title: Prognostic Role of Soluble Urokinase Plasminogen Activator Receptor at the Emergency Department: A Position Paper by the Hellenic Sepsis Study Group

text: In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of this statement is that sUPAR is a non-specific marker associated with a high negative predictive value for unfavourable outcomes; levels < 4 ng/ml indicate that it is safe to discharge the patient, whereas levels > 6 ng/ml are an alarming sign of risk for unfavourable outcomes. However, the suPAR levels should always be interpreted in light of the patient's history.


title: COVID-19 and Acute Heart Failure: Screening the Critically Ill – A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ)

text: Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.


title: Rapid diagnosis of avian infectious bronchitis virus by the polymerase chain reaction

text: Abstract A simple, sensitive and specific polymerase chain reaction (PCR) procedure was developed in order to detect infectious bronchitis virus (IBV) directly in tissue samples. Viral RNA was extracted from allantoic fluids and cell cultures infected experimentally with different strains of IBV and from tissues of naturally infected birds. Viral RNA was then amplified and identified by a nested RT-PCR assay using two sets of primers flanking a well-conserved region of the nucleocapsid gene. The selected IBV nucleocapsid sequence was detected successfully by simple direct electrophoresis of amplified material.


title: Viral pathogens in water: occurrence, public health impact, and available control strategies

text: The public health impact of the transmission of viruses in water is significant worldwide. Waterborne viruses can be introduced into our recreational and finished drinking water sources through a variety of pathways ultimately resulting in the onset of illness in a portion of the exposed population. Although there have been advances in both drinking water treatment technologies and source water protection strategies, waterborne disease outbreaks (WBDOs) due to viral pathogens still occur each year worldwide. By highlighting the prevalence of viral pathogens in water as well as (1) the dominant viruses of concern, (2) WBDOs due to viruses, and (3) available water treatment technologies, the goal of this review is to provide insight into the public health impact of viruses in water.


title: Dead Body Management in Times of Covid‐19 and its Potential Impact on the Availability of Cadavers for Medical Education in India

text: Technology integration in teaching is an evolving concept in modern medical education like other study disciplines in India. The domain of medical science education is presently deficient of deploying technology-based practices. Currently, majority of medical schools and colleges continue to choose traditional wet laboratory dissections over new virtual dissections which are being followed in institutions such as All India Institute of Medical Sciences (AIIMS) and handful of other governmental as well as private medical schools of India like AIIMS Rishikesh, AIIMS Jodhpur, Government Medical College Vimsar, Burla, Odisha, GSL Medical College Rajahmundry, Andhra Pradesh, Yennapoya University Mangalore, Dutta Megha Medical College, GMC Chindwara Madhya Pradesh, Symbiosis Institute Pune and Apollo Medical College Chitoor. Not to mention, as the current push for technology integration increases, it is likely that a large number of Indian academic scholars will begin seeing virtual dissections as beneficial to their classroom.


title: Environmental Contamination and Hygienic Measures After Feline Calicivirus Field Strain Infections of Cats in a Research Facility

text: Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the presence and viability of FCV in the environment after sequential oronasal infections of specified pathogen-free cats with two FCV field strains in a research facility. Replicating virus was detected in saliva swabs from all ten cats after the first and in four out of ten cats after the second FCV exposure using virus isolation to identify FCV shedders. In the environment, where cleaning, but no disinfection took place, FCV viral RNA was detectable using RT-qPCR on all tested items and surfaces, including cat hair. However, only very limited evidence was found of replicating virus using virus isolation. Viral RNA remained demonstrable for at least 28 days after shedding had ceased in all cats. Disinfection with 5% sodium bicarbonate (and Incidin(TM) Plus) and barrier measures were effective in that no viral RNA was detectable outside the cat rooms. Our findings are important for any multicat environment to optimize hygienic measures against FCV infection.


title: Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus KOR/KNIH/002_05_2015, Isolated in South Korea

text: The full genome sequence of a Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from cultured and isolated in Vero cells. The viral genome sequence has high similarity to 53 human MERS-CoVs, ranging from 99.5% to 99.8% at the nucleotide level.


title: Pediatric Asthma and Viral Infection

text: Abstract Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1 year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40 years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.


title: Chapter 40 The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development

text: Abstract Rotaviruses (RVs) are important causative agents of viral gastroenteritis in the young of most mammalian species studied, including humans, in which they are the most important cause of severe gastroenteritis worldwide despite the availability of several safe and effective vaccines. Replication of RVs is restricted in a host species-specific manner, and this barrier is determined predominantly by the host interferon (IFN) signaling and the ability of different RV strains to successfully negate IFN activation and amplification pathways. In addition, viral attachment to the target intestinal epithelial cells also regulates host range restriction. Several studies have focused on the role of the innate immune response in regulating RV replication and pathogenesis. The knowledge accrued from these efforts is likely to result in rational attenuation of RV vaccines to closely match circulating (and host species-matched) virus strains. In this chapter, we review prevalent models of RV interactions with innate immune factors, viral strategies employed to regulate their function, and the implications of these findings for improved RV vaccine development.


title: Survival of aerosolized coronavirus in the ambient air

text: Abstract An inactivation of airborne pathogenic Middle East Respiratory Syndrome (MERS-CoV) virus was investigated under controlled laboratory conditions. Two sets of climatic conditions were used in the experiments; (1) representing common office environment (25°C and 79% RH) and (2) climatic conditions of the Middle Eastern region where the virus was originated from (38°C and 24% RH). At the lower temperature, the virus demonstrated high robustness and strong capability to survive with about 63.5% of microorganisms remaining infectious 60min after aerosolisation. Fortunately, virus decay was much stronger for hot and dry air scenario with only 4.7% survival over 60min procedure.


title: Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection

text: The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II–specific inhibitors. The PS–annexin II connection may represent a new target to prevent HIV-1 infection.


title: High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease

text: Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.


title: Role of children in the transmission of the COVID-19 pandemic: a rapid scoping review

text: BACKGROUND: As a response to the COVID-19 pandemic, most countries have adopted measures of social distance, with the childhood population being one of the main focus of attention in these measures. METHODS: A rapid scoping review was carried out by searching PubMed to know if children are more contagious than adults, and the proportion of asymptomatic cases in children. Google Scholar and MedRxiv/bioRxiv were also searched. The time period was restricted from 1 December 2019 until 28 May 2020. Only studies published in English, Italian, French or Spanish were included. RESULTS: Fourteen out of 1099 identified articles were finally included. Studies included cases from China (n=9 to 2143), China and Taiwan (n=536), Korea (n=1), Vietnam (n=1), Australia (n=9), Geneva (n=40), the Netherlands (n=116), Ireland (n=3) and Spain (population-based study of IgG, n=8243). Although no complete data were available, between 15% and 55%–60% were asymptomatic, and 75%–100% of cases were from family transmission. Studies analysing school transmission showed children as not a driver of transmission. Prevalence of COVID-19 IgG antibody in children <15 years was lower than the general population in the Spanish study. CONCLUSIONS: Children are not transmitters to a greater extent than adults. There is a need to improve the validity of epidemiological surveillance to solve current uncertainties, and to take into account social determinants and child health inequalities during and after the current pandemic.


title: Environmental Contamination of SARS-CoV-2 in Healthcare Premises

text: Abstract Objectives A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Methods We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. Conclusion Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.


title: Virus factories: biogenesis and structural design

text: Replication and assembly of many viruses occur in specific intracellular compartments known as ‘virus factories’. Our knowledge of the biogenesis and architecture of these unique structures has increased considerably in the last 10 years, due to technical advances in cellular, molecular and structural biology. We now know that viruses build replication organelles, which recruit cell and viral components in a macrostructure in which viruses assemble and mature. Cell membranes and cytoskeleton participate in the biogenesis of these scaffolds and mitochondria are present in many factories, where they might supply energy and other essential factors. New inter‐organelle contacts have been visualized within virus factories, whose structure is very dynamic, as it changes over time. There is increasing interest in identifying the factors involved in their biogenesis and functional architecture, and new microscopy techniques are helping us to understand how these complex entities are built and work. In this review, we summarize recent findings on the cell biology, biogenesis and structure of virus factories.


title: Chapter Four Structural insights into coronavirus entry

text: Abstract Coronaviruses (CoVs) have caused outbreaks of deadly pneumonia in humans since the beginning of the 21st century. The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and was responsible for an epidemic that spread to five continents with a fatality rate of 10% before being contained in 2003 (with additional cases reported in 2004). The Middle-East respiratory syndrome coronavirus (MERS-CoV) emerged in the Arabian Peninsula in 2012 and has caused recurrent outbreaks in humans with a fatality rate of 35%. SARS-CoV and MERS-CoV are zoonotic viruses that crossed the species barrier using bats/palm civets and dromedary camels, respectively. No specific treatments or vaccines have been approved against any of the six human coronaviruses, highlighting the need to investigate the principles governing viral entry and cross-species transmission as well as to prepare for zoonotic outbreaks which are likely to occur due to the large reservoir of CoVs found in mammals and birds. Here, we review our understanding of the infection mechanism used by coronaviruses derived from recent structural and biochemical studies.


title: The Impact of the COVID-19 “Infodemic” on Drug-Utilization Behaviors: Implications for Pharmacovigilance

text: The coronavirus disease 2019 (COVID-19) pandemic that hit the world in 2020 triggered a massive dissemination of information (an “infodemic”) about the disease that was channeled through the print, broadcast, web, and social media. This infodemic also included sensational and distorted information about drugs that likely first influenced opinion leaders and people particularly active on social media and then other people, thus affecting choices by individual patients everywhere. In particular, information has spread about some drugs approved for other indications (chloroquine, hydroxychloroquine, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, favipiravir, and umifenovir) that could have led to inappropriate and therefore hazardous use. In this article, we analyze the rationale behind the claims for use of these drugs in COVID-19, the communication about their effects on the disease, the consequences of this communication on people’s behavior, and the responses of some influential regulatory authorities in an attempt to minimize the actual or potential risks arising from this behavior. Finally, we discuss the role of pharmacovigilance stakeholders in emergency management and possible strategies to deal with other similar crises in the future.


title: Lung involvement in patients with coronavirus disease-19 (COVID-19): a retrospective study based on quantitative CT findings

text: PURPOSE: To explore lung involvement in patients with coronavirus disease-19 (COVID-19) using quantitative computed tomography (QCT). METHODS: A total of 52 patients with COVID-19 who were admitted to three hospitals in China from January 23, 2020 to February 1, 2020 were retrospectively analyzed using QCT. The accuracy of QCT segmentation was assessed. The relationship between the time from symptom onset to initial CT and QCT parameters acquired on the initial CT were explored. RESULTS: First, the ability of QCT to detect and segment lesions was investigated and it was unveiled that results of segmentation of the majority of cases (42/52) were satisfactory and for 8 out of 52 patients, the images depicted lesions with miss-segmentation; besides, 2 out of 52 cases had negative finding on chest CT achieved by both radiologists and QCT. QCT-related parameters showed to have a relationship with the time from symptom onset to initial CT. In the early-stage (0–3 days), the percentage of lung involvement was 4%, with a mean density of − 462 ± 99 HU. The peak density of lesions appeared at the range of − 500 to − 700 HU on density histogram. In the intermediate-stage (4–6 days), the mean percentage of lung involvement noticeably increased compared with that in early stage (7%, p < 0.05). In late stage (7–14 days), the percentage of lung involvement decreased to 5%. The mean density of lesions was the highest (− 430 ± 80), and heterogeneity density distribution showed a dual-peak on density histogram. CONCLUSION: COVID-19 can be promptly detected by QCT. In addition, the QCT-related parameters can highly facilitate assessment of pulmonary involvement.


COVID-19 and healthcare workers: emerging patterns in Pamplona, Asia and Boston


title: A retrospective study detects a novel variant of porcine epidemic diarrhea virus in England in archived material from the year 2000

text: Outbreaks of porcine epidemic diarrhea (PED) were first recorded in England in the 1970s and continued to be confirmed until 2002. Retrospective analysis of archived material from one of the last confirmed cases in England in the year 2000 demonstrates the previous existence of a very diverse PED virus strain. Following the outbreaks of PED in North America in 2013, there has been renewed interest in phylogenetic analysis of sequences from PEDV strains worldwide. There is a gap in the available sequence data between the mid 1980s and the mid 2000s. This work is an example of how this gap can be at least partially filled by the examination of archived material.


title: The Evolution of Endogenous Viral Elements

text: Endogenous retroviruses are a common component of the eukaryotic genome, and their evolution and potential function have attracted considerable interest. More surprising was the recent discovery that eukaryotic genomes contain sequences from RNA viruses that have no DNA stage in their life cycle. Similarly, several single-stranded DNA viruses have left integrated copies in their host genomes. This review explores some major evolutionary aspects arising from the discovery of these endogenous viral elements (EVEs). In particular, the reasons for the bias toward EVEs derived from negative-sense RNA viruses are considered, as well as what they tell us about the long-term “arms races” between hosts and viruses, characterized by episodes of selection and counter-selection. Most dramatically, the presence of orthologous EVEs in divergent hosts demonstrates that some viral families have ancestries dating back almost 100 million years, and hence are far older than expected from the phylogenetic analysis of their exogenous relatives.


title: Longitudinal Monitoring of SARS-CoV-2 IgM and IgG Seropositivity to Detect COVID-19

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel beta-coronavirus that has recently emerged as the cause of the 2019 coronavirus pandemic (COVID-19). Polymerase chain reaction (PCR) based tests are optimal and recommended for the diagnosis of an acute SARS-CoV-2 infection. Serology tests for viral antibodies provide an important tool to diagnose previous exposure to the virus. Here we evaluate the analytical performance parameters of the Diazyme SARS-CoV-2 IgM/IgG serology assays and describe the kinetics of IgM and IgG seroconversion observed in patients with PCR confirmed COVID-19 who were admitted to our hospital. METHODS: We validated the performance of the Diazyme assay in 235 subjects to determine specificity. Subsequently, we evaluated the SARS-CoV-2 IgM and IgG seroconversion of 54 PCR confirmed COVID-19 patients and determined sensitivity of the assay at three different timeframes. RESULT: Sensitivity and specificity for detecting seropositivity at ≥ 15 days following a positive SARS-CoV-2 PCR result, was 100.0% and 98.7% when assaying for the panel of IgM and IgG. The median time to seropositivity observed for a reactive IgM and IgG result from the date of a positive PCR was 5 days (IQR: 2.75-9 days) and 4 days (IQR: 2.75-6.75 days), respectively. CONCLUSIONS: Our data demonstrates that the Diazyme IgM/IgG assays are suited for the purpose of detecting SARS-CoV-2 IgG and IgM in patients with suspected SARS-CoV-2 infections. For the first time, we report longitudinal data showing the evolution of seroconversion for both IgG and IgM in a cohort of acutely ill patients in the United States. We also demonstrate a low false positive rate in patients who were presumed to be disease free.


title: Evaluating the evidence for direct central nervous system invasion in patients infected with the nCOVID-19 virus

text: The current nCOVID-19 pandemic is raising several questions in the approximately 25% of patients who present with neurological symptoms. While secondary brain injury from the systemic manifestations of the disease account for the majority of non-specific neurological symptoms that include headache, nausea, and progressive confusion, the question that remains unanswered is does the nCOVID-19 virus use the olfactory mucosa as a portal to directly invade the brain ? A second question is how common does direct CNS invasion complicate the classical cardiorespiratory severe form of the disease? We know from previous studies that almost all members of the Corona virus family have neurotropism. We also know from the current pandemic that deteriorating consciousness and cerebrovascular accidents are not uncommon. Several previous scattered case reports, and post-mortem examinations of brain tissue, demonstrated nCOVID-19 nucleic acid in the CSF, and brain tissue, of infected and deceased individuals. We performed a PubMed review of the literature to specifically assess the evidence for the direct CNS invasion by the nCOVID-19 virus. This phenomenon would explain the cerebral oedema and encephalitis, that does occur, and bring Neurosurgeons into the management of these patients by for example directed intra-cranial pressure management post insertion of an intra-cranial pressure monitor. Unfortunately, the answers to these questions were not definitively answered by the research reviewed. While suggestive that direct CNS invasion does occur, the exact scale and manifestations of the problem remains, to date, essentially unknown.


title: Single Cell Metabolomics: A Future Tool to Unmask Cellular Heterogeneity and Virus-Host Interaction in Context of Emerging Viral Diseases

text: Viral emergence is an unpredictable but obvious event, particularly in the era of climate change and globalization. Efficient management of viral outbreaks depends on pre-existing knowledge and alertness. The potential hotspots of viral emergence often remain neglected and the information related to them is insufficient, particularly for emerging viruses. Viral replication and transmission rely upon usurping the host metabolic machineries. So altered host metabolic pathways can be exploited for containment of these viruses. Metabolomics provides the insight for tracing out such checkpoints. Consequently introspection of metabolic alteration at virus-host interface has evolved as prime area in current virology research. Chromatographic separation followed by mass spectrometry has been used as the predominant analytical platform in bulk of the analyses followed by nuclear magnetic resonance (NMR) and fluorescence based techniques. Although valuable information regarding viral replication and modulation of host metabolic pathways have been extracted but ambiguity often superseded the real events due to population effect over the infected cells. Exploration of cellular heterogeneity and differentiation of infected cells from the nearby healthy ones has become essential. Single cell metabolomics (SCM) emerges as necessity to explore such minute details. Mass spectrometry imaging (MSI) coupled with several soft ionization techniques such as electrospray ionization (ESI), laser ablation electrospray ionization (LAESI), matrix assisted laser desorption/ionization (MALDI), matrix-free laser desorption ionization (LDI) have evolved as the best suited platforms for SCM analyses. The potential of SCM has already been exploited to resolve several biological conundrums. Thus SCM is knocking at the door of virus-host interface.


title: COVID-19 and its implications for thrombosis and anticoagulation

text: Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.


title: Triage tool for the rationing of blood for massively bleeding patients during a severe national blood shortage: guidance from the National Blood Transfusion Committee

text: The emerging COVID‐19 pandemic has overwhelmed healthcare resources worldwide, and for transfusion services this could potentially result in rapid imbalance between supply and demand due to a severe shortage of blood donors. This may result in insufficient blood components to meet every patient's needs resulting in difficult decisions about which patients with major bleeding do and do not receive active transfusion support. This document, which was prepared on behalf of the National Blood Transfusion Committee in England, provides a framework and triage tool to guide the allocation of blood for patients with massive haemorrhage during severe blood shortage. Its goal is to provide blood transfusions in an ethical, fair, and transparent way to ensure that the greatest number of life years are saved. It is based on an evidence‐ and ethics‐based Canadian framework, and would become operational where demand for blood greatly exceeds supply, and where all measures to manage supply and demand have been exhausted. The guidance complements existing national shortage plans for red cells and platelets.


Consideration of povidone-iodine as a public health intervention for COVID-19: Utilization as “Personal Protective Equipment” for frontline providers exposed in high-risk head and neck and skull base oncology care


title: The global pool of simulation exercise materials in health emergency preparedness and response: a scoping review with a health system perspective

text: Simulation Exercises (SimEx) are an established tool in defence and allied security sectors, applied extensively in health security initiatives under national or international legislative requirements, particularly the International Health Regulations (2005). There is, however, a paucity of information on SimEx application to test the functionality of health systems alongside emergency preparedness, response and recovery. Given the important implications health services resilience has for the protection and improvement of human life, this scoping review was undertaken to determine how the publicly available body of existing global SimEx materials considers health systems, together with health security functions in the event of disruptive emergencies. The global review identified 668 articles from literature and 73 products from institutional sources. Relevant screening identified 51 materials suitable to examine from a health system lens using the six health system building blocks as per the WHO Health System Framework. Eight materials were identified for further examination of their ability to test health system functionality from a resilience perspective. SimEx are an effective approach used extensively within health security and emergency response sectors but is not yet adequately used to test health system resilience. Currently available SimEx materials lack an integrated health system perspective and have a limited focus on the quality of services delivered within the context of response to a public health emergency. The materials do not focus on the ability of systems to effectively maintain core services during response. Without adjustment of the scope and focus, currently available SimEx materials do not have the capacity to test health systems to support the development of resilient health systems. Dedicated SimEx materials are urgently needed to fill this gap and harness their potential as an operational tool to contribute to improvements in health systems. They can act as effective global goods to allow testing of different functional aspects of health systems and service delivery alongside emergency preparedness and response. The work was conducted within the scope of the Tackling Deadly Diseases in Africa Programme, funded by the UK Department for International Development, which seeks to strengthen collaboration between the health system and health security clusters to promote health security and build resilient health systems.


title: From Infection to the Microbiome: An Evolving Role of Microbes in Schizophrenia

text: The study of microorganisms such as bacteria, viruses, archaea, fungi, and protozoa in the context of psychiatric disorders may be surprising to some. This intersection of disciplines, however, has a rich history and is currently revitalized by newfound functions of the microbiome and the gut-brain axis in human diseases. Schizophrenia, in particular, fits this model as a disorder with gene and environmental roots that may be anchored in the immune system. In this context, the combination of a precisely timed pathogen exposure in a person with genetically encoded altered immunity may have especially destructive consequences for the central nervous system (CNS). Furthermore, significant components of immunity, such as the development of the immune response and the concept of immune tolerance, are largely dictated by the commensal residents of the microbiome. When this community of microbes is imbalanced, perhaps as the result of a pathogen invasion, stress, or immune gene deficiency, a pathological cycle of localized inflammation, endothelial barrier compromise, translocation of gut-derived products, and systemic inflammation may ensue. If these pathologies enable access of gut and microbial metabolites and immune molecules to the CNS across the blood-brain barrier (BBB), and studies of the gut-brain axis support this hypothesis, a worsening of cognitive deficits and psychiatric symptoms is predicted to occur in susceptible individuals with schizophrenia. In this chapter, we review the role of microbes in various stages of this model and how these organisms may contribute to documented phenotypes of schizophrenia. An increased understanding of the role of pathogens and the microbiome in psychiatric disorders will better guide the development of microbial and immune-based therapeutics for disease prevention and treatment.


title: Inhibitory effects of homoharringtonine on foot and mouth disease virus in vitro

text: Foot‐and‐mouth disease (FMD) is a highly contagious disease that affects cloven‐hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS‐2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time‐of‐addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti‐FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo.


title: A Case of Statin-Induced Interstitial Pneumonitis due to Rosuvastatin

text: Statins lower the hyperlipidemia and reduce the incidence of cardiovascular events and related mortality. A 60-year-old man who was diagnosed with a transient ischemic attack was started on acetyl-L-carnitine, cilostazol, and rosuvastatin. After rosuvastatin treatment for 4 weeks, the patient presented with sudden onset fever, cough, and dyspnea. His symptoms were aggravated despite empirical antibiotic treatment. All infectious pathogens were excluded based on results of culture and polymerase chain reaction of the bronchoscopic wash specimens. Chest radiography showed diffuse ground-glass opacities in both lungs, along with several subpleural ground-glass opacity nodules; and a foamy alveolar macrophage appearance was confirmed on bronchoalveolar lavage. We suspected rosuvastatin-induced lung injury, discontinued rosuvastatin and initiated prednisolone 1 mg/kg tapered over 2weeks. After initiating steroid therapy, his symptoms and radiologic findings significantly improved. We suggest that clinicians should be aware of the potential for rosuvastatin-induced lung injury.


title: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study

text: The 2019 novel coronavirus (renamed SARS-CoV-2, and generally referred to as the COVID-19 virus) has spread to 184 countries with over 1.5 million confirmed cases. Such major viral outbreaks demand early elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 virus genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 virus genomes. The proposed method combines supervised machine learning with digital signal processing (MLDSP) for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman’s rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp, including the 29 COVID-19 virus sequences available on January 27, 2020. Our results support a hypothesis of a bat origin and classify the COVID-19 virus as Sarbecovirus, within Betacoronavirus. Our method achieves 100% accurate classification of the COVID-19 virus sequences, and discovers the most relevant relationships among over 5000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.


The ABC's of disaster management: Managing apheresis operations during the SARS‐CoV‐2 pandemic


title: Analysis of protein expression changes of the Vero E6 cells infected with classic PEDV strain CV777 by using quantitative proteomic technique

text: Abstract Recent outbreaks of porcine epidemic diarrhea virus (PEDV) have caused widespread concern. The identification of proteins associated with PEDV infection might provide insight into PEDV pathogenesis and facilitate the development of novel antiviral strategies. We analyzed the differential protein profile of PEDV-infected Vero E6 cells using mass spectrometry and an isobaric tag for relative and absolute quantification. A total of 126 proteins were identified that were differentially expressed between the PEDV-infected and mock-infected groups (P <0.05, quantitative ratio ≥1.2), among which the expression of 58 proteins was up-regulated and that of 68 proteins was down-regulated in the PEDV-infected Vero E6 cells, involving in integrin β2/β3, cystatin-C. The Gene Ontology analysis indicated that the molecular function of the differentially expressed proteins (DEPs) was primarily related to binding and catalytic activity, and that the biological functions in which the DEPs are involved included metabolism, organismal systems, cellular processes, genetic information processing, environmental information processing, and diseases. Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection. Our findings provide valuable insight into PEDV-Vero E6 cell interactions.


COVID‐19 pandemic: A challenge to a child with cancer


title: High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan

text: Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation.


Life in the pandemic: Some reflections on nursing in the context of COVID‐19


title: Recomendaciones sobre reanimación cardiopulmonar en pacientes con sospecha o infección confirmada por SARS-CoV-2 (COVID-19). Resumen ejecutivo

text: Resumen La pandemia por SARS-CoV-2 ha generado nuevos escenarios que requieren modificaciones de los protocolos habituales de reanimación cardiopulmonar. Las guías clínicas vigentes sobre el manejo de la parada cardiorrespiratoria no incluyen recomendaciones para situaciones aplicables a este contexto. Por ello, el Plan Nacional de Reanimación Cardiopulmonar de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias, en colaboración con el Grupo Español de RCP Pediátrica y Neonatal y con el programa de Enseñanza de Soporte Vital en Atención Primaria de la Sociedad Española de Medicina Familiar y Comunitaria, ha redactado las siguientes recomendaciones, que están divididas en cinco partes que tratan los principales aspectos para cada entorno asistencial. En este artículo se presenta un resumen ejecutivo de las mismas. Abstract The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into five parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them.


title: How a Barcelona post-acute facility became a referral center for comprehensive management of subacute patients with COVID-19

text: Abstract The COVID-19 pandemic’s greatest impact is among older adults. Management of the situation requires a systemic response, and post-acute care (PAC) can provide an adequate mix of active treatment, management of associated geriatric syndromes and palliative care, both in the acute phase, and in post-COVID-19 recovery. In the region of Catalonia, Spain, selected PAC centers have become a site to treat COVID-19 older patients. Referrals come from the emergency department (ED) or COVID-19 wards of the acute reference hospitals, nursing homes or private homes. We critically review the actions taken by Parc Sanitari Pere Virgili, a PAC facility in Barcelona, to manage the pandemic, including its administration, healthcare, communication, psychological support and ethical frameworks. We believe that the strategies we employed and the lessons we learned can be useful for other sites and countries where similar adaptation of existing facilities may be implemented.


title: Field trial to evaluate the effect of an intranasal respiratory vaccine protocol on bovine respiratory disease incidence and growth in a commercial calf rearing unit

text: BACKGROUND: Bovine respiratory disease (BRD) continues to be great challenge in calf rearing units. The urgent need to decrease the use of antibiotics and increase animal welfare in beef production has forced us to introduce new preventive methods. Vaccinations could contribute to the solution, but the high incidence of BRD already at an early age has made it difficult to introduce suitable vaccination programs. Challenge studies have shown promising results in 3–14 day old calves vaccinated with intranasal BRD vaccine, but very few field trials are available to assess the efficacy of the intranasal vaccines in field conditions. We evaluated the effect of one dose of commercial intranasal vaccination on calf mortality, daily gain, and treatment incidence for BRD in one calf rearing unit. In total, 497 calves (mean age 19 days) were included in our study, 247 of which were vaccinated at the time of arrival to the unit and 250 served as negative controls (unvaccinated). Vaccinated and unvaccinated calves were situated in separate compartments until weaning. Daily gain, treatment incidence, and mortality were recorded until the calves were transported to the finishing unit, which averaged 154.5 days from arrival. RESULTS: Average daily gain over the complete study period was 1151.9 g/day (SD 137.9) for the vaccinated calves and 1139.5 g/day (SD 135.9) for the unvaccinated calves. Intranasal vaccination combined with older arrival age (17 days or older) resulted in a higher daily gain (47.8 g/day) compared with unvaccinated calves (coef. 0.0478, p = 0.003). This association was not recorded in calves that were younger than 17 days upon arrival. Intranasal vaccination was not significantly associated either with mortality (OR 0.976, p = 0.968) or treatment incidence for BRD (OR 1.341, p = 0.120). In total, six vaccinated calves (2.43%) and six unvaccinated calves (2.40%) died during the study period. CONCLUSIONS: Vaccinating arriving calves with intranasal vaccine in the calf rearing unit did not decrease the mortality or treatment incidence for BRD, but it significantly improved the weight gain in calves transported to the unit at the age of 17 days or older.


title: Hospital resuscitation teams: a review of the risks to the healthcare worker

text: BACKGROUND: “Code blue” events and related resuscitation efforts involve multidisciplinary bedside teams that implement specialized interventions aimed at patient revival. Activities include performing effective chest compressions, assessing and restoring a perfusing cardiac rhythm, stabilizing the airway, and treating the underlying cause of the arrest. While the existing critical care literature has appropriately focused on the patient, there has been a dearth of information discussing the various stresses to the healthcare team. This review summarizes the available literature regarding occupational risks to medical emergency teams, characterizes these risks, offers preventive strategies to healthcare workers, and highlights further research needs. METHODS: We performed a literature search of PubMed for English articles of all types (randomized controlled trials, case-control and cohort studies, case reports and series, editorials and commentaries) through September 22, 2016, discussing potential occupational hazards during resuscitation scenarios. Of the 6266 articles reviewed, 73 relevant articles were included. RESULTS: The literature search identified six potential occupational risk categories to members of the resuscitation team—infectious, electrical, musculoskeletal, chemical, irradiative, and psychological. Retrieved articles were reviewed in detail by the authors. CONCLUSION: Overall, we found there is limited evidence detailing the risks to healthcare workers performing resuscitation. We identify these risks and offer potential solutions. There are clearly numerous opportunities for further study in this field.


title: A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

text: BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao(2)) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao(2)) to the fraction of inspired oxygen (Fio(2)) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.)


title: Beyond Antibodies: The DARPin(®) Drug Platform

text: The DARPin(®) drug platform was established with a vision to expand the medical use of biologics beyond what was possible with monoclonal antibodies. It is based on naturally occurring ankyrin repeat domains that are typically building blocks of multifunctional human proteins. The platform allows for the generation of diverse, well-behaved, multifunctional drug candidates. Recent clinical data illustrate the favorable safety profile of the first DARPin(®) molecules tested in patients. With the positive phase III results of the most advanced DARPin(®) drug candidate, abicipar, the DARPin(®) drug platform is potentially about to achieve its first marketing approval. This review highlights some of the key milestones and decisions encountered when transforming the DARPin(®) platform from an academic concept to a biotech drug pipeline engine.


title: A new visually improved and sensitive loop mediated isothermal amplification (LAMP) for diagnosis of symptomatic falciparum malaria

text: Abstract Molecular diagnosis of malaria by nucleotide amplification requires sophisticated and expensive instruments, typically found only in well-established laboratories. Loop-mediated isothermal amplification (LAMP) has provided a new platform for an easily adaptable molecular technique for molecular diagnosis of malaria without the use of expensive instruments. A new primer set has been designed targeting the 18S rRNA gene for the detection of Plasmodium falciparum in whole blood samples. The efficacy of LAMP using the new primer set was assessed in this study in comparison to that of a previously described set of LAMP primers as well as with microscopy and real-time PCR as reference methods for detecting P. falciparum. Pre-addition of hydroxy napthol blue (HNB) in the LAMP reaction caused a distinct color change, thereby improving the visual detection system. The new LAMP assay was found to be 99.1% sensitive compared to microscopy and 98.1% when compared to real-time PCR. Meanwhile, its specificity was 99% and 100% in contrast to microscopy and real-time PCR, respectively. Moreover, the LAMP method was in very good agreement with microscopy and real-time PCR (0.94 and 0.98, respectively). This new LAMP method can detect at least 5parasites/μL of infected blood within 35min, while the other LAMP method tested in this study, could detect a minimum of 100parasites/μL of human blood after 60min of amplification. Thus, the new method is sensitive and specific, can be carried out in a very short time, and can substitute PCR in healthcare clinics and standard laboratories.


title: Clinical presentation, cardiovascular findings, etiology, and outcome of myocarditis in dogs: 64 cases with presumptive antemortem diagnosis (26 confirmed postmortem) and 137 cases with postmortem diagnosis only (2004-2017)

text: Abstract Introduction To describe presentation, cardiovascular abnormalities, etiology, and outcome of canine myocarditis in geographic areas not endemic for Trypanosoma or Leishmania. Animals Sixty-four (presumed antemortem diagnosis) and 137 (postmortem diagnosis only) client-owned dogs at two tertiary care facilities. Materials and Methods Medical records of dogs with clinical or histopathological diagnosis of myocarditis were reviewed retrospectively. Results Common examination findings in dogs with a presumed antemortem diagnosis included fever (21%) and heart murmur (19%). Median cardiac troponin I was 12.2 ng/mL (range 0.2-808.0 ng/mL), and troponin exceeded 1.0 ng/mL in 26/29 (90%) dogs. Ventricular ectopy was the most common arrhythmia (54%), while decreased left ventricular systolic function was the most common echocardiographic abnormality (56%). An infectious etiology was diagnosed in 35/64 (55%) dogs. Confirmed infectious etiologies included bacterial sepsis (n = 9) or extension of endocarditis (3), toxoplasmosis or neosporosis (3), parvovirus (2), and one case each of bartonellosis, trypanosomiasis, leptospirosis, and dirofilariasis. Median survival time was 4 days (range 0 - 828 days) for all dogs, versus 82 days for dogs who survived at least two weeks following diagnosis. Presence of pericardial effusion or azotemia were significant predictors of nonsurvival. The most common inflammatory infiltrate on histopathology was neutrophilic (47%), and 20/137 (15%) dogs had concurrent bacterial endocarditis on postmortem. Conclusions Bacterial infection was the most common confirmed etiology of myocarditis in this study. Prognosis for canine myocarditis is guarded and similar to that reported for infective endocarditis. Criteria for the antemortem diagnosis of canine myocarditis are suggested.


title: Going Online for Groceries: Drivers of Category-Level Share of Wallet Expansion

text: Abstract Some grocery product categories may be more successful than others in terms of stimulating consumers to increase their share of wallet (SoW) when they start buying through the online channel of a grocery chain. This study explores the circumstances in which online and multichannel marketing mix instruments determine the extent of category-level SoW expansion. To do so, the authors use U.K. household scanner panel data, covering online and offline purchases by 3,311 households in 59 categories of four multichannel retail chains. The results indicate that the effectiveness of online and multichannel marketing mix instruments for stimulating expansion is moderated by category characteristics, such that a selective approach to making decisions about the online price, online assortment breadth, online/offline assortment integration, and online national brand proliferation, tuned to account for category differences, can increase category-level SoW for the online-visited chain.


title: Introduction: Finding a way in daily clinical practice during COVID‐19 pandemic

text: Since some months, the Covid-19 pandemic changed our world drastically. At the start of the pandemic, in a single week, our medical communities, both in primary care , nursing homes, as in secondary and tertiary facilities have been forced to stop all regular clinical care and to shift towards hospital care that was ultimately restricted to Covid-19 related disease. The clinical presentation of Covid-19 occurred predominantly in the elderly patients (most > 65 years old) displaying a respiratory disability, and in a small proportion among them displayed a respiratory failure, in association with a broad range of pre-existing co-morbidities. Covid-19 had not been taught in university and to prepare ourselves, we aimed to retract data published from especially Chinese studies. Most literature was published without a peer-review procedure (fast track), and most intervention designs existed of small groups and a not blinded/not randomized inclusion. After an extensive week of patients' contact, we experienced various differences (compared to the prior reports) in their first presentation and in their individual course of disease.


title: Coronavirus-like particles in nonhuman primate feces

text: Coronavirus-like particles were detected by electron microscopy in normal and diarrhea stool specimens from baboons, chimpanzees, macaques, and marmosets. There was a high prevalence of particles in both normal and diarrhea stools of older animals, whereas stools from nonweaned animals rarely contained these coronavirus-like particles.


title: Opportunities Revealed for Antimicrobial Stewardship and Clinical Practice with Implementation of a Rapid Respiratory Multiplex Assay

text: Few studies assess the utility of rapid multiplex molecular respiratory panels in adult patients. Previous multiplex PCR assays took hours to days from order time to result. We analyze the clinical impact of switching to a molecular assay with a 3-h test-turnaround-time (TAT). We performed a retrospective review of adult patients who presented to our emergency departments with respiratory symptoms and had a respiratory viral panel (xTAG RVP; RVP) or respiratory pathogen panel (ePlex RP; RPP) within 48 h of presentation. The average TATs for the RVP and RPP were 27.9 and 3.0 h, respectively (P < 0.0001). In RVP-positive and RPP-positive patients, 68.9 and 44.5% of those with normal chest imaging received antibiotics (P = 0.013), while 95.4 and 89.6% of those with abnormal imaging received antibiotics, respectively (P = 0.187). There was no difference in antibiotic duration in RVP-positive and RPP-positive patients with abnormal chest imaging (6.2 and 6.0 days, respectively; P = 0.923) and normal chest imaging (4.5 and 4.3 days, respectively; P = 0.922). Fewer patients were admitted in the RPP-positive compared to the RVP-positive group (76.9 and 88.6%, respectively; P = 0.013), while the proportion of admissions were similar among RPP-negative and RVP-negative patients (85.3 and 87.1%, P = 0.726). Switching to a multiplex respiratory panel with a clinically actionable TAT is associated with reduced hospital admissions and, in admitted adults without focal radiographic findings, reduced antibiotic initiation. Opportunities to further mitigate inappropriate antibiotic use may be realized by combining rapid multiplex PCR with provider education, clinical decision-care algorithms, and active antibiotic stewardship.


Proteomics and genomics: perspectives on drug and target discovery


title: Socioeconomic Correlates of Obesity in African-American and Caribbean-Black Men and Women

text: The high prevalence of obesity among Black Americans warrants additional investigation into its relationship with socioeconomic position (SEP), sex, and ethnicity. This cross-sectional study utilizes 2001–2003 data from the National Survey of American Life, a nationally representative sample of 3570 African-Americans and 1621 Caribbean-Blacks aged 18 years and older. Multivariate logistic regression models stratified by ethnicity and sex describe the independent associations between obesity and multilevel socioeconomic factors after adjustment for age, other SEP measures at the individual, family and neighborhood levels, and health behaviors such as physical activity, alcohol intake, and smoking. A positive relationship was observed between obesity and family income among African-American and Caribbean-Black men. Receipt of public assistance was a strongly associated factor for obesity in Caribbean-Black men and women. Among African-American women, inverse relationships were observed between obesity and education, occupation, and family income; residence within a neighborhood with a supermarket also decreased their odds of obesity. Residence in a neighborhood with a park decreased the odds of obesity only among African-American men, whereas residence in a neighborhood with a supermarket decreased the odds of obesity among Caribbean-Black men. The social patterning of obesity by individual, household, and neighborhood socioeconomic resources differs for African-American and Caribbean-Black men and women within these cross-sectional analyses; an appreciation of these differences may be a prerequisite for developing effective weight control interventions and policies for these two populations.


Emerging viral mutants in Australia suggest RNA recombination event in the SARS‐CoV‐2 genome


title: Chinese Medicine in the Management of New and Emerging Infectious Diseases

text: ABSTRACT Emerging infectious diseases are an important problem in medicine, and many continue to pose a global threat. However, the management of new and emerging infections is usually difficult due to a lack of knowledge and tools to address the problem. The use of Chinese medicine to manage new and emerging infectious diseases, however, has attracted significant attention. This brief article summarizes and discusses the use of Chinese medicine in the management of new and emerging infectious diseases.


title: Arenavirus reverse genetics: New approaches for the investigation of arenavirus biology and development of antiviral strategies

text: Abstract Several arenaviruses, chiefly Lassa virus, cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. On the other hand the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus–host interactions and associated disease. The development of novel antiviral strategies to combat pathogenic arenaviruses would be facilitated by a detailed understanding of the arenavirus molecular and cell biology. To this end, the development of reverse genetic systems for several arenaviruses has provided investigators with novel and powerful approaches to dissect the functions of arenavirus proteins and their interactions with host factors required to complete each of the steps of the virus life cycle, as well as to cause disease.


title: Novel coronaviruses, astroviruses, adenoviruses and circoviruses in insectivorous bats from northern China

text: Bats are considered as the reservoirs of several emerging infectious disease, and novel viruses are continually found in bats all around the world. Studies conducted in southern China found that bats carried a variety of viruses. However, few studies have been conducted on bats in northern China, which harbours a diversity of endemic insectivorous bats. It is important to understand the prevalence and diversity of viruses circulating in bats in northern China. In this study, a total of 145 insectivorous bats representing six species were collected from northern China and screened with degenerate primers for viruses belonging to six families, including coronaviruses, astroviruses, hantaviruses, paramyxoviruses, adenoviruses and circoviruses. Our study found that four of the viruses screened for were positive and the overall detection rates for astroviruses, coronaviruses, adenoviruses and circoviruses in bats were 21.4%, 15.9%, 20% and 37.2%, respectively. In addition, we found that bats in northern China harboured a diversity of novel viruses. Common Serotine (Eptesicus serotinu), Fringed long‐footed Myotis (Myotis fimriatus) and Peking Myotis (Myotis pequinius) were investigated in China for the first time. Our study provided new information on the ecology and phylogeny of bat‐borne viruses.


title: Preventing Facial Pressure Injury for Health Care Providers Adhering to COVID-19 Personal Protective Equipment Requirements

text: OBJECTIVE: To determine if a repurposed silicone-based dressing used underneath a N95 mask is a safe and beneficial option for facial skin injury prevention without compromising the mask’s seal. METHODS: Since February 21, 2020, staff in high risk areas such as the ED and ICU of King Hamad University Hospital have worn N95 masks when doing aerosol-generating procedures to protect against the novel coronavirus 2019. At that time, without education enablers or resources that could be directly translated into practice, the hospital’s Pressure Injury Prevention Committee explored and created a stepwise process to protect the skin under these masks. This procedure was developed over time and tested to make sure that it did not interfere with the effectiveness of the N95 mask seal. RESULTS: Skin protection was achieved by repurposing a readily available silicone border dressing cut into strips. This was tested on 10 volunteer staff members of various skin types and both sexes who became part of this evidence generation project. Oxygen saturation values taken before and after the 4-hour wear test confirmed that well-fitted facial protection did not compromise the mask seal, but rather improved it. An added advantage was increased comfort with less friction as self-reported by the staff. An educational enabler to prevent MDRPI from N95 mask wear was an important additional resource for the staff. CONCLUSIONS: This creative and novel stepwise process of developing a safe skin protection method by which staff could apply a repurposed silicone border dressing beneath an N95 mask was largely effective and aided by the creation of the enabler.


title: Clinical Features, Epidemiology, and Climatic Impact of Genotype-specific Human Metapneumovirus Infections: Long-term Surveillance of Hospitalized Patients in South Korea

text: BACKGROUND: Human metapneumovirus (hMPV) commonly causes upper and lower respiratory tract infections. Here, we performed long-term retrospective surveillance of hMPV infection among patients hospitalized in South Korea between 2007 and 2016 and investigated seasonal dynamics and clinical characteristics associated with each virus subtype/genotype. METHODS: Patient specimens were tested for hMPV and other respiratory viruses by commercial molecular assays. Medical records of hMPV-positive patients were reviewed, and hMPV subtype/genotype analysis was performed. We also collected meteorological data and analyzed relationships with hMPV activity. RESULTS: Of 23 694 specimens, 1275 (5.4%) were positive; among them, 94.0% were classified into 5 subtypes (A1, A2a, A2b, B1, and B2). Some clinical manifestations differed according to hMPV genotype; however, there was no correlation between hMPV subtype and clinical outcome. Viral activity peaked at 13–20 weeks (April and May) and was associated with climate-specific factors, including temperature, relative humidity, diurnal temperature variation, wind speed, and sunshine duration. CONCLUSIONS: This large-scale, 10-year study provides valuable information about the clinical characteristics associated with hMPV subtypes and climate factors contributing to virus transmission.


title: Pathophysiology and aetiology of hypoglycaemic crises

text: Hypoglycaemia is a common, life‐threatening complication that occurs as a component of a wide variety of disease processes. Despite its frequent occurrence, information concerning the aetiology, characteristics and outcomes of hypoglycaemic crises in veterinary medicine is limited. This review summarises the current understanding of the pathophysiology of hypoglycaemia, the body's counter‐regulatory response, underlying aetiologies, diagnosis and treatment. Disease mechanisms are discussed and published evidence in veterinary literature regarding prognostic indicators, prevalence, diagnosis and treatment is examined for hypoglycaemia‐related disease processes including insulinoma, glucose‐lowering toxins and medications.


title: Molecular targets for the rational design of drugs to inhibit SARS coronavirus

text: Despite years of research, the precise determinants of coronavirus replication and pathogenesis remain unidentified. What is known of the pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV) is limited, but clinical observations suggest that both viral-induced cytotoxicity and host immune-mediated destruction contribute to the severity of disease. This summary discusses recent advances in coronavirus research that will facilitate the identification of crucial molecular targets for the rational design of SARS therapeutics. Section Editor: Anne Moscona – Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, NY 10029, USA When the SARS coronavirus came dramatically to attention as a fatal and potentially pandemic respiratory disease, the scientific response was swift and effective. The etiological agent was identified, the genome was cloned and sequenced, and large strides have been made in understanding key points in the viral life cycle, including recent identification of a functional host cell receptor and solution of the three-dimensional structure of the viral attachment protein. Much of this progress was possible only because a foundation of basic coronavirus biology existed. The Denison laboratory has been at the forefront of the small group of investigators who have dissected the basic features of coronaviruses. Denison has discovered critical mechanisms in the life cycle of the coronaviruses and is a key figure in the effective and urgent application of this knowledge to SARS.


title: CHAPTER 13 FERRETS

text: Publisher Summary This chapter familiarizes veterinarians with basic knowledge of ferret biology, medicine, surgery, and care. Ferrets have a long, slender body with short muscular legs, a long thin tail, small eyes, and short ears. The life span of the ferret is 5 to 8 years. Ferrets may be housed singly or in groups, inside or outside of a house. When kept outdoors, however, they must be protected from extreme weather. Ferrets have difficulty tolerating temperatures above 90°F or below 20°F, and appropriate precautions must be taken to prevent their exposure to these extremes. Ferrets are carnivorous and require a suitable diet. A diet that is high in good-quality animal protein and fat and low in complex carbohydrates and fiber is recommended. Ferrets are routinely immunized against canine distemper virus (CDV) and rabies virus. Ferrets are quite susceptible to CDV, and there is a 100% mortality rate in unvaccinated ferrets infected with CDV. When a new ferret is brought into the household, a quarantine period is recommended before introducing it to other animals, particularly other ferrets. The purpose of the quarantine period is to identify and prevent transmission of infectious disease potentially carried by the new ferret. The duration of this period allows for the development of any clinical signs in a seemingly healthy ferret following entrance into the new household.


Infarto renal en paciente con infección activa por COVID -19


title: One-Shot Recognition of Manufacturing Defects in Steel Surfaces

text: Abstract Quality control is an essential process in manufacturing to make the product defect-free as well as to meet customer needs. The automation of this process is important to maintain high quality along with the high manufacturing throughput. With recent developments in deep learning and computer vision technologies, it has become possible to detect various features from the images with near-human accuracy. However, many of these approaches are data intensive. Training and deployment of such a system on manufacturing floors may become expensive and time-consuming. The need for large amounts of training data is one of the limitations of the applicability of these approaches in real-world manufacturing systems. In this work, we propose the application of a Siamese convolutional neural network to do one-shot recognition for such a task. Our results demonstrate how one-shot learning can be used in quality control of steel by identification of defects on the steel surface. This method can significantly reduce the requirements of training data and can also be run in real-time.


title: The role of children in transmission of SARS-CoV-2: A rapid review

text: BACKGROUND: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. METHODS: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. RESULTS: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. CONCLUSIONS: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. NOTE: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.


title: Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience

text: The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods. The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results. Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions. Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations.


title: Cost-Effectiveness Analysis of Influenza A (H1N1) Chemoprophylaxis in Brazil

text: Background: Oseltamivir and zanamivir are recommended for treating and preventing influenza A (H1N1) worldwide. In Brazil, this official recommendation lacks an economic evaluation. Our objective was to assess the efficiency of influenza A chemoprophylaxis in the Brazilian context. Methods: We assessed the cost-effectiveness of oseltamivir and zanamivir for prophylaxis of influenza for high risk population, compared to no prophylaxis, in the perspective of Brazilian public health system. Quality-adjusted life years (QALY) and effectiveness data were based on literature review and costs in Brazilian real (BRL) were estimated from official sources and micro-costing of 2016’s H1N1 admissions at a university hospital. We used a decision-tree model considering prophylaxis and no prophylaxis and the probabilities of H1N1, ambulatory care, admission to hospital, intensive care, patient discharge, and death. Adherence and adverse events from prophylaxis were included. Incremental cost-effectiveness ratio was converted to 2016 United States dollar (USD). Uncertainty was assessed with univariated and probabilistic sensitivity analysis. Results: Adherence to prophylaxis was 0.70 [95% confidence interval (CI) 0.54; 0.83]; adverse events, 0.09 (95% CI 0.02; 0.18); relative risk of H1N1 infection in chemoprophylaxis, 0.43 (95% CI 0.33; 0.57); incidence of H1N1, 0.14 (95% CI 0.11; 0.16); ambulatory care, 0.67 (95% CI 0.58; 0.75); hospital admission, 0.43 (CI 95% 0.39; 0.42); hospital mortality, 0.14 (CI 95% 0.12; 0.15); intensive care unit admission, 0.23 (95% CI 0.20; 0.27); and intensive care mortality, 0.40 (95% CI 0.29; 0.52). QALY in H1N1 state was 0.50 (95% CI 0.46; 0.53); in H1N1 inpatients, 0.23 (95% CI 0.18; 0.28); healthy, 0.885 (95% CI 0.879; 0.891); death, 0. Adverse events estimated to affect QALY in –0.185 (95% CI –0.290; –0.050). Cost for chemoprophylaxis was BRL 39.42 [standard deviation (SD) 17.94]; ambulatory care, BRL 12.47 (SD 5.21); hospital admission, BRL 5,727.59 (SD 7,758.28); intensive care admission, BRL 19,217.25 (SD 7,917.33); and adverse events, BRL 292.05 (SD 724.95). Incremental cost-effectiveness ratio was BRL –4,080.63 (USD –1,263.74)/QALY and –982.39 (USD –304.24)/H1N1 prevented. Results were robust to sensitivity analysis. Conclusion: Chemoprophylaxis of influenza A (H1N1) is cost-saving in Brazilian health system context.


title: The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents

text: Abstract Objective To evaluate the anti-mycobacterial activity of Melia azedarach L. (M. azedarach) and Lobelia chinensis Lour. (L. chinensis) extracts against the growth of Mycobacterium tuberculosis (M. tuberculosis). Methods The anti-M. tuberculosis activity of M. azedarach and L. chinensis extracts were evaluated using different indicator methods such as resazurin microtiter assay (REMA) and mycobacteria growth indicator tube (MGIT) 960 system assay. The M. tuberculosis was incubated with various concentrations (50–800 μg/mL) of the extracts for 5 days in the REMA, and for 4 weeks in MGIT 960 system assay. Results M. azedarach and L. chinensis extracts showed their anti-M. tuberculosis activity by strongly inhibiting the growth of M. tuberculosis in a concentration-dependent manner in the REMA and the MGIT 960 system assay. Particularly, the methanol extract of M. azedarach and n-hexane extract of L. chinensis consistently exhibited their effects by effectively inhibiting the growth of M. tuberculosis in MGIT 960 system for 4 weeks with a single-treatment, indicating higher anti-M. tuberculosis activity than other extracts, and their minimum inhibitory concentrations were measured as 400 μg/mL and 800 μg/mL, respectively. Conclusions These results demonstrate that M. azedarach and L. chinensis extracts not only have unique anti-M. tuberculosis activity, but also induce the selective anti-M. tuberculosis effects by consistently inhibiting or blocking the growth of M. tuberculosis through a new pharmacological action. Therefore, this study suggests the potential of them as effective candidate agents of next-generation for developing a new anti-tuberculosis drug, as well as the advantage for utilizing traditional medicinal plants as one of effective strategies against tuberculosis.


Derailment as a Risk Factor for Greater Mental Health Issues following Pandemic


Acute hypothermia in Covid 19: A case report


Teaching in the time of COVID‐19


Middle East respiratory syndrome (MERS) coronavirus: Putting one health principles into practice?


title: Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice

text: It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2–11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.


title: Novel Wastewater Surveillance Strategy for Early Detection of COVID – 19 Hotspots

text: The novel coronavirus disease 2019 (COVID -19), a pandemic of global concern, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has severely revealed the need for public monitoring and efficient screening techniques. In spite of the various advancements made in the medical and research field, containment of this virus has proven to be difficult on several levels. As such, it is a necessary requirement to identify possible hotspots in the early stages of any disease. Based on previous studies carried out on coronaviruses, there is a high likelihood that SARS-CoV-2 may also survive in wastewater. Hence, we propose the use of nanofiber filters as a wastewater pre-treatment routine and up-gradation of existing wastewater evaluation and treatment system, to serve as a beneficial surveillance tool.


title: COVID-19 impact on early career investigators: a call for action

text: The COVID-19 pandemic has broadly impacted biomedical research and health care. Here we discuss current challenges for the cancer research community as they apply to early career investigators (ECIs). We propose a series of collaborative initiatives aimed to sustain ECIs and preserve and accelerate the ability to innovate with long-lasting impact.


title: Chapter 6 Design and Creativity in Synthesis of Multivalent Neoglycoconjugates

text: Abstract From the authors' opinion, this chapter constitutes a modest extension of the seminal and inspiring contribution of Stowell and Lee on neoglycoconjugates published in this series [C. P. Stowell and Y. C. Lee, Adv. Carbohydr. Chem. Biochem., 37 (1980) 225–281]. The outstanding progresses achieved since then in the field of the “glycoside cluster effect” has witnessed considerable creativity in the design and synthetic strategies toward a vast array of novel carbohydrate structures and reflects the dynamic activity in the field even since the recent chapter by the Nicotra group in this series [F. Nicotra, L. Cipolla, F. Peri, B. La Ferla, and C. Radaelli, Adv. Carbohydr. Chem. Biochem., 61 (2007) 353–398]. Beyond the more classical neoglycoproteins and glycopolymers (not covered in this work) a wide range of unprecedented and often artistically beautiful multivalent and monodisperse nanostructures, termed glycodendrimers for the first time in 1993, has been created. This chapter briefly surveys the concept of multivalency involved in carbohydrate–protein interactions. The topic is also discussed in regard to recent steps undertaken in glycobiology toward identification of lead candidates using microarrays and modern analytical tools. A systematic description of glycocluster and glycodendrimer synthesis follows, starting from the simplest architectures and ending in the most complex ones. Presentation of multivalent glycostructures of intermediate size and comprising, calix[n]arene, porphyrin, cyclodextrin, peptide, and carbohydrate scaffolds, has also been intercalated to better appreciate the growing synthetic complexity involved. A subsection describing novel all-carbon-based glycoconjugates such as fullerenes and carbon nanotubes is inserted, followed by a promising strategy involving dendrons self-assembling around metal chelates. The chapter then ends with those glycodendrimers that have been prepared using commercially available dendrimers possessing varied functionalities, or systematically synthesized using either divergent or convergent strategies.


title: (Un)Covering the COVID-19 Pandemic: Framing Analysis of the Crisis in Canada

text: The current COVID-19 crisis is unprecedented in recent history. On April 1, 2020, the Secretary-General of the United Nations, Antonio Guterres, warned that the world was facing the most challenging crisis since World War II (Associated Press, 2020). With the pandemic taking on an unprecedented magnitude in the twenty-first century, it quickly monopolized media attention. As of early April, Radar+'s large dataset showed that about 65 per cent of headlines on major Canadian media websites were related to the COVID-19 pandemic.


title: Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia

text: Many respiratory viruses cocirculate in the population and multiple infections are commonly reported. The clinical impact of coinfection is unclear and may vary depending on the viral couples involved. Using three-dimensional reconstituted human airway epithelia and clinical viral strains, we investigated the interaction between influenza virus (Flu), respiratory syncytial virus (RSV) and rhinovirus (RV). We showed that Flu and RSV interfere with RV replication, whereas RV does not interfere with either of these viruses. We then experimentally demonstrated that, when present, the interference is not related to a block of viral entry but rather to type I and type III interferon (IFN), the front-line antiviral defense of the respiratory mucosa. Consistent with this observation, we highlighted the differential sensitivity of each virus to IFNs, with RV being the only virus significantly inhibited by IFN-λ and the most sensitive to IFN-α. Finally, as type III IFN is of therapeutic interest due to its low proinflammatory profile, we also assessed and confirmed an inhibitory effect of IFN-λ in the context of persistent RV infections. The present work provides mechanistic clues concerning innate immunity involvement during respiratory virus interactions and confirms that IFN-λ is a promising candidate in the treatment of RV infections.


Comment on “Minimally Invasive Surgery and the Novel Coronavirus Outbreak: Lessons Learned in China and Italy”


title: Potent Inhibition of Junín Virus Infection by Interferon in Murine Cells

text: The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.


title: SARS-CoV-2: Repurposed Drugs and Novel Therapeutic Approaches-Insights into Chemical Structure-Biological Activity and Toxicological Screening

text: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic represents the primary public health concern nowadays, and great efforts are made worldwide for efficient management of this crisis Considerable scientific progress was recorded regarding SARS-CoV-2 infection in terms of genomic structure, diagnostic tools, viral transmission, mechanism of viral infection, symptomatology, clinical impact, and complications, but these data evolve constantly Up to date, neither an effective vaccine nor SARS-CoV-2 specific antiviral agents have been approved, but significant advances were enlisted in this direction by investigating repurposed approved drugs (ongoing clinical trials) or developing innovative antiviral drugs (preclinical and clinical studies) This review presents a thorough analysis of repurposed drug admitted for compassionate use from a chemical structure-biological activity perspective highlighting the ADME (absorption, distribution, metabolism, and excretion) properties and the toxicophore groups linked to potential adverse effects A detailed pharmacological description of the novel potential anti-COVID-19 therapeutics was also included In addition, a comprehensible overview of SARS-CoV-2 infection in terms of general description and structure, mechanism of viral infection, and clinical impact was portrayed


title: Does subsidy work? Price elasticity of demand for influenza vaccination among the elderly in Japan

text: Abstract Objectives Subsidy for influenza vaccination is often provided to the elderly in order to encourage them to receive a flu shot in developed countries. However, its effect on uptake rate, i.e., price elasticity of demand, has not been well studied. Methods Japan's decentralised vaccination programme allows observation of various pairs in price and uptake rate of flu shots among the elderly by the municipality from 2001/2002 to 2004/2005 season. We combine our sample survey data (n =281), which monitor price, subsidy and uptake rate, with published data on local characteristics in order to estimate price elasticity of demand with panel model. Results We find price elasticity of demand for influenza vaccine: nearly zero in nationwide, nearly zero in urban area, and −1.07 in rural area. Conclusions The results question the rationale for subsidy, especially in urban area. There are cases where maintaining or increasing the level of subsidy is not an efficient allocation of finite health care resources. When organising a vaccination programme, health manager should be careful about the balance between subsidy and other efforts in order to encourage the elderly to receive shots with price elasticity in mind.


title: miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

text: Abstract MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment.


Del empirismo a la evidencia científica en el tratamiento con antivíricos en los casos graves de infección por Coronavirus en tiempos de epidemia


SEVERE IBD FLARES AND COVID-19: EXPAND THE GASTROENTEROLOGY-SURGERY TEAM TO INCLUDE AN INFECTIOUS DISEASE SPECIALIST