are frequently involved in asthma exacerbations. Objective To determine the value of measuring serum IgG concentrations in asthma exacerbations and assess their link with viral infections in patients hospitalized for asthma. Methods Patients hospitalized for asthma exacerbation were included in an observational study from January 1, 2015, to December 31, 2015. Serum IgG concentrations on admission were compared between patients with a positive upper airway viral sample and those with a negative viral sample. Results Among the 82 patients included, those with positive viral nasopharyngeal samples (n = 40) presented with lower serum IgG concentrations during exacerbation than those with a negative viral sample (n = 42) (10.1 ± 2.3 g/L vs 11.5 ± 3.6 g/L; P < .05). The median concentration of serum IgG was lower in patients hospitalized for more than 3 days compared with those hospitalized for less than 3 days (10.0 g/L [8.2-12.4] vs 11.4 g/L [10.1-12.8]; P < .05) and in patients who received oral corticosteroid therapy for more than 5 days compared with those treated with oral steroids for less than 5 days (10.1 g/L [8.3-12.2] vs 11.6 g/L [10.0-13.8]; P < .05). Conclusions Serum IgG level was significantly lower when asthma exacerbations were associated with positive viral samples. The patients with lower serum IgG concentrations required longer hospitalizations and longer courses of steroids.


title: MERS Coronaviruses in Dromedary Camels, Egypt

text: We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.


title: Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination

text: Porcine epidemic diarrhea virus (PEDV) causes severe economic losses in the swine industry in China and other Asian countries. Infection usually leads to an acute, often lethal diarrhea in piglets. Despite the impact of the disease, no system is yet available to manipulate the viral genome which has severely hampered research on this virus until today. We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. Using this system, we deleted the ORF3 gene entirely from the viral genome and showed that the ORF3 protein is not essential for replication of the virus in vitro. In addition, we inserted heterologous genes (i.e. the GFP and Renilla luciferase genes) at two positions in the viral genome, either as an extra expression cassette or as a replacement for the ORF3 gene. We demonstrated the expression of both GFP and Renilla luciferase as well as the application of these viruses by establishing a convenient and rapid virus neutralization assay. The new PEDV reverse genetics system will enable functional studies of the structural proteins and the accessory ORF3 protein and will allow the rational design and development of next generation PEDV vaccines.


title: Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient

text: SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its’ own patient sera. Appropriate precautions should be taken to avoid transmission from urine.


title: 32 Special Considerations for Infants and Young Children

text: • The care of infants and small children with suspected asthma deserves special consideration because of the potential to modulate the disease process early on and alleviate the increased morbidity associated with uncontrolled asthma in this age group. • After confounders and masqueraders of asthma have been excluded in the evaluation of children with suspected asthma, recurrent wheezing in infants and young children still comprises a heterogeneous group of conditions with different risk factors and prognoses. • The diagnosis of asthma in infants and small children is often based on clinical grounds and complicated by the lack of clinically available tools that meet the criteria for the definition of asthma used in older children and adults such as airway inflammation, bronchial hyperresponsiveness and airflow limitation. • Difficulties in the management of asthma include limited effective and convenient delivery devices, complete dependence on the caregivers to carry out the treatment regimen, and an inadequate selection of medications completely devoid of adverse effects. • A partnership approach with emphasis on education, monitoring and training is key in the effective management of chronic cough or recurrent wheezing illnesses in very young children. • Clinical trials using as needed treatment interventions have shown favorable efficacy outcomes, aimed at preventing severe exacerbations in young children with recurrent wheezing; however, trials aimed at primary prevention are still lacking.


title: Molecular structure analyses suggest strategies to therapeutically target SARS-CoV-2

text: Amid the COVID-19 pandemic, scientists around the globe have been working resolutely to find therapies to treat patients and avert the spreading of the SARS-CoV-2 virus. In this commentary, we highlight some of the latest studies that provide atomic-resolution structural details imperative for the development of vaccines and antiviral therapeutics.


title: Deadly viral syndrome mimics

text: Upper respiratory tract infections (ie, "the common cold") have several hundred causes, the most common of which include rhino-virus, coronavirus, and respiratory syncytial virus. The clinical presentation varies with symptoms. Every emergency department, no matter what the demographics, cares for patients with this constellation of symptoms. Emergency physicians examine, diagnose, and treat these disorders frequently. With increasing burdens being placed on emergency physicians, it is possible to assume a diagnosis of upper respiratory tract infection without generating a complete differential diagnosis. The challenge is to identify and recognize the distinctions between an innocuous upper respiratory tract infection and a life-threatening disease "mimic" or entities. This article discusses some of these life-threatening mimics.


Keep Your Community Safe While COVID‐19 Spreads Globally


title: Global health activists’ lessons on building social movements for Health for All

text: BACKGROUND: The People’s Health Movement (PHM) was formed in 2000 and drew inspiration from the Alma Ata Declaration on Primary Health Care’s ‘Health for All’ (1978). Since then PHM has been an active part of a global counter-hegemonic social movement. This study aimed to gain insights on social movement building, drawing on the successes and failures reported by activists over their experiences of working in the Health for All social movement to improve health, justice and equity. METHODS: Qualitative research methods were employed in this study to capture complex and historical narratives of individual activists, through semi-structured interviews and subsequent thematic analysis of transcripts. The research design and analysis were informed by social movement theory and literature on health activism as a pathway for social change. In this study we examine the semi-structured interviews of 15 health activists who are part of the PHM, with the aim of deriving lessons for strengthening movements for Health for All. RESULTS: This study locates the activists’ narratives within a socio-political analysis of the global trends of late modern individualism and capitalist neoliberalism. This highlights the challenges faced by civil society groups mobilising collective action and building social movements for Health for All. The study found that within the constraints of the neoliberal socio-political and economic conditions which have caused the rise in social and health inequities, this group of long-term health activists have been nurturing alternative approaches to structuring society and building collective agency to improve health. CONCLUSION: The practical long-term experiences of the PHM activists examined in this study contribute to a better understanding of the processes and motivations that lead to and sustain health activism, and the dilemmas, strategies, impacts and achievements of such activism.


title: Four cases of aortic thrombosis in patients with COVID-19

text: Abstract Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of thrombotic complications. We describe four cases of aortic thrombosis in patients admitted for COVID-19, between the 26th of March and the 12th of April 2020, in Mulhouse (France).


title: Next-generation sequencing and single-cell RT-PCR reveal a distinct variable gene usage of porcine antibody repertoire following PEDV vaccination

text: Porcine epidemic diarrhea virus (PEDV) is the most common diarrhea-causing pathogen in newborn piglets. The clarifications of the overall antibody repertoire and antigen-specific antibody repertoire are essential to provide important insights into the B-cell response and reshape new vaccines. Here, we applied next-generation sequencing (NGS) technology to investigate immunoglobulin (Ig) variable (V) gene segment usage of swine B-cells from peripheral blood lymphocytes (PBL) and mesenteric lymph node (MLN) cells following PEDV vaccination. We identified the transcripts of all functional Ig V-genes in antibody repertoire. IgHV1S2, IgKV1-11, and IgLV3-4 were the most prevalent gene segments for heavy, kappa, and lambda chains, respectively, in PBL and MLN. Unlike previous studies, IgKV1, instead of IgKV2, and IgLV3, instead of IgLV8, were the prevalent Ig V-gene families for kappa and lambda light chains, respectively. We further examined the antibody repertoire of PEDV spike-specific B cells by single-cell RT-PCR. In contrast to the overall antibody repertoire, Ig V-gene segments of PEDV spike-specific B cells preferentially adopted IgHV1-4 and IgHV1-14 for heavy chain, IgKV1-11 for kappa chain, and IgLV3-3 for lambda chain. These results represent a comprehensive analysis to characterize the Ig V-gene segment usage in the overall and PEDV spike-specific antibody repertoire in PBL and MLN.


title: The effect of incidence functions on the dynamics of a quarantine/isolation model with time delay

text: Abstract The problem of the asymptotic dynamics of a quarantine/isolation model with time delay is considered, subject to two incidence functions, namely standard incidence and the Holling type II (saturated) incidence function. Rigorous qualitative analysis of the model shows that it exhibits essentially the same (equilibrium) dynamics regardless of which of the two incidence functions is used. In particular, for each of the two incidence functions, the model has a globally asymptotically stable disease-free equilibrium whenever the associated reproduction threshold quantity is less than unity. Further, it has a unique endemic equilibrium when the threshold quantity exceeds unity. For the case with the Holling type II incidence function, it is shown that the unique endemic equilibrium of the model is globally asymptotically stable for a special case. The permanence of the disease is also established for the model with the Holling type II incidence function. Furthermore, it is shown that adding time delay to and/or replacing the standard incidence function with the Holling type II incidence function in the corresponding autonomous quarantine/isolation model with standard incidence (considered in Safi and Gumel (2010) [10]) does not alter the qualitative dynamics of the autonomous system (with respect to the elimination or persistence of the disease). Finally, numerical simulations of the model with standard incidence show that the disease burden decreases with increasing time delay (incubation period). Furthermore, models with time delay seem to be more suitable for modeling the 2003 SARS outbreaks than those without time delay.


title: Prevalence of enteropathogens and their antibiotic sensitivity pattern in puppies with hemorrhagic gastroenteritis

text: AIM: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. MATERIALS AND METHODS: The canine HGE activity index, with little modification, was adopted to identify Grade III/severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control. RESULTS: Canine parvovirus 2b was identified in 90.3% of the diarrheic and 10% of the non-diarrheic healthy puppies. Clostridium difficile was identified in all the diarrheic puppies and in 80% of the healthy puppies. Among the diarrheic puppies, 17.7% were positive for Clostridium perfringens enterotoxin, 9.7% were positive for C. perfringens alpha toxin, 6.4% were positive for Escherichia coli shiga toxin, 6.4% were positive for E. coli enterotoxin (LT), and 3.2% were positive for canine distemper virus. Whereas, none of the healthy puppies were positive for these bacteria and toxins. Fecal antibiotic sensitivity test pattern revealed gentamicin to be sensitive in 95% of the cases, azithromycin in 50%, enrofloxacin in 25%, cefotaxime in 20%, and tetracycline in 5% of the cases. CONCLUSION: Parvoviral enteritis is predominant among puppies. Yet, bacteria and their toxins also play an important role in HGE. Gentamicin has higher sensitivity against the enteropathogens associated with the condition.


title: Guillain–Barré syndrome with unilateral peripheral facial and bulbar palsy in a child: A case report

text: Guillain–Barré syndrome is characterized by progressive motor weakness, sensory changes, dysautonomia, and areflexia. Cranial nerve palsies are frequent in Guillain–Barré syndrome. Among cranial nerve palsies in Guillain–Barré syndrome, facial nerve palsy is the most common affecting around half of the cases. Facial palsy in Guillain–Barré syndrome is usually bilateral. We describe a pediatric Guillain–Barré syndrome variant presenting with unilateral peripheral facial palsy and dysphagia. A 5-year-old boy had progressive lower extremity weakness and pain 3 days prior to onset of unilateral peripheral facial palsy. On presentation, diagnosis of Guillain–Barré syndrome was supported by areflexia and albuminocytologic dissociation. His condition deteriorated with a decline in his respiratory effort and inability to handle secretions. He was given non-invasive ventilation to prevent worsening of his acute respiratory failure. Brain and spine magnetic resonance imaging scans showed enhancement of the left bulbar nerve complex and anterior and posterior cervical nerve roots with gadolinium. Treatment with intravenous immunoglobulin led to an uneventful clinical course with partial recovery within 2 weeks. In summary, Guillain–Barré syndrome should be considered as a possible cause of unilateral peripheral facial palsy. Guillain–Barré syndrome patients with facial nerve and bulbar palsy require close monitoring as they are at risk of developing acute respiratory failure. Early intervention with intravenous immunoglobulin may benefit these patients. Magnetic resonance imaging findings may lend support to early intervention.


title: The effectiveness of full and partial travel bans against COVID-19 spread in Australia for travellers from China during and after the epidemic peak in China

text: BACKGROUND: Australia implemented a travel ban on China on February 1(st) 2020, while COVID-19 was largely localised to China. We modelled three scenarios to test the impact of travel bans on epidemic control. Scenario one was no ban, scenario two and three were the current ban followed by a full or partial lifting (allow over 100 000 university students to enter Australia, but not tourists) from the 8(th) of March 2020. METHODS: We used disease incidence data from China and air travel passenger movements between China and Australia during and after the epidemic peak in China, derived from incoming passenger arrival cards. We used the estimated incidence of disease in China, using data on expected proportion of under-ascertainment of cases, and an age specific deterministic model to model the epidemic in each scenario. RESULTS: The modelled epidemic with the full ban fitted the observed incidence of cases well, predicting 57 cases on March 6(th) in Australia, compared to 66 observed on this date, however we did not account for imported cases from other countries. The modelled impact without a travel ban results in more than 2000 cases and about 400 deaths, if the epidemic remained localised to China and no importations from other countries occurred. The full travel ban reduced cases by about 86%, while the impact of a partial lifting of the ban is minimal, and may be a policy option. CONCLUSIONS: Travel restrictions were highly effective for containing the COVID-19 epidemic in Australia during the epidemic peak in China and averted a much larger epidemic at a time when COVID-19 was largely localised to China. This research demonstrates the effectiveness of travel bans applied to countries with high disease incidence. This research can inform decisions on placing or lifting travel bans as a control measure for the COVID-19 epidemic.


The Coronavirus Pandemic: Adaptations in Medical Education


title: Possible role of an animal vector in the SARS outbreak at Amoy Gardens

text: Summary A mass outbreak of severe acute respiratory syndrome (SARS) in the Amoy Gardens housing complex in Hong Kong at the end of March, 2003, affected more than 300 residents in less than a month, and has epidemiologists all over the world puzzled about the mode of transmission of this new disease, which until then was thought to be transmitted solely by respiratory droplets. The source of the outbreak was later traced to an individual with SARS who spent two nights at Amoy Gardens. Official explanations failed to account for the large number of residents infected over a wide area within a short time. A powerful environmental mechanism that efficiently amplified and distributed the causal agent must have been at work to cause this outbreak. One such mechanism could be an animal vector, most probably roof rats, that was infected by the index patient and subsequently spread the disease to more than 150 households.


title: Prevalence of human parainfluenza virus in patients with acute respiratory tract infections in Beijing, 2011–2014

text: Human parainfluenza viruses (HPIVs) are one of the most frequent pathogens that circulate worldwide[1] . Four types of HPIVs were identified, including HPIV-1, HPIV-2, HPIV-3 and HPIV-4. HPIVs can lead to acute respiratory infection in young[2] , the immunocompromised[3] and the elderly patients[4] . The epidemiological character of parainfluenza virus in Beijing has not been previously reported. In a consecutive 4-year surveillance of acute respiratory infections (ARIs) between January 2011 and December 2014, a total of 3978 specimens were collected from the fever outpatients with ARIs (with acute fever (temperature of ≥38℃) and cough or sore throat fewer than 5 days) by throat swab and sputum for those also with abnormal chest X-ray. This article is protected by copyright. All rights reserved.


title: hCLE/C14orf166 Associates with DDX1-HSPC117-FAM98B in a Novel Transcription-Dependent Shuttling RNA-Transporting Complex

text: hCLE/C14orf166 is a nuclear and cytoplasmic protein that interacts with the RNAP II, modulates nuclear RNA metabolism and is present in cytoplasmic RNA granules involved in localized translation. Here we have studied whether hCLE shares common interactors in the nucleus and the cytosol, which could shed light on its participation in the sequential phases of RNA metabolism. Nuclear and cytoplasmic purified hCLE-associated factors were identified and proteins involved in mRNA metabolism, motor-related proteins, cytoskeletal and translation-related factors were found. Purified hCLE complexes also contain RNAs and as expected some hCLE-interacting proteins (DDX1, HSPC117, FAM98B) were found both in the nucleus and the cytoplasm. Moreover, endogenous hCLE fractionates in protein complexes together with DDX1, HSPC117 and FAM98B and silencing of hCLE down-regulates their nuclear and cytosolic accumulation levels. Using a photoactivatable hCLE-GFP protein, nuclear import and export of hCLE was observed indicating that hCLE is a shuttling protein. Interestingly, hCLE nuclear import required active transcription, as did the import of DDX1, HSPC117 and FAM98B proteins. The data indicate that hCLE probably as a complex with DDX1, HSPC117 and FAM98B shuttles between the nucleus and the cytoplasm transporting RNAs suggesting that this complex has a prominent role on nuclear and cytoplasmic RNA fate.


title: Animal models of multiple sclerosis: the good, the bad and the bottom line

text: Multiple sclerosis (MS) is a spontaneous, acquired, inflammatory demyelinating disease of the human CNS. Because it involves a complex interaction between two of the most intricate biological systems, immune system and CNS, animal modeling has been critical for addressing MS pathogenesis. MS models were originally developed serendipitously more than 75 years ago. Immune-mediated, toxic, viral and genetic models of demyelination are now used to understand the manifold aspects of MS. MS treatments evolved in part from animal model research, and further progress is envisaged in large part because these systems have been continually refined and their use focused on questions whose relevance was established by studying the human disease.


title: Antioxidant Potential of Antiviral Drug Umifenovir

text: Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol(®)). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM(−1) min.(−1), for Umifenovir k(1) = 300 nM(−1)min.(−1), k(2) = 4 nM(−1)min.(−1). Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.


title: Influenza C virus–associated community‐acquired pneumonia in children

text: To evaluate the impact of influenza C (ICV) infection in children with community‐acquired pneumonia (CAP), all of the children consecutively seen during 4 influenza seasons with respiratory symptoms and radiographically confirmed CAP were prospectively evaluated. ICV was identified in the respiratory secretions of five of 391 patients (1·3%). In children with ICV‐associated CAP, clinical data were similar to those observed in children with IAV‐associated CAP and worse than those observed in children with IBV‐associated. The phylogenetic tree showed that the sequenced strains clustered in two of the six ICV lineages. These findings highlight that ICV can be a cause of CAP of children and that this can be severe enough to require hospitalization.


title: Correction to: Detection and full genome characterization of two beta CoV viruses related to Middle East respiratory syndrome from bats in Italy

text: CORRECTION After Publication of the article [1], it has been brought to our attention that an author's name has been spelt incorrectly. The correct spelling should be "Massimo Ciccozzi", but it was previously included as "Massimo Cicozzi". The original version has now been revised to reflect this.


title: Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird

text: Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes—the Toll-like receptors (TLRs)—across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world’s most rapidly changing environments.


COVID‐19: implementing sustainable low cost physical distancing and enhanced hygiene


title: 2.6 Anti-infective Agents

text: Abstract Infections may be hazardous to the health of the mother, the course of pregnancy, and the unborn child. They can lead to premature labor or premature rupture of membranes and thereby increase the risk for spontaneous abortion and prematurity. Furthermore, certain germs can pass to the unborn child and harm it directly. Therefore, an anti-infective treatment which should be both effective and safe for the mother and the unborn child is often required. The use of penicillines and older cephalosporines is well documented and considered to be safe. Consequently, they are the drug of choice during pregnancy. In selected cases of bacterial resistance or intolerance to first-line antibiotics, other anti-infective agents might be recommended. Especially for life-threatening infections, a therapy with not so well-tried agents might be needed. The potential benefit of treatment in such cases most often outbalances the potential risk for the unborn child.


title: Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus

text: The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 10(0) TCID(50) MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10(−5) TCID(50) MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs.


title: Tourism economics and policy analysis: Contributions and legacy of the Sustainable Tourism Cooperative Research Centre

text: Abstract The Centre for Economic Policy (CEP) located within Australia's Sustainable Tourism Cooperative Research Centre, engaged with government, industry and researchers for over a decade to advance policy analysis in tourism contexts. This paper discusses the contributions of the CEP in three major areas-the development of tourism satellite accounts, economic impact analysis and policy evaluation. The conceptual and empirical work undertaken by CEP, and the fertile research agenda it developed, is incomplete and poses an ongoing challenge to tourism researchers, practitioners and destination managers internationally to help to progress the advances already made.


title: Toll-like receptor 4 is not involved in host defense against respiratory tract infection with Sendai virus

text: Abstract Toll-like receptors (TLR) induce innate immune responses upon stimulation by a wide variety of pathogens. TLR4 has been implicated in innate immunity against respiratory syncytial virus (RSV) by an interaction with the viral envelope fusion (F) protein. Sendai virus (mouse parainfluenza type 1) shares many features with RSV, including a structurally and functionally similar F protein. To determine the role of TLR4 in host defense against Sendai virus respiratory tract infection, TLR4 mutant and wildtype mice were intranasally infected with Sendai virus. Sendai infection resulted in an increase in viral RNA copies in lung homogenates peaking on day 4. Pulmonary viral loads, histopathology, cytokine levels and leukocyte influx were similar in TLR4 mutant and wildtype mice. In spite of the structural similarities shared by the F proteins of Sendai virus and RSV, TLR4 is not involved in host defense against respiratory tract infection with Sendai virus.


title: Four‐step approach to efficiently develop capillary gel electrophoresis methods for viral vaccine protein analysis

text: Vaccines against infectious diseases are urgently needed. Therefore, modern analytical method development should be as efficient as possible to speed up vaccine development. The objectives of the study were to identify critical method parameters (CMPs) and to establish a set of steps to efficiently develop and validate a CE‐SDS method for vaccine protein analysis based on a commercially available gel buffer. The CMPs were obtained from reviewing the literature and testing the effects of gel buffer dilution. A four‐step approach, including two multivariate DoE (design of experiments) steps, was proposed, based on CMPs and was verified by CE‐SDS method development for: (i) the determination of influenza group 1 mini‐haemagglutinin glycoprotein; and (ii) the determination of polio virus particle proteins from an inactivated polio vaccine (IPV). The CMPs for sample preparation were incubation temperature(s) and time(s), pH, and reagent(s) concentration(s) and the detection wavelength. The effects of gel buffer dilution revealed the CMPs for CE‐SDS separation to be the effective length, the gel buffer concentration, and the capillary temperature. The four‐step approach based on the CMPs was efficient for the development of the two CE methods. A four‐step approach to efficiently develop capillary gel electrophoresis methods for viral vaccine protein analysis was successfully established. This article is protected by copyright. All rights reserved


title: Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children

text: Bacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection. We evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP). Plasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96). LCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies.


title: Scenario-driven forecasting: modeling peaks and paths. Insights from the COVID-19 pandemic in Belgium

text: The recent ‘outburst’ of COVID-19 spurred efforts to model and forecast its diffusion patterns, either in terms of infections, people in need of medical assistance (ICU occupation) or casualties. Forecasting patterns and their implied end states remains cumbersome when few (stochastic) data points are available during the early stage of diffusion processes. Extrapolations based on compounded growth rates do not account for inflection points nor end-states. In order to remedy this situation, we advance a set of heuristics which combine forecasting and scenario thinking. Inspired by scenario thinking we allow for a broad range of end states (and their implied growth dynamics, parameters) which are consecutively being assessed in terms of how well they coincide with actual observations. When applying this approach to the diffusion of COVID-19, it becomes clear that combining potential end states with unfolding trajectories provides a better-informed decision space as short term predictions are accurate, while a portfolio of different end states informs the long view. The creation of such a decision space requires temporal distance. Only to the extent that one refrains from incorporating more recent data, more plausible end states become visible. Such dynamic approach also allows one to assess the potential effects of mitigating measures. As such, our contribution implies a plea for dynamically blending forecasting algorithms and scenario-oriented thinking, rather than conceiving them as substitutes or complements.


title: The use of exhaled nitric oxide and peak expiratory flow to demonstrate improved breathability and antimicrobial properties of novel face mask made with sustainable filter paper and Folium Plectranthii amboinicii oil: additional option for mask shortage during COVID-19 pandemic

text: BACKGROUND: Medical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks. METHODS: This prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FE(NO)) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth. RESULTS: Subjects assigned the LMC mask had a lowered FE(NO) (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius. CONCLUSIONS: The LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.


title: Differences in virus receptor for type I and type II feline infectious peritonitis virus

text: Feline infectious peritonitis viruses (FIPVs) are classified into type I and type II serogroups. Here, we report that feline aminopeptidase N (APN), a cell-surface metalloprotease on the intestinal, lung and kidney epithelial cells, is a receptor for type II FIPV but not for type I FIPV. A monoclonal antibody (MAb) R-G-4, which blocks infection of Felis catus whole fetus (fcwf-4) cells by type II FIPV, was obtained by immunizing mice with fcwf-4 cells which are highly susceptible to FIPV. This MAb also blocked infection of fcwf-4 cells by type II feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV). On the other hand, it did not block infection by type I FIPVs. MAb R-G-4 recognized a polypeptide of relative molecular mass 120–130 kDa in feline intestinal brush-border membrane (BBM) proteins. The polypeptide possessed aminopeptidase activity, and the first 15 N-terminal amino acid sequence was identical to that of the feline APN. Feline intestinal BBM proteins and the polypeptide reacted with MAb R-G-4 (feline APN) inhibited the infectivity of type II FIPV, type II FECV, CCV and TGEV to fcwf-4 cells, but did not inhibit the infectivity of type I FIPVs.


title: Multicolor two-photon imaging of in vivo cellular pathophysiology upon influenza virus infection using the two-photon IMPRESS

text: In vivo two-photon imaging is a valuable technique for studies of viral pathogenesis and host responses to infection in vivo. In this protocol, we describe a methodology for analyzing influenza virus–infected lung in vivo by two-photon imaging microscopy. We describe the surgical procedure, how to stabilize the lung, and an approach to analyzing the data. Further, we provide a database of fluorescent dyes, antibodies, and reporter mouse lines that can be used in combination with a reporter influenza virus (Color-flu) for multicolor analysis. Setup of this model typically takes ~30 min and enables the observation of influenza virus–infected lungs for >4 h during the acute phase of the inflammation and at least 1 h in the lethal phase. This imaging system, which we termed two-photon IMPRESS (imaging pathophysiology research system), is broadly applicable to analyses of other respiratory pathogens and reveals disease progression at the cellular level in vivo.


CoronaVirus Disease 2019: Withdrawing Mechanical Ventilation to Reallocate Life Support Under Crisis Standards of Care—Nonequivalence of the Equivalence Thesis


title: The prospects for the SARS‐CoV‐2 pandemic in Africa

text: On December 31, 2019, the Chinese government officially announced the identification of a new type of coronavirus (SARS‐CoV‐2) as the etiological cause of a severe acute respiratory syndrome in Wuhan city, Hubei Province. Over the next weeks, SARS‐CoV‐2 caused a global pandemic as officially declared by the WHO on March 11, 2020, with confirmed cases and deaths in more than 166 countries. We are experiencing a worldwide phenomenon of unprecedented social and economic consequences. Since the beginning of the COVID‐19 outbreak, there have been fears that the epidemic could strongly impact weaker healthcare systems in poor‐resource settings, especially in Sub‐Saharan Africa (SSA). The 2 million Chinese nationals that live and work in Africa could potentially contribute to the spread of COVID‐19 on the continent.


title: Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis

text: BACKGROUND: Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. RESULTS: We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. CONCLUSIONS: The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms.


title: Intrinsic Cellular Defenses (TRIMS) in Modulating Viral Infection and Immunity

text: Abstract The prompt and tightly controlled induction of type I interferon is a central event of the immune response against viral infection. This response relies on the recognition of incoming pathogens by cellular pattern recognition receptors (PRRs), which then trigger various signaling cascades that result in proinflammatory cytokines and interferon production. Tripartite motif (TRIM)–containing proteins recently emerged as a large family of RING-finger E3 ubiquitin ligases with essential regulatory roles during many phases of the antiviral response, either acting as restriction factors or by modulating PRR signaling. In this article, we discuss recent advances in understanding the role of TRIMs in conferring direct antiviral activity as well as in regulating immune signaling pathways.


COVID‐19 first stage in Japan – how we treat ‘Diamond Princess Cruise Ship’ with 3700 passengers?


title: Les zoonoses (tableaux synthétiques: animaux réservoirs de pathogènes et modes de transmission)

text: The knowledge of animals which act as reservoirs for human pathogenic agents is essential for the understanding of the epidemiology of zoonotic diseases and for the application of relevant methods of control. In the present article, synthetic tables present the main zoonoses due to viruses, bacteria, protozoa, helminths, arthropods and fungi. A list of the main pathogenic agents, the animal reservoirs and the way of transmission to man is detailed in each table.


title: Effects of feeding polyclonal antibody preparations on ruminal bacterial populations and ruminal pH of steers fed high-grain diets

text: Three experiments with factorial arrangements of treatments were designed to test the efficacy of avian-derived polyclonal antibody preparations (PAP) against Streptococcus bovis (PAP-Sb) or Fusobacterium necrophorum (PAP-Fn) in reducing ruminal counts of target bacteria in beef steers supplemented or not with feed additives (300 mg of monensin/d and 90 mg of tylosin/d; MT). Feeding increasing doses of PAP-Sb in Exp. 1 or a single dose in Exp. 2 reduced S. bovis counts in a cubic fashion (P = 0.014). In Exp. 1 and 2, inclusion of MT in the diet had no effect (P > 0.05) on ruminal S. bovis counts. In Exp. 2, ruminal pH was increased (P < 0.05) by feeding PAP-Sb, MT, and PAP-Sb plus MT. Ruminal F. necrophorum counts were reduced by feeding PAP-Fn (P = 0.002) and MT (P < 0.001). Reduction in ruminal F. necrophorum counts was greater (P = 0.008) when feeding MT alone than when feeding PAP-Fn and MT together. In Exp. 3, ruminal S. bovis counts were not affected (P = 0.64) by PAP-Fn. Ruminal pH was not affected (P = 0.61) by feeding PAP-Fn, and the total anaerobic bacterial count was not affected (P > 0.05) by either PAP-Sb or PAP-Fn in Exp. 1 or Exp. 3. In conclusion, PAP of avian origin and against S. bovis or F. necrophorum were effective in reducing target ruminal bacterial populations. These PAP could be effective in preventing the deleterious effects associated with these bacteria, and possibly in enhancing animal performance.


title: Chapter 28 Lectin-like interactions in virus–cell recognition Human immunodeficiency virus and C-type lectin interactions

text: Publisher Summary The calcium-dependent lectin dendritic cell-specific ICAM-grabbing nonintegrin (DC-SIGN) is involved in human immunodeficiency virus (HIV) interactions with dendritic cells. Attachment of HIV to dendritic cells can potentiate viral infectivity for adjacent T-cells and it has been postulated that this process contributes to the dissemination of sexually transmitted virus. More recent research has revealed that the consequences of lectin-dependent HIV interactions with dendritic cells are diverse and can include uptake for major histocompatibility complex presentation, productive infection, and transfer of virus to T-cells. This chapter introduces DC-SIGN and other cellular lectins known to recognize HIV, and discusses how lectin binding might impact viral dissemination. An intricate interplay between viruses and C-type lectins impacts the balance between viral attack and host defense, as specified below for HIV, and elucidation of the underlying mechanisms can provide important insights into the pathogenesis of viral infections and may uncover attractive targets for therapy and prevention.


title: Aspects spécifiques de la production dans le domaine des vaccins

text: Résumé La production de vaccin à l’échelle industrielle connaît son essor au cours de la seconde moitié du xx e siècle. Le vaccin est un médicament qui a la particularité de s’adresser à des sujets bien portants. Les principes actifs qui le composent sont issus d’organismes vivants et se différencient de ceux de la chimie classique par leurs structures moléculaires souvent complexes et parfois mal identifiées. Les propriétés de la préparation vaccinale dépendent étroitement du procédé de production mis en œuvre et il est commun d’admettre que « le procédé fait le produit ». La fabrication s’effectue en zones confinées, due aux caractères pathogènes de la plupart des microorganismes impliqués. Les matières premières sont soumises à des contrôles rigoureux afin de garantir l’intégrité des produits vis-à-vis de contaminants viraux ou d’agents transmissibles non conventionnels comme le prion. L’industrie du vaccin est caractérisée par la longueur des cycles de production. La complexité des produits implique celle des contrôles qualité dont l’activité représente en moyenne 75 % de la durée du cycle total de fabrication. En tant qu’élément majeur de santé publique, le monde du vaccin est soumis à des à-coups de production en fonction de la demande extérieure, en particulier dans les contextes d’épidémie ou de menaces de bioterrorisme. En parallèle, l’industrie du vaccin doit intégrer les exigences toujours plus pressantes des autorités de santé. Le développement spectaculaire des départements assurance qualité et contrôle qualité, ces quinze dernières années, témoignent de cette évolution. Summary The industrial development of vaccine manufacturing expanded during the second half of the 20th century. Vaccines are medicines which target healthy people. The active principles of vaccines arise from live organisms and can be distinguished from standard pharmaceutical compounds by their extreme complexity. The properties of vaccines depend mainly of the manufacturing process and it common to state that “the process makes the product”. The manufacturing is done in confined rooms because of the pathogenic characters of the organisms involved. Raw materials are subjected to rigorous controls to guarantee the integrity of products towards non-conventional agents like prion. The vaccine industry is characterized by the length of the manufacturing cycle. The complexity of the products implies heavy quality controls, which represent 75% of the total duration of the manufacture cycle. As a key element of public health, the vaccine production can be subjected to variations and adaptations, in particular in the context of outbreaks or bioterrorism. The vaccine industry must integrate the regulatory requirements, which are more and more pressing. The spectacular development of the quality assurance and quality control departments these last 15 years testifies to this evolution.


title: Dairy calf rearing unit and infectious diseases: diarrhea outbreak by bovine coronavirus as a model for the dispersion of pathogenic microorganisms

text: Dairy calf rearing unit is a management system that is only recently being implemented by some milk producer’s cooperatives in southern Brazil. However, aspects related to the health profile of the heifer calves that arrive in the rearing unit as well as about biosecurity practices and microbiological challenges have not yet been evaluated in this rearing system in a tropical country. Diarrhea is the main and most frequent consequence of enteric infections in newborn calves. This study, through some etiological and epidemiological characteristics of an outbreak of neonatal diarrhea, has the aim to alert to the possibility of pathogenic microorganism spread in a dairy heifer calf rearing unit. The diarrhea outbreak presented some non-regular characteristics observed in bovine coronavirus (BCoV) enteric infections in dairy calves. The spread of infection was extremely rapid (1 week); the attack rate (> 50%) was much higher than that observed in calves subjected to conventional rearing; and the age range (5 to 90 days) of the affected heifer calves was much broader than that often observed in the BCoV diarrhea worldwide. These unusual epidemiological characteristics observed in this BCoV diarrhea outbreak raise awareness of the health threat present in calf rearing units as well as of the easy and rapid viral spread in a population of young animals from different dairy herds and, therefore, with very distinct immunological status.