title: Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia

text: BACKGROUND: Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. METHODS: From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. RESULTS: A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). CONCLUSIONS: Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.


title: An in-depth study of Crohn's disease in two French families

text: Abstract Background: Two French families were investigated. In the first a husband, wife, and 4 children had Crohn's disease; in the second 7 of 11 children had the disease. There was no history of Crohn's disease in antecedent generations and no linkage to HLA haplotypes. Methods: Methods included family interviews; review of medical records, radiographs, and pathology slides; serology; selective stool culture; enzyme-linked immunosorbent assay for fecal viral detection; and immunocytochemistry. Results: In both families multiple cases occurred among siblings in 7–13-month periods. There appeared to be a 4–8-year recurrence of new disease in both families. Radiographs showed a remarkable similarity in the pattern of disease, confined to distal ileum and cecum, in the members of family 1. Examination for pathology showed granulomas in all 8 patients for whom tissues were available. Acid-fast organisms or Campylobacter-like organisms were not found in tissue sections, and immunocytochemistry was negative for mycobacteria and Yersinia. Stool cultures were negative for mycobacteria, Yersinia, and Mycoplasma. Torovirus and coronavirus antigens were not found in stool. Serology was negative for antibodies to Brucella, Yersinia, influenza, and three enteropathogenic viruses of animals. Conclusions: The circumstances and data suggest that an infectious microorganism is responsible for these clusterings of Crohn's disease.


title: Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

text: Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient’s cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient’s cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.


title: Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know

text: Two medications often used for treatment of immune-mediated conditions, hydroxychloroquine and chloroquine, have recently attracted widespread interest as potential therapies for coronavirus disease 2019. The authors of this commentary provide guidance for clinical decision making for patients with coronavirus disease 2019 as well as for patients with rheumatologic conditions, such as systemic lupus erythematosus and rheumatoid arthritis


docid: wgrhywrn

title: Towards a thermodynamic mechanistic model for the effect of temperature on arthropod vector competence for transmission of arboviruses

text: Abstract Arboviruses such as West Nile virus (WNV), bluetongue virus (BTV), dengue virus (DENV) and chikungunya virus (CHIKV) infect their arthropod vectors over a range of average temperatures depending on the ambient temperature. How the transmission efficiency of an arbovirus (i.e. vector competence) varies with temperature influences not only the short term risk of arbovirus outbreaks in humans and livestock but also the long term impact of climate change on the geographical range of the virus. The strength of the interaction between viral surface (glyco)protein (GP) and the host cell receptor (Cr) on binding of virus to host cell is defined by the thermodynamic dissociation constant Kd_receptor which is assumed to equal 10−3 M (at 37 °C) for binding of a sialic acid (SA) on the arthropod midgut epithelial cell surface to a SA-binding site on the surface of BTV, for example. Here virus binding affinity is modelled with increasing number of GP/Cr contacts at temperatures from 10 °C to 35 °C taking into account the change in entropy on immobilization of the whole virus on binding (ΔSa_immob). Based on published data, three thermodynamic GP/Cr binding scenarios, namely enthalpy-driven, entropy-assisted and entropy-driven, are shown to affect the temperature sensitivity of virus binding in different ways. Thus for enthalpy-driven GP/Cr binding, viruses bind host cells much more strongly at 10 °C than 35 °C. A mechanistic model is developed for the number of arthropod midgut cells with bound virus and by building in a kinetic component for the rate of arbovirus replication and subsequent spread to the arthropod salivary glands, a model for the effect of temperature on vector competence is developed. The model separates the opposing effects of temperature on midgut cell binding affinity from the kinetic component of virogenesis. It successfully accommodates both increases in vector competence with temperature as for DENV and WNV in mosquitoes and decreases as for the CHIKV 2010–1909 strain in various populations of Aedes albopictus mosquitoes. Enhanced cell binding at lower temperatures through enthalpy-driven GP/Cr binding compensates for the lower replication rate to some degree such that some transmission can still occur at lower temperatures. In contrast, the strength of entropy-driven GP/Cr binding diminishes at low temperatures although there is no minimum temperature threshold for transmission efficiency. The magnitude of ΔSa_immob is an important data gap. It is concluded that thermodynamic and kinetic data obtained at the molecular level will prove important in modelling vector competence with temperature.


title: Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal Betacoronaviruses

text: In order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other Betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.


title: Better late than never: a re-examination of ethical dilemmas in coping with severe acute respiratory syndrome

text: Summary At the end of 2002 severe acute respiratory syndrome (SARS) emerged and spread worldwide. The pathogen was unknown, as was its mechanism of transfer, and there was no effective therapy for the disease. There was a large element of hysteria and anxiety in society's reaction to SARS. The initial steps taken to cope with SARS were clear-cut and even dramatic. Decision-making in a time of emergency is associated with a high potential for ethical dilemmas and conflicts. In the course of efforts to cope with a threatening disease, it is important to appraise our activities from an ethical point of view. A retrospective look at this period of time shows that we did not do this. This article examines the ethical aspects of the process undertaken to cope with SARS in our medical centre.


title: 2 methylate or not 2 methylate: viral evasion of the type I interferon response

text: Recent work highlights the requirement for 2′-O-methylation of capped mRNA to prevent recognition by the antiviral host response.


title: Pay dispute resolution service at work on first batch of cases

text: The BDA has begun of the process of resolving the first pay disputes between and associates over pay during the COVID-19 pandemic Following successful lobbying corporate bodies and practice owners with NHS contracts will continue to be paid assuming certain conditions are met One of those is that they are obliged to pass on income due to associates Practices are also required to support the wider NHS pandemic effort, and this is likely to involve associates if NHS money is to be passed on


A synthetic consensus anti-Spike protein DNA vaccine induces protective immunity against Middle East Respiratory Syndrome Coronavirus in non-human primates


title: Patterns of heart Injury in COVID – 19 and relation to outcome

text: We read with much interest the article “Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China” by Han et al as published in March 2020. In this retrospective, single center study authors have discussed the role of acute cardiovascular injury marker including CK‐MB, Myoglobulin, cardiac troponin I (cTnI) and NT‐ proBNP on the outcome of 273 patients with COVID‐19 disease. This article is protected by copyright. All rights reserved.


title: Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor

text: Methamphetamine (METH) is a psychostimulant with high abuse potential and severe neurotoxicity. Recent studies in animal models have indicated that METH can impair the blood–brain barrier (BBB), suggesting that some of the neurotoxic effects resulting from METH abuse could be due to barrier disruption. We report here that while chronic exposure to METH disrupts barrier function of primary human brain microvascular endothelial cells (HBMECs) and human umbilical vein endothelial cells (HUVECs), an early pro-survival response is observed following acute exposure by induction of autophagic mechanisms. Acute METH exposure induces an early increase in Beclin1 and LC3 recruitment. This is mediated through inactivation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70S6K pathway, and upregulation of the ERK1/2. Blockade of Kappa opioid receptor (KOR), and treatment with autophagic inhibitors accelerated METH-induced apoptosis, suggesting that the early autophagic response is a survival mechanism for endothelial cells and is mediated through the kappa opioid receptor. Our studies indicate that kappa opioid receptor can be therapeutically exploited for attenuating METH-induced BBB dysfunction.


title: Evaluating Weight of Evidence in the Mystery of Balkan Endemic Nephropathy

text: Balkan Endemic Nephropathy (BEN) is a chronic, progressive wasting disease of the kidneys, endemic in certain rural regions of the Balkan nations Croatia, Serbia, Bulgaria, and Romania. It is irreversible, and ultimately fatal. Though this disease was first described in the 1920s, its causes have been a mystery and a source of much academic and clinical contention. Possible etiologic agents that have been explored include exposure to metals and metalloids, viruses and bacteria, and the environmental toxins aristolochic acid (AA) and ochratoxin A (OTA). Aristolochic acid is a toxin produced by weeds of the genus Aristolochia, common in Balkan wheat fields. Aristolochia seeds may intermingle with harvested grains and thus inadvertently enter human diets. Ochratoxin A is a mycotoxin (fungal toxin) common in many foods, including cereal grains. In this study, we analyzed the weight of evidence for each of the suspected causes of BEN using the Bradford Hill Criteria (BHC): nine conditions that determine weight of evidence for a causal relationship between an agent and a disease. Each agent postulated to cause BEN was evaluated using the nine criteria, and for each criterion was given a rating based on the strength of the association between exposure to the substance and BEN. From the overall available scientific evidence for each of these suspected risk factors, aristolochic acid is the agent with the greatest weight of evidence in causing BEN. We describe other methods for testing causality from epidemiological studies, which support this conclusion of AA causing BEN.


title: Best Practice in Cardiac Anesthesia during the COVID-19 Pandemic: Practical Recommendations

text: The COVID-19 outbreak has influenced the entire health care system, including cardiac surgery. In this review, the authors reveal practical aspects that are important during the COVID-19 pandemic with regards to the safe delivery of cardiac anesthesia. Timing for operations of the cardio-vascular system may be well programmed, in most cases. Hence, the level of priorities must be defined for any single patient. The postponement of surgery may be convenient for most cases, if it is made in the best interest of the patient. The preanesthetic evaluation should keep attention to the respiratory history of the patient. Cardiac anesthesia is always implying some respiratory monitoring; hence the existing clinical situation of the patient’s respiratory system should be clear. In case of emergency surgery, the patient should be treated as if they potentially have or are at risk for the virus. In the case of a COVID-19 confirmed or suspected patient, attention must be made to preserve operating room and team integrity. The machineries are to be draped with plastic, in order to simplify the disinfection after the operation. Perioperative management of suspected or confirmed COVID-19 patients must strictly follow the most relevant international guidelines. This review article has synthesized the common aspect present in the most important of these.


title: Control Measures Used during Lymphogranuloma Venereum Outbreak, Europe

text: To assess the response to the reemergence of lymphogranuloma venereum, we conducted a cross-sectional survey by administering a structured questionnaire to representatives from 26 European countries. Responses were received from 18 countries. The ability to respond quickly and the measures used for outbreak detection and control varied. Evidence-based criteria were not consistently used to develop recommendations. We did not develop criteria to determine the effectiveness of the recommendations. The degree of preparedness for an unexpected outbreak, as well as the ability of countries to respond quickly to alerts, varied, which indicates weaknesses in the ability to control an outbreak. More guidance is needed to implement and evaluate control measures used during international outbreaks.


title: COVID-19 and Tuberculosis: A mathematical model based forecasting in Delhi, India

text: BACKGROUND: There is emerging evidence that patients with Latent Tuberculosis Infection(LTBI) and Tuberculosis(TB) disease have an increased risk of the SARS-CoV-2 infection and predisposition towards developing severe COVID-19 pneumonia. In this study we attempted to estimate the number of TB patients infected with SARS-CoV-2 and have severe disease during the COVID-19 epidemic in Delhi, India. METHODS: Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to estimate the number of COVID-19 cases in Delhi. Assuming the prevalence of TB in Delhi to be 0.55%, 53% of SARS-CoV2 infected TB cases to present with severe disease we estimated the number of SARS-CoV2 infected TB cases and the number of severe patients. The modelling used estimated R(0) for two scenarios, without any intervention and with public health interventions. RESULTS: We observed that the peak of SARS-CoV-2-TB co-infected patients would occur on the 94th day in absence of public health interventions and on 138(th) day in presence of interventions. There could be 20,880 SARS-CoV-2 infected TB cases on peak day of epidemic when interventions are implemented and 27,968 cases in the absence of intervention. Among them, there could be 14,823 patients with severe disease when no interventions are implemented and 11,066 patients with severe disease in the presence of intervention. CONCLUSION: The importance of primary prevention measures needs to be emphasized especially in TB patients. The TB treatment centres and hospitals needs to be prepared for early diagnosis and management of severe COVID-19 in TB patients.


title: Épidémiologie et diagnostic des infections à virus respiratoire syncytial de l’adulte

text: Résumé Introduction Le virus respiratoire syncytial (VRS) est rarement recherché dans les infections respiratoires de l’adulte. Ce travail en étudie la fréquence et le diagnostic. Méthodes Trois enquêtes distinctes ont été menées chez des adultes atteints soit d’un syndrome pseudo-grippal, d’une infection respiratoire basse communautaire ou hospitalisés pour une pneumopathie infectieuse grave. La recherche du VRS a été faite par PCR dans tous les cas et comparée à la détection antigénique et la culture dans deux enquêtes. Résultats Le VRS est identifié chez 20 (11,7 %) des 170 adultes vaccinés contre la grippe atteints d’un syndrome pseudo-grippal. Dans 270 infections respiratoires basses communautaires sans signes de gravité on trouve un virus dans 86 (31,8 %) cas, dont 13 VRS (4,8 %) ; un virus est détecté dans 64 (36,7 %) des 164 bronchites aiguës : 11 VRS (6,3 %), 37 rhinovirus (21,3 %), 5 virus influenza A et B, et 12 autres virus ; dans les 60 bronchites chroniques surinfectées, il y a 9 rhinovirus (15 %), 2 virus parainfluenza 3 et aucun VRS ; dans les 21 pneumopathies infectieuses aiguës, on trouve 1 VRS, 1 virus influenza A et 2 rhinovirus, et dans les 11 cas d’infections respiratoires basses sur poumon pathologique, 1 VRS, 1 virus parainfluenza 3 et 4 rhinovirus ; il y a au total 19 infections bactériennes et virales associées. Enfin, dans les 51 pneumopathies infectieuses avec détresse respiratoire hospitalisées en réanimation, un virus est isolé dans 17 (33,3 %) cas : 3 VRS (5,8 %), 6 virus influenza A, 3 rhinovirus, 2 adénovirus, 2 herpes simplex et un CMV ; il y a 6 infections bactériennes associées dont 4 d’origine nosocomiale. Tous les patients infectés par le VRS sont âgés et présentent un facteur de risque respiratoire ou cardiaque. Conclusions Chez l’adulte le VRS est responsable de fréquents syndromes pseudo-grippaux et parfois d’infections respiratoires basses, qui peuvent être graves et qu’il faut penser à rechercher. La technique PCR est particulièrement efficace mais non disponible en routine. Summary Introduction Respiratory syncytial virus (RSV) is rarely searched for in respiratory infections in adults. This study assessed its frequency and diagnosis. Methods Three separate studies were conducted in adults presenting with (1) a flu-like illness, (2) a lower respiratory tract infection in the community, and (3) a severe pneumonia requiring hospitalisation. The diagnosis of RSV infection was sought by PCR in all cases, and compared to antigen detection and culture in two studies. Results RSV was identified in 20 (11.7%) of 170 influenza-vaccinated adults suffering from flu-like symptoms. In the 270 cases of non-severe lower respiratory tract illnesses in the community, viruses were identified in 86 (31.8%) cases, with RSV accounting for 13 (4.8%). In the 164 cases of acute bronchitis, a virus was detected in 64 (36.7%) of which 11 (6.3%) were RSV, 37 (21.3%) rhinovirus, 5 influenza viruses A and B, and 12 other viruses. In the 60 cases of infective exacerbations of chronic bronchitis, rhinovirus was detected in 9 (15%) and para-influenza 3 virus in 2 cases. In the 21 acute pneumonia's, 1 RSV, 1 influenza virus A and 2 rhinovirus cases were detected as well as 1 RSV, 1 parainfluenza 3 viruses and 4 rhinovirus cases in the 11 lower respiratory tract illnesses in patients with pre-existing lung disease. There were overall 19 viral and bacterial associated infections. Finally, in the 51 acute pneumonias hospitalised with respiratory distress syndrome, a virus was identified in 17 (33.3%) cases, including 3 (5.5%) RSV, 6 influenza A, 3 rhinovirus, 2 adenovirus, 2 herpes simplex virus and 1 cytomegalovirus. There were 6 bacterial-associated infections, and 4 were hospital-acquired. All RSV-infected patients were old people and had chronic pulmonary or cardiac disease. Conclusions In adults, RSV is a frequent cause of flu-like symptoms. It can sometimes cause lower respiratory tract illness, which can be severe, and should be considered in the differential diagnosis in such cases. The PCR method is a particularly effective diagnostic test, but as yet is not routinely available.


title: Anorectal Cancer with Bone Marrow and Leptomeningeal Metastases

text: This is an interesting case of anorectal signet ring carcinoma with first presentation of an early stage disease, showing the aggressive disease and the undetectable behavior of this type of histology which can mislead diagnosis. Brain/CNS metastasis from colorectal cancer (CRC) is rare occurring in 3% of cases, and leptomeningeal carcinomatosis (LMC) is extremely rare in CRC (<0.02%). Symptoms and signs of LMC are pleomorphic and may be localized to three compartments: cerebral hemispheres, cranial nerves, and spinal cords and roots. Treatment of metastatic rectal cancer has been improving over the last few years with a lot of changes toward longer survival and improvement in quality of life and to change the disease into a chronic condition. However, in our case, the overall survival from the onset of LMC was 3 weeks only. Revising the evidence in the treatment of signet ring histology of rectal cancer, there is no specific treatment recommendation that is for this histology and for such very aggressive behavior which could be considered as a separate entity to the classic adenocarcinoma histology.


title: Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015–2017: cross sectional 1-day surveys

text: Abstract Objectives To assess risk factors for respiratory tract infection symptoms and signs in sheltered homeless people in Marseille during the winter season, including pathogen carriage. Methods Data on 479 male participants within two shelters who completed questionnaires and a total of 950 nasal and pharyngeal samples were collected during the winters of 2015–2017. Respiratory pathogen carriage including seven viruses and four bacteria was assessed by quantitative PCR. Results The homeless population was characterized by a majority of individuals of North African origin (300/479, 62.6%) with a relatively high prevalence of chronic homelessness (175/465, 37.6%). We found a high prevalence of respiratory symptoms and signs (168/476, 35.3%), a very high prevalence of bacterial carriage (313/477, 65.6%), especially Haemophilus influenzae (280/477, 58.7%), and a lower prevalence of virus carriage (51/473, 10.8%) with human rhinovirus being the most frequent (25/473, 5.3%). Differences were observed between the microbial communities of the nose and throat. Duration of homelessness (odds ratio (OR) 1.77, p 0.017), chronic respiratory diseases (OR 5.27, p <0.0001) and visiting countries of origin for migrants (OR 1.68, p 0.035) were identified as independent risk factors for respiratory symptoms and signs. A strong association between virus (OR 2.40, p 0.012) or Streptococcus pneumoniae (OR 2.32, p 0.014) carriage and respiratory symptoms and signs was also found. Conclusions These findings allowed identification of the individuals at higher risk for contracting respiratory tract infections to better target preventive measures aimed at limiting the transmission of these diseases in this setting.


title: An empirical assessment of the CO2-sensitive productivity of European airlines from 2000 to 2010

text: Abstract Due to the ongoing increase in the number of commercial flights, greenhouse gas emissions from aviation are expected to rise significantly. Balancing the pursuit of productivity growth with environmental-footprint control policies comprises a long-term regulatory challenge. In this light, the main goals of the present paper are: (i) to measure the CO2 emissions of European airlines from 2000 to 2010, (ii) to compute airlines’ productivity in developing an environmental-sensitive productivity index, (iii) to compare the obtained results with those resulting from a traditional index, and (iv) to identify the drivers affecting productivity changes. Our results show that on average, airlines’ relative CO2 emissions have decreased. Although the airlines we studied experienced an average productivity increase—both considering and not considering negative externalities production—environmentally sensible productivity growth is lower than traditional productivity growth. Finally, we find that improvements in load factor as well as a combined increase in stage length and aircraft size affect productivity changes positively, while fuel efficiency is significant only in the case of a CO2-sensitive measure of productivity.


title: A Multiplex Asymmetric Reverse Transcription-PCR Assay Combined With an Electrochemical DNA Sensor for Simultaneously Detecting and Subtyping Influenza A Viruses

text: The reliable and rapid detection of viral pathogens that cause respiratory infections provide physicians several advantages in treating patients and managing outbreaks. The Luminex respiratory virus panel (RVP) assay has been shown to be comparable to or superior to culture/direct fluorescent-antibody assays (DFAs) and nucleic acid tests that are used to diagnose respiratory viral infections. We developed a multiplex asymmetric reverse transcription (RT)-PCR assay that can simultaneously differentiate all influenza A virus epidemic subtypes. The amplified products were hybridized with an electrochemical DNA sensor, and the results were automatically acquired. The limits of detection (LoDs) of both the Luminex RVP assay and the multiplex RT-PCR-electrochemical DNA sensor were 10(1) TCID(50) for H1N1 virus and 10(2) TCID(50) for H3N2 virus. The specificity assessment of the multiplex RT-PCR-electrochemical DNA sensor showed no cross-reactivity among different influenza A subtypes or with other non-influenza respiratory viruses. In total, 3098 respiratory tract specimens collected from padiatric patients diagnosed with pneumonia were tested. More than half (43, 53.75%) of the specimens positive for influenza A viruses could not be further subtyped using the Luminex RVP assay. Among the remaining 15 specimens that were not subtyped, not degraded, and in sufficient amounts for the multiplex RT-PCR-electrochemical DNA sensor test, all (100%) were H3N2 positive. Therefore, the sensitivity of the Luminex RVP assay for influenza A virus was 46.25%, whereas the sensitivity of the multiplex RT-PCR-electrochemical DNA sensor for the clinical H1N1 and H3N2 specimens was 100%. The sensitivities of the multiplex RT-PCR-electrochemical DNA sensor for the avian H5N1, H5N6, H9N2, and H10N8 viruses were 100%, whereas that for H7N9 virus was 85.19%. We conclude that the multiplex RT-PCR-electrochemical DNA sensor is a reliable method for the rapid and accurate detection of highly variable influenza A viruses in respiratory infections with greater detection sensitivity than that of the Luminex xTAG assay. The high mutation rate of influenza A viruses, particularly H3N2 during the 2014 to 2016 epidemic seasons, has a strong impact on diagnosis. A study involving more positive specimens from all influenza A virus epidemic subtypes is required to fully assess the performance of the assay.


title: Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis

text: BACKGROUND: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF. METHODS: Thirty young children with CF [median (range) 1.5 years (0.2–4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant. RESULTS: Over 2 years, participants experienced a median of two PEx (range 0–13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = −0.48 and R = −0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV(1))] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44). CONCLUSIONS: Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV(1) and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0546-8) contains supplementary material, which is available to authorized users.


Integrated Hospital Quarantine System against COVID‐19


title: Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

text: BACKGROUND: SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. RESULTS: A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. CONCLUSION: Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.


title: A review on microbial contaminants in stormwater runoff and outfalls: Potential health risks and mitigation strategies

text: Abstract Demands on global water supplies are increasing in response to the need to provide more food, water, and energy for a rapidly growing population. These water stressors are exacerbated by climate change, as well as the growth and urbanisation of industry and commerce. Consequently, urban water authorities around the globe are exploring alternative water sources to meet ever-increasing demands. These alternative sources are primarily treated sewage, stormwater, and groundwater. Stormwater including roof-harvested rainwater has been considered as an alternative water source for both potable and non-potable uses. One of the most significant issues concerning alternative water reuse is the public health risk associated with chemical and microbial contaminants. Several studies to date have quantified fecal indicators and pathogens in stormwater. Microbial source tracking (MST) approaches have also been used to determine the sources of fecal contamination in stormwater and receiving waters. This review paper summarizes occurrence and concentrations of fecal indicators, pathogens, and MST marker genes in urban stormwater. A section of the review highlights the removal of fecal indicators and pathogens through water sensitive urban design (WSUD) or Best Management Practices (BMPs). We also discuss approaches for assessing and mitigating health risks associated with stormwater, including a summary of existing quantitative microbial risk assessment (QMRA) models for potable and non-potable reuse of stormwater. Finally, the most critical research gaps are identified for formulating risk management strategies.


title: Volatility transmission between oil prices and banks' stock prices as a new source of instability: Lessons from the United States experience

text: This paper examines whether American banks' exposure to the oil industry could lead to instability in both oil and financial markets. To bring under discussion this issue not already addressed by literature, we investigate volatility spillovers between oil prices and the stock prices of the four major American banks involved in the oil industry by employing the vector autoregressive fractionally integrated moving average framework. We use high-frequency data from January 3, 2006, to June 30, 2016. Our results support the existence of such volatility spillovers, as evidenced by the significant volatility responses of oil price (banks' stock price) to a shock in banks' stock price (oil price). These responses, more pronounced following the banks' exposure to the shale industry, mainly reflect the financial fragility of shale companies and their high indebtedness levels. Thus, this paper emphasises how the shale oil industry could trigger turmoil in both oil and financial markets.


title: Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

text: Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.


title: Relaxin as a diagnostic tool for pregnancy in the coyote (Canis latrans)

text: Abstract The diagnosis of pregnancy in the domestic dog (Canis familiaris) often employs specialized equipment, experienced staff, and the cooperation of the bitch. These procedures can be challenging when the subject is a wild canid, particularly in a field setting. In addition, reproductive hormone assays are unreliable as a diagnostic tool because the estrous profiles of pregnant and pseudopregnant canines are similar. However, research has demonstrated that the hormone relaxin can be detected in maternal blood after embryonic implantation, but remains negligible in non-pregnant females. We investigated the use of relaxin as a diagnostic marker of pregnancy in the coyote (C. latrans). A commercially available canine relaxin enzyme immunoassay (ReproCHEK™) was used to test plasma collected from 124 female coyotes over four consecutive breeding seasons. Mating activities of the captive females were observed; then peripheral blood samples were collected at intervals throughout pregnancy, as well as after parturition. Results demonstrated that relaxin could be detected in the plasma of pregnant coyotes after 28 days of gestation, and in some cases as early as 23 days, while non-pregnant females and male coyotes consistently tested negative. Relaxin also remained detectable in the plasma of the majority of females tested 10–12 weeks after parturition. This qualitative assay for relaxin proved to be a reliable diagnostic tool for pregnancy in the coyote. In addition, blood sampling was relatively easy, could be accomplished with minimal handling, and did not require sedation or anesthesia.


title: Fitness barriers limit reversion of a proofreading-deficient coronavirus

text: The 3′-to-5′ exoribonuclease in coronavirus (CoV) nonstructural protein 14 (nsp14-ExoN) mediates RNA proofreading during genome replication. ExoN catalytic residues are arranged in three motifs: I (DE), II (E), III (D). Alanine substitution of the motif I residues (AA-E-D, four nucleotide substitutions) in murine hepatitis virus (MHV) and SARS-CoV yields viable mutants with impaired replication and fitness, increased mutation rates, and attenuated virulence in vivo. Despite these impairments, MHV- and SARS-CoV ExoN motif I AA mutants (ExoN-AA) have not reverted at motif I in diverse in vitro and in vivo environments, suggesting that profound fitness barriers prevent motif I reversion. To test this hypothesis, we engineered MHV-ExoN-AA with 1, 2 or 3 nucleotide mutations along genetic pathways to AA-to-DE reversion. We show that engineered intermediate revertants were viable but had no increased replication or competitive fitness compared to MHV-ExoN-AA. In contrast, a low passage (P10) MHV-ExoN-AA showed increased replication and competitive fitness without reversion of ExoN-AA. Finally, engineered reversion of ExoN-AA to ExoN-DE in the presence of ExoN-AA passage-adaptive mutations resulted in significant fitness loss. These results demonstrate that while reversion is possible, at least one alternative adaptive pathway is more rapidly advantageous than intermediate revertants and may alter the genetic background to render reversion detrimental to fitness. Our results provide an evolutionary rationale for lack of ExoN-AA reversion, illuminate potential multi-protein replicase interactions and coevolution, and support future studies aimed at stabilizing attenuated CoV ExoN-AA mutants. Coronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. Instead, compensatory mutations outside of ExoN-AA motif I are more accessible and beneficial than partial reversion. We also show that coevolution between replicase proteins over long-term passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-inactivating mutations, illuminate complex functional and evolutionary relationships between coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA coronavirus mutants.


title: Efficacy of an inactivated oil-adjuvanted rotavirus vaccine in the control of calf diarrhoea in beef herds in Argentina

text: Abstract We have assessed the potency of an inactivated oil-adjuvanted rotavirus vaccine in beef herds in Argentina. Two different vaccine trials were conducted. In a small-scale experimental trial, involving 21 pregnant cows (13 vaccinated and eight unvaccinated controls), a significant increase in neutralizing antibody titres against different serotypes of bovine rotaviruses was found in both the colostrum and serum of vaccinated cows compared with that of unvaccinated controls. Seven days after birth, half of the calves born to vaccinated dams or to control cows were challenged with live virulent virus whereas the other half of both groups were left in contact with the infected calves in order to mimic a natural field challenge. Although no statistically significant differences in the rate of protection were observed among the different groups of animals, a larger number of vaccinated calves were protected in comparison with their controls, particularly where animals in contact with infected calves were concerned. Secondly, a large-scale field trial was carried out in 17 beef herds involving a total of 4066 vaccinated pregnant cows. In 11 farms morbidity and mortality in calves from vaccinated cows were compared with historical data from the previous 3 years at the same locations. In the other six herds, control groups were used to compare data of the same year: 1540 cows were vaccinated and 2700 were left as controls. Taking into account the previous and current incidence of diarrhoea, morbidity and mortality were significantly reduced in 16 of the 17 beef herds tested. Vaccine effectiveness was also evident in farms where other enteropathogens such as cryptosporidium and coronaviruses were present, together with rotavirus.


title: Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research

text: Abstract Ethnopharmacological relevance The African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments. Aim of the study The article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV. The review also provide an account of the in vitro assays, anti-viral activity and phytochemistry of these plants. Materials and methods Peer-reviewed articles investigating plants with ethnobotanical information for the treatment or management of HIV or HIV-related symptoms from the southern African region were acquired from Science Direct, PubMed central and Google Scholar. The selection criteria was that (1) plants should have a record of traditional/popular use for infectious or viral diseases, HIV treatment or symptoms similar to HIV infection, (2) if not traditionally/popularly used, plants should be closely related to plants with popular use and HIV activity identified by means of in vitro assays, (3) plants should have been identified scientifically, (4) should be native to southern African region and (5) anti-HIV activity should be within acceptable ranges. Results Many plants in Africa and specifically the southern African region have been used for the treatment of HIV or HIV related symptoms and have been investigated suing various in vitro techniques. In vitro assays using HIV enzymes such as reverse transcriptase (RT), integrase (IN) and protease (PR), proteins or cell-based assays have been employed to validate the use of these plants with occasional indication of the selectivity index (SI) or therapeutic index (TI), with only one study, that progressed to in vivo testing. The compounds identified from plants from southern Africa is similar to compounds identified from other regions of the world, and the compounds have been divided into three groups namely (1) flavonoids and flavonoid glycosides, (2) terpenoids and terpenoid glycosides and (3) phenolic acids and their conjugated forms. Conclusions An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.


Effective coronavirus reduction by various production steps during the manufacture of plasma‐derived medicinal products


title: Feminism and gendered impact of COVID‐19: Perspective of a counselling psychologist

text: When women, girls and gender‐diverse people — who have been disproportionately impacted by the COVID‐19 pandemic outbreak since the public health crisis has also become a crisis for feminism — will identify and acknowledge their organismic phenomenological self, wholeness and growth will be fully functioning. Psychological aspects for the public health emergency operated through counselling psychologists to manage mental health, emotional, psychological, cognitive, behavioural, relational and social impacts are fundamental. And the role of counselling psychologists in maintaining personal mental health and their clients is a crucial indicator of collective wellbeing. This perspective is embedded in the gendered approach and feminist framework which attempts to explore and offer the embodied intersectional and divergent impact on living during the COVID‐19 pandemic lockdown.


title: Porcine Epidemic Diarrhea in Europe: In-Detail Analyses of Disease Dynamics and Molecular Epidemiology

text: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by the eponymous virus (PEDV) which belongs to the genus Alphacoronavirus within the Coronaviridae virus family. Following the disastrous outbreaks in Asia and the United States, PEDV has been detected also in Europe. In order to better understand the overall situation, the molecular epidemiology, and factors that might influence the most variable disease impact; 40 samples from swine feces were collected from different PED outbreaks in Germany and other European countries and sequenced by shot-gun next-generation sequencing. A total of 38 new PEDV complete coding sequences were generated. When compared on a global scale, all investigated sequences from Central and South-Eastern Europe formed a rather homogeneous PEDV S INDEL cluster, suggesting a recent re-introduction. However, in-detail analyses revealed two new clusters and putative ancestor strains. Based on the available background data, correlations between clusters and location, farm type or clinical presentation could not be established. Additionally, the impact of secondary infections was explored using the metagenomic data sets. While several coinfections were observed, no correlation was found with disease courses. However, in addition to the PEDV genomes, ten complete viral coding sequences from nine different data sets were reconstructed each representing new virus strains. In detail, three pasivirus A strains, two astroviruses, a porcine sapelovirus, a kobuvirus, a porcine torovirus, a posavirus, and an enterobacteria phage were almost fully sequenced.


title: Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain

text: The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected.


Can gendered personal protective equipment design account for high infection rates in female healthcare workers following intubation? A reply


title: Microbial volatile compounds in health and disease conditions

text: Microbial cultures and/or microbial associated diseases often have a characteristic smell. Volatile organic compounds (VOCs) are produced by all microorganisms as part of their normal metabolism. The types and classes of VOC produced is wide, including fatty acids and their derivatives (e.g. hydrocarbons, aliphatic alcohols and ketones), aromatic compounds, nitrogen containing compounds, and volatile sulfur compounds. A diversity of ecological niches exist in the human body which can support a polymicrobial community, with the exact VOC profile of a given anatomical site being dependent on that produced by both the host component and the microbial species present. The detection of VOCs is of interest to various disciplines, hence numerous analytical approaches have been developed to accurately characterize and measure VOCs in the laboratory, often from patient derived samples. Using these technological advancements it is evident that VOCs are indicative of both health and disease states. Many of these techniques are still largely confined to the research laboratory, but it is envisaged that in future bedside ‘VOC profiling’ will enable rapid characterization of microbial associated disease, providing vital information to healthcare practitioners.


title: Dual priming oligonucleotide system for the multiplex detection of respiratory viruses and SNP genotyping of CYP2C19 gene

text: Successful PCR starts with proper priming between an oligonucleotide primer and the template DNA. However, the inevitable risk of mismatched priming cannot be avoided in the currently used primer system, even though considerable time and effort are devoted to primer design and optimization of reaction conditions. Here, we report a novel dual priming oligonucleotide (DPO) which contains two separate priming regions joined by a polydeoxyinosine linker. The linker assumes a bubble-like structure which itself is not involved in priming, but rather delineates the boundary between the two parts of the primer. This structure results in two primer segments with distinct annealing properties: a longer 5′-segment that initiates stable priming, and a short 3′-segment that determines target-specific extension. This DPO-based system is a fundamental tool for blocking extension of non-specifically primed templates, and thereby generates consistently high PCR specificity even under less than optimal PCR conditions. The strength and utility of the DPO system are demonstrated here using multiplex PCR and SNP genotyping PCR.


Elective Reconstructive Surgery During a Pandemic: A Moral Dilemma


title: Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study

text: BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. METHODS: The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. RESULTS: Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. CONCLUSION: The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.


The continuum of SARS-CoV-2's neutropism and the potential for immune-mediated neuronal injury


title: Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

text: BACKGROUND: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. METHODS: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. RESULTS: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. CONCLUSIONS: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.


title: Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” Nutrients 2020, 12(4), 988

text: There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.


Bats reveal the true power of influenza A virus adaptability


title: The Group-Specific Murine Coronavirus Genes Are Not Essential, but Their Deletion, by Reverse Genetics, Is Attenuating in the Natural Host

text: Abstract In addition to a characteristic set of essential genes coronaviruses contain several so-called group-specific genes. These genes differ distinctly among the three coronavirus groups and are specific for each group. While the essential genes encode replication and structural functions, hardly anything is known about the products and functions of the group-specific genes. As a first step to elucidate their significance, we deleted the group-specific genes from the group 2 mouse hepatitis virus (MHV) genome via a novel targeted recombination system based on host switching (L. Kuo, G. J.Godeke, M. J. Raamsman, P. S. Masters, and P. J. M. Rottier, 2000, J. Virol. 74, 1393–1406). Thus, we obtained recombinant viruses from which the two clusters of group-specific genes were deleted either separately or in combination in a controlled genetic background. As all recombinant deletion mutant viruses appeared to be viable, we conclude that the MHV group-specific genes are nonessential, accessory genes. Importantly, all deletion mutant viruses were attenuated when inoculated into their natural host, the mouse. Therefore, deletion of the coronavirus group-specific genes seems to provide an attractive approach to generate attenuated live coronavirus vaccines.


docid: yonxcvvw

title: Market clustering and performance of U.S. OD markets

text: Abstract We segment the U.S. OD markets into peer groups, using a statistical cluster analysis on OD city-pair data on the basis of market concentration, passenger volume and yield. The results show: 1) that high yield markets have, on average, consistently underperformed the industry in both passenger and revenue growth, whereas low yield markets have led the industry in both areas; and 2) mid-sized ODs have experienced higher average growth and lower volatility than the largest U.S. domestic ODs, which have accounted for the least revenue per passenger as compared to all other market types. Financial portfolio analysis indicates the prospect of long-term decision making based on OD market risk and return rather than the aggregated market share analysis used by airlines today.


Anestesiologia pediátrica e o paradoxo da COVID-19: opinião do Comitê de Anestesia em Pediatria da Sociedade Brasileira de Anestesiologia


Psychological impact of ‘Lockdown’ due to COVID-19 pandemic in Nepal: An Online Survey


title: Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

text: Abstract The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually led to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.


title: Viral Pathogens of Domestic Animals and Their Impact on Biology, Medicine and Agriculture

text: Infectious diseases of farm animals are one of the major threats to agriculture and can cause considerable damage at local, regional, and even at the international level both in industrialized and in developing countries. In the last two centuries considerable efforts have been invested in understanding the causes and pathogenesis of viral and bacterial diseases of domestic animals. These studies have introduced new methodologies for the diagnosis, treatment, and control of veterinary diseases. Importantly, research on veterinary pathogens also had a major impact in understanding basic biological processes of viruses and bacteria. In some cases, studies on veterinary pathogens have revolutionized biology and established entire new disciplines. This article will furnish a historical perspective on how studies of animal diseases, focusing on viral diseases in particular, have made a major contribution on the current understanding of pathogen biology. In addition, the main features of some of the most important viral diseases of farm animals will be described. Climate and environmental changes can favor the emergence of new pathogens or the reemergence of old ones. It is critical that resources be devoted to research and surveillance of veterinary pathogens in order to preserve and improve both animal and human health.


title: Regional Infectious Disease Surveillance Networks and their Potential to Facilitate the Implementation of the International Health Regulations

text: The International Health Regulations (IHR) 2005 present a challenge and opportunity for global surveillance and control of infectious diseases. This article examines the opportunity for regional networks to address this challenge. Two regional infectious disease surveillance networks, established in the Mekong Basin and the Middle East, are presented as case studies. The public-private partnerships in the networks have led to an upgrade in infectious disease surveillance systems in capacity building, purchasing technology equipment, sharing of information, and development of preparedness plans in combating avian influenza. These regional networks have become an appropriate infrastructure for the implementation of the IHR 2005.


title: Evaluation of three commercial multiplex assays for the detection of respiratory viral infections

text: Abstract Background Timely identification of respiratory virus infection is essential to mitigate inappropriate antibiotic use and to implement appropriate treatment and/or infection control procedures. As such, multiplexed PCR assays have become standard in many virology laboratories. Objectives To compare the Seeplex RV15 (test of record) with two newer generation multiplex assays, the Anyplex II RV16 and the xTAG respiratory virus panels. Study design Two hundred and three retrospective and 36 prospective respiratory samples were tested by all three assays. Samples were deemed to be positive if they tested positive for a virus by at least two of the three respective assays. Negative samples also had to test negative by at least two of the three assays. Inconclusive samples were those that showed band signal intensity between 0 and 100 on the RV15, but had not been previously tested on the RV16 or xTAG. Results and conclusions Overall sensitivity and specificity of all three assays were similar (∼85% and 100%, respectively). Given each assay can identify multiple different viruses, the targets reported by one assay did not always agree with each target from another assay. Partial discordant rates were 47% and 21% for positive and negative samples, respectively. These higher than expected partial discordant rates may be due to primer or chemistry differences amongst the three multiplex assays.


title: Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia

text: BACKGROUND: Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. METHODS: Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1–3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. RESULTS: Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%–4.4% and 0.8%–2.8% in children and adults, respectively; relative differences were 1.1–3.0 times higher. CONCLUSIONS: Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.


docid: hnuvcctm

title: Balancing governance capacity and legitimacy ‐ how the Norwegian government handled the COVID‐19 crisis as a high performer

text: This paper addresses how the Norwegian government has handled the corona pandemic. Compared to many other countries Norway performs well in handling the crises and this must be understood in the context of competent politicians, a high trust society with a reliable and professional bureaucracy, a strong state, a good economic situation, a big welfare state and low density of the population. The government managed to control the pandemic rather quickly by adopting a suppression strategy, followed by a control strategy, based on a collaborative and pragmatic decision‐making style, successful communication with the public, a lot of resources and a high level of citizens' trust in government. The alleged success of the Norwegian case is about the relationship between crisis management capacity and legitimacy. Crisis management is most successful when it is able to combine democratic legitimacy with government capacity. This article is protected by copyright. All rights reserved.


title: ET-traps as a potential treatment for COVID-19

text: The ET-traps are Fc-fusion proteins that have shown a therapeutic potential in the diabetes disease space. Previous studies have also discussed the potential use of ET-traps for other diseases, including HIV / AIDS. These diseases are all associated with pathologically elevated endothelin −1 (ET-1) levels. This paper discusses the potential use of ET-traps for the COVID-19 pandemic, which previous studies have shown involves high cytokine levels. Research has also shown that ET-1 is a stimulus for the induction of these pro-inflammatory cytokines. Hence, the ET-traps would likely be effective in patients suffering from COVID-19. If successful at the preclinical and clinical testing, the ET- traps would provide a much-awaited therapy.


title: Further studies on human enteric coronaviruses

text: Comparisons were made between human enteric coronaviruses and the enteric coronaviruses of pigs and calves by negative staining. Examination of human intestinal organ culture fluids at various time intervals after inoculation with the human enteric coronavirus showed increasing numbers of particles in the fluids. Thin sections of the columnar epithelial cells of these explants showed a number of features consistent with the replication of known human and animal coronaviruses. Virus particles found in thin sections had a mean diameter of 68 nm. In addition, a structure was found in thin sections which has not been described previously. This structure may represent the viral nucleocapsid.


title: Uvéites et tatouages()

text: The complications of tattoos are multiple and known for many years. However, their success explains their exponential multiplication in all countries. This confirmed the development of two new complications: a localized or remote skin sarcoidosis reaction, as well as the development of clinical and histological uveitis. This is in the context of a delayed hypersensitivity reaction, or a granulomatous reaction. Their prevention remains rather poorly known. It requires that each tattoo-carrying subject perform a systemic sarcoidosis check-up as well as an ophthalmological investigation in search of possible uveitis. If confirmed, preventive and therapeutic measures will be carried out in emergencies to avoid blindness. These new complications confirm the extreme severity of the use of uncontrolled inks, real toxic and sensitizing mixtures, especially apparently during extensive colorful tattoos. These particularly aggressive colored inks release multiple substances and nanoparticles into the body, not all of which are measured in the medium and long term.


COVID-19 and fungal superinfection


title: Chapter 9 Molecular Pathology and Infectious Diseases

text: Publisher Summary This chapter discusses the pathogenesis and progression of infectious diseases. Agricultural and industrial development has resulted in the increased density of humans living in close proximity to each other. This lifestyle change from more rural existence has brought humans in closer proximity to wild animals that harbor potential future human pathogens. Most diseases are transmitted by insect vectors. Molecular diagnostic tests can be divided into two primary groups. The first are tests designed to detect the presence of mutations in the human genome that are associated with specific diseases. These tests need to be performed only once in a specific individual’s lifetime. The second group of molecular diagnostic assays is designed to detect infectious agents or the recurrence of a mutation specifically associated with a tumor the patient has had in the past. Bacterial, viral, fungal, or parasitic infections can be eradicated and recur at a time in the future requiring repetition of the same molecular assay for detection. Minimal residual disease detection refers to the analysis of tissue/cells in a patient previously diagnosed with a malignancy to evaluate if therapy was completed successfully or if rare malignant cells are present.


title: Assessment of Potential Zoonotic Disease Exposure and Illness Related to an Annual Bat Festival — Idanre, Nigeria

text: Bats provide vital ecologic services that humans benefit from, such as seed dispersal and pest control, and are a food source for some human populations. However, bats also are reservoirs for a number of high-consequence zoonoses, including paramyxoviruses, filoviruses, and lyssaviruses. The variety of viruses that bats harbor might be related to their evolutionary diversity, ability to fly large distances, long lifespans, and gregarious roosting behaviors. Every year a festival takes place in Idanre, Nigeria, in which males of all ages enter designated caves to capture bats; persons are forbidden from entering the caves outside of these festivities. Festival participants use a variety of techniques to capture bats, but protective equipment rarely is used, placing hunters at risk for bat scratches and bites. Many captured bats are prepared as food, but some are transported to markets in other parts of the country for sale as bushmeat. Bats also are presented to dignitaries in elaborate rituals. The health consequences of contact with these bats are unknown, but a number of viruses have been previously identified among Nigerian bats, including lyssaviruses, pegiviruses, and coronaviruses. Furthermore, the caves are home to Rousettus aegyptiacus bats, which are reservoirs for Marburg virus in other parts of Africa.


title: Travel-acquired infections and illnesses in Canadians: surveillance report from CanTravNet surveillance data, 2009–2011

text: BACKGROUND: Important knowledge gaps exist in our understanding of migration medicine practice and the impact of pathogens imported by Canadian travellers. We present here a comprehensive, Canada-specific surveillance summary of illness in a cohort of returned Canadian travellers and new immigrants. METHODS: We extracted and analyzed (using standard parametric and nonparametric techniques) data from the Canadian Travel Medicine Network (CanTravNet) database for ill returned Canadian travellers and new immigrants who presented to a Canadian GeoSentinel Surveillance Network site between September 2009 and September 2011. RESULTS: During the study period, 4365 travellers and immigrants presented to a CanTravNet site, 3943 (90.3%) of whom were assigned a travel-related diagnosis. Among the 3115 non-immigrant travellers with a definitive travel-related diagnosis, arthropod bite (n = 127 [4.1%]), giardiasis (n = 91 [2.9%]), malaria (n = 77 [2.5%]), latent tuberculosis (n = 73 [2.3%]), and strongyloidiasis (n = 66 [2.1%]) were the most common specific etiologic diagnoses. Among the 828 immigrants with definitive travel-related diagnoses, the most frequent etiologies were latent tuberculosis (n = 229 [27.7%]), chronic hepatitis B (n = 182 [22.0%]), active tuberculosis (n = 97 [11.7%]), chronic hepatitis C (n = 89 [10.7%]), and strongyloidiasis (n = 41 [5.0%]). Potentially serious infections, such as dengue fever (61 cases) and enteric fever due to Salmonella enterica serotype Typhi or Paratyphi (36 cases), were common. Individuals travelling for the purpose of visiting friends and relatives (n = 500 [11.6% of those with known reason for travel]) were over-represented among those diagnosed with malaria and enteric fever, compared with other illnesses (for malaria 34/94 [36.2%] v. 466/4221 [11.0%]; for enteric fever, 17/36 [47.2%] v. 483/4279 [11.3%]) (both p < 0.001). For cases of malaria, there was also overrepresentation (compared with other illnesses) from business travellers (22/94 [23.4%] v. 337/4221 [8.0%]) and males (62/94 [66.0%] v. 1964/4269 [46.0%]) (both p < 0.001). Malaria was more likely than other illnesses to be acquired in sub-Saharan Africa (p < 0.001), whereas dengue was more likely than other illnesses to be imported from the Caribbean and South East Asia (both p = 0.003) and enteric fever from South Central Asia (24/36 [66.7%]) (p < 0.001). INTERPRETATION: This analysis of surveillance data on ill returned Canadian travellers has detailed the spectrum of imported illness within this cohort. It provides an epidemiologic framework for Canadian practitioners encountering ill returned travellers. We have confirmed that travel to visit friends and relatives confers particularly high risks, which underscores the need to improve pretravel intervention for a population that is unlikely to seek specific pretravel advice. Potentially serious and fatal illnesses such as malaria and enteric fever were common, as were illnesses of public health importance, such as tuberculosis and hepatitis B.


title: A Novel, Inexpensive Portable Respiratory Protection Unit for Prehospital Use: A Technical Note

text: There is a heightened concern for exposure to infectious aerosols during the intubation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) patients. We took our previously designed portable, inexpensive, and easily constructed device and modified it for the prehospital setting. Using polyvinyl chloride pipe and automobile collision wrap, a prehospital unit can be constructed in less than 30 minutes, and the cost of material is under 50 U.S. dollars. The box stores easily in an ambulance and can be assembled on the scene within two minutes. This easily built device likely provides some limited protection from aerosolization during video laryngoscopy and can be replicated easily.


title: SARS: future research and vaccine

text: Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. A novel coronavirus (CoV) was identified as its aetiological agent and its genome was sequenced within months of the World Health Organisation issuing a global threat on SARS. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. This will depend on understanding the pathogenesis and immune response to SARS CoV. Further understanding of the ecology of SARS CoV in human and animals will help prevent future cross species transmission. Likewise for the super-spreading events, clarification of the underlying reasons will be important to prevent a large scale outbreak of SARS. Lastly it is of utmost importance that international research collaboration should be strengthened to deal with SARS and any other emerging infectious disease that can seriously threaten our future.


title: Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients

text: Abstract The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients.


title: Public Engagement and Government Responsiveness in the Communications About COVID-19 During the Early Epidemic Stage in China: Infodemiology Study on Social Media Data

text: BACKGROUND: Effective risk communication about the outbreak of a newly emerging infectious disease in the early stage is critical for managing public anxiety and promoting behavioral compliance. China has experienced the unprecedented epidemic of the coronavirus disease (COVID-19) in an era when social media has fundamentally transformed information production and consumption patterns. OBJECTIVE: This study examined public engagement and government responsiveness in the communications about COVID-19 during the early epidemic stage based on an analysis of data from Sina Weibo, a major social media platform in China. METHODS: Weibo data relevant to COVID-19 from December 1, 2019, to January 31, 2020, were retrieved. Engagement data (likes, comments, shares, and followers) of posts from government agency accounts were extracted to evaluate public engagement with government posts online. Content analyses were conducted for a random subset of 644 posts from personal accounts of individuals, and 273 posts from 10 relatively more active government agency accounts and the National Health Commission of China to identify major thematic contents in online discussions. Latent class analysis further explored main content patterns, and chi-square for trend examined how proportions of main content patterns changed by time within the study time frame. RESULTS: The public response to COVID-19 seemed to follow the spread of the disease and government actions but was earlier for Weibo than the government. Online users generally had low engagement with posts relevant to COVID-19 from government agency accounts. The common content patterns identified in personal and government posts included sharing epidemic situations; general knowledge of the new disease; and policies, guidelines, and official actions. However, personal posts were more likely to show empathy to affected people (χ(2)(1)=13.3, P<.001), attribute blame to other individuals or government (χ(2)(1)=28.9, P<.001), and express worry about the epidemic (χ(2)(1)=32.1, P<.001), while government posts were more likely to share instrumental support (χ(2)(1)=32.5, P<.001) and praise people or organizations (χ(2)(1)=8.7, P=.003). As the epidemic evolved, sharing situation updates (for trend, χ(2)(1)=19.7, P<.001) and policies, guidelines, and official actions (for trend, χ(2)(1)=15.3, P<.001) became less frequent in personal posts but remained stable or increased significantly in government posts. Moreover, as the epidemic evolved, showing empathy and attributing blame (for trend, χ(2)(1)=25.3, P<.001) became more frequent in personal posts, corresponding to a slight increase in sharing instrumental support, praising, and empathizing in government posts (for trend, χ(2)(1)=9.0, P=.003). CONCLUSIONS: The government should closely monitor social media data to improve the timing of communications about an epidemic. As the epidemic evolves, merely sharing situation updates and policies may be insufficient to capture public interest in the messages. The government may adopt a more empathic communication style as more people are affected by the disease to address public concerns.


title: Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease

text: Abstract Based on the tenet of a common mucosal immune system, antigenic stimulation at one mucosal site results in the distribution of antigen-specific IgA precursor cells to distant mucosal sites. However, recent studies suggest that functional compartmentalization and limited reciprocity may exist within some components of the common mucosal immune system. Although oral immunization is often very effective in inducing immunity to respiratory pathogens, the converse (respiratory immunization to prevent enteric diseases) may not be as effective. To address this question and to study interactions between the bronchus-associated (BALT) and gut-associated (GALT) lymphoid tissues related to protective immunity, we used as a model two antigenically related porcine coronaviruses which replicate primarily in the intestine (transmissible gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory coronavirus, PRCV). The tissue distribution and magnitude of the antibody secreting cell (ASC) responses (measured by ELISPOT) and cell-mediated immune responses (measured by lymphoproliferative assays, LPA) coincided with the viral tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes, BLN) and induced complete protection against enteric TGEV challenge. In contrast immunization via BALT (respiratory infection with PRCV) elicited systemic type responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses in the gut LP or MLN and induced only partial protection against enteric TGEV challenge. Thus administration of vaccines intranasally may not be optimally effective for inducing intestinal immunity in contrast to the reported efficacy of oral vaccines for inducing respiratory immunity.


title: First molecular characterization of canine parvovirus strains in Sardinia, Italy

text: Canine parvovirus type 2 (CPV-2) is responsible of acute hemorrhagic gastroenteritis in young dogs. CPV-2 emerged in 1978 in the USA, but new antigenic types, CPV-2a, 2b and 2c, have completely replaced the original type. In this study, we analyzed 81 animals collected in Sardinia, Italy. The VP2 sequence analysis of 27 positive samples showed that all antigenic CPV-2 types are circulating. CPV-2b seems to be the most widespread variant, followed by CPV-2a. Furthermore, 12 CPV-2b strains displayed further amino acid substitutions and formed a separate cluster in a phylogenetic tree, indicating regional genetic variation.


title: Viral load and outcome in SARS infection: The role of personal protective equipment in the emergency department

text: Abstract This study was conducted to evaluate the effectiveness of personal protective equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non-HCWs were studied. We compared the initial viral load by nasopharyngeal swabs, clinical progression, and outcome of this cluster. The HCWs had a lower viral load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation, and a higher incidence of intubation and death. Secondary household transmission developed in three of the non-HCWs’ families. One month after discharge, non-HCWs had more signs of fibrosis on high resolution computed tomography (HRCT) scan and an impaired pulmonary function test. Although most of the PPE do not confer absolute protection against SARS, it seems that they may lower exposure to the virus, leading to a lower risk of secondary transmission, and be associated with relatively mild disease and a better early outcome.


title: DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome

text: Abstract Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2.


docid: umpuwnsw

title: Evaluation of a recombinant nucleocapsid protein‐based assay for Anti‐SARS‐CoV IgG detection

text: A high throughput accurate assay for anti‐SARS‐CoV IgG detection is needed for large‐scale epidemiological studies. The evaluation of a commercial recombinant nucleocapsid protein‐based microtitre plate enzyme immunoassay, ELISARS™ is described. The results on 150 sera from SARS patients and 450 sera from non‐SARS controls showed that this assay had a high level of sensitivity (96.2% for late serum samples) and specificity (97.8%). The performance and setup of this assay fulfills the requirement as a screening test for large‐scale studies. A vast majority of SARS patients developed antibodies against the nucleocapsid protein. In some patients (10/45), a high level of anti‐nucleocapsid antibody appeared very early in the course of the illness. In contrast, a minority (4 of 105 patients) never developed these antibodies. The implication of differences in antibody response to the nucleocapsid protein deserves further investigation. J. Med. Virol. 75:181–184, 2005. © 2004 Wiley‐Liss, Inc.


Potential clinical treatment for Ebola pandemic


title: Paediatric COVID‐19 admissions in a region with open schools during the two first months of the pandemic

text: According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country‐wide school closures by April 1(st) 2020 in an effort to combat the COVID‐19 pandemic. It’s estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day care centres and schools for children up to 15 years of age remained open. The strategy decision to shift schools to distance learning only for children aged 16 years and older was influenced by multiple factors, including the potential impact on school closures on the availability of the healthcare work force, the increasing evidence of mainly mild infections among children and the potential negative consequences of school closures for younger children.


title: Outpatient Antibiotic Stewardship: A Growing Frontier—Combining Myxovirus Resistance Protein A With Other Biomarkers to Improve Antibiotic Use

text: BACKGROUND: The majority of oral antibiotics are prescribed in outpatient primary and urgent care clinics for acute respiratory infections. Effective antibiotic stewardship must include proper prescribing for outpatients as well as for those in a hospital or long-term care facility. METHODS: Major databases, including MEDLINE and the Cochrane Library, were searched for prospective human clinical studies, including children and/or adults published between January 1966 and November 2017 that evaluated Myxovirus resistance protein A (MxA) as a biomarker for diagnosing viral infections as well as both C-reactive protein (CRP) and procalcitonin (PCT) as potential biomarkers for identifying and differentiating true bacterial upper respiratory infection (URI) from colonization. RESULTS: Ten prospective human studies, totaling 1683 patients, were identified that evaluated MxA as a viral biomarker in children and/or adults. Both systematic review articles, meta-analyses, and randomized controlled clinical trials that examined CRP and/or PCT as a biomarker for identifying clinically significant bacterial infections and supporting antibiotic stewardship were identified. CONCLUSIONS: Quick and accurate differentiation between a viral and bacterial respiratory infection is critical to effectively combat antibiotic misuse. MxA expression in peripheral blood is a highly specific marker for viral infection. Combining MxA with other inflammatory biomarkers to test for respiratory infections offers enhanced sensitivity and specificity, forming an excellent tool for antibiotic stewardship in the outpatient setting.


title: Political economy and the emergence of a hybrid mode of governance of tourism planning

text: This paper examines how Hong Kong's political economy influences its local modes of tourism governance and development planning. The study explores how a destination can exhibit a hybrid mode of tourism governance, and also how that emerged in Hong Kong in relation to three phases of socio-economic and tourism development. The three phases are 1842–1966, 1967–1997, and post-1997. Hong Kong's present mode of tourism governance combines pro-growth and pluralist elements. It is affected by the need for capital accumulation and political legitimacy and by the relative influence of government and civil society.


title: Systemic Causes of Cholestasis

text: Systemic causes of cholestasis constitute a diverse group of diseases across organ systems. The pathophysiology of cholestasis in systemic disease can be a consequence of direct involvement of a disease process within the liver or extrahepatic biliary system or secondary to immune-mediated changes in bile flow. Evaluating a patient with cholestasis for a systemic cause requires an understanding of the patient's risk factors, clinical setting (eg, hospitalized or immunosuppressed patient), clinical features, and pattern of laboratory abnormalities.


title: Dynamics of Zika virus outbreaks: an overview of mathematical modeling approaches

text: BACKGROUND: The Zika virus was first discovered in 1947. It was neglected until a major outbreak occurred on Yap Island, Micronesia, in 2007. Teratogenic effects resulting in microcephaly in newborn infants is the greatest public health threat. In 2016, the Zika virus epidemic was declared as a Public Health Emergency of International Concern (PHEIC). Consequently, mathematical models were constructed to explicitly elucidate related transmission dynamics. SURVEY METHODOLOGY: In this review article, two steps of journal article searching were performed. First, we attempted to identify mathematical models previously applied to the study of vector-borne diseases using the search terms “dynamics,” “mathematical model,” “modeling,” and “vector-borne” together with the names of vector-borne diseases including chikungunya, dengue, malaria, West Nile, and Zika. Then the identified types of model were further investigated. Second, we narrowed down our survey to focus on only Zika virus research. The terms we searched for were “compartmental,” “spatial,” “metapopulation,” “network,” “individual-based,” “agent-based” AND “Zika.” All relevant studies were included regardless of the year of publication. We have collected research articles that were published before August 2017 based on our search criteria. In this publication survey, we explored the Google Scholar and PubMed databases. RESULTS: We found five basic model architectures previously applied to vector-borne virus studies, particularly in Zika virus simulations. These include compartmental, spatial, metapopulation, network, and individual-based models. We found that Zika models carried out for early epidemics were mostly fit into compartmental structures and were less complicated compared to the more recent ones. Simple models are still commonly used for the timely assessment of epidemics. Nevertheless, due to the availability of large-scale real-world data and computational power, recently there has been growing interest in more complex modeling frameworks. DISCUSSION: Mathematical models are employed to explore and predict how an infectious disease spreads in the real world, evaluate the disease importation risk, and assess the effectiveness of intervention strategies. As the trends in modeling of infectious diseases have been shifting towards data-driven approaches, simple and complex models should be exploited differently. Simple models can be produced in a timely fashion to provide an estimation of the possible impacts. In contrast, complex models integrating real-world data require more time to develop but are far more realistic. The preparation of complicated modeling frameworks prior to the outbreaks is recommended, including the case of future Zika epidemic preparation.