title: Caring for the carers: Advice for dealing with sleep problems of hospital staff during the COVID‐19 outbreak

text: Hospital staff are at the frontline in the COVID‐19 outbreak. The stressors they experience may induce sleep problems in a population already at risk. Sleep deprivation, long shifts and insomnia in hospital staff have been associated with individual, organizational and public health hazards. These include increased risk of mental and somatic disorders, altered immune responses, medical errors, misunderstandings, drowsy driving and burnout. In March 2020, the World Health Organization called for providing access to mental health and counselling for health professionals involved in the COVID‐19 outbreak. To answer this call, we propose practical advice for the management of sleep problems (sleep deprivation, insomnia and shift work) that can be included in supportive interventions. The advice is based on psychobiological principles of sleep regulation and on guidelines for the treatment of insomnia and was implemented within an initiative offering psychological support to the staff of three university hospitals in Rome.


title: Reappearance of effector T cells is associated with recovery from COVID-19

text: BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and γδ T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14–76,103–184CORONA-11/20 and German Research Foundation, Excellence Strategy – EXC2155“RESIST”–Project ID39087428, and DFG-SFB900/3–Project ID158989968, grants SFB900-B3, SFB900-B8.


title: Facteurs infectieux et non infectieux des otites et des sinusites

text: Résumé Les infections de la sphère ORL sont fréquentes et les otites chez l’enfant, les sinusites de l’adulte sont généralement perçues comme étant d’origine bactérienne ou virale. Cependant de nombreux facteurs non infectieux jouent un rôle non négligeable, mais restent souvent méconnus et d’interprétation difficile : ils conduisent encore trop souvent à des thérapeutiques antibiotiques inutiles. Ainsi dans l’otite, ont été reconnus divers facteurs de risque non infectieux tels que : atteinte mécanique de la trompe d’Eustache, immaturité immunitaire, tabagisme passif, carence martiale etc… susceptibles de favoriser l’infection de l’oreille moyenne, souvent virale dans un 1er temps, secondairement surinfectée par les espèces bactériennes du rhinopharynx ((pneumocoques, Haemophilus influenzae, Moraxella catarrhalis). Les sinusites sont d’étiologie multifactorielle et, si les mécanismes et les agents des sinusites infectieuses (virus et bactéries) sont bien connus, en revanche de multiples facteurs non infectieux peuvent être identifiés : l’allergie est un facteur fréquent qui favorise les sinusites à répétition ; moins souvent reconnus sont le diabète, le reflux gastro-oesophagien, des facteurs anatomiques, des anomalies de la fonction muco-ciliaire ou l’immunodépression dans le cadre VIH. Des recherches doivent être poursuivies pour approfondir ces mécanismes complexes. Abstract Infections of the ENT area are frequent and otitis media in children, sinusitis in adults are generally attributed to viruses or bacterial species. However many non infectious factors play an important role and may lead to useless antibiotic treatments. In otitis media, several factors such as mechanical defect in Eustachian tube, immature immunity, passive tobacco environment are capable to initiate a first viral step of otitis media, followed by bacterial infection due to S. pneumoniae, H. influenzae or Moraxella catarrhalis. Sinusitis are associated to multiple factors and mechanical as well as infective agents (viruses and bacteria) are well established. But several non infectious factors should be analysed and one major factor is allergy which is responsible for repeated sinusitis. Diabetes, anatomical factors, inappropriate muco-ciliary structure, HIV immunodepression can play a significant role in non infectious sinusitis. More work should be done to improve understanding of these complex mechanisms.


title: Genetically delivered antibody protects against West Nile virus

text: Gene-based delivery of recombinant antibody genes is a promising therapeutic strategy offering numerous advantages including sustained antibody levels, better safety profile and lower production cost. Here we describe generation of a recombinant antibody Fc-9E2 comprising a fusion protein between human Fc of IgG1 and a single-chain Fv derived from a hybridoma 9E2 secreting a mAb neutralizing West Nile virus (WNV). Fc-9E2 was shown to retain parental mAb's specificity and WNV-neutralizing capacity. Adenovirus-mediated in vivo delivery of the antibody gene resulted in sustained Fc-9E2 serum levels leading to abrogation of lethal WNV infection in an animal model.


title: Expression, crystallization and preliminary crystallographic study of the C-terminal half of nsp2 from SARS coronavirus

text: SARS coronavirus (SARS-CoV) is the aetiological agent of the highly infectious severe acute respiratory syndrome (SARS). To gain a better understanding of SARS-CoV replication and transcription proteins, a preliminary X-ray crystallographic study of the C-terminal domain of SARS-CoV nonstructural protein 2 (nsp2) is reported here. The C-terminal domain of SARS-CoV nsp2 was cloned, overexpressed, purified and crystallized using polyethylene glycol 5000 monomethyl ether as the precipitant; the crystals diffracted to 2.5 Å resolution. The crystals belonged to space group P6(5), with unit-cell parameters a = b = 112.8, c = 91.1 Å, α = β = 90, γ = 120°. One molecule is assumed to be present per asymmetric unit, which gives a Matthews coefficient of 2.89 Å(3) Da(−1) and a solvent content of 56.2%.


title: A longitudinal study of bovine coronavirus enteric and respiratory infections in dairy calves in two herds in Ohio

text: Abstract This prospective longitudinal study examined the epidemiology and disease syndrome associated with bovine coronavirus (BCV) infections in a cohort of 8 conventional calves from 0 to 120 days of age, in two dairy herds in Ohio. The periods of respiratory shedding of BCV were determined by direct immunofluorescent (DIF) staining of nasal epithelial cells and ELISA of nasal swab supernatant fluids. The periods of fecal shedding of BCV were determined by ELISA and immunoelectron microscopy (IEM). The isotype-specific antibody titers to BCV in serum (at selected intervals between 0 and 120 days of age) and the post-suckling (24 to 48 h after birth) total immunoglobulin levels were examined by ELISA and zinc sulfate turbidity tests, respectively. Of the 8 calves studied, 4 had evidence of BCV respiratory (by DIF or ELISA) or enteric infections (by IEM or ELISA) in association with diarrhea or rhinitis, even though 7 or 8 calves showed increases in one or more serum antibody isotypes to BCV and 6 of 8 calves showed BCV respiratory or enteric antigen shedding by ELISA. Serological antibody titer increases occurred in 3 calves before 30 days of age and in 4 calves after 30 days of age; two of the latter calves had a second rise in serum antibody titers to BCV after the initial rise. A serological antibody titer increase was not observed in one calf. This suggests that BCV infections may be very common in a closed herd and may occur in older calves, although many may be subclinical and some may be recurrent. There were no statistically significant correlations between total serum immunoglobulin levels or BCV antibody isotype titers in serum (24–48 h after birth) and clinical disease or infection by BCV; however, calves with low levels of IgA BCV antibodies in serum (24–48 h after birth) had a significantly greater average number of days with diarrhea than those calves having high levels of IgA BCV-specific antibodies in serum.


title: Environmental and Occupational Health Response to SARS, Taiwan, 2003

text: Environmental and Occupational Health Industrial hygiene emergency response to SARS in Taiwan.


title: COVID‐19 and Alternative: Conceptualisations of Value and Risk in GPN Research

text: The COVID‐19 pandemic represents a major disturbance that has rippled across the world’s population, states, economy, and central nervous system or global production networks transforming the traditional roles of states, firms, individuals/consumers, and geographies of production. This paper offers a critical and context‐based approach to understanding globalization and localization by challenging the conceptualization of ‘value’ and ‘risk’ within the current global production networks framework as well as identifying key operational strategies in risk management and national security. An analysis of the adaptation strategies of the GPNs of 91 companies identifies the role played by four different forms of value in configuring production networks. This is to balance ‘economic value’ with non‐price‐based sources of value and alternative values. The analysis underscores the critical role of the state in ensuring national and human security as well as its increasing power as a key actor in GPNs and the global economy.


title: Dysregulation of type I interferon responses in COVID-19

text: Infection with SARS-CoV-2 can lead to excessive production of pro-inflammatory cytokines, but the production of type I interferons, which are key antiviral mediators, is reportedly blunted. Here, we discuss how imbalanced interferon responses may contribute to the pathology of COVID-19.


title: Ready for malaria elimination: zero indigenous case reported in the People’s Republic of China

text: BACKGROUND: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. METHODS: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. RESULTS: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. CONCLUSION: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2444-9) contains supplementary material, which is available to authorized users.


title: Oncology clinical trials during the COVID-19 outbreak: lessons learnt during the crisis and future opportunities

text: The COVID-19 pandemic affected many activities in the healthcare system including oncology drug development. Clinical trial recruitment was temporary halted in many centres to reduce patients and healthcare workers’ potential exposure to the virus. Conversely, to continue offering treatments for patients already on effective therapies, multiple actions were timely put in place, resulting in simplification of trial-related procedures for patients and clinicians’ best interest, reduction of the operational burden and effective communication. Here, we suggest maintaining effective measures for future trial simplification and to expedite drug development.


title: Epidemiological and Evolutionary Analysis of Dengue-1 Virus Detected in Guangdong during 2014: Recycling of Old and Formation of New Lineages

text: The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.


title: Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System

text: Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Rapid clearance of pathogens allows for a quick return to a healthy state and increased survival. Pathogen-targeted approaches to combating infection have inherent limitations, including their pathogen-specific nature, the potential for antimicrobial resistance, and poor vaccine efficacy, among others. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. Given its importance and sensitivity, the lung is a good system for understanding host tolerance to infectious disease. Pneumonia is the leading cause of death for children under five worldwide. One reason for this is because when the pulmonary system is altered dramatically it greatly impacts the overall health and survival of a patient. Targeting host pathways involved in maintenance of pulmonary host tolerance during infection could provide an alternative therapeutic avenue that may be broadly applicable across a variety of pathologies. In this review, we will summarize recent findings on tolerance to host lung infection. We will focus on the involvement of innate immune responses in tolerance and how an initial viral lung infection may alter tolerance mechanisms in leukocytic, epithelial, and endothelial compartments to a subsequent bacterial infection. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.


Akute Ausweitung von inhalativem Sauerstoff in einer Pandemie


Comment on “COVID-19 Preparedness Within the Surgical, Obstetric, and Anesthetic Ecosystem in Sub Saharan Africa”


docid: evyoflxf

title: Nieuws

text: Deze maand laten we de nieuwsrubriek in het teken staan van de mogelijke beschermingsmaatregelen die we in onze praktijkvoering kunnen treffen. Volgens de Leidraad Mondzorg Corona, opgesteld door een gelijknamige commissie en de mondzorgkoepels, mag de reguliere tandheelkundige zorg worden hervat voor patiënten die in de aan het bezoek voorgaande 14 dagen niet in contact zijn geweest met het coronavirus SARS-CoV-2, veroorzaker van de ziekte Covid-19.


title: Ifitm3 Limits the Severity of Acute Influenza in Mice

text: Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation.


title: Subclinical Infection with Avian Influenza A H5N1 Virus in Cats

text: Avian influenza A virus subtype H5N1 was transmitted to domestic cats by close contact with infected birds. Virus-specific nucleic acids were detected in pharyngeal swabs from 3 of 40 randomly sampled cats from a group of 194 animals (day 8 after contact with an infected swan). All cats were transferred to a quarantine station and monitored for clinical signs, virus shedding, and antibody production until day 50. Despite unfamiliar handling, social distress and the presence of other viral and nonviral pathogens that caused illness and poor health and compromised the immune systems, none of the cats developed clinical signs of influenza. There was no evidence of horizontal transmission to other cats because only 2 cats developed antibodies against H5N1 virus.


title: Financial contagion during COVID–19 crisis

text: Abstract This study examines how financial contagion occurs through financial and nonfinancial firms between China and G7 countries during the COVID–19 period. The empirical results show that listed firms across these countries, financial and non-financial firms alike, experience significant increase in conditional correlations between their stock returns. However, the magnitude of increase in these correlations is considerably higher for financial firms during the COVID-19 outbreak, indicating the importance of their role in financial contagion transmission. They also show that optimal hedge ratios increase significantly in most cases, implying higher hedging costs during the COVID-19 period.


title: Evaluation of modelling study shows limits of COVID-19 importing risk simulations in sub-Saharan Africa

text: Mathematical modelling studies predicting the spread of the coronavirus disease 2019 (COVID-19) have been used worldwide, but precisions are limited. Thus, continuous evaluation of the modelling studies is crucial. We investigated situations of virus importation in sub-Saharan Africa (SSA) to assess effectiveness of a modelling study by Haider N et al. titled ‘Passengers’ destinations from China: low risk of novel coronavirus (2019-nCoV) transmission into Africa and South America’. We obtained epidemiological data of 2417 COVID-19 cases reported by 40 countries in SSA within 30 days of the first case confirmed in Nigeria on 27 February. Out of 442 cases which had travel history available, only one (0.2%) had a travel history to China. These findings underline the result of the model. However, the fact that there were numbers of imported cases from other regions shows the limits of the model. The limits could be attributed to the characteristics of the COVID-19 which is infectious even when the patients do not express any symptoms. Therefore, there is a profound need for all modelling researchers to take asymptomatic cases into account when they establish modelling studies.


title: Persistent shedding of viable SARS-CoV in urine and stool of SARS patients during the convalescent phase

text: In order to further the present knowledge of the emerging severe acute respiratory syndrome-associated coronavirus (SARS-CoV), 486 different specimens from 54 patients with a clinical diagnosis of SARS were investigated for the presence of viral RNA, and 314 plasma specimens of 73 patients were examined for IgM and IgG antibodies specific against SARS-CoV using an indirect ELISA. Viral RNA was detectable in 28 of the 54 patients tested. Cumulative data showed that 67 of the 73 SARS patients demonstrated seroconversion by week 5 of illness. In contrast, only 1 of 278 healthy subjects enrolled in the study was found to be positive for the IgG antibody. Coexistence of viral RNA in plasma and specific antibodies was simultaneously observed over three consecutive weeks in two critical cases. In three convalescent patients in particular, cultivable SARS-CoV was detected in stool or urine specimens for longer than 4 weeks (29–36 days). These findings suggest that SARS-CoV may remain viable in the excretions of convalescent patients.


title: Prediction of cross-species infection propensities of viruses with receptor similarity

text: Abstract Studies of host factors that affect susceptibility to viral infections have led to the possibility of determining the risk of emerging infections in potential host organisms. In this study, we constructed a computational framework to estimate the probability of virus transmission between potential hosts based on the hypothesis that the major barrier to virus infection is differences in cell-receptor sequences among species. Information regarding host susceptibility to virus infection was collected to classify the cross-species infection propensity between hosts. Evolutionary divergence matrices and a sequence similarity scoring program were used to determine the distance and similarity of receptor sequences. The discriminant analysis was validated with cross-validation methods. The results showed that the primary structure of the receptor protein influences host susceptibility to cross-species viral infections. Pair-wise distance, relative distance, and sequence similarity showed the best accuracy in identifying the susceptible group. Based on the results of the discriminant analysis, we constructed ViCIPR (http://lcbb3.snu.ac.kr/ViCIPR/home.jsp), a server-based tool to enable users to easily extract the cross-species infection propensities of specific viruses using a simple two-step procedure. Our sequence-based approach suggests that it may be possible to identify virus transmission between hosts without requiring complex structural analysis. Due to a lack of available data, this method is limited to viruses whose receptor use has been determined. However, the significant accuracy of predictive variables that positively and negatively influence virus transmission suggests that this approach could be improved with further analysis of receptor sequences.


title: Evaluation of a Multiplex Real-time PCR Assay for the Detection of Respiratory Viruses in Clinical Specimens

text: BACKGROUND: In this study, we evaluated the analytical performance and clinical potential of a one-step multiplex real-time PCR assay for the simultaneous detection of 14 types of respiratory viruses using the AdvanSure RV real-time PCR Kit (LG Life Sciences, Korea). METHODS: Three hundred and twenty clinical specimens were tested with the AdvanSure RV real-time PCR Kit and conventional multiplex reverse transcription (RT)-PCR assay. The assay results were analyzed and the one-step AdvanSure RV real-time PCR Kit was compared with the conventional multiplex RT-PCR assay with respect to the sensitivity and specificity of the detection of respiratory viruses. RESULTS: The limit of detection (LOD) was 1.31 plaque-forming units (PFU)/mL for human rhinoviruses (hRVs), 4.93 PFU/mL for human coronavirus HCoV-229E/NL63, 2.67 PFU/mL for human coronavirus HCoV-OC43, 18.20 PFU/mL for parainfluenza virus 1 (PIV)-1, 24.57 PFU/mL for PIV-2, 1.73 PFU/mL for PIV-3, 1.79 PFU/mL for influenza virus group (Flu) A, 59.51 PFU/mL for FluB, 5.46 PFU/mL for human respiratory syncytial virus (hRSV)-A, 17.23 PFU/mL for hRSV-B, 9.99 PFU/mL for human adenovirus (ADVs). The cross-reactivity test for this assay against 23 types of non-respiratory viruses showed negative results for all viruses tested. The agreement between the one-step AdvanSure multiplex real-time PCR assay and the conventional multiplex RT-PCR assay was 98%. CONCLUSIONS: The one-step AdvanSure RV multiplex real-time PCR assay is a simple assay with high potential for specific, rapid and sensitive laboratory diagnosis of respiratory viruses compared to conventional multiplex RT-PCR.


title: Assessing the impact of structured education on the knowledge of hospital pharmacists about adverse drug reactions and reporting methods in Saudi Arabia: an open-label randomised controlled trial

text: BACKGROUND: Pharmacists have limited knowledge about adverse drug reactions (ADRs) in Saudi Arabia. OBJECTIVE: The aim of this study was to assess the impact of educational intervention on the knowledge of hospital pharmacists about ADRs. METHODS: This was a 3-month randomized controlled trial conducted in Saudi Arabia between January 2018 and March 2018. Participants in both groups were required to complete an online questionnaire at baseline and at 12-week follow-up. Participants in the intervention group received a structured information sheet about ADRs 2 weeks after the first assessment. The main outcome measure was difference in mean knowledge score about ADRs. MAIN OUTCOME MEASURE: Difference in mean knowledge score about ADRs. RESULTS: A total of 46 participants were included in the study. At the 12-week follow-up, there was a significant improvement in the mean knowledge score (± standard deviation) of intervention participants from 7.67 (± 2.1) at baseline to 11.22 (± 0.4) (95% CI −4.5 to −2.5; p < 0.0001). The mean knowledge score of control participants remained unchanged at 6.71 (± 2.3) during both baseline and follow-up assessments. CONCLUSION: ADR-specific education was associated with a significant improvement in the knowledge and understanding of pharmacists about ADRs and their methods of reporting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40267-019-00621-z) contains supplementary material, which is available to authorized users.


docid: fmetxqqf

title: Uso de antipalúdicos en el tratamiento del COVID-19: ¿una ventana de oportunidad?


docid: gsnjlhjd

title: Fundamentals of aerosol therapy in critical care

text: Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.


COVID-19: Introducing Low Dose Radiation as an Effective Treatment for Pneumonia that Shouldn’t Induce Selective Pressure and New Mutations


The challenging times and opportunities for pharmacovigilance in Africa during the COVID-19 pandemic


title: Prediction Model Based on the Combination of Cytokines and Lymphocyte Subsets for Prognosis of SARS-CoV-2 Infection

text: BACKGROUND: There are currently rare satisfactory markers for predicting the death of patients with coronavirus disease 2019 (COVID-19). The aim of this study is to establish a model based on the combination of serum cytokines and lymphocyte subsets for predicting the prognosis of the disease. METHODS: A total of 739 participants with COVID-19 were enrolled at Tongji Hospital from February to April 2020 and classified into fatal (n = 51) and survived (n = 688) groups according to the patient’s outcome. Cytokine profile and lymphocyte subset analysis was performed simultaneously. RESULTS: The fatal patients exhibited a significant lower number of lymphocytes including B cells, CD4(+) T cells, CD8(+) T cells, and NK cells and remarkably higher concentrations of cytokines including interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor-α on admission compared with the survived subjects. A model based on the combination of interleukin-8 and the numbers of CD4(+) T cells and NK cells showed a good performance in predicting the death of patients with COVID-19. When the threshold of 0.075 was used, the sensitivity and specificity of the prediction model were 90.20% and 90.26%, respectively. Meanwhile, interleukin-8 was found to have a potential value in predicting the length of hospital stay until death. CONCLUSIONS: Significant increase of cytokines and decrease of lymphocyte subsets are found positively correlated with in-hospital death. A model based on the combination of three markers provides an attractive approach to predict the prognosis of COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-020-00821-7) contains supplementary material, which is available to authorized users.


title: Feasibility and Acceptability of Inpatient Palliative Care E-Family Meetings During COVID-19 Pandemic

text: Family meetings are fundamental to the practice of palliative medicine and serve as a cornerstone of intervention on the inpatient palliative care consultation service. The COVID-19 pandemic disrupted the structure and process of in-patient family meetings, due to necessary but restrictive visitor policies that did not allow families to be present in the hospital. We describe implementation of telemedicine to facilitate electronic family (e-family) meetings to facilitate in-patient palliative care. Of 67 scheduled meetings and performed by the palliative care service, only 2 meetings were aborted for a 97% success rate of scheduled meetings occurring. On a five-point Likert-type scale, the average clinician rating of the e-family meeting overall quality was 3.18 (SD, 0.96). Of the 10 unique family participants that agreed to be interviewed, their overall ratings of the e-family meetings were high. Over 80% of respondent families participants reported that they agreed or strongly agreed that they were able to ask all of their questions, felt comfortable expressing their thoughts and feelings with the clinical team, felt like they understood the care their loved one received, and that the virtual family meeting helped them trust the clinical team. Of patients who were able to communicate 50% of family respondents reported that the e-family meeting helped them understand their loved one’s thoughts and wishes.


title: Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

text: Abstract Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefit health and prevent disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how activity mitigates disease.


title: The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID‐19 in Wuhan, China: A retrospective study

text: Studies have demonstrated that comorbidities, especially cardiovascular and endocrine diseases, correlated with poorer clinical outcomes. However, the impact of digestive system diseases has not been issued. The aim of this study is to determine the impact of laryngopharyngeal reflux disease (LPRD) on hospitalized patients with coronavirus disease 2019 (COVID‐19). We extracted clinical data regarding 95 patients in Wuhan Jinyintan Hospital, Wuhan, China, between 26 January and 21 February 2020. The Reflux Symptom Index (RSI) was used to assess the presence and severity of LPRD. An RSI greater than 13 is considered to be abnormal. A total of 95 patients with COVID‐19 were enrolled, with 61.1% (58/95), 32.6% (31/95), and 6.3% (6/95) being moderately ill, severely ill, and critically ill, respectively. In this study, 38.9% (37/95) of the patient had an RSI score over 13, which was indicative of LPRD. In univariable analysis, the age and RSI scores of severely or critically ill patients were statistically significantly higher than patients with moderate disease (P = .026 and P = .005, respectively). After controlling for age difference in a multivariable model, the RSI greater than 13, compared to RSI equal to 0, was associated with significantly higher risk of severe infection (P < .001; odds ratio [OR] = 11.411; 95% confidence interval [CI], 2.95‐42.09) and critical infection (P = .028; OR= 19.61; 95% CI, 1.38‐277.99). Among hospitalized patients with COVID‐19, RSI scores greater than 13, indicative of LPRD, correlated with poorer clinical outcomes. The prevalence of LPRD may be higher than the general population, which indicated that COVID‐19 can impair the upper esophageal sphincter and aggravate reflux.


title: COVID‐2019 and pregnancy: A plea for transparent reporting of all cases

text: We read with great interest a recent editorial by Liang et al. on the management of COVID-19 in pregnancy. Their recommendations are clinically oriented and are likely to be useful to obstetricians and other healthcare professionals caring for such patients. However, we feel that development of evidence-based guidelines has been hindered by selective reporting of cases. We hereby would like to discuss a few additional points with regards to the challenges encountered while managing pregnant patients with COVID-19.


title: Applications of coding theory to the design of somatic cell hybrid panels

text: Abstract The somatic cell hybridization technique for gene mapping depends on assembling panels of rodent-human hybrid clones containing random subsets of the human chromosomes. Such panels should be as informative as possible and permit error detection and error correction for assays of the human gene in the various clones. We derive estimates of the number of randomly generated clones required to be reasonably confident of accurately and unambiguously assigning a gene to a particular human chromosome. The collection of clones in such a random panel is contrasted with minimal panels suggested by algebraic coding theory. To approximate minimal panels we suggest the method of simulated annealing for selecting small, informative panels from larger existing collections of clones. These theoretical insights emphasize the need for more collaboration and coordination among gene mapping groups so that optimal clone panels can be assembled, stored, and distributed.


title: Short term change in relative humidity during the festival of Diwali in India

text: Abstract The changes in humidity levels during the Diwali festivities have been examined over a period of 13 years at three Indian metro cities: Ahmedabad, New Delhi and Kolkata. A small short term increase in relative humidity even in the absence of transport of humid air from Arabian Sea and Bay of Bengal has been observed. The relative humidity levels were found to be exceeding the ambient levels during night and lying below the ambient levels during morning hours, indicating an increase in the survival rates of viruses responsible for the transmission of viral infections, as well as triggering immune-mediated illnesses such as asthma during Diwali.


title: Can COVID‐19 in pregnancy cause preeclampsia?

text: In this issue of BJOG, Mendoza and colleagues report in an observational study the occurrence of a preeclampsia‐like syndrome in six out of eight pregnant patients with novel coronavirus disease (COVID‐19) who were admitted to the Intensive Care Unit (ICU) with severe pneumonia (Mendoza M, et al. BJOG 2020). There were no symptoms of preeclampsia amongst the 34 pregnant women who had mild forms of COVID‐19.


title: Development of a diagnostic system for detection of specific antibodies and antigens against Middle East respiratory syndrome coronavirus

text: Middle East respiratory syndrome coronavirus (MERS‐CoV) is a single‐stranded RNA virus that causes severe respiratory disease in humans with a high fatality rate. Binding of the receptor binding domain (RBD) of the spike (S) glycoprotein to dipeptidyl peptidase 4 is the critical step in MERS‐CoV infection of a host cell. No vaccines or clinically applicable treatments are currently available for MERS‐CoV. Therefore, rapid diagnosis is important for improving patient outcomes through prompt treatment and protection against viral outbreaks. In this study, the aim was to establish two ELISA systems for detecting antigens and antibodies against MERS‐CoV. Using a recombinant full‐length S protein, an indirect ELISA was developed and found to detect MERS‐CoV‐specific antibodies in animal sera and sera of patient with MERS. Moreover, MAbs were induced with the recombinant S protein and RBD and used for sandwich ELISA to detect the MERS‐CoV S protein. Neither ELISA system exhibited significant intra‐assay or inter‐assay variation, indicating good reproducibility. Moreover, the inter‐day precision and sensitivity were adequate for use as a diagnostic kit. Thus, these ELISAs can be used clinically to diagnose MERS‐CoV.


docid: tycuoslv

title: Comparison of hemagglutinating, receptor-destroying, and acetylesterase activities of avirulent and virulent bovine coronavirus strains

text: Hemagglutinating and acetylesterase functions as well as the 124 kDa glycoprotein were present in the highly cell-culture adapted, avirulent bovine coronavirus strain BCV-L9, in the Norden vaccine strain derived from it, and in 5 wild-type, virulent strains that multiplied in HRT-18 cells but were restricted in several types of cultured bovine cells. The BCV-L9 and the wild-type strain BCV-LY-138 agglutinated chicken and mouse erythrocytes. The acetylesterase facilitated break-down of the BCV-erythrocyte complex with chicken but only to a minimal extent with mouse erythrocytes in the receptor-destroying enzyme test. Purified preparations of the vaccine and the wild-type strains agglutinated chicken erythrocytes at low titers and mouse erythrocytes at 128 to 256 times higher titers whereas receptor destroying enzyme activity was detectable only with chicken erythrocytes. When wild-type strains were propagated in HRT cells at low passage levels, they produced 5×10(5) to 4.5×10(6) plaque forming units per 50 µl which agglutinated erythrocytes from mice but not from chickens. Diisopropylfluoro-phosphate moderately increased the hemagglutination titers, but completely inhibited the receptor destroying enzyme of purified virus of all strains. It had virtually no influence on the plaque-forming infectivity of the different BCV strains. The acetylesterase of strain BCV-L9 reacting in the receptor-destroying enzyme test was stable for 3h at 37 and 42°C. It was inactivated within 30 min at 56°C while the hemagglutinin function of this strain was stable for 3 h at 37, 42, and 56°C, but it was inactivated at 65°C within 1 h.


title: A survey on infection control in emergency departments in Japan

text: AIM: Infection control in the emergency department is important for hospital risk management; however, few clinical guidelines have been established. This study aimed to determine whether hospitals in Japan have infection control manuals, and investigate the contents of manuals, consulting systems, and isolation facilities for emergency departments. METHODS: A total of 517 hospitals certified as educational institutions for board‐certified acute care physicians in Japan were requested between March and May 2015 to provide a written evaluation of the infection control in the emergency department. RESULTS: A total of 51 of 303 (16.8%) hospitals had no manuals regarding infection control in the emergency department. Among 250 hospitals having emergency department manuals, 115 (46.0%) did not include contents regarding disinfection and sterilization for imaging examination rooms, and only 44 (17.6%) had criteria for contacting the emergency medical service when patients are suspected of, or diagnosed with, communicable diseases. Of the 303 hospitals, 277 (91.4%) prepared specific manuals for the 2009 pandemic influenza. Of the 303 hospitals, 80 (26.4%) did not prepare manuals for the Ebola virus disease outbreak in West Africa in 2014. Furthermore, 92 (30.4%) of the 303 hospitals did not have any negative‐pressure isolation rooms. CONCLUSIONS: Practices and guidelines necessary for infection control in the emergency department were not sufficiently covered in the hospitals studied. Education, information sharing, and a checklist for preparing manuals are needed to establish better infection control systems in emergency departments.


title: Molecular characterization and phylogenetic analysis of the genome of porcine torovirus

text: In this study, we amplified and sequenced the first genome of porcine torovirus (PToV SH1 strain). The genome was found to be 28,301 bp in length, sharing 79 % identity with Breda virus. It mainly consists of replicase (20,906 bp) and structural genes: spike (4,722 bp), membrane (702 bp), hemagglutinin-esterase (1,284 bp), and nucleocapsid (492 bp). Sequence alignments and structure prediction suggest genetic differences among toroviruses, mainly in NSP1 (papain-like cysteine proteinase domain). Rooted phylogenetic trees were constructed based on the 3C-like proteinase and RNA-dependent RNA polymerase genes. PToV, Berne virus and Breda virus were clustered together, forming a separate branch from white bream virus that was distant from that of the coronaviruses.


title: A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals

text: The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.


title: Low-dose oral interferon modulates expression of inflammatory and autoimmune genes in cattle

text: Abstract While the safety and efficacy profiles of orally administered bovine interferon (IFN) alpha have been documented, the mechanism(s) that result in clinical benefits remain elusive. One approach to delineating the molecular pathways of IFN efficacy is through the use of gene expression profiling technologies. In this proof-of-concept study, different (0, 50, 200 and 800 units) oral doses of natural bovine IFN (type I) were tested in cattle to determine if oral IFN altered the expression of genes that may be pivotal to the development of systemic resistance to viral infections such as foot-and-mouth disease (FMD). Oral IFN was administered twice: Time 0 and 8h later. Blood was collected at 0, 8 and 24h after the first IFN administration, and DNA isolated from peripheral blood mononuclear cells (PBMCs) was employed in quantitative polymerase chain reaction (qPCR) microarray assays. Within 8h, 50 and 200 units of oral IFN induced significant (P<0.05) changes in expression of 41 of 92 tested autoimmune and inflammatory response-associated genes. These data suggest that orally administered IFN is a viable approach for providing short-term antiviral immunity to livestock exposed to viruses such as FMD virus (FMDV) until such a time that an effective vaccine can be produced and distributed to producers.


title: Complete Genome Sequences of Five Human Coronavirus NL63 Strains Causing Respiratory Illness in Hospitalized Children in China

text: We report the complete genome sequences of five human coronavirus NL63 (HCoV-NL63) strains obtained using next-generation sequencing. The five HCoV-NL63 strains were obtained from hospitalized children with severe acute respiratory infection detected in Guangdong, China. This study provides several complete genomes of HCoV-NL63 and improves our understanding of HCoV-NL63 evolution in China.


title: Review of Participatory Epidemiology Practices in Animal Health (1980-2015) and Future Practice Directions

text: In this study we combined an inventory of the major applications, geographic regions and diseases covered by participatory epidemiology (PE) activities in the field of animal health since 1980, together with an email discussion forum with PE practitioners from different regions of the world. The inventory included the search of peer-reviewed papers, master and technical reports, conference proceedings, manuals, training materials and projects. The search resulted in a low number of PE activity results until the year 2000, followed by a considerable increase (especially from 2012). Most of the identified activities were implemented in Africa and Asia, and focused on surveillance, disease survey and prioritization, and disease control. Seventy-nine PE practitioners working predominantly in Africa, Asia and Europe (29, 22 and 18 respectively) contributed to the email discussion forum. They proposed various modifications to the existing PE definition and discussed different issues related to the applicatoin of PE, its institutionalization for use in policy development, as well as the priorities for future development. The need to increase the number of PE trained people together with some methodological developments and the application of this methodology in developed countries, were some of the points highlighted during the forum. These factors stress the importance of further developing PE as a useful approach for engaging communities in addressing animal and related public health risks.


title: De Novo synthesis of PCR templates for the development of SARS diagnostic assay

text: A novel coronavirus was identified as the cause for severe acute respiratory syndrome (SARS). The complete sequence of SARS genome has provided an opportunity for the development of molecular diagnostic assays. To restrain further outbreak of SARS, the World Health Organization has posted several pairs of polymerase chain reaction (PCR) primers for early diagnosis and urged more research to be done on PCR protocols. Here we report a strategy for the de novo synthesis of PCR templates complimentary to the SARS virus genome, which has the advantage of working on PCR templates without concern about viral infection and also has the advantage that it can be used by those who do not have access to the SARS virus. This highly efficient and safe strategy for obtaining SARS gene fragments is useful for the development of PCR assays, as well as for the preparation of reliable positive controls for PCR testing kits.


title: One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries

text: Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive ‘One Health’ interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.


title: Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

text: BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014–2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33–0.72 vs median, 0.96; IQR, 0.94–0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.


title: Research disruptions and recovery

text: With the pandemic of COVID-19, the routine work of surgeons has been reduced to release resources to critical care and other functions. This is necessary and right, in order to protect the health of our communities now. As a consequence, many of us who undertake clinical research have seen our work suspended. With a rich portfolio of colorectal research, this includes studies such as ROSSINI2, PITSTOP, & MASH, and has delayed the start of other important studies such as ELF 2 and Damascus]. When we return to something akin to normality, we shall be looking to re-establish the studies in a timely manner. Funders have generally been flexible with regards to the disruption and have provided guidance on how the disruption might be managed1 . There is no doubt that they may be asked to provide additional support for studies in progress, which may impact future funding opportunities.


title: Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine

text: Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans.


title: Our Italian experience using lung ultrasound for identification, grading and serial follow‐up of severity of lung involvement for management of patients with COVID‐19

text: Lung ultrasound (LU) has rapidly become a tool for assessment of patients stricken by the novel coronavirus 2019 (COVID‐19). Over the past two and a half months (January, February, and first half of March 2020) we have used this modality for identification of lung involvement along with pulmonary severity in patients with suspected or documented COVID‐19 infection. Use of LU has helped us in clinical decision making and reduced the use of both chest x‐rays and computed tomography (CT).


title: Graphene vs. silica coated refractory nitrides based core-shell nanoparticles for nanoplasmonic sensing

text: Plasmonic nanoparticles based on conventional metals like gold (Au) and silver (Ag) has attracted significant attention of biosensor researchers. Core-shell nanoparticles (CSNP) have shown specific advantages by virtue of unique combination of strong field enhancement and wide ranging spectral tuneability of localized surface plasmon resonances (LSPR). In view of the remarkable plasmonic properties of refractory nitrides (e.g., ZrN and TiN) like higher degree of spectral tuneability, growth compatibility, high melting point, inherent CMOS and biocompatibility etc., and reported high surface area, excellent bio-molecular compatibility, improvement in the speed, higher sensitivity in graphene, the present work assess the feasibility of graphene coated refractory nitrides based CSNP as an efficient refractive index sensor. Mie theory is employed for the theoretical analysis and simulation of such plasmonic structures. The results reported in the present work have been corroborated using COMSOL. The comparison of plasmonic properties and sensing characteristics e.g., FWHM, quality factor, sensitivity and figure of merit is presented for graphene and silica based sensors. It is reported that the sensitivity = 171.68 (nm/RIU) and figure of merit = 3.57 × 10(4) (nm/RIU) can be attained. The present work suggests that graphene coated refractory nitrides based core-shell structures may emerge as ultrasensitive biosensor.


title: The SARS‐CoV‐2/COVID‐19 pandemic and challenges in stroke care in India

text: Stroke care in India has evolved rapidly in the last decade with a focus on stroke awareness, prevention, rapid triage, treatment, and rehabilitation. But acute stroke care and poststroke rehabilitation in the country have limitations owing to the economic constraints and poor access to health care. The SARS‐CoV‐2/COVID‐19 pandemic has made stroke care even more challenging. We outline the unfavorable circumstances in stroke care induced by the pandemic; propose mitigating measures; crisis management; and provide a comparative evaluation of stroke care between India and the United States during the pandemic. There is a need for public health systems in both developed and developing countries to improve awareness, implement proper strategies of triage, acute treatment, well‐defined rehabilitation plans, telemedicine services, and virtual check‐ins.


title: Multi-zone simulation of outdoor particle penetration and transport in a multi-story building

text: In areas with poor ambient air quality, indoor particle concentrations can be significantly affected by particulate matter originating outdoors. The indoor environments of multi-zone and multi-story buildings are affected differently by outdoor particles compared with single-family houses, because of the buildings’ more complicated airflow characteristics. The objective of this study is to analyze outdoor particle penetration and transport, and their impact on indoor air, in a multi-zone and multi-story building using a CONTAMW simulation. For the airflow and particle transport analysis, the building leakage, penetration coefficients, and deposition rates were determined by on-site experiments. The results of airflow simulations for cold winters show that outdoor air infiltrates through the lower part of building and exfiltrates from the upper part. The results of the particle simulation also indicated that the airflow characteristics, combined with deposition rates, cause the lower floors of a multi-story building to be exposed to higher fine particle concentrations compared with the upper floors of the building. The study demonstrated that the CONTAMW simulation can be useful in analyzing the impact of outdoor particles on indoor environments through the identification of key particle transport parameters and validated airflow simulations.


docid: flcxkvve

title: Artificial Intelligence in Radiology—Ethical Considerations

text: Artificial intelligence (AI) is poised to change much about the way we practice radiology in the near future. The power of AI tools has the potential to offer substantial benefit to patients. Conversely, there are dangers inherent in the deployment of AI in radiology, if this is done without regard to possible ethical risks. Some ethical issues are obvious; others are less easily discerned, and less easily avoided. This paper explains some of the ethical difficulties of which we are presently aware, and some of the measures we may take to protect against misuse of AI.


title: Pulmonary pathology of severe acute respiratory syndrome in Toronto

text: The severe acute respiratory syndrome (SARS) pandemic in Toronto resulted in a large number of autopsies on its victims. We describe the pulmonary pathology of patients who died in the 2003 Toronto outbreak. Autopsy material from the lungs of 20 patients who died between March and July 2003 were characterized by histology, molecular biology, and immunohistochemistry for cytokeratins, thyroid transcription factor-1, CD68, Epstein–Barr virus, cytomegalovirus, and human herpes simplex viruses. Matched controls were obtained from patients who died of other causes over the same interval. The mean duration of illness was 27 days (range 5–108 days). Post-mortem lung tissues from 19 of 20 patients with probable SARS were positive for SARS-associated coronavirus by RT-PCR. Histologically, all patients showed varying degrees of exudative and proliferative phase acute lung injury, evidenced in conventional and immunohistochemical stains by edema, inflammatory infiltrate, pneumocyte hyperplasia, fibrinous exudates, and organization. Eight of 20 patients showed predominantly a diffuse alveolar damage pattern of acute lung injury, six showed predominantly an acute fibrinous and organizing pneumonia pattern, and the remainder showed an admixture of the two patterns. Squamous metaplasia and scattered multinucleate giant cells were present in most cases. Vascular fibrin thrombi were a common finding and were often associated with pulmonary infarcts. Special stains demonstrated vascular endothelial damage of both small- and mid-sized pulmonary vessels. Two cases were complicated by invasive fungal disease consistent with Aspergillosis, and another by coinfection with cytomegalovirus. Our findings indicate that the lungs of patients who die of SARS are almost always positive for the SARS-associated coronavirus by RT-PCR, and may show features of both diffuse alveolar damage and acute fibrinous and organizing pneumonia patterns of acute injury. Cases of SARS may be complicated by coexistent infections and therapy-related lung injury.


title: Possibly critical role of wearing masks in general population in controlling COVID‐19

text: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is now overwhelming spreading in the world. As of April 11, 2020, totally 1.61 million COVID‐19 patients were confirmed in more than 200 countries and regions with 99690 deaths. This article is protected by copyright. All rights reserved.


title: Financial Inclusion and Stability in the Asian Region Using Bank-Level Data

text: Abstract Financial inclusion drives human development by supporting inclusive growth, economic development, and financial deepening. It has become a key enabler in reducing poverty and boosting prosperity. Financial inclusion can provide billions of currently unbanked adults with access to and active use of affordable financial products and services for their needs from transactions, payments, savings, credit, and insurance. The Asian region is generally considered to have a low level of financial inclusion. In addition, financial inclusion has mostly been ignored in current academic studies on the region. The governments in the region have expressed their concerns about macroeconomic instability associated with extensive financial inclusion. As such, this paper examines the linkage between financial inclusion and financial market stability using a dataset of 3,071 banks in the Asian region over the period from 2008 to 2017. This paper uses a generalized method of moments (GMM) approach. Findings in this paper indicate that the higher level of financial inclusion from providing access to banking facilities contributes positively and significantly to stability in the banking sector, leading to greater bank resilience. Financial inclusion can help banks increase revenue, reduce cost, and expand their market share. Policy implications are outlined based on the findings in this paper.


title: Working in the emergency and inpatient COVID-19 special wards: a different experience for Iranian psychiatric trainees amid the outbreak Running title: Experience of Iranian psychiatric trainees in COVID-19 special wards

text: • Authorities of Iran University of Medical Sciences decided to invite all of medical faculty members as well as medical trainees, regardless to their specialty to shift-work in the emergency and inpatient COVID-19 special wards. • Following this decision, 12 psychiatric trainees were scheduled to visit patients with COVID-19. • After the shift, trainees were asked to fill out an online anonymous form and submit their written comments. The present letter is the result of this brief survey. • Less than 42% answered they volunteered for the shift, as well as, only 16.7% would be volunteer if be asked again. • Only 16.7% of them showed their interest to visit the COVID-19 patients again for medical management, whereas more than 83% of them expressed their readiness to handle psychiatric problems of these patients. • We conclude that although all medical personnel should be sufficiently prepared for critical conditions, it seems better that mental health personnel be involved in more specialized tasks.


Covid 19- Journal de Bord – 26/04/2020 : Le dernier village gaulois


docid: vhtllsvl

title: Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus

text: Abstract To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines.


Infection Prevention and Control in Asia: Current Evidence and Future Milestones


title: Who will get ventilators in a covid-19 crisis?

text: If there is a shortage of breathing machines, doctors and ethicists say priority should go to people with the best chance of recovery, reports Alice Klein


title: Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: Crosstalk among calorie restriction, autophagy and immune response

text: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting (IF) in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary restriction also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, IF could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing IF as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of IF that may constitute a promising preventive approach against COVID-19.


title: Chapter 7 Viral Vectors

text: Abstract Traditional vaccine development platforms such as live-attenuated virus, killed virus, or recombinant subunit-based vaccines are often effective in eliciting long-term immunity to a number of infectious human pathogens. However, for many human pathogens, vaccine platforms such as these are unsuitable for human use due to safety concerns, poor efficacy, or simple impracticality. As a result, much work has focused on the use of recombinant virus vectors as a means for vaccination against human pathogens. Viral vectors can express foreign proteins at high levels in host cells, resulting in strong, long-lasting immune responses against the target proteins. This chapter describes the use of virus vectors in the context of vaccination against human pathogens. Various vector platforms are discussed, compared, and contrasted.


title: Molecular mechanisms of the secretion of cytokines and chemokines from human monocytes activated by pneumococcal surface protein A (PspA): Roles of mitogen-activated protein kinases and NF-kappaB

text: Abstract Pneumococcal surface protein A (PspA) plays a key role in the pathogenesis of invasive pneumococcal infection. PspA might modulate specific immune responses in human population. Circulating monocytes are essential for the innate responses and subsequent acquired immune responses to Streptococcus pneumoniae. In this study, we investigated the effects of PspA on cytokine and chemokine secretion from human peripheral blood monocytes and the underlying intracellular signaling mechanisms. Stimulation of monocytes with purified PspA protein induced the significant release of inflammatory cytokine IL-6 and chemokines including CXCL8, CCL2, CCL4 and CCL5. Products from PspA-deficient mutant pneumococcus that did not express PspA induced significantly less secretion of these mediators than those from wild type pneumococcus. Further investigations showed that PspA activated the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways in human monocytes. Moreover, inhibition of these pathways using selective inhibitors could significantly reduce the cytokine and chemokine secretion induced by PspA. Taken together, our findings provide insight for PspA-mediated activation of human monocytes via NF-κB and MAPKs signaling cascades in the pathogenesis of invasive pneumococcal infection.


title: Enteric virus contamination of foods through industrial practices: a primer on intervention strategies

text: Hepatitis A and E viruses, rotaviruses, Norwalk-like caliciviruses, and astroviruses are among the enteric viruses known to cause food- and waterborne illness. These viruses are spread by the fecal–oral route and are a major cause of morbidity and mortality worldwide. Foods may be contaminated at any time pre- or post-harvest; however, many outbreaks are associated with foods handled by infected restaurant workers. Produce may be contaminated by improper irrigation or fertilization practices, by the hands of infected pickers or processors, or as the result of adulteration during any stage of handling. Outbreaks have been commonly associated with foods which are served raw or only lightly cooked, such as molluscan shellfish, fruits and vegetables, and salads or products contaminated after cooking like frosted bakery products. The farming, shellfish, processing, transportation, and restaurant industries must maintain vigilance to reduce outbreaks of enteric virus illness. Intervention strategies to enhance product safety include increased industry and consumer education; changes in industrial practices, product management, and processing technologies; worker immunizations; and the development of improved monitoring tools for the detection of enteric viruses in foods. Journal of Industrial Microbiology & Biotechnology (2001) 27, 117–125.


title: The influence of the SARS-CoV-2 pandemic on esophagogastric cancer services: an international survey of esophagogastric surgeons

text: BACKGROUND: Several guidelines to guide clinical practice among esophagogastric surgeons during the COVID-19 pandemic were produced. However, none provide reflection of current service provision. This international survey aimed to clarify the changes observed in esophageal and gastric cancer management and surgery during the COVID-19 pandemic. METHODS: An online survey covering key areas for esophagogastric cancer services, including staging investigations and oncological and surgical therapy before and during (at two separate time-points—24th March 2020 and 18th April 2020) the COVID-19 pandemic were developed. RESULTS: A total of 234 respondents from 225 centers and 49 countries spanning six continents completed the first round of the online survey, of which 79% (n = 184) completed round 2. There was variation in the availability of staging investigations ranging from 26.5% for endoscopic ultrasound to 62.8% for spiral computed tomography scan. Definitive chemoradiotherapy was offered in 14.8% (adenocarcinoma) and 47.0% (squamous cell carcinoma) of respondents and significantly increased by almost three-fold and two-fold, respectively, in both round 1 and 2. There were uncertainty and heterogeneity surrounding prioritization of patients undergoing cancer resections. Of the surgeons symptomatic with COVID-19, only 40.2% (33/82) had routine access to COVID-19 polymerase chain reaction testing for staff. Of those who had testing available (n = 33), only 12.1% (4/33) had tested positive. CONCLUSIONS: These data highlight management challenges and several practice variations in caring for patients with esophagogastric cancers. Therefore, there is a need for clear consistent guidelines to be in place in the event of a further pandemic to ensure a standardized level of oncological care for patients with esophagogastric cancers.


title: A Well Infant With Coronavirus Disease 2019 With High Viral Load

text: A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs up to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19, as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.


title: COVID-19 and Plasmodium vivax malaria co-infection

text: The ongoing outbreak of COVID-19 poses an unprecedented global health challenge. With its variety of clinical manifestations including, but not limited to, fever, cough, diarrhea, vomiting, headache, myalgia and fatigue, it may be challenging to distinguish COVID-19 from a spectrum of diseases with similar presentations, such as malaria, especially in endemic areas. Risk of concomitant infections also remains a concern owing to overburdening of healthcare services and possible scarcity of resources. We present the first reported case of confirmed COVID and malaria co-infection. In this case, we emphasize the need for vigilance from frontline clinicians for timely diagnosis and appropriate clinical management of potential co-infections in the COVID era.


title: DBatVir: the database of bat-associated viruses

text: Emerging infectious diseases remain a significant threat to public health. Most emerging infectious disease agents in humans are of zoonotic origin. Bats are important reservoir hosts of many highly lethal zoonotic viruses and have been implicated in numerous emerging infectious disease events in recent years. It is essential to enhance our knowledge and understanding of the genetic diversity of the bat-associated viruses to prevent future outbreaks. To facilitate further research, we constructed the database of bat-associated viruses (DBatVir). Known viral sequences detected in bat samples were manually collected and curated, along with the related metadata, such as the sampling time, location, bat species and specimen type. Additional information concerning the bats, including common names, diet type, geographic distribution and phylogeny were integrated into the database to bridge the gap between virologists and zoologists. The database currently covers >4100 bat-associated animal viruses of 23 viral families detected from 196 bat species in 69 countries worldwide. It provides an overview and snapshot of the current research regarding bat-associated viruses, which is essential now that the field is rapidly expanding. With a user-friendly interface and integrated online bioinformatics tools, DBatVir provides a convenient and powerful platform for virologists and zoologists to analyze the virome diversity of bats, as well as for epidemiologists and public health researchers to monitor and track current and future bat-related infectious diseases. Database URL: http://www.mgc.ac.cn/DBatVir/


title: Structural Vulnerability in the United States Revealed in Three Waves of Novel Coronavirus Disease (COVID-19)

text: The novel coronavirus disease (COVID-19) pandemic has unveiled underlying health inequities throughout the United States. The pandemic has spread across U.S. states, affecting different vulnerable populations, including both inner-city and rural populations, and those living in congregate settings such as nursing homes and assisted-living facilities. In addition, since early April, there has been an increasing number of outbreaks of COVID-19 in jails and prisons. We describe three overlapping epidemiologic waves of spread of COVID-19 linked to three different kinds of structural vulnerabilities.


title: Variability in Results of the Microscopic Agglutination Test in Dogs with Clinical Leptospirosis and Dogs Vaccinated against Leptospirosis

text: Background: The microscopic agglutination test (MAT) is commonly used for the diagnosis of canine leptospirosis. In dogs it is sometimes suggested that the serogroup with the highest MAT titer is the infecting serogroup; however, this is not true in humans with confirmed leptospirosis. We sought to investigate the value of MAT results in predicting the infecting serogroup by comparing results across several laboratories and within individual dogs over time. Objectives: To examine the variability in MAT results across different laboratories in dogs recently vaccinated against leptospirosis, and in dogs with clinical leptospirosis, and to investigate variability over time in MAT results in individual dogs with leptospirosis. Animals: Eighteen dogs from a research colony, 9 of which had been vaccinated against leptospirosis, and 17 dogs clinically diagnosed with leptospirosis. Methods: Serum samples were submitted to up to 5 veterinary diagnostic laboratories for MAT titers from each dog on at least 1 occasion. MAT results also were followed over time in 6 dogs diagnosed with leptospirosis. Results: MAT results were discordant across different laboratories in dogs recently vaccinated against leptospirosis and in dogs with clinical leptospirosis. MAT results varied over time in individual dogs with the disease. Conclusions and Clinical Importance: The MAT is a valuable test for the diagnosis of leptospirosis in dogs, but it is unlikely that test results can be used to predict the infecting serogroup. Laboratories offering the MAT should consider participation in a proficiency scheme.


title: Riley Oxidation of Heterocyclic Intermediates on Paths to Hydroporphyrins—A Review

text: Riley oxidation of advanced heterocyclic intermediates (dihydrodipyrrins and tetrahydrodipyrrins) is pivotal in routes to synthetic hydroporphyrins including chlorins, bacteriochlorins, and model (bacterio)chlorophylls. Such macrocycles find wide use in studies ranging from energy sciences to photomedicine. The key transformation (–CH(3) → –CHO) is often inefficient, however, thereby crimping the synthesis of hydroporphyrins. The first part of the review summarizes 12 representative conditions for Riley oxidation across diverse (non-hydrodipyrrin) substrates. An interlude summarizes the proposed mechanisms and provides context concerning the nature of various selenium species other than SeO(2). The second part of the review comprehensively reports the conditions and results upon Riley oxidation of 45 1-methyltetrahydrodipyrrins and 1-methyldihydrodipyrrins. A comparison of the results provides insights into the tolerable structural features for Riley oxidation of hydrodipyrrins. In general, Riley oxidation of dihydrodipyrrins has a broad scope toward substituents, but proceeds in only modest yield. Too few tetrahydrodipyrrins have been examined to draw conclusions concerning scope. New reaction conditions or approaches will be required to achieve high yields for this critical transformation in the synthesis of hydroporphyrins.


title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus

text: Summary Porcine reproductive and respiratory syndrome (PRRS) is caused by a virus that predominantly replicates in alveolar macrophages. The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Expression of interleukin (IL) 1α, IL-6 and tumour necrosis factor (TNF)-α correlated with the severity of pulmonary pathology and the numbers of pulmonary macrophages. Significant correlations were observed between PRRSV infection and the expression of IL-10, between the expression of IL-12p40 and interferon (IFN)-γ, and between the expression of TNF-α and IFN-γ. These findings suggest that PRRSV modulates the immune response by the up-regulation of IL-10, which may in turn reduce expression of cytokines involved in viral clearance (e.g. IFN-α, IFN-γ, IL-12p40 and TNF-α). The results also suggest that expression of IFN-γ is stimulated by IL-12p40 and TNF-α, but not by IFN-α. All of these cytokines were expressed mainly by septal macrophages with weaker expression by alveolar macrophages, lymphocytes and neutrophils. There appears to be differential activation of septal and alveolar macrophages in PRRSV infection, with septal macrophages being the major source of cytokines.


title: Perioperative neonatal and paediatric blood transfusion

text: Paediatric patients undergoing surgical procedures commonly require some volume of blood or blood component replacement in the perioperative period. Paediatric patients undergoing major surgery associated with substantial blood loss should be evaluated pre-operatively. Pre-operative correction of anaemia may be done considering the age, plasma volume status, clinical status and comorbidities. Maximum allowable blood loss (MABL) for surgery must be calculated, and appropriate quantity of blood and blood components should be arranged. Intraoperative monitoring of blood loss should be done, and volume of transfusion should be calculated in a protocol based manner considering the volemia and the trigger threshold for transfusion for the patient and the MABL. Early haemostasis should be achieved by judicious administration of red blood cells, blood components and pharmacological agents.


title: A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease

text: BACKGROUND: Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of calves in a short period of time. The extent of commensal overgrowth and agreement of BAL with DNS culture results in preweaned calves are unknown. OBJECTIVES: To compare commensal overgrowth and bacterial culture results between DNS and BAL samples. ANIMALS: A total of 183 preweaned calves (144 with bovine respiratory disease and 39 healthy animals). METHODS: Cross‐sectional study. Deep nasopharyngeal swab and BAL samples were taken from each calf and cultured to detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between culture results of DNS and BAL samples were determined by kappa statistics and logistic regression. RESULTS: Bronchoalveolar lavage samples were less often polymicrobial, more frequently negative and yielded more pure cultures compared to DNS, leading to a clinically interpretable culture result in 79.2% of the cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in healthy animals, but not different between DNS and BAL samples. Only Histophilus somni was more likely to be isolated from BAL samples. In clinical cases, a polymicrobial DNS culture result did not increase the probability of a polymicrobial BAL result by ≥30%, nor did it influence the probability of a negative culture. A significant herd effect was noted for all observed relationships. CONCLUSIONS AND CLINICAL RELEVANCE: Nonendoscopic BAL samples are far less overgrown by bacteria compared to DNS samples under the conditions of this study, facilitating clinical interpretation and resulting in a higher return on investment in bacteriologic culturing.


title: Lower Respiratory Multiplex Panels for the Detection of Bacterial and Viral Infections

text: Development of commercial multiplex panels for the detection and diagnosis of lower respiratory tract infections is rapidly progressing, and FDA-cleared assays are currently available. This review provides a comprehensive overview of the current or soon-to-be available commercial assays, focusing on their analytical performance, advantages, and challenges and the potential impact on patient outcomes when laboratories deploy the assays.


title: Lymphoid tissue tropism of porcine reproductive and respiratory syndrome virus replication during persistent infection of pigs originally exposed to virus in utero

text: Abstract The ability of porcine reproductive and respiratory syndrome virus (PRRSV) to establish a persistent infection is the principal contributing factor to the world-wide spread of the disease. Several studies have documented the course of viral infection in postnatally infected pigs; however, very little is known regarding sites of virus replication during persistent infection of pigs exposed to PRRSV in utero. In this study, virus replication and PRRSV-specific antibody were followed for several hundred days in a group of pigs derived from three sows infected at 90 days of gestation with PRRSV isolate VR-2332. Eighty-four percent of pigs were born viremic with a mortality of 54% within 21 days after birth. At approximately 60 days sera from pigs were negative for virus by virus isolation. Analysis of virus replication in the tissues of pigs randomly sacrificed between 63 and 132 days showed no evidence of virus in lung and other non-lymphoid organs. However, virus was easily recovered from tonsil and lymph nodes and in situ hybridization identified these tissues as sites of virus replication. Even though replication was at a low level, virus was easily transmitted to sentinel pigs. By 260 days pigs became seronegative and did not transmit virus to sentinel pigs. Sacrifice of remaining pigs after 300 days showed no evidence of virus in blood and tissues. This study shows that congenital PRRSV-infected pigs can support virus replication for an extended period during which virus replication is primarily restricted to tonsil and lymph nodes.


title: Global stability and cost-effectiveness analysis of COVID-19 considering the impact of the environment:using data from Ghana

text: COVID-19 potentially threatens the lives and livelihood of people all over the world. The disease is presently a major health concern in Ghana and the rest of the world. Although, human to human transmission dynamics has been established, not much research is done on the dynamics of the virus in the environment and the role human play by releasing the virus into the environment. Therefore, investigating the human-environment-human by use of mathematical analysis and optimal control theory is relatively necessary. The dynamics of COVID-19 for this study is segregated into compartments as: Susceptible (S), Exposed (E), Asymptomatic (A), symptomatic (I), Recovered (R) and the Virus in the environment/surfaces (V). The basic reproduction number [Formula: see text] without controls is computed. The application of Lyapunov’s function is used to analyse the global stability of the proposed model. We fit the model to real data from Ghana in the time window 12th March 2020 to 7th May 2020, with the aid of python programming language using the least-squares method. The average basic reproduction number without controls, [Formula: see text] is approximately 2.68. An optimal control is formulated based on the sensitivity analysis. Numerical simulation of the model is also done to verify the analytic results. The admissible control set such as: effective testing and quarantine when boarders are opened, the usage of masks and face shields through media education, cleaning of surfaces with home-based detergents, practising proper cough etiquette and fumigating commercial areas; health centers is simulated in MATLAB. We used forward-backward sweep Runge-Kutta scheme which gave interesting results in the main text, for example, the cost-effectiveness analysis shows that, Strategy 4 (cleaning of surfaces with home-based detergents) is the most cost-effective strategy among all the six control intervention strategies under consideration.


title: Viruses and Evolution – Viruses First? A Personal Perspective

text: The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even in vitro the loss of genes can be recapitulated all the way from coding to non-coding RNA. Furthermore, the giant viruses may indicate that there is no sharp border between living and non-living entities but an evolutionary continuum. Here, it is discussed how viruses can lose and gain genes, and that they are essential drivers of evolution. This discussion may stimulate the thinking about viruses as early possible forms of life. Apart from our view “viruses first”, there are others such as “proteins first” and “metabolism first.”