title: Evaluation of the RealStar® SARS-CoV-2 RT-PCR Kit RUO performances and limit of detection

text: BACKGROUND: The use of efficient, reliable and sensitive PCR assays is a cornerstone in the race to contain the SARS-CoV-2 pandemic. In this work we performed an independent evaluation of the RealStar® SARS-CoV-2 RT-PCR Kit Researh Use Only (Altona) for SARS-CoV-2 detection. METHODS: A comparative limit of detection (LoD) assessment was performed between RealStar® SARS-CoV-2 and the currently WHO recommended RT-PCR (WHO-PCR) workflow using a quantified clinical sample. Assessment of the RealStar® SARS-CoV-2 assay was also performed using 83 primary clinical samples in comparison with the WHO-PCR. RESULTS: The RealStar® SARS-CoV-2 demonstrated a slightly higher sensitivity than the WHO recommended assay with a limit of detection at 625 copies/mL instead of 1250 copies/mL for the WHO-PCR in our conditions. The overall percent agreement between RealStar® SARS-CoV-2 and WHO-PCR on 83 clinical samples was 97.6% (81/83) with a sensitivity at 97.8% (45/46) and specificity at 97.3% (36/37). No cross reaction was encountered for the other human coronaviruses (HKU1, OC43, NL63, 229E). CONCLUSIONS: In this comparison of the RealStar® SARS-CoV-2 assay with the reference WHO assay, we observed a slightly better sensitivity of the RealStar® assay. It provides a robust option for all molecular biology laboratories, with a strong real-life LoD and is compatible with various real-time PCR platforms.


title: Evaluation of FilmArray respiratory panel multiplex polymerase chain reaction assay for detection of pathogens in adult outpatients with acute respiratory tract infection

text: Abstract Although viruses are the major pathogen that causes upper respiratory tract infection (URTI) and acute bronchitis, antibiotics have been prescribed. This was a prospective observational study in influenza epidemics that enrolled adult outpatients who visited a hospital with respiratory tract infection symptoms. In this study, we evaluated the usefulness of FilmArray respiratory panel (RP). Fifty patients were enrolled. FilmArray RP detected the pathogens in 28 patients. The common pathogens were influenza virus (n = 14), respiratory syncytial virus (n = 6), and human rhinovirus (n = 6). Of the 14 patients with influenza virus, 6 were negative for the antigen test. The physicians diagnosed and treated the patients without the result of FilmArray in this study. Of the patients with positive FilmArray RP, 9 were treated with antibiotics; however, bacteria were detected in only 3 patients. By implementing FilmArray RP, URTI and acute bronchitis would be precisely diagnosed, and inappropriate use of antibiotics can be reduced.


title: Regional differences in job satisfaction for mainland Chinese nurses

text: Abstract Background Although there is an abundance of research on nurses’ job satisfaction, there is a paucity of publications on the regional differences that impact on nurses’ job satisfaction. Purpose To compare the differences between northern and southern hospitals in Mainland China with respect to nurses’ job satisfaction. Methods A cross-sectional survey design was selected. Data were analyzed using descriptive statistics, independent t test, chi-square test, correlation, and linear regression. Results Nurses in northern hospitals were older, had higher educational levels yet received lower pay in comparison with their counterparts in the southern region. Despite these salary differences, those in the north consistently rated their job satisfaction greater in all areas except professional opportunities. Conclusion Regional differences were related to nurses’ job satisfaction. Potential contributing factors included philosophical, cultural, and economic differences between the 2 regions. The noteworthy regional differences that potentially related to nurse’ job satisfaction should be investigated in future studies.


title: Heteroaggregation of microparticles with nanoparticles changes the chemical reversibility of the microparticles’ attachment to planar surfaces

text: Abstract This study theoretically investigated detachment of homoaggregates and heteroaggregates attached on the planar surfaces at primary minima during transients in solution chemistry. The homoaggregates were represented as small colloidal clusters with well-defined structures or as clusters generated by randomly packing spheres using Monte Carlo method. The heteroaggregates were modeled as microparticles coated with nanoparticles. Surface element integration technique was adopted to calculate Derjaguin–Landau–Verwey–Overbeek (DLVO) interaction energies for the homoaggregates and heteroaggregates at different ionic strengths. Results show that attached homoaggregates on the planar surface at primary minima are irreversible to reduction in solution ionic strength whether the primary spheres of the homoaggregates are nano- or micro-sized. Heteroaggregation of nanoparticles with a microparticle can cause DLVO interaction energy to decrease monotonically with separation distance at low ionic strengths (e.g., ⩽0.01M), indicating that the heteroaggregates experience repulsive forces at all separation distances. Therefore, attachment of the heteroaggregates at primary minima can be detached upon reduction in ionic strength. Additionally, we showed that the adhesive forces and torques that the aforementioned heteroaggregates experience can be significantly smaller than those experienced by the microspheres without attaching nanoparticles, thus, the heteroaggregates are readily detached via hydrodynamic drag. Results of study provide plausible explanation for the observations in the literature that attached/aggregated particles can be detached/redispersed from primary minima upon reduction in ionic strength, which challenges the common belief that attachment/aggregation of particles in primary minima is chemically irreversible.


title: Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents

text: Biochemical analysis revealed that angiotensin-converting enzyme related carboxy-peptidase (ACE2) cleaves angiotensin (Ang) II to Ang-(1–7), a heptapeptide identified as an endogenous ligand for the G protein-coupled receptor Mas. No data are currently available that systematically describe ACE2 distribution and activity in rodents. Therefore, we analyzed the ACE2 expression in different tissues of mice and rats on mRNA (RNase protection assay) and protein levels (immunohistochemistry, ACE2 activity, western blot). Although ACE2 mRNA in both investigated species showed the highest expression in the ileum, the mouse organ exceeded rat ACE2, as also demonstrated in the kidney and colon. Corresponding to mRNA, ACE2 activity was highest in the ileum and mouse kidney but weak in the rat kidney, which was also confirmed by immunohistochemistry. Contrary to mRNA, we found weak activity in the lung of both species. Our data demonstrate a tissue- and species-specific pattern for ACE2 under physiological conditions.


title: Capacity in the time of Coronavirus

text: Abstract In the course of a few short weeks, many of the established legal frameworks relating to decision-making in England & Wales in respect of those with impaired decision-making capacity have been ripped up, or apparently rendered all but unusable. Although the Mental Capacity Act 2005 itself was not amended, the impact of other legislation (especially the Coronavirus Act 2020) means that duties towards those with impaired decision-making capacity have been radically changed. This article reflects the experience of a practising barrister in England & Wales grappling with the impact of COVID-19 upon the Mental Capacity Act 2005 across a range of fields in the weeks after the world appeared to change in mid-March 2020.


title: Early Safety Indicators of COVID-19 ConvalescentPlasma in 5,000 Patients

text: Background: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. Methods: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. Results: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. Conclusion: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.


title: The spectrum of viral pathogens in children with severe acute lower respiratory tract infection: A 3‐year prospective study in the pediatric intensive care unit

text: BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute lower respiratory tract infection (SALRTI) in Southern China. METHODS: Cohort of 659 hospitalized children (2 months to 14 years) with SALRTI admitted to the Pediatric Intensive Care Unit (PICU) in the Guangzhou from May 2015 to April 2018 was enrolled in this study. Nasopharyngeal aspirate specimens or induced sputum were tested for eight categories respiratory viral targets. The viral distribution and its clinical characters were statistically analyzed. RESULTS: Viral pathogen was detected in 326 (49.5%) of children with SALRTI and there were 36 (5.5%) viral coinfections. Overall, the groups of viruses identified were, in descending order of prevalence: Influenza virus (IFV) (n = 94, 14.3%), respiratory syncytial virus (RSV) (n = 75, 11.4%), human rhinovirus (HRV) (n = 56, 8.5%), adenovirus (ADV) (n = 55, 8.3%), parainfluenza (PIV) (n = 47, 7.1%), human coronavirus (HCoV) (n = 15, 2.3%), human metapneumovirus (HMPV) (n = 14, 2.1%) and human bocavirus (HBoV) (n = 11, 1.7%). The positive rate in younger children (< 5 years) was significantly higher than the positive rate detected in elder children (> 5 years) (52.5% vs 35.1%, P = 0.001). There were clear seasonal peaks for IFV, RSV, HRV, ADV, PIV, and HMPV. And the individuals with different viral infection varied significantly in terms of clinical profiles. CONCLUSIONS: Viral infections are present in a consistent proportion of patients admitted to the PICU. IFV, RSV, HRV, and ADV accounted for more than two‐thirds of all viral SALRTI. Our findings could help the prediction, prevention and potential therapeutic approaches of SALRTI in children.


title: Implementation of the mini-clinical evaluation exercise in postgraduate Year 1 residency training in emergency medicine: Clinical experience at Chang Gung Memorial Hospital

text: Abstract Background Although the mini-clinical evaluation (mini-CEX) exercise has been adapted to a broad range of clinical situations, limited studies of the mini-CEX for postgraduate residency training in emergency medicine (EM) have been documented. Aim The purpose of this study is to analyze the results of implementing the mini-CEX into the one-month postgraduate residency training in EM. Materials and methods This study is a retrospective review of mini-CEXs completed by ED faculty members from August 2009 to December 2010. All PGY-1 residents enrolled in this study rotated through the one-month EM training. Each PGY-1 resident received one week of trauma training and three weeks of non-trauma training. The clinical competencies of each PGY-1 resident were evaluated with mini-CEXs, rated by a trauma surgeon and three emergency physicians (EPs). We analyzed the validity of weekly mini-CEX and the impact of seniority and specialty training of ED faculties on observation time, feedback time and rating scores. Results Fifty-seven ED faculty members (42 EPs and 15 trauma surgeons) evaluated 183 PGY-1 residents during the 17 months of EM training. ED faculties with different specialty training provided similar assessment processes. Most competencies were rated significantly higher by trauma surgeons than by EPs. On the computerized mini-CEX rating, no data was missed and junior EPs rated all competencies significantly higher. The evaluators and PGY-1 residents were generally satisfied with the computerized format. As compared to the first assessment, only some competencies of PGY-1 residents were rated significantly higher in subsequent evaluations. Conclusion The seniority and specialty training of ED faculty affected the mini-CEX ratings. The computer-based mini-CEX facilitated complete data gathering but showed differences for ED faculty with different levels of seniority. Further studies of the reliability and validity of the mini-CEX for PGY-1 EM training are needed.


title: Realtime 2-5A kinetics suggests interferons β and λ evade global arrest of translation by RNase L

text: Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here we developed a biosensor for 2’,5’-oligoadenylate (2-5A), the natural activator of RNase L. We found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes (ISGs) and secreted IFNs of types I and III (IFN-β and IFN-λ). Our data suggests that IFNs escape from the action of RNase L on translation. We propose that 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system. RNase L is a mammalian enzyme that can stop global protein synthesis during interferon response. Cells must balance the need to make interferons (which are proteins) with the risk to lose cell-wide translation due to RNase L. This balance can most simply be achieved if RNase L was activated late in the interferon response. However, we show by engineering a biosensor for the RNase L pathway, that on the contrary, RNase L activation precedes interferon synthesis. Further, translation of interferons evades the action of RNase L. Our data suggest that RNase L facilitates a switch of protein synthesis from homeostasis to specific needs of innate immune signaling.


title: Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus

text: Abstract Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76 ± 108.06 ng/ml) was significantly lower than those of healthy controls (703.42 ± 169.96 ng/ml), but there were no significant differences among the patient groups. Interestingly, plasma levels of IL-10 and EGF were negatively and positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels in sputa were less than 300 ng/ml. Viral infection was inhibited by 50% in the presence of more than 8000 ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma of MERS patients are significantly reduced below the threshold needed to exert an antiviral effect against MERS-CoV infection.


title: An RNA Aptamer Provides a Novel Approach for the Induction of Apoptosis by Targeting the HPV16 E7 Oncoprotein

text: BACKGROUND: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, which is a major causative agent of cervical cancer. Cellular transformation is associated with deregulated expression of the E6 and E7 oncogenes. E7 has been shown to bind a number of cellular proteins, including the cell cycle control protein pRb. In this study, RNA aptamers (small, single-stranded oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed as molecular tools to further investigate these protein-protein interactions. METHODOLOGY/PRINCIPAL FINDINGS: This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining). GST-pull down and bead binding assays were used to demonstrate that the binding of A2 required N-terminal residues of E7 known to be involved in interaction with the cell cycle control protein, pRb. Using a similar approach, A2 was shown to disrupt the interaction between E7 and pRb in vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels, as observed by immunoblotting. CONCLUSIONS/SIGNIFICANCE: This paper includes the first characterisation of the effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis. Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials. In addition to its role as a molecular tool, A2 could have further applications in the future.


title: Management of Acute Myocardial Infarction During the COVID-19 Pandemic

text: Abstract The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with COVID-19. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating a ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.


title: Contamination of hospital surfaces with respiratory pathogens in Bangladesh

text: With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. In this study, we aimed to identify if surfaces near hospitalized patients with respiratory infections were contaminated with respiratory pathogens and to identify which surfaces were most commonly contaminated. Between September-November 2013, we collected respiratory (nasopharyngeal and oropharyngeal) swabs from patients hospitalized with respiratory illness in adult medicine and paediatric medicine wards at two public tertiary care hospitals in Bangladesh. We collected surface swabs from up to five surfaces near each case-patient including: the wall, bed rail, bed sheet, clinical file, and multipurpose towel used for care giving purposes. We tested swabs using real-time multiplex PCR for 19 viral and 12 bacterial pathogens. Case-patients with at least one pathogen detected had corresponding surface swabs tested for those same pathogens. Of 104 patients tested, 79 had a laboratory-confirmed respiratory pathogen. Of the 287 swabs collected from surfaces near these patients, 133 (46%) had evidence of contamination with at least one pathogen. The most commonly contaminated surfaces were the bed sheet and the towel. Sixty-two percent of patients with a laboratory-confirmed respiratory pathgen (49/79) had detectable viral or bacterial nucleic acid on at least one surface. Klebsiella pneumoniae was the most frequently detected pathogen on both respiratory swabs (32%, 33/104) and on surfaces near patients positive for this organism (97%, 32/33). Surfaces near patients hospitalized with respiratory infections were frequently contaminated by pathogens, with Klebsiella pneumoniae being most common, highlighting the potential for transmission of respiratory pathogens via surfaces. Efforts to introduce routine cleaning in wards may be a feasible strategy to improve infection control, given that severe space constraints prohibit cohorting patients with respiratory illness.


Eritema multiforme en contexto de infección por SARS-Coronavirus-2: reporte de dos casos


title: Emerging roles of deubiquitinases in cancer‐associated pathways

text: Deubiquitinases (DUBs) are emerging as important regulators of many pathways germane to cancer. They may regulate the stability of key oncogenes, exemplified by USP28 stabilisation of c‐Myc. Alternatively they can negatively regulate ubiquitin‐dependent signalling cascades such as the NF‐κB activation pathway. We review the current literature that associates DUBs with cancer and discuss their suitability as drug targets of the future. © 2010 IUBMB IUBMB Life, 62(2): 140–157, 2010


title: Changes of Adult Population Health Status in China from 2003 to 2008

text: OBJECTIVES: The purpose of this study was to examine the change in health status of China's adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement. METHODS: Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged >18 years were analyzed. RESULTS: Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. CONCLUSIONS: Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China's reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults.


title: Determining the Replication Kinetics and Cellular Tropism of Influenza D Virus on Primary Well-Differentiated Human Airway Epithelial Cells

text: Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed higher replication kinetics compared to Influenza C virus, despite sharing the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock.


title: L'ampleur de la réaction des gens aux rumeurs et aux fausses nouvelles à la lumière de la crise du virus Corona

text: Résumé Contexte: Avec la propagation du virus Corona à l'échelle mondiale, les effets négatifs ont augmenté à tous les niveaux, en particulier dans les secteurs économique et social. La situation a été aggravée par la propagation de rumeurs et de fausses informations sur ce qu'est ce virus et les moyens de le prévenir. Objectif: Tester comment les gens interagissent avec différentes informations circulant sur les réseaux sociaux et les plateformes en ligne. Méthodes: Les données ont été extraites d'une enquête menée en 2020 auprès de 1500 personnes en quarantaine âgées de 18 à 60 ans. Un questionnaire a été créé contenant la plupart des rumeurs et fausses informations diffusées, en plus des informations correctes avec une source fiable. Les résultats ont été analysés sous forme de tableaux montrant les proportions de partisans et d'opposants et exprimés en nombre et en pourcentage. Résultats: Deux mille personnes en quarantaine (âge moyen (30,35 ± 9,9 ans) ont participé à l'étude avec un taux de réponse de 100 %. L'analyse a montré un large pourcentage de soutien aux protections de la santé contre le virus Corona et un large rejet de la plupart des fausses informations et rumeurs circulant sur les plateformes Internet. Conclusion: L'ampleur de la propagation des rumeurs et des fausses informations diminue en raison de l’action des gouvernements et des autorités compétentes à travers leurs plateformes officielles dans le cadre du mécanisme de lutte contre le virus Corona, et en prenant appui sur les erreurs actuelles pour faire face à ces crises à l'avenir. Abstract Background: With the spread of the Corona virus globally, the negative effects increased at all levels, especially the economic and social sectors. The situation was made worse by the spread of rumors and false information about what this virus is and ways to prevent it. Objective: Test how people interact with different information circulating through social media and online platforms. Methods: The DATA was taken from a survey conducted in 2020 on 1500 quarantined people between the ages 18-60 years old. A questionnaire was created containing most of the rumors and false information circulated, in addition to the correct information with a reliable source. The results were analyzed in the form of tables showing the proportions of supporters and opponents and expressed in numbers and percentages. Results: A total of 2000 quarantined people participated in the study with the mean age (30.35 ± 9.9 years). Where the response rate is 100%. The analysis showed a large percentage of support for health protections against the Corona virus, and a large rejection of most of the fake information and rumors circulating across the Internet platforms, in addition to their solidarity within the principles of social responsibility. Conclusion: The extent of the spread of rumors and false information is decreasing based on the presence of governments and the competent authorities through their official platforms within the mechanism of fighting against the Corona virus, and also taking advantage of the current mistakes to be a shield in the future in dealing with such crises.


title: Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic

text: PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.


Transcriptional Regulation of RNA3 of Infectious Bronchitis Virus


title: Global health improvement and WHO: shaping the future

text: Summary A world torn by gross health inequalities is in serious trouble. The global health community can do much to reduce suffering and death among vulnerable groups. WHO is changing its way of working, alongside member states and financial and technical partners, to reach key national health goals and strengthen equity. The most urgent objectives include the health-related Millennium Development Goals, the 3 by 5 target in HIV/AIDS treatment (to provide 3 million people in developing regions with access to antiretroviral treatment by the end of 2005), and addressing the growing epidemics of non-communicable diseases. The key to achieving these objectives is strengthening of health systems guided by the values of Health For All.


title: High‐throughput analysis of mumps virus and the virus‐specific monoclonal antibody on the arrays of a cationic polyelectrolyte with a spectral SPR biosensor

text: We investigated the potential use of a spectral surface plasmon resonance (SPR) biosensor in a high‐throughput analysis of mumps virus and a mumps virus‐specific mAb on the arrays of a cationic polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA). The PDDA surface was constructed by electrostatic adsorption of the polyelectrolyte onto a monolayer of 11‐mercaptoundecanoic acid (MUA). Poly‐l‐lysine was also adsorbed onto the MUA monolayer and compared with the PDDA surface in the capacity of mumps virus immobilization. The PDDA surface showed a higher adsorption of mumps virus than the poly‐l‐lysine surface. The SPR signal caused by the virus binding onto the PDDA surface was proportional to the concentration of mumps virus from 0.5 × 10(5) to 14 × 10(5) pfu/mL. The surface structure of the virus arrays was visualized by atomic force microscopy. Then, a dose‐dependent increase in the SPR signal was observed when various concentrations of the antimumps virus antibody in buffer or human serum were applied to the virus arrays, and their interaction was specific. Thus, it is likely that the spectral SPR biosensor based on the cationic polyelectrolyte surface may provide an efficient system for a high‐throughput analysis of intact virus and serodiagnosis of infectious diseases.


title: Global experience of orthopaedic trauma surgeons facing COVID-19: a survey highlighting the global orthopaedic response

text: BACKGROUND: The COVID-19 (SARS-CoV-2) pandemic has significantly affected all aspects of healthcare, including orthopaedics. Due to the unique challenges presented by COVID-19 as well as the distinct timeframes that it will surge in different geographies, much can be learned from the experiences of orthopaedic professionals in many global settings. The goal of this project is to characterize the preparations, strategies, lessons, and personal experiences of orthopaedic trauma surgeons and departments across the world in combating COVID-19. In doing so, we will shed light on current practices and challenges, which may help us manage the current pandemic in addition to preparing for future global pandemics that may arise. METHODS: A 20-item questionnaire was sent out to 150 orthopaedic trauma surgeons representing 42 countries who were identified based on professional relationships and/or prior involvement in international meetings either led or participated by the senior author. RESULTS: The questionnaire was completed by 63 orthopaedic trauma surgeons representing 28 countries and 14 US states. The results of this study show that orthopaedic trauma departments across the world have been greatly impacted by COVID-19 with 91% of participating hospitals currently having a reduced case load compared with pre-COVID-19 and only 17% of respondents currently performing elective orthopaedic surgery. Furthermore, 30% of orthopaedic departments have deployed orthopaedic personnel to non-orthopaedic floors in order to help mitigate the increased patient load and 86% of respondents noted at least some shortage of PPE. Lastly 73% of participating orthopedic departments including those in LMICs, have incorporated telemedicine into their practice with a majority stating that it would most likely become a permanent change to their practice post-COVID-19. CONCLUSION: To our knowledge, this is the largest data set characterizing global COVID-19 situations and responses of orthopaedic trauma practices around the world. There is much to be learned from each of the participants’ responses in order to persevere during the current pandemic, as well as to prepare for future pandemics as it relates specifically to orthopaedic trauma practices.


title: Personal protection equipment for biological hazards: Does it affect tracheal intubation performance?

text: Summary Purpose Personal protection equipment (PPE) is recommended for use during airway management of patients with highly contagious respiratory tract illness. While its use in chemical hazards and its effect on airway management has been assessed previously, there has been no research assessing whether this equipment affects the ability to perform tracheal intubation. It is the intention of this investigation to answer this question. Methods Eighteen workers at various level of training were asked to wear three different types of PPE while performing four different types of tracheal intubation. The PPE used included the eye shield, face shield and the “Dustmaster™”. The intubation techniques were direct laryngoscopy, intubation through the intubating laryngeal mask (Fastrach™) and flexible bronchoscopy using the eyepiece and an eyepiece with camera attached. We assessed the time to intubate as well as the incidence of oesophageal intubation. A short questionnaire was used to examine participants’ subjective experiences of wearing the various types of PPE. Results There was no significant effect on the time to intubation for any of the methods studied. However, all subjects found that the face shield was uncomfortably hot to wear. Fibreoptic bronchoscopic intubation using the eyepiece was particularly difficult with all of the PPE used due to the distance of the subjects’ eye from the eyepiece. Conclusion Although the use of PPE may not affect the length of time to intubate manikins, certain types of PPE may be uncomfortable to wear and noisy. Further research is needed to investigate whether this could be a problem in the clinical setting or in actual difficult intubations.


Coronavirus and diabetes: an update


title: A High Capacity Microbial Screen for Inhibitors of Human Rhinovirus Protease 3C

text: We have developed a high capacity screen for compounds that inhibit the 3C protease of human rhinovirus–1b. The assay uses a recombinant strain of Escherichia coli expressing both the protease and a tetracycline resistance–conferring protein modified to contain the minimal protease cleavage site. Cultures growing in microtiter plates containing tetracycline are treated with potential inhibitors and simultaneously monitored for change in growth over time using an oxygen probe. Most of the cultures, not containing an inhibitor of the 3C protease, show reduced growth due to cleavage of the essential gene product; normal growth is seen only in the infrequent culture that contains an inhibitor. In the present example, we have used the tetA gene of plasmid pACYC184 as the modified gene. The system has been validated using inhibitors of protease 3C, and has been used to identify three new inhibitors of the enzyme, active in the micromolar range.


title: Viral calciomics: Interplays between Ca(2+) and virus

text: Ca(2+) is one of the most universal and versatile signaling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca(2+) signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca(2+) homeostasis and utilize Ca(2+) and cellular Ca(2+)-binding proteins to their benefit in their replication cycles. Ca(2+) plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear “EF-hand” Ca(2+)-binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca(2+)-binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca(2+) interactions had not been formerly appreciated. The presence of linear Ca(2+)-binding motifs in viral proteins enlarges the spectrum of Ca(2+)–virus interplay and expands the total scenario of viral calciomics.


title: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020

text: Abstract Objectives Infection due to the 2019 novel coronavirus disease (COVID-19) is widespread dramatically around the world. This COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and decreasing another infectious disease. Methods This study was performed to show trends in seasonal influenza cases from the 2014–2015 season to the 2019–2020 season in 11 countries and regions, and evaluate whether the trends in the 2019–2020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. Results In East Asia, the number of seasonal influenza cases in the 2019–20 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in the American countries or in European countries. Conclusion The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.


title: Stress Granules in the Viral Replication Cycle

text: As intracellular parasites, viruses require a host cell in order to replicate. However, they face a series of cellular responses against infection. One of these responses is the activation of the double-stranded RNA (dsRNA)-activated protein kinase R (PKR). PKR phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), which in turn results in global protein synthesis inhibition and formation of stress granules (SGs). Recent studies have shown that SGs can interfere with the replicative cycle of certain viruses. This review addresses how viruses have evolved different control strategies at the SG level to ensure an efficient replication cycle during the cellular stress response triggered by the viral infection.


title: Recent advances in the role of non-invasive ventilation in acute respiratory failure

text: Non-invasive positive pressure ventilation (NIPPV) is the technique of delivering mechanical ventilation without endotracheal intubation or tracheostomy. This is increasingly being utilised in both acute and chronic conditions. Strong evidence supports the use of NIPPV for acute respiratory failure (ARF) to prevent endotracheal intubation (ETI) and to facilitate extubation in patients with acute exacerbations of chronic obstructive pulmonary disease, to avoid ETI in acute cardiogenic pulmonary oedema (ACPO), and in immunocompromised patients. Weaker evidence supports the use of NIPPV for patients with ARF due to asthma exacerbations, with postoperative ARF, pneumonia and acute lung injury/acute respiratory distress syndrome. NIPPV should be applied under close monitoring for signs of treatment failure and, in such cases, ETI should be promptly available. A trained team, at an appropriate location, with careful patient selection and optimal choice of devices can optimise the outcome of NIPPV.


docid: hidirfkv

title: A COMPREHENSIVE ANALYSIS OF GENOME COMPOSITION AND CODON USAGE PATTERNS OF EMERGING CORONAVIRUSES

text: Abstract An outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS-CoV-2 has been declared a public health emergency of international concern by the World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A- and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.


title: The role of posttranslational modifications in the assembly of stress granules

text: Stress granules (SGs) are aggregates of translationally silenced messenger ribonucleoprotein (mRNP) complexes induced by oxidative, osmotic, hypoxic, thermal, viral, and genotoxic stresses. Over the past decade, extensive research has identified key components of SGs, their molecular interactions, and impact on stress‐induced reprogramming of protein expression and cell survival. However, studies defining the signaling pathways that modulate SG assembly have only been launched recently. These studies reveal that posttranslational modifications of selected SG proteins play important roles in the regulation of SG assembly and function. Here we provide an overview of the signaling pathways and posttranslational protein modifications that regulate the assembly and function of SGs. Copyright © 2010 John Wiley & Sons, Ltd. 1.. Translation > Translation Regulation; 2.. RNA Export and Localization > RNA Localization; 3.. RNA Turnover and Surveillance > Regulation of RNA Stability.


title: Identifying Public Health Competencies Relevant to Family Medicine

text: Abstract Public health situations faced by family physicians and other primary care practitioners, such as severe acute respiratory syndrome (SARS) and more recently H1N1, have resulted in an increased interest to identify the public health competencies relevant to family medicine. At present there is no agreed-on set of public health competencies delineating the knowledge and skills that family physicians should possess to effectively face diverse public health challenges. Using a multi-staged, iterative process that included a detailed literature review, the authors developed a set of public health competencies relevant to primary care, identifying competencies relevant across four levels, from “post-MD” to “enhanced.” Feedback from family medicine and public health educator–practitioners regarding the set of proposed “essential” competencies indicated the need for a more limited, feasible set of “priority” areas to be highlighted during residency training. This focused set of public health competencies has begun to guide relevant components of the University of Toronto's Family Medicine Residency Program curriculum, including academic half-days; clinical experiences, especially identifying “teachable moments” during patient encounters; resident academic projects; and elective public health agency placements. These competencies will also be used to guide the development of a family medicine–public health primer and faculty development sessions to support family medicine faculty facilitating residents to achieve these competencies. Once more fully implemented, an evaluation will be initiated to determine the degree to which these public health competencies are being achieved by family medicine graduates, especially whether they attained the knowledge, skills, and confidence necessary to effectively face diverse public health situations—from common to emergent.


title: Trust in Humanitarian Aid From the Earthquake in 2017 to COVID-19 in Iran: A Policy Analysis

text: The earthquake of November 2017, the great flood of April 2019, and the COVID-19 outbreak in 2020 are 3 major emergencies in Iran during the last 3 years. A common issue in all of these crises seems to be the issue of “trust.” Official authorities, including the Iranian President, ministers, and the judiciary system, tried to gain people’s trust by either changing policies or developing new ones. In August 2019, the new law on crisis management in Iran went into effect and the issue of public donation has been considered, too. Also, in their response to the COVID-19 outbreak, Iranian officials ordered all sectors to cooperate with the Ministry of Health and provide it with all necessary facilities. Therefore, it seems that new policies are still needed to overcome mistrust in Iran at times of emergency. Developing a policy on donation management was the first step, and there are several factors that could have contributed to the perception of the mistrust and failure in emergency missions. Mistrust can be the result of different causes, including but not limited to lack of knowledge on capabilities and efficiencies of humanitarian organizations, engagement of a wide range of organizations from different categories, extension of mistrust of an organization to other emergency organizations in the area or all of operation, lack of unity in emergency response, and poor public relations.


title: Rationing in a Pandemic: Lessons from Italy

text: In late February and early March 2020, Italy became the European epicenter of the COVID-19 pandemic. Despite increasingly stringent containment measures enforced by the government, the health system faced an enormous pressure, and extraordinary efforts were made in order to increase overall hospital beds’ availability and especially ICU capacity. Nevertheless, the hardest-hit hospitals in Northern Italy experienced a shortage of ICU beds and resources that led to hard allocating choices. At the beginning of March 2020, the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) issued recommendations aimed at supporting physicians in prioritizing patients when the number of critically ill patients overwhelm the capacity of ICUs. One motivating concern for the SIAARTI guidance was that, if no balanced and consistent allocation procedures were applied to prioritize patients, there would be a concrete risk for unfair choices, and that the prevalent “first come, first served” principle would lead to many avoidable deaths. Among the drivers of decision for admission to ICUs, age, comorbidities, and preexisting functional status were included. The recommendations were criticized as ageist and potentially discriminatory against elderly patients. Looking forward to the next steps, the Italian experience can be relevant to other parts of the world that are yet to see a significant surge of COVID-19: the need for transparent triage criteria and commonly shared values give the Italian recommendations even greater legitimacy.


title: Crystal Structure of Human Interferon-λ1 in Complex with Its High-Affinity Receptor Interferon-λR1

text: Abstract Interferon (IFN)-λ1 [also known as interleukin (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-λR1 and IL-10R2. We have determined the structure of human IFN-λ1 complexed with human IFN-λR1, a receptor unique to type III IFNs. The overall structure of IFN-λ1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-λR1 consists of two distinct domains having fibronectin type III topology. The ligand–receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-λR1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it.


title: Impact of point-of-care testing for respiratory viruses on antibiotic use in adults with exacerbation of airways disease

text: Summary Background The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with early discontinuation of unnecessary antibiotics compared to routine clinical care. Subgroup analysis suggests these changes occur predominantly in patients with exacerbation of airways disease. Use of molecular POCT for respiratory viruses is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels versus POCT for influenza only. Materials/methods We evaluated patients from the ResPOC study with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive and negative for viruses by POCT, and controls. Patients testing positive for viruses by POCT were compared according to virus types. Results 118 patient with exacerbation of airways disease received antibiotics in the POCT group and 111 in the control group. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses 17/49 (35%) had early discontinuation of antibiotics versus 9/69 (13%) testing negative and 7/111 (6%) of controls, p<0.0001. Of those positive for viruses by POCT 10/49 (20%) were positive for influenza, 21/49 (43%) for rhinovirus and 18/49 (37%) for other viruses. The proportion with early discontinuation of antibiotics was not different between the virus types (p = 0.34). Conclusions This data suggests that syndromic molecular POCT for respiratory viruses should be favoured over POCT for influenza alone in adults with exacerbation of airways disease.


title: Agents infectieux émergents

text: Résumé De nombreuses maladies infectieuses émergentes ou ré-émergentes sont survenues au cours des dernières décennies, certaines posant des problèmes de santé publique majeurs. SRAS, MERS-CoV, grippe aviaire hautement pathogène A(H5N1), MERS-CoV, maladie à virus Ebola ont été très préoccupants en raison de la virulence, de la mortalité, des modalités de transmission, de l’impact sur la transmission maternofœtale (Zika). La prise de conscience de ces émergences a conduit les autorités sanitaires à élaborer des plans et des recommandations, d’imaginer de nouvelles organisations des systèmes de soins de manière à identifier tout cas de maladie infectieuse émergente hautement transmissible virulente pour isolement immédiat et prise en charge adéquate. Abstract Emergence of many emerging or re-emerging infectious diseases have occurred over the past decade, some of which are major public threat. SARS, MERS-CoV, highly pathogenic avian influenza A(H5N1), Ebola virus disease have raised concerns because of their virulence, their mortality, and/or their modality of transmission, or their impact on maternofoetal transmission (Zika virus). The witness of these emergences have conducted health authorities to have policies and plans and to imagine new organizations for health systems in order to identify any case of highly communicable virulent disease for immediate isolation, and adequate management.


title: Hyponatraemia in cases of children with pneumonia

text: INTRODUCTION: Hyponatraemia is the most common electrolyte imbalance seen in clinical practice, and a common laboratory finding in children with community-acquired pneumonia (CAP). This study aimed to identify the incidence of hyponatraemia in cases of CAP, to find predictive tools in order to classify the severity and outcome of CAP and to explore possible differences of clinical importance between the two sexes. MATERIAL AND METHODS: The medical files of 54 children (66.4% males), 4.67 ±2.88 years old, were retro-prospectively reviewed. RESULTS: 35/54 (64.8%) children with pneumonia had normal values of sodium at admission, 18/54 (33.3%) had mild hyponatraemia and 1 child (1.9%) moderate hyponatraemia. Increased heart rhythm and tachypnoea at admission were correlated with lower values of sodium (z= −2.664, p = 0.007 and z = −1.705, p = 0.089 respectively). No differences were found between the two sexes concerning the characteristics of pneumonia or the range of sodium in serum at admission. A correlation was found between sodium admission values and: a) C-reactive protein (p = 0.000), and b) leukocyte count (p = 0.006). Sedimentation rate (p = 0.021) was also considered as a possible risk factor affecting the value of sodium at admission to hospital. Finally, a negative association was also observed between the degree of hyponatraemia and the duration of hospitalization (z = −3.398, p = 0.001). CONCLUSIONS: Although studies in larger population groups are needed, in our study increased heart rhythm, tachypnoea, leucocyte count, C-reactive protein, and also erythrocyte sedimentation rate could be considered as possible risk factors influencing the degree of hyponatraemia, and thus the outcome of hospitalized children with CAP.


title: Cytologic and histologic samples from patients infected by the novel coronavirus 2019 SARS‐CoV‐2: An Italian institutional experience focusing on biosafety procedures

text: The 2019 coronavirus pandemic, which started in Wuhan, China, spread around the globe with dramatic and lethal effects. From the initial Chinese epicenter, the European diaspora taxed the resources of several countries and especially those of Italy, which was forced into a complete social and economic shutdown. Infection by droplets contaminating hands and surfaces represents the main vehicle of diffusion of the virus. The common and strong efforts to contain the pandemic have relevant effects on the management of samples from histopathology laboratories. The current commentary reports and focuses on the protocols and guidelines in use at a large tertiary Italian hospital that accordingly are proposed for adoption in Italian laboratories as a potential model for national guidelines for the coronavirus emergency.


title: Ferret Wellness Management and Environmental Enrichment

text: The domestic ferret is a commonly kept companion animal. Knowledge of proper husbandry of companion ferrets and their common disease processes by veterinarians assists pet owners in providing the healthiest environment possible. Attentiveness to the environmental needs of pet ferrets results in physically and psychologically healthy animals and a positive, enriched relationship with owners.


title: Emergence and genetic analysis of variant pathogenic 4/91 (serotype 793/B) infectious bronchitis virus in Egypt during 2019

text: Infectious bronchitis virus (IBV) affects both vaccinated and unvaccinated flocks worldwide, with a significant impact on the poultry industry. The aim of the present study is to characterize an emerging variant pathogenic IBV originating from field outbreaks in vaccinated Egyptian layer flock. Samples were collected from disease-suspected flock with a history of administration of live and inactivated IBV vaccines (Ma5 type). Virus propagation in embryonated chicken eggs (ECEs), after three successive passages, revealed typical IBV lesions such as curling and dwarfism. The reported isolate was identified by a real-time reverse transcriptase PCR assay targeting nucleocapsid (N) gene and, further characterized by full-length spike (S1) gene sequencing. Phylogenetic analysis revealed clustering of the isolated virus within 4/91 genotype of GI-13 lineage. Deduced amino acid sequences identity revealed 75–76% and 88–90% similarity with the currently used classic (H120, Ma5, and M41) and variant vaccine strains (4/91 and CR88) in Egypt, respectively. Recombination analysis gave an evidence for distinct patterns of origin for the studied isolate providing another example of intra-genotypic recombination among IBVs and the first example of recombination within the GI-13 lineage in the Egyptian field. The studied isolate (IBV/CK/EG/Fadllah-10/2019) emerged as a result of recombination between the variant group (Egy/var I genotype, GI-23 lineage) as a major parent and the CR88 variant vaccine strain (4/91 genotype, GI-13 lineage) as minor parent. Our data suggest that both mutation and recombination may be contributing to the emergence of IBV variants which ascertain the importance of disease monitoring in vaccinated flocks as well as re-appropriation for the current vaccine strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01693-9) contains supplementary material, which is available to authorized users.


title: Using drug-excipient interactions for siRNA delivery

text: Abstract SiRNA is the trigger of RNA interference, a mechanism discovered in the late 1990s. To release the therapeutic potential of this versatile but large and fragile molecule, excipients are used which either interact by electrostatic interaction, passively encapsulate siRNA or are covalently attached to enable specific and safe delivery of the drug substance. Controlling the delicate balance between protective complexation and release of siRNA at the right point and time is done by understanding excipients–siRNA interactions. These can be lipids, polymers such as PEI, PLGA, Chitosans, Cyclodextrins, as well as aptamers and peptides. This review describes the mechanisms of interaction of the most commonly used siRNA delivery vehicles, and looks at the results of their clinical and preclinical studies.


title: Molecular and serological surveys of canine distemper virus: A meta-analysis of cross-sectional studies

text: BACKGROUND: Canine morbillivirus (canine distemper virus, CDV) persists as a serious threat to the health of domestic dogs and wildlife. Although studies have been conducted on the frequency and risk factors associated with CDV infection, there are no comprehensive data on the current epidemiological magnitude in the domestic dog population at regional and national levels. Therefore, we conducted a cross-sectional study and included our results in a meta-analysis to summarize and combine available data on the frequency and potential risk factors associated with CDV infection. METHODS: For the cross-sectional study, biological samples from dogs suspected to have canine distemper (CD) were collected and screened for viral RNA. Briefly, the PRISMA protocol was used for the meta-analysis, and data analyses were performed using STATA IC 13.1 software. RESULTS: CDV RNA was detected in 34% (48/141) of dogs suspected to have CD. Following our meta-analysis, 53 studies were selected for a total of 11,527 dogs. Overall, the pooled frequency of CDV positivity based on molecular and serological results were 33% (95% CI: 23–43) and 46% (95% CI: 36–57), respectively. The pooled subgroup analyses of clinical signs, types of biological samples, diagnostic methods and dog lifestyle had a wide range of CDV positivity (range 8–75%). Free-ranging dogs (OR: 1.44, 95% CI: 1.05–1.97), dogs >24 months old (OR: 1.83, 95% CI: 1.1–3) and unvaccinated dogs (OR: 2.92, 95% CI: 1.26–6.77) were found to be positively associated with CDV infection. In contrast, dogs <12 months old (OR: 0.36, 95% CI: 0.20–0.64) and dogs with a complete anti-CDV vaccination (OR: 0.18, 95% CI: 0.05–0.59) had a negative association. CONCLUSION: Considering the high frequency of CDV positivity associated with almost all the variables analyzed in dogs, it is necessary to immediately and continuously plan mitigation strategies to reduce the CDV prevalence, especially in determined endemic localities.


An Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in South Korea, 2015


title: Proteomics Computational Analyses Suggest That the Envelope Glycoproteins of Segmented Jingmen Flavi-Like Viruses are Class II Viral Fusion Proteins (β-Penetrenes) with Mucin-Like Domains

text: Jingmen viruses are newly described segmented flavi-like viruses that have a worldwide distribution in ticks and have been associated with febrile illnesses in humans. Computational analyses were used to predict that Jingmen flavi-like virus glycoproteins have structural features of class II viral fusion proteins, including an ectodomain consisting of beta-sheets and short alpha-helices, a fusion peptide with interfacial hydrophobicity and a three-domain architecture. Jingmen flavi-like virus glycoproteins have a sequence enriched in serine, threonine, and proline at the amino terminus, which is a feature of mucin-like domains. Several of the serines and threonines are predicted be modified by the addition of O-linked glycans. Some of the glycoproteins are predicted to have an additional mucin-like domain located prior to the transmembrane anchor, whereas others are predicted to have a stem consisting of two alpha-helices. The flavivirus envelope protein and Jingmen flavi-virus glycoproteins may have diverged from a common class II precursor glycoprotein with a mucin-like domain or domains acquired after divergence.


title: A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold

text: There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log(10)/day (p = 0.04). We hence need a larger trial to confirm our findings.


docid: eftwcysg

title: Eating the enemy within: autophagy in infectious diseases

text: Autophagy is emerging as a central component of antimicrobial host defense against diverse viral, bacterial, and parasitic infections. In addition to pathogen degradation, autophagy has other functions during infection such as innate and adaptive immune activation. As an important host defense pathway, microbes have also evolved mechanisms to evade, subvert, or exploit autophagy. Additionally, some fungal pathogens harness autophagy within their own cells to promote pathogenesis. This review will highlight our current understanding of autophagy in infection, focusing on the most recent advances in the field, and will discuss the potential implications of these studies in the design of anti-infective therapeutics.


title: Multiplex real-time RT-PCR assay for bovine viral diarrhea virus type 1, type 2 and HoBi-like pestivirus

text: Abstract HoBi-like pestiviruses are emerging pestiviruses that infect cattle causing clinical forms overlapping to those induced by bovine viral diarrhea virus (BVDV) 1 and 2. As a consequence of their widespread distribution reported in recent years, molecular tools for rapid discrimination among pestiviruses infecting cattle are needed. The aim of the present study was to develop a multiplex real-time RT-PCR assay, based on the TaqMan technology, for the rapid and unambiguous characterisation of all bovine pestiviruses, including the emerging HoBi-like strains. The assay was found to be sensitive, specific and repeatable, ensuring detection of as few as 100–101 viral RNA copies. No cross-reactions between different pestiviral species were observed even in samples artificially contaminated with more than one pestivirus. Analysis of field samples tested positive for BVDV-1, BVDV-2 or HoBi-like virus by a nested PCR protocol revealed that the developed TaqMan assay had equal or higher sensitivity and was able to discriminate correctly the viral species in all tested samples, whereas a real-time RT-PCR assay previously developed for HoBi-like pestivirus detection showed cross-reactivity with few high-titre BVDV-2 samples.


title: IMAGING DIAGNOSIS: FIBRODYSPLASIA OSSIFICANS PROGRESSIVA IN A CAT

text: A 1‐year‐old female cat was presented for progressive alopecia, gait abnormalities, and stiffness. Radiography demonstrated multiple calcified lesions within the soft tissues of the cervical and thoracic spine, shoulder, and limbs. Postmortem computed tomography provided more detailed information on the distribution, pattern, and extension of lesions. In addition, computed tomography helped guide sample selection for histopathology. The final diagnosis was fibrodysplasia ossificans progressiva. This is a rare disorder of unknown etiology, characterized by fibrosis and heterotopic bone formation in connective tissues. To the authors’ knowledge, this is the first report describing this disease in a European cat.


title: Benchmarking of antibiotic usage: An adjustment to reflect antibiotic stewardship program outcome in a hospital in Saudi Arabia

text: Abstract Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7–94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 bed-days compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r −0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking.


title: Forecasting COVID-19-Associated Hospitalizations under Different Levels of Social Distancing in Lombardy and Emilia-Romagna, Northern Italy: Results from an Extended SEIR Compartmental Model

text: The outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China, in December 2019. As of 17 April 2020, more than 2 million cases of COVID-19 have been reported worldwide. Northern Italy is one of the world’s centers of active coronavirus cases. In this study, we predicted the spread of COVID-19 and its burden on hospital care under different conditions of social distancing in Lombardy and Emilia-Romagna, the two regions of Italy most affected by the epidemic. To do this, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) deterministic model, which encompasses compartments relevant to public health interventions such as quarantine. A new compartment [Formula: see text] was added to the model for isolated infected population, i.e., individuals tested positives that do not need hospital care. We found that in Lombardy restrictive containment measures should be prolonged at least until early July to avoid a resurgence of hospitalizations; on the other hand, in Emilia-Romagna the number of hospitalized cases could be kept under a reasonable amount with a higher contact rate. Our results suggest that territory-specific forecasts under different scenarios are crucial to enhance or take new containment measures during the epidemic.


title: Fc Receptors as Adaptive Immunoreceptors

text: Most biological activities of antibodies depend on their ability to engage Receptors for the Fc portion of immunoglobulins (FcRs) on a variety of cell types. As FcRs can trigger positive and negative signals, as these signals control several biological activities in individual cells, as FcRs are expressed by many cells of hematopoietic origin, mostly of the myeloid lineage, as these cells express various combinations of FcRs, and as FcR-expressing cells have different functional repertoires, antibodies can exert a wide spectrum of biological activities. Like B and T Cell Receptors (BCRs and TCRs), FcRs are bona fide immunoreceptors. Unlike BCRs and TCRs, however, FcRs are immunoreceptors with an adaptive specificity for antigen, with an adaptive affinity for antibodies, with an adaptive structure and with an adaptive signaling. They induce adaptive biological responses that depend on their tissue distribution and on FcR-expressing cells that are selected locally by antibodies. They critically determine health and disease. They are thus exquisitely adaptive therapeutic tools.


title: Monoclonal antibodies as anti-infective products: a promising future?

text: Abstract Background The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. Aims This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. Sources A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. Content We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. Implications mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.


title: Cutaneous manifestations of hospitalized coronavirus disease 2019 patients: a report of six cases with clinicopathologic features and viral RNA in situ hybridization

text: Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic on March, 2020.1 Recalcati et al. reported cutaneous manifestations in 20.4% of COVID-19 patients.2 We identified six patients (five female, one male) with COVID-19-associated cutaneous manifestations in April 2020 on the inpatient dermatology consultation service. The mean age was 51 years (range, 28-71 years).


title: The link between bike sharing and subway use during the COVID-19 pandemic: The case-study of New York's Citi Bike

text: Abstract The full societal impact COVID-19 pandemic is laid bare in urban mobility patterns. This research explored the recently published data on the operation of subway and bike share systems (BSS) during the COVID-19 outbreak in New York city, providing evidence on its impact over urban transport systems, but also on how its different components can work in conjunction. The BSS has proved to be more resilient than the subway system, with a less significant ridership drop (71% vs 90% ridership drop and 50% decrease on the ridership ratio) and an increase on its trips' average duration (from 13 min to 19 min per trip). Moreover, the study found evidence of a modal transfer from some subway users to the bike sharing system. The first effects of the free BSS programs aimed at essential service workers were also evaluated. BSS can improve the resilience of urban transport systems to disruptive events. Overall, this paper offers clues on how bike sharing, and cycling in general, can support the transition to a post-coronavirus society.


title: Development and validation of a semi-automated surveillance system—lowering the fruit for non-ventilator-associated hospital-acquired pneumonia (nvHAP) prevention

text: Abstract Objectives Conducting manual surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP) using ECDC (European Centre for Disease Prevention and Control) surveillance criteria is very resource intensive. We developed and validated a semi-automated surveillance system for nvHAP, and describe nvHAP incidence and aetiology at our hospital. Methods We applied an automated classification algorithm mirroring ECDC definition criteria to distinguish patients ‘not at risk’ from patients ‘at risk’ for suffering from nvHAP. ‘At risk’-patients were manually screened for nvHAP. For validation, we applied the reference standard of full manual evaluation to three validation samples comprising 2091 patients. Results Among the 39 519 University Hospital Zurich inpatient discharges in 2017, the algorithm identified 2454 ‘at-risk’ patients, reducing the number of medical records to be manually screened by 93.8%. From this subset, nvHAP was identified in 251 patients (0.64%, 95%CI: 0.57–0.73). Sensitivity, negative predictive value, and accuracy of semi-automated surveillance versus full manual surveillance were lowest in the validation sample consisting of patients with HAP according to the International Classification of Diseases (ICD-10) discharge diagnostic codes, with 97.5% (CI: 93.7–99.3%), 99.2% (CI: 97.9–99.8%), and 99.4% (CI: 98.4–99.8%), respectively. The overall incidence rate of nvHAP was 0.83/1000 patient days (95%CI: 0.73–0.94), with highest rates in haematology/oncology, cardiac and thoracic surgery, and internal medicine including subspecialties. Conclusions The semi-automated surveillance demonstrated a very high sensitivity, negative predictive value, and accuracy. This approach significantly reduces manual surveillance workload, thus making continuous nvHAP surveillance feasible as a pivotal element for successful prevention efforts.


Anesthetic Management of Patients Undergoing Aortic Dissection Repair With Suspected Severe Acute Respiratory Syndrome COVID-19 Infection


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title: Entwicklung und Implementierung eines Betriebskonzeptes in einer Universitätsaugenklinik im Rahmen der SARS-CoV-2-Pandemie

text: The SARS-CoV‑2 pandemic poses major challenges for the entire medical care system. Especially in maximum care clinical facilities, a higher exposure to potentially infectious patients or positively tested COVID-19 patients is to be expected. A hospital facility concept was developed in the Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany with the aim of achieving maximum patient safety with maximum employee protection. The current infection control hygiene recommendations of the Robert Koch Institute (RKI), the leading specialist association, were taken into consideration along with the existing hospital hygiene plan of the University Hospital Frankfurt am Main. Incorporated into the developmental process were the Institute for Medical Microbiology and Hospital Hygiene, the occupational medical service department and the board of the University Hospital Frankfurt am Main. The operational concept with individualized measures ensures that (i) the care of outpatients; (ii) the performance of outpatient operations; (iii) and the care of admitted patients and patients undergoing surgery are also guaranteed during the COVID-19 pandemic. All measures have been documented in writing in the clinic’s internal quality manual and are thus accessible to all employees. The concept is regularly checked for functionality, so-called stress tests and hygiene inspections are carried out and improvements are made as necessary.


Methicillin-resistant Staphylococcus aureus—the new zoonosis


title: Rapid and sensitive detection of SARS-CoV-2 RNA using the Simplexa™ COVID-19 direct assay

text: BACKGROUND: So far, one of the major drawbacks of the available molecular assays for the diagnosis of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) is the need for viral nucleic acid extraction from clinical specimens. OBJECTIVE: The aim of this study was to evaluate the performances of a newly designed real-time RT-PCR (Simplexa™ COVID-19 Direct assay), that is established with an all-in-one reagent mix and no separate extraction required. RESULTS: The lower limit of detection (LOD) for both target genes resulted the same: 3.2 (CI: 2.9–3.8) log10 cp/mL and 0.40 (CI: 0.2–1.5) TCID50/mL for S gene while 3.2 log10 (CI: 2.9–3.7) log10 cp/mL and 0.4 (CI: 0.2–1.3) TCID50/mL for ORF1ab. The LOD obtained with extracted viral RNA for both S gene or ORF1ab was 2.7 log10 cp/mL. Crossreactive analysis performed in 20 nasopharyngeal swabs confirmed a 100% of clinical specificity of the assay. Clinical performances of Simplexa™ COVID-19 Direct assay were assessed in 278 nasopharyngeal swabs tested in parallel with Corman's method. Concordance analysis showed an "almost perfect" agreement in SARS-CoV-2 RNA detection between the two assays, being κ = 0.938; SE = 0.021; 95% CI = 0.896-0.980. CONCLUSIONS: The high sensitivity and specificity of this new assay indicate that it is promising for laboratory diagnosis, enabling highspeed detection in just over one hour, which is significantly faster than the up to five hours currently required by traditional extraction followed by amplification technologies, thus allowing prompt decision making regarding isolation of infected patients.


Is it time to consider an income guarantee for the period that patients with COVID-19 spend in isolation: An Indian perspective


title: Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence

text: Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.


title: Chapter 14 Kampo Medicines for Infectious Diseases

text: Abstract Numerous Kampo medicines and Oriental herbs have been used for the treatment of infectious diseases for several reasons, such as genetic background, economical reasons, fewer adverse effects, and so on. This chapter describes Kampo medicines and related Oriental herbs that are effective or promising in the treatment of infectious diseases at the clinical level and/or in animal models. In addition, effective Kampo medicines tested in vitro in cultured-cell studies are also included in this chapter. Each section is categorized by infectious disease and according to the popularity of the Kampo medicine.


docid: qnfyauqh

title: Assessment of intestinal damage in rotavirus infected neonatal mice by a d-xylose absorption test

text: Abstract A d-xylose absorption test has been standardized for use in newborn mice. It was used to measure small intestine dysfunction in neonate mice following infection with various isolates of rotaviruses. A xylose dose of 1 mg/g body weight was required to produce a maximum level of 100 μg/100 μl of plasma 2 h after administration of d-xylose. The mice inoculated with rotavirus absorbed significantly less d-xylose compared with uninoculated control mice. A micromethod is described which proved to be suitable to quantitate d-xylose for determination of absorptive function of the small intestine in small animals such as newborn mice.


title: Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection

text: NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation and effects during ribonucleic acid (RNA) viral infection are the focus of a wide range of research currently. Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. However, aberrant activation of the NLRP3 inflammasome can instead support viral pathogenesis and promote disease progression. Here, we summarize and expound upon the recent literature describing the molecular mechanisms underlying the activation and effects of the NLRP3 inflammasome in RNA viral infection to highlight how it provides protection against RNA viral infection.


title: Vaccines in a hurry

text: Abstract Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public–private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.


title: Some Cell Culture Procedures in Diagnostic Medical Virology

text: This chapter discusses the cell culture procedures as an invaluable tool in diagnostic medical virology. Culture of cells in monolayers is the most common method used in diagnostic virology laboratories. Primary or secondary cultures cells retain their diploid chromosome number, a factor which makes them particularly susceptible to certain viruses. The ideal cell system for a diagnostic virology laboratory would be a continuous line which retained its diploid chromosome number. It would be impossible in a routine laboratory to inoculate each specimen into every type of cell culture. A routine procedure is therefore employed and the specimen is inoculated into three types of cells which will support the growth of as many viruses as possible. Mixed culture technique (cocultivation) has proved of value when a viral agent is difficult to isolate from the original tissue, for example, isolation of measles from a brain biopsy. Cultures of chopped tissues have been used for many years to support the growth of viruses but the techniques were not readily applicable to diagnostic virology. A simple method of cultivating fragments of ciliated epithelium was described, which resulted in the isolation of new rhinoviruses and a new member of the corona virus group.


COVID-19 and the Challenges of Frailty Screening in Older Adults


title: Clinical course and treatment efficacy of COVID‐19 near Hubei Province, China: a multicentre, retrospective study

text: Currently, COVID‐19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course, and treatment efficacy of COVID‐19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from January 20 to February 8, 2020. Clinical outcomes were followed up until March 26, 2020. The viral shedding duration, full clinical course, and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID‐19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS‐CoV‐2. In total, the median SARS‐CoV‐2 shedding period and clinical course were 12 (IQR: 9‐17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16‐24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively; and ICU patients had longer median viral shedding periods (21 [17‐24] vs 11 [9‐15]) and clinical courses (30 [22‐33] vs 19 [15.8‐22]) than non‐ICU patients (both p<0.0001). SARS‐CoV‐2 clearances occurred at least 2 days before fatality in 3 non‐survivors. Current treatment with any antiviral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p>0.05) in real‐life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current antiviral therapies were ineffective for shortening viral shedding duration and clinical course in real‐world settings. These findings expand our knowledge of the SARS‐CoV‐2 infection and may be helpful for management of the epidemic outbreak of COVID‐19 worldwide. Further studies concerning effective antiviral agents and vaccines are urgently needed.


title: Characterisation of bubaline coronavirus strains associated with gastroenteritis in water buffalo (Bubalus bubalis) calves

text: Abstract Recently, a coronavirus strain (179/07-11) was isolated from water buffalo (Bubalus bubalis) and the virus which displayed a strict genetic and biological relatedness with bovine coronavirus (BCoV) was referred to as bubaline coronavirus (BuCoV). Here, we report the characterisation of four BuCoVs strains identified in the faeces or intestinal contents of water buffalo calves with acute gastroenteritis. Single BuCoV infections were detected in all but one cases from which two clostridia species were also isolated. Sequence and phylogenetic analyses of the 5′ end of the spike-protein gene showed that three BuCoVs were closely related to the prototype strain 179/07-11, whereas the fourth isolate (339/08-C) displayed a higher genetic identity to recent BCoV reference strains. Three strains adapted to the in vitro grow on human rectal tumour cells were also evaluated for their ability to replicate in a bovine cell line (Madin Darby bovine kidney) and to cause haemagglutination of chicken erythrocytes and all displayed biological properties similar to those already described for the prototype BuCoV. The present report shows that albeit genetically heterogeneous, the different BuCoV strains possess a common biological pattern which is different from most BCoV and BCoV-like isolates.


docid: rrzvlktb

title: Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors

text: Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.


COVID-19 - Computed tomography findings in two patients in Petrópolis, Rio de Janeiro, Brazil


title: Estimation of incubation period distribution of COVID-19 using disease onset forward time: a novel cross-sectional and forward follow-up study

text: BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) has quickly spread across countries and become a global crisis. However, one of the most important clinical characteristics in epidemiology, the distribution of the incubation period, remains unclear. Different estimates of the incubation period of COVID-19 were reported in recent published studies, but all have their own limitations. In this study, we propose a novel low-cost and accurate method to estimate the incubation distribution. METHODS: We have conducted a cross-sectional and forward follow-up study by identifying those asymptomatic individuals at their time of departure from Wuhan and then following them until their symptoms developed. The renewal process is hence adopted by considering the incubation period as a renewal and the duration between departure and symptom onset as a forward recurrence time. Under mild assumptions, the observations of selected forward times can be used to consistently estimate the parameters in the distribution of the incubation period. Such a method enhances the accuracy of estimation by reducing recall bias and utilizing the abundant and readily available forward time data. FINDINGS: The estimated distribution of forward time fits the observations in the collected data well. The estimated median of incubation period is 8·13 days (95% confidence interval [CI]: 7·37–8·91), the mean is 8·62 days (95% CI: 8·02–9·28), the 90th percentile is 14·65 days (95% CI: 14·00–15·26), and the 99th percentile is 20·59 days (95% CI: 19·47, 21·62). Compared with results in other studies, the incubation period estimated in this study is longer. INTERPRETATION: Based on the estimated incubation distribution in this study, about 10% of patients with COVID-19 would not develop symptoms until 14 days after infection. Further study of the incubation distribution is warranted to directly estimate the proportion with long incubation periods.


title: Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions

text: Summary Crimean-Congo haemorrhagic fever (CCHF) is the most widespread, tick-borne viral disease affecting humans. The disease is endemic in many regions, such as Africa, Asia, Eastern and Southern Europe, and Central Asia. Recently, the incidence of CCHF has increased rapidly in the countries of the World Health Organization Eastern Mediterranean Region (WHO EMR), with sporadic human cases and outbreaks of CCHF being reported from a number of countries in the region. Despite the rapidly growing incidence of the disease, there are currently no accurate data on the burden of the disease in the region due to the different surveillance systems used for CCHF in these countries. In an effort to increase our understanding of the epidemiology and risk factors for the transmission of the CCHF virus (CCHFV; a Nairovirus of the family Bunyaviridae) in the WHO EMR, and to identify the current knowledge gaps that are hindering effective control interventions, a sub-regional meeting was organized in Muscat, Oman, from December 7 to 9, 2015. This article summarizes the current knowledge of the disease in the region, identifies the knowledge gaps that present challenges for the prevention and control of CCHFV, and details a strategic framework for research and development activities that would be necessary to curb the ongoing and new threats posed by CCHFV.