title: Telehealth Utilization in Response to the Novel Coronavirus (COVID-19) Pandemic in Orthopaedic Surgery

text: INTRODUCTION: The purpose of this investigation is to assess the current utilization of telehealth capabilities at academic orthopaedic departments in the United States and to determine how practice patterns have been directly influenced by the coronavirus disease 19 (COVID-19) pandemic. METHODS: Orthopaedic surgery programs participating in the Electronic Residency Application Service were identified. One hundred seventy-five (175) programs were presented with a seven-item questionnaire addressing whether each program is using telehealth services in response to the COVID-19 pandemic. RESULTS: Of the 175 Electronic Residency Application Service participant orthopaedic programs, 168 responded for a total response rate of 96%. Of the 106 institutions using telehealth services, 88 (83%) cited the COVID-19 pandemic as the impetus for implementation of telehealth services. Institutions located in the Northeast and South regions were markedly more likely to offer telehealth services. Heat map analysis demonstrates an associative overlap of regional “hot spots” with direct comparison of COVID-19 cases in the United States and orthopaedic departments providing telehealth services. DISCUSSION: This study demonstrates the impressive measures academic orthopaedic institutions are taking to meet the needs of our patients by identifying a notable increase in new telehealth offerings throughout the United States with a positive correlation with COVID-19 disease burden.


title: Chapter 8 Quasispecies dynamics in disease prevention and control

text: Abstract Medical interventions to prevent and treat viral disease constitute evolutionary forces that may modify the genetic composition of viral populations that replicate in an infected host and influence the genomic composition of those viruses that are transmitted and progress at the epidemiological level. Given the adaptive potential of viruses in general and the RNA viruses in particular, the selection of viral mutants that display some degree of resistance to inhibitors or vaccines is a tangible challenge. Mutant selection may jeopardize control of the viral disease. Strategies intended to minimize vaccination and treatment failures are proposed and justified based on fundamental features of viral dynamics explained in the preceding chapters. The recommended use of complex, multiepitopic vaccines, and combination therapies as early as possible after initiation of infection falls under the general concept that complexity cannot be combated with simplicity. It also follows that sociopolitical action to interrupt virus replication and spread as soon as possible is as important as scientifically sound treatment designs to control viral disease on a global scale.


title: Rates of Microbiologically Diagnosed Infection and Pathogen Detection in Hematopoietic Stem Cell Transplant Patients

text: Infections remain a significant cause of mortality in hematopoietic stem cell transplant patients. Evaluations of causes of infection are often unrevealing, and at some sites, increasing rates of antimicrobial resistance have been noticed. We performed a retrospective analysis of infection rates and microbiologic testing yield, or percent of tests ordered to diagnose an infection, in the first 100 days of 30 allogeneic and 56 autologous stem cell transplants performed at San Antonio Military Medical Center from July 2011 to April 2014. Blood stream infections were diagnosed in 11.6% with a yield of 6%. Urinary tract infections were diagnosed in 2.3% with a yield of 3%. Clostridium difficile infections were diagnosed in 9.3% and testing yield was 6%. Incidence of respiratory viruses was 5.8% with 4 rhinoviruses/enteroviruses and 1 influenza virus identified. One Proteus mirabilis urinary isolate was an extended spectrum beta-lactamase producer. Five patients, 13% of allogeneic and 4% of autologous patients, died within the first 100 days post-transplantation. History of bacteremia was present in 60% of patients who died; however, only one died due to a microbiologically diagnosed infection. Improved diagnostic tests and methods are needed to increase yield of detection of infection in hematopoietic stem cell transplant patients.


title: House Building Industries Asia Pacific

text: Abstract The house-building industry has three main functional sectors: residential land development, housing production, and house marketing and sales. It also has close links with hundreds of upstream and downstream industries in an economy. While the house-building industries in North America and Western Europe are relatively mature, those found in many parts of the Asia-Pacific region are still under development. Despite their short average history, the house-building industries in the region are growing fast and have been the engines for economic development in the region. This overview of the house-building industries in Japan, South Korea, Singapore, China, Thailand, and Malaysia focuses on important differences in the maturity and pace of development across jurisdictions. Fast economic growth in the less developed countries has offered opportunities for intensive development in the industry. Yet, issues like quality assurance and environmental sustainability have posed challenges to the house-building sector in the region.


Per‐ and Polyfluoroalkyl Substances, Microplastics, and COVID‐19: Will We Ever Learn?


title: Novel Orthoreovirus from Mink, China, 2011

text: We identified a novel mink orthoreovirus, MRV1HB-A, which seems to be closely related to human strain MRV2tou05, which was isolated from 2 children with acute necrotizing encephalopathy in 2005. Evolution of this virus should be closely monitored so that prevention and control measures can be taken should it become more virulent.


title: Clinical review: A systematic review of corticosteroid use in infections

text: Traditional teaching suggests that corticosteroids should be avoided during acute infectious episodes for fear of compromising the immune response. However, the outcome benefit shown through steroid administration in early septic shock implies this paranoia may be misplaced. We therefore performed a systematic review of the literature to identify the current strength of evidence for the use of corticosteroids in specified infections, and to make appropriate graded recommendations.


title: Interactions between the innate immune and blood coagulation systems

text: Blood coagulation and inflammation are universal responses to infection and there is crosstalk between inflammation and coagulation that can either amplify or dampen the responses. Loss of appropriate interactions between these systems probably contributes to morbidity and mortality in infectious diseases. For instance, inflammatory cytokines and leukocyte elastase can downregulate natural anticoagulant proteins that help to maintain endothelial-cell integrity, control clotting, inhibit vasoactive peptides and dampen leukocyte infiltration into the vessel wall. This Review will summarize our current understanding of the mechanisms involved in the crosstalk between these two important systems.


title: Are Online Searches for the Novel Coronavirus (COVID-19) Related to Media or Epidemiology? A Cross-sectional Study

text: Abstract Background Previous studies on the novel Coronavirus (COVID-19) have found strong correlations between online searches and the epidemiology of the disease. Aim Our aim was to determine if online searches for COVID-19 related to international media announcements or national epidemiology. Methods Searches for “coronavirus” were made on Google Trends from December 31, 2019 to April 13, 2020 for 40 European countries. The online COVID-19 searches for all countries were correlated with each other. COVID-10 epidemiology (i.e. incidence and mortality) was correlated with the national online searches. Major announcements by the World Health Organization (WHO) were taken into consideration with peaks in online searches. Correlations were made using Spearman's rank correlation coefficient. Results Overall, the online searches for COVID-19 were not correlated with the actual incidence and mortality of COVID-19. The mean Spearman correlation for incidence was 0.20 (range -0.66 to 0.76) and for mortality was 0.35 (range -0.75 to 0.85). Online searches in Europe were all strongly synchronized with each other; a mean Spearman correlation of 0.93 (range 0.62 to 0.99). Conclusions Online searches for COVID-19 in Europe are not correlated with epidemiology but strongly correlated with international WHO announcements. Our study challenges previous Google Trends studies and emphasizes the role of the WHO in raising awareness of a new disease.


title: Telemedicine for ENT: effect on quality of care during Covid-19 pandemic

text: Abstract Aims To assess the benefit of telemedicine consultation during the Covid-19 pandemic. Material and Methods A prospective study of patient satisfaction with telemedicine consultation was carried out in the ENT department of a university hospital center where telemedicine consultations were set up to replace scheduled out-patient consultations. Patients were divided into two groups according to overall satisfaction, in order to identify predictive factors. The significance threshold was set at p<0.005. The main endpoint was patient satisfaction after an ENT telemedicine consultation during global lockdown. The secondary endpoint comprised predictive factors for overall satisfaction. Results One hundred of the 125 patients with telemedicine consultation over a 7-day inclusion period completed the questionnaire. Overall satisfaction was 87%. There were no clinically relevant predictive factors significantly associated with satisfaction. Sound and video quality was satisfactory for 76% and 61% of patients respectively, without significant impact on overall satisfaction (respectively: OR = 3.40, p-value = 0.049; and OR = 3.79, p-value = 0.049). Lack of physical examination did not significantly correlate with reduced overall satisfaction (OR = 0.30, p-value = 0.027). Conclusion Telemedicine consultation did not allow complete medical care but, in a difficult time like the global pandemic, was well accepted by patients. It is a simple way to maintain continuity of care while reducing contamination risk by avoiding direct contact between patients and healthcare professionals.


title: Mannose‐binding lectin in innate immunity: past, present and future

text: The human collectin, mannose‐binding lectin (MBL), is an important protein of the humoral innate immune system. With multiple carbohydrate‐recognition domains, it is able to bind to sugar groups displayed on the surfaces of a wide range of microorganisms and thereby provide first‐line defence. Importantly, it also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex. Three single point mutations in exon 1 of the expressed human MBL‐2 gene appear to impair the generation of functional oligomers. Such deficiencies of functional protein are common in certain populations, e.g. in sub‐Saharan Africa, but virtually absent in others, e.g. indigenous Australians. MBL disease association studies have been a fruitful area of research and implicate a role for MBL in infective, inflammatory and autoimmune disease processes. Overall, there appears to be a genetic balance in which individuals generally benefit from high levels of the protein. However, in certain situations, reduced levels of circulating MBL may be beneficial to the host and this may explain the persistence of the deleterious gene polymorphisms in many population groups.


title: A Prospective Hospital-Based Study of the Clinical Impact of Non–Severe Acute Respiratory Syndrome (Non-SARS)–Related Human Coronavirus Infection

text: Background. In addition to the human coronaviruses (HCoVs) OC43 and 229E, which have been known for decades to cause infection in humans, 2 new members of this genus have recently been identified: HCoVs NL63 and HKU1. Their impact as a cause of respiratory tract disease in adults at risk for complications needs to be established. Methods. We prospectively assessed the clinical impact of coronavirus infection (excluding cases of severe acute respiratory syndrome) among hospitalized adults. All patients with respiratory disease for whom bronchoalveolar lavage was performed were screened by reverse-transcriptase polymerase chain reaction for the presence of all 4 HCoVs. Results. HCoV was identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279 subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4 isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were negative for bacteria, and 2 persons were coinfected with other respiratory viruses. Transplantation was the most common underlying condition. Of the 29 patients who had HCoV identified in their bronchoalveolar lavage fluid specimens, 9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior respiratory infection, and 18 (62%) had a new infiltrate that was visible on chest radiograph. The most frequent final diagnosis was a lower respiratory tract infection. Conclusions. The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most cases.


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title: Response to the letter of L. Santacroce regarding article “Enhancing immunity in viral infections, with special emphasis on COVID-19: A review” (Jayawardena et al.)


title: COVID‐19 in a patient with HIV infection

text: The worldwide pandemic of the novel coronavirus disease 2019 (COVID-19) has raised many challenges and uncertainties regarding disease management and prognosis in immunocompromised patient populations. The concurrence of human immunodeficiency virus (HIV) infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, presents an intriguing problem and only a handful of these cases exist in the literature, despite 37.9 million people living with HIV throughout the world. Previous reports suggest the possibility of a protective factor from standard antiretroviral treatment for HIV patients that could have significant clinical benefits for these patients when co-infected with SARS-CoV-2. HIV patients also generally present with atypical clinical presentation and have a less severe form of COVID-19 than the general population. Here, we present the first case of an HIV positive patient who was diagnosed with COVID-19 in the United States. This article is protected by copyright. All rights reserved.


COVID-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome


title: Le confinement: Points de vue d’étudiants masseurs-kinésithérapeutes de première année au travers de références bibliographiques choisies

text: Résumé Après le début du confinement, nous avons sollicité les étudiants de première année de masso-kinésithérapie pour qu’ils sélectionnent un article scientifique ou de presse abordant les conséquences de celui-ci, en justifiant leur choix et exposant les liens effectués avec les sciences humaines et sociales. Les étudiants nous ont envoyé des travaux pertinents et riches pouvant constituer une archéologie du confinement par les thématiques sociologiques, psychologiques, pédagogiques et philosophiques traitées. Ces travaux témoignent de la capacité des étudiants à l’analyse des conséquences d’une situation pandémique exceptionnelle et de leurs capacités réflexives. Abstract After the beginning of the confinement, we asked first year students of physiotherapy to select a scientific or press article dealing with the consequences of it, justifying their choice and explaining the links made with the human and social sciences. The students sent back relevant and rich work that could constitute an archaeology of confinement by the sociological, psychological, educational and philosophical themes treated. These works testify to the students' ability to analyze the consequences of an exceptional pandemic situation and their reflexive capacities.


The resilience of Taiwan's health system to address the COVID-19 pandemic


title: Sudden cardiac death in COVID-19 patients, a report of three cases

text: The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1–6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.


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title: Proteomic Profiling in Biracial Cohorts Implicates DC-SIGN as a Mediator of Genetic Risk in COVID-19

text: COVID-19 is one of the most consequential pandemics in the last century, yet the biological mechanisms that confer disease risk are incompletely understood. Further, heterogeneity in disease outcomes is influenced by race, though the relative contributions of structural/social and genetic factors remain unclear. Very recent unpublished work has identified two genetic risk loci that confer greater risk for respiratory failure in COVID-19: the ABO locus and the 3p21.31 locus. To understand how these loci might confer risk and whether this differs by race, we utilized proteomic profiling and genetic information from three cohorts including black and white participants to identify proteins influenced by these loci. We observed that variants in the ABO locus are associated with levels of CD209/DC-SIGN, a known binding protein for SARS-CoV and other viruses, as well as multiple inflammatory and thrombotic proteins, while the 3p21.31 locus is associated with levels of CXCL16, a known inflammatory chemokine. Thus, integration of genetic information and proteomic profiling in biracial cohorts highlights putative mechanisms for genetic risk in COVID-19 disease.


The SARS Coronavirus: Rapid Diagnostics in the Limelight


SARS: epidemiología y mecanismos de transmisión


title: A 25-Year-Old Sample Contributes the Complete Genome Sequence of Avian Coronavirus Vaccine Strain ArkDPI, Reisolated from Commercial Broilers in the United States

text: Here, we report the complete genome sequence of Avian coronavirus strain ArkDPI of the GI-9 lineage, isolated from broiler chickens in North Georgia in 1994. This is the complete genome sequence of this vaccine strain, reisolated from broilers in the United States.


title: Trump’s “America first” energy policy, contingency and the reconfiguration of the global energy order

text: The global energy system is in transition to a new energy order characterized by the emergence of the United States as a net oil exporter, the shale revolution and the gradual shift towards low-carbon sources and renewables. The shale boom in the US was a game changer, as was the election of Donald Trump as US president. Trump pushed an ambitious “America first” agenda aimed at transforming the US into a global energy superpower. The purpose of this article is two-fold: first, it outlines the key pillars of the emerging global energy order. Second, it underscores the role of contingent events, a factor neglected by some previous studies because of their reliance on what A.O.Hirschman (1970) termed “paradigmatic thinking”. The recent transition in the international energy order is an outcome of two paramount, yet largely unanticipated events: the shale revolution in the US and Trump’s neomercantilist and unilateralist economic policies. While contingencies are an inherent feature of social reality, the scenario approach can be a useful heuristic for dealing with uncertainties. The article concludes by discussing the implications of these developments for global energy governance.


title: Azithromycin and SARS-CoV-2 infection: where we are now and where we are going

text: • Due to its mechanism of action and various anti-inflammatory effects, azithromycin is a promising medicine for the treatment of the coronavirus COVID-19. • The studies that have been done so far on the use of azithromycin in the management of the COVID-19 coronavirus have had various methodological limitations. At the moment, no conclusions can be drawn about the efficacy of this drug as an adjunct to hydroxychloroquine. • Azithromycin has serious cardiac adverse effects such as QT prolongation. Hydroxychloroquine also has them. The combination of these two drugs should be determined with caution. • At the moment 21 clinical trials are being carried out on the use of azithromycin in COVID-19.


title: Drug Development and Medicinal Chemistry Efforts toward SARS‐Coronavirus and Covid‐19 Therapeutics

text: The COVID‐19 pandemic caused by SARS‐CoV‐2 infection is spreading at an alarming rate and has created an unprecedented health emergency around the globe. There is no effective vaccine or approved drug treatment against COVID‐19 and other pathogenic coronaviruses. The development of antiviral agents is an urgent priority. Biochemical events critical to the coronavirus replication cycle provided a number of attractive targets for drug development. These include, spike protein for binding to host cell‐surface receptors, proteolytic enzymes that are essential for processing polyproteins into mature viruses, and RNA‐dependent RNA polymerase for RNA replication. There has been a lot of ground work for drug discovery and development against these targets. Also, high‐throughput screening efforts have led to the identification of diverse lead structures, including natural product‐derived molecules. This review highlights past and present drug discovery and medicinal‐chemistry approaches against SARS‐CoV, MERS‐CoV and COVID‐19 targets. The review hopes to stimulate further research and will be a useful guide to the development of effective therapies against COVID‐19 and other pathogenic coronaviruses.


title: Novel insights into proteolytic cleavage of influenza virus hemagglutinin

text: The influenza virus hemagglutinin (HA) mediates the first essential step in the viral life cycle, virus entry into target cells. Influenza virus HA is synthesised as a precursor protein in infected cells and requires cleavage by host cell proteases to transit into an active form. Cleavage is essential for influenza virus infectivity and the HA‐processing proteases are attractive targets for therapeutic intervention. It is well established that cleavage by ubiquitously expressed subtilisin‐like proteases is a hallmark of highly pathogenic avian influenza viruses (HPAIV). In contrast, the nature of the proteases responsible for cleavage of HA of human influenza viruses and low pathogenic avian influenza viruses (LPAIV) is not well understood. Recent studies suggest that cleavage of HA of human influenza viruses might be a cell‐associated event and might be facilitated by the type II transmembrane serine proteases (TTSPs) TMPRSS2, TMPRSS4 and human airway trypsin‐like protease (HAT). Here, we will introduce the different concepts established for proteolytic activation of influenza virus HA, with a particular focus on the role of TTSPs, and we will discuss their implications for viral tropism, pathogenicity and antiviral intervention. Copyright © 2010 John Wiley & Sons, Ltd.


title: The Impact of COVID-19 Epidemic Declaration on Psychological Consequences: A Study on Active Weibo Users

text: COVID-19 (Corona Virus Disease 2019) has significantly resulted in a large number of psychological consequences. The aim of this study is to explore the impacts of COVID-19 on people’s mental health, to assist policy makers to develop actionable policies, and help clinical practitioners (e.g., social workers, psychiatrists, and psychologists) provide timely services to affected populations. We sample and analyze the Weibo posts from 17,865 active Weibo users using the approach of Online Ecological Recognition (OER) based on several machine-learning predictive models. We calculated word frequency, scores of emotional indicators (e.g., anxiety, depression, indignation, and Oxford happiness) and cognitive indicators (e.g., social risk judgment and life satisfaction) from the collected data. The sentiment analysis and the paired sample t-test were performed to examine the differences in the same group before and after the declaration of COVID-19 on 20 January, 2020. The results showed that negative emotions (e.g., anxiety, depression and indignation) and sensitivity to social risks increased, while the scores of positive emotions (e.g., Oxford happiness) and life satisfaction decreased. People were concerned more about their health and family, while less about leisure and friends. The results contribute to the knowledge gaps of short-term individual changes in psychological conditions after the outbreak. It may provide references for policy makers to plan and fight against COVID-19 effectively by improving stability of popular feelings and urgently prepare clinical practitioners to deliver corresponding therapy foundations for the risk groups and affected people.


title: A Sensitive DNA Capacitive Biosensor Using Interdigitated Electrodes

text: This paper presents a label-free affinity-based capacitive biosensor using interdigitated electrodes. Using an optimized process of DNA probe preparation to minimize the effect of contaminants in commercial thiolated DNA probe, the electrode surface was functionalized with the 24-nucleotide DNA probes based on the West Nile virus sequence (Kunjin strain). The biosensor has the ability to detect complementary DNA fragments with a detection limit down to 20 DNA target molecules (1.5 aM range), making it suitable for a practical point-of-care (POC) platform for low target count clinical applications without the need for amplification. The reproducibility of the biosensor detection was improved with efficient covalent immobilization of purified single-stranded DNA probe oligomers on cleaned gold microelectrodes. In addition to the low detection limit, the biosensor showed a dynamic range of detection from 1 μL(−1) to 10(5) μL(−1) target molecules (20 to 2 million targets), making it suitable for sample analysis in a typical clinical application environment. The binding results presented in this paper were validated using fluorescent oligomers.


docid: mtgfjyww

title: A Simulation Study on Hypothetical Ebola Virus Transmission in India Using Spatiotemporal Epidemiological Modeler (STEM): A Way towards Precision Public Health

text: Background. Precision public health is a state-of-the-art concept in public health research and its application in health care. Application of information technology in field of epidemiology paves the way to its transformation to digital epidemiology. A geospatial epidemiological model was simulated to estimate the spread of Ebola virus disease after a hypothetical outbreak in India. Methods. It was a simulation study based on SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. Simulation was done in Spatiotemporal Epidemiological Modeler (STEM). Epidemiological profile of Ebola virus, that transmitted throughout the Sierra Leon in 2014–2016, was fitted into the SEIR deterministic compartment model designed for India. Result. Spatiotemporal distribution of EVD exposed, infectious, and recovered population at 4-month interval represented by different figures. It is estimated that if no intervention is taken to stop the spread, within 2 years, almost half of the country will be effected by EVD and cumulative number of exposed individuals, infectious persons, and deaths will be 106947760, 30651674, and 18391005, respectively. Conclusion. Precision public health may play the key role to achieve the health related targets in the Sustainable Development Goals. Policy makers, public health specialists, and data scientists need to put their hands together to make precision public health a reality.


title: Chapter One The Eukaryotic Translation Initiation Factor 4E (eIF4E) as a Therapeutic Target for Cancer

text: Abstract Cancer cells depend on cap-dependent translation more than normal tissue. This explains the emergence of proteins involved in the cap-dependent translation as targets for potential anticancer drugs. Cap-dependent translation starts when eIF4E binds to mRNA cap domain. This review will present eIF4E's structure and functions. It will also expose the use of eIF4E as a therapeutic target in cancer.


title: Enteroviral proteases: structure, host interactions and pathogenicity

text: Enteroviruses are common human pathogens, and infections are particularly frequent in children. Severe infections can lead to a variety of diseases, including poliomyelitis, aseptic meningitis, myocarditis and neonatal sepsis. Enterovirus infections have also been implicated in asthmatic exacerbations and type 1 diabetes. The large disease spectrum of the closely related enteroviruses may be partially, but not fully, explained by differences in tissue tropism. The molecular mechanisms by which enteroviruses cause disease are poorly understood, but there is increasing evidence that the two enteroviral proteases, 2A(pro) and 3C(pro), are important mediators of pathology. These proteases perform the post‐translational proteolytic processing of the viral polyprotein, but they also cleave several host‐cell proteins in order to promote the production of new virus particles, as well as to evade the cellular antiviral immune responses. Enterovirus‐associated processing of cellular proteins may also contribute to pathology, as elegantly demonstrated by the 2A(pro)‐mediated cleavage of dystrophin in cardiomyocytes contributing to Coxsackievirus‐induced cardiomyopathy. It is likely that improved tools to identify targets for these proteases will reveal additional host protein substrates that can be linked to specific enterovirus‐associated diseases. Here, we discuss the function of the enteroviral proteases in the virus replication cycle and review the current knowledge regarding how these proteases modulate the infected cell in order to favour virus replication, including ways to avoid detection by the immune system. We also highlight new possibilities for the identification of protease‐specific cellular targets and thereby a way to discover novel mechanisms contributing to disease. Copyright © 2016 John Wiley & Sons, Ltd.


title: The Infectious Diseases Physician in the Future of Healthcare: Not Only About Antibiotic Prescribing

text: The uncertainties of healthcare payment and delivery reform on income and care process have created a sense of foreboding, concern, and fear that a career in medicine is not what it used to be and that a career in infectious diseases in particular may no longer be viable. Fears have been raised that the need for infectious diseases consultation and management will be curtailed because we provide cognitive services that are not perceived as being needed in a health system filled with intensivists, hospitalists, and skilled nursing facility physicians. Now is the time for us to reframe our role in the health system that is evolving to a process of care focused on population health and patient safety that pays providers for value they bring to achieve those goals. Specific suggestions are made to enhance the infectious diseases physician's profile with the intent of encouraging debate, discussion, and action.


title: Production impact of influenza A(H1N1)pdm09 virus infection on fattening pigs in Norway

text: Newly emerged influenza A(H1N1)pdm09 virus infection in Norwegian pigs, although often observed in a subclinical form, can lower the pig's growth performance by reducing feed efficiency in terms of a poorer feed conversion ratio. Infected pigs would consume more feed and require protracted production time to reach market weight. In our observational longitudinal study, growth performance data from 728 control pigs and 193 infected pigs with known viral shedding time points were analyzed using mixed linear regression models to give estimates of the marginal effects of infection. Gaussian curves describing the variability of the estimates at the individual pig level formed the fundamental inputs to our stochastic models. The models were constructed to simulate the summed negative effects of the infection at the batch level of 150 fattening pigs growing from 33 to 100 kg. Other inputs of variability and uncertainty were 1) batch transmission points, 2) pig infection points to reflect the disease transmission dynamics of the virus, and 3) final prevalence of infected pigs in the batch. Monte Carlo random sampling gave 5,000 estimates on the outputs of the marginal effects for each pig. These results were summed up to provide estimates for a batch size of 150 pigs. This figure was adjusted by our final prevalence distribution function, which was also derived from the longitudinal study with 12 cohorts of infected pigs. For a 150-fattening-pig herd randomly selected from the population, the marginal effects of the infection were 1) 835 kg (fifth percentile) to 1,350 kg (95th percentile) increased feed intake and 2) 194 (fifth percentile) to 334 (95th percentile) pig days in excess of expected figures for an uninfected batch. A batch infected during growth phase 3 (81 to 100 kg BW) gave the worst results since the longitudinal study showed that a pig infected during growth phase 3 required more feed and a greater protracted production time compared to younger infected pigs. Sensitivity analysis showed that final prevalence had the greatest impact on the conditional mean and variation of the marginal effects of infections. Batch transmission point was the next most influential factor. Lowering the final prevalence and preventing older fattening pigs from being infected will have the greatest benefit in saving feed cost and reducing delay in getting the pigs to the market.


title: Financials

text: Our roundup of composites-related financial reports over the last two months.


title: Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

text: A novel coronavirus has been recently identified as the causative agent of the severe acute respiratory syndrome (SARS) outbreak that has accounted for more than 8000 infected people worldwide. This review will discuss current knowledge on coronavirus replication, pathogenesis, evolution, and vaccine strategies, as well as the most recent findings on SARS coronavirus.


title: Exploration of the mechanisms of Ge Gen Decoction against influenza A virus infection

text: Abstract Ge Gen Decoction (GGD), a Traditional Chinese Medicine prescription, is mainly used to treat infectious respiratory diseases and can relieve the symptoms of influenza A virus (IAV) infection. However, the underlying mechanism of GGD against IAV infection remains unclear. In this study, we found that GGD had moderate anti-IAV activity in vitro. GGD was more effective when given before the viral infection and targeted the viral attachment and replication stages rather than the internalization stage. In vivo, GGD treatment reduced thevirus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes in H1N1-infected mice. We observed the changes in several key immuno-related indexes in GGD administrated H1N1-infected mice with anti-IAV drug oseltamivir phosphate as the control. GGD treatment decreased the expression of TNF-α and improved Th1/Th2 immune balance to reduce the excessive immune response in H1N1-infected mice. Besides, the expression of the toll-like receptor 7 signaling pathway in H1N1-infected mice decreased after GGD treatment. Our results showed that GGD has anti-IAV activity and can modulate the immune system to relieve lung inflammation.


title: CRISPR/cas systems redefine nucleic acid detection: Principles and methods

text: Methods that enable rapid, sensitive and specific analyses of nucleic acid sequences have positive effects on precise disease diagnostics and effective clinical treatments by providing direct insight into clinically relevant genetic information. Thus far, many CRISPR/Cas systems have been repurposed for diagnostic functions and are revolutionizing the accessibility of robust diagnostic tools due to their high flexibility, sensitivity and specificity. As RNA-guided targeted recognition effectors, Cas9 variants have been utilized for a variety of diagnostic applications, including biosensing assays, imaging assays and target enrichment for next-generation sequencing (NGS), thereby enabling the development of flexible and cost-effective tests. In addition, the ensuing discovery of Cas proteins (Cas12 and Cas13) with collateral cleavage activities has facilitated the development of numerous diagnostic tools for rapid and portable detection, and these tools have great potential for point-of-care settings. However, representative reviews proposed on this topic are mainly confined to classical biosensing applications; thus, a comprehensive and systematic description of this fast-developing field is required. In this review, based on the detection principle, we provide a detailed classification and comprehensive discussion of recent works that harness these CRISPR-based diagnostic tools from a new perspective. Furthermore, current challenges and future perspectives of CRISPR-based diagnostics are outlined.


Comment on “Digital Mental Health and COVID-19: Using Technology Today to Accelerate the Curve on Access and Quality Tomorrow”: A UK Perspective


title: COVID-19-Pandemie: Belastungen des medizinischen Personals: Ein kurzer aktueller Review

text: Aim Review of studies on the psychological stress of healthcare workers caused by the COVID-19 pandemic. Methods A literature search of PubMed was performed using the terms “COVID-19”, “stress”, “mental health”, “healthcare worker”, “staff”, “psychiatry”. Quantitative studies (including letters to the editor) published from January to March 2020 were included. Results 14 studies on healthcare workers in departments of infectiology, internal medicine, and fever wards including intensive care wards as well as surgery and psychiatry, were included. The Patient Health Questionnaire 9 (PHQ9), Self-rating-Anxiety Scale (SAS) and Impact of Event Scale (IES-R) were the most often used test instruments. The sample size ranged between 37 and 1257 participants consisting of mostly nursing and medical personnel. The fraction of COVID-19-associated activities varied from 7.5 % to 100 %. An extensive strain was reported due to stress experience as well as depression and anxiety symptoms. Severe degrees of those symptoms were found in 2.2 % to 14.5 % of all participants. The severity of mental symptoms was influenced by age, gender, occupation, specialization, type of activities performed and proximity to COVID-19 patients. As mediator variables selection of personnel, preventive interventions, resilience, and social support were reported. Conclusion Considering the frequency of mental symptoms occurring in healthcare workers, accompanying mental health informed interventions to facilitate coping are necessary. Further research in this field is needed.


title: Stability of the spreading in small-world network with predictive controller

text: Abstract In this Letter, we apply the predictive control strategy to suppress the propagation of diseases or viruses in small-world network. The stability of small-world spreading model with predictive controller is investigated. The sufficient and necessary stability condition is given, which is closely related to the controller parameters and small-world rewiring probability p. Our simulations discover a phenomenon that, with the fixed predictive controller parameters, the spreading dynamics become more and more stable when p decreases from a larger value to a smaller one, and the suitable controller parameters can effectively suppress the spreading behaviors even when p varies within the whole spectrum, and the unsuitable controller parameters can lead to oscillation when p lies within a certain range.


title: Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis

text: BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.


title: Identification of Plant Virus IRES

text: Plant RNA viruses exploit nonorthodox strategies, such as the use of internal ribosomal entry sites (IRES), to express multiple genes from a single RNA species. IRES elements have been reported in tobacco etch virus (TEV), crucifer infecting tobamovirus (crTMV), hibiscus chlorotic ringspot virus (HCRSV), and many other animal and plant RNA viruses. In this chapter, the methodology used to identify and characterize a plant virus IRES element, including construction of a translation reporter vector for testing the IRES activity, testing the IRES activity in coupled in vitro transcription and translation systems and mammalian cells analysis of RNA stability, and sucrose gradient analysis and polysome profiling, is presented.


Descriptive Epidemiology, Clinical Characteristics and Outcomes for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infected Patients in AlAin – Abu Dhabi Emirate


title: What Could “Fair Allocation” during the Covid‐19 Crisis Possibly Mean in Sub‐Saharan Africa?

text: The Covid‐19 pandemic has sparked rapid and voluminous production of bioethics commentary in popular media and academic publications. Many of the discussions are new twists on an old theme: how to fairly allocate scarce medical resources, such as ventilators and intensive care unit beds. In this essay, we do not add another allocation scheme to the growing pile, partly out of appreciation that such schemes should be products of inclusive and transparent community engagement and partly out of recognition of their limited utility for physicians working in the field. Instead, we make the more modest claim that context matters when making such decisions and, more specifically, that recommendations from high‐income countries about fair allocation during Covid‐19 should not be cut and pasted into low‐income settings. We offer a few examples of why seemingly universal, well‐intentioned ethical recommendations could have adverse consequences if unreflectively applied in sub‐Saharan Africa.


COVID-19: Risk of increase in smoking rates among England’s 6 million smokers and relapse among England’s 11 million ex-smokers


title: Quarantine through History

text: Abstract This article reviews in a historical perspective and by means of documented examples the scientific principles relevant to the concept and effectiveness of quarantine, the logistic, economic, and political barriers to its correct implementation through time, and the health impact of local and large-scale quarantine. Quarantine is overall one of the oldest and most disseminated and, despite its limits, most effective health measures elaborated by mankind. The evidence-based history of medicine and evidence-based modern epidemiology indicate that the implementation of correct quarantine procedures is today still feasible and useful provided that a proactive collaboration is operative among those concerned and that the measures are tailored according to geographical, social, and health conditions.


title: Immune Heterogeneity in Neuroinflammation: Dendritic Cells in the Brain

text: Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC’s act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain’s response to neuroinflammatory disease with emphasis on how the brain’s microenvironment impacts these actions.


docid: plameyxb

title: Change in practice due to COVID-19 – Early experiences of a United Kingdom district general hospital in trauma & orthopaedics

text: COVID-19 is a significant worldwide challenge to many healthcare systems. In Trauma and Orthopaedics, there has been a significant change in the workload but departments have been compelled to change their practice in order to match the demand, as well as respond to the escalating situation of COVID. Some guidance is available on these changes from bodies such as the National Health Service (NHS), Public Health England and the British Orthopaedic Association (BOA). We have implemented certain changes in our university district general hospital trauma and orthopaedic department with regard to staff roles, outpatient and inpatient care and operative protocols. We aim to present some of these changes and their effects on patient care in an attempt to share these with colleagues who may face similar pressures and make some recommendations to help others prepare for a possible second wave of COVID-19.


Mapping trauma support onto the shifting landscape of seeking refuge in Sweden: insights from an ongoing programme of research on refugee minors’ mental health


title: Antipsychotic-Induced Immune Dysfunction: A Consideration for COVID-19 Risk

text: Patients with severe mental illness are more susceptible to infections for a variety of reasons, some associated with the underlying disease and some due to environmental factors including housing insecurity, smoking, poor access to healthcare, and medications used to treat these disorders. This increased susceptibility to respiratory infections may contribute to risk of COVID-19 infection in patients with severe mental illness or those in inpatient settings. Atypical antipsychotic (AA) medications are FDA approved to treat symptoms associated with schizophrenia, bipolar disorder, depression and irritability associated with autism. Our team and others have shown that AA may have anti-inflammatory properties that may contribute to their efficacy in the treatment of mental health disorders. Additionally, AA are widely prescribed off-label for diverse indications to non-psychotic patients including older adults, who are also at increased risk for COVID-19 complications and mortality. The aim of this study was to determine if AA medications such as risperidone (RIS) alter the ability to mount an appropriate response to an acute inflammatory or adaptive immune challenge using a preclinical model. Short-term treatment of healthy mice with a dose of RIS that achieves plasma concentrations within the low clinical range resulted in disrupted response to an inflammatory (LPS) challenge compared to vehicle controls. Furthermore, RIS also prevented treated animals from mounting an antibody response following vaccination with Pneumovax23®. These data indicate that short- to intermediate-term exposure to clinically relevant levels of RIS dysregulate innate and adaptive immune responses, which may affect susceptibility to respiratory infections, including COVID-19.


title: Protective effect of sildenafil on the genotoxicity and cytotoxicity in apolipoprotein E-deficient mice bone marrow cells

text: BACKGROUND: The pharmacological inhibitor of phosphodiesterase 5 (PDE5), sildenafil, is a promising candidate for antioxidant therapy that can result in cardiovascular protection. In addition to its known effects on the cardiovascular system, hypercholesterolemia leads to increased oxidative stress and DNA damage in the bone marrow, which is a non-classical target organ of atherosclerosis. In the present study, we evaluate oxidative stress and assess the effect of genomic instability on cell cycle kinetics in atherosclerotic animals and determine if sildenafil reverses these detrimental effects in bone marrow cells. METHODS: Experiments were performed in male wild-type (WT) and apolipoprotein E knockout mice (apoE(−/−)) (9 weeks of age). apoE(−/−) mice were randomly distributed into the following 2 groups: sildenafil-treated (40 mg/kg/day for 3 weeks, n = 8) and vehicle-treated (n = 8), by oral gavage. After treatment, bone marrow cells were isolated to assess the production of superoxide anions and hydrogen peroxide, determine cell cycle kinetics and evaluate the presence of micronucleated cells. RESULTS: Sildenafil treatment reduced the cytoplasmic levels of superoxide anion (~95 % decrease, p < 0.05) and decreased hydrogen peroxide (~30 % decrease, p < 0.05). Moreover, we observed protective effects on the DNA of bone marrow cells, including normal cell cycling, decreased DNA fragmentation and a diminished frequency of micronucleated cells. CONCLUSION: Our data reveal that the excessive production of ROS in atherosclerotic mice overcome the DNA repair pathways in bone marrow cells. The novelty of the present study is that the administration of sildenafil reduced ROS to baseline levels and, consequently, reverted the DNA damage and its outcomes in bone marrow cells.


COVID-19 Pandemie und Gastroenterologie: Update


title: 8 Composite nonwovens in filters: applications

text: Abstract: This chapter discusses the role of composite nonwoven filters in different structural forms such as combining mechanical support and durability with filtration, providing two or more layers of different filtration efficiency and combining different separation technologies/functionality into one filter medium. In many situations, composite nonwovens might fulfill multiple objectives. Applications of composite nonwovens are quite diverse and increasing in the area of air, liquid and engine filtration. The developmental objectives of composite filtering media are lower energy consumption, longer filter life, high filtration capacity, greater dust holding (in depth filtration) and easy cleanability (of surface filter), satisfying more than one functional requirement and easier maintenance.


Response to letter to the editor: “Lung Ultrasound early detection and monitoring in Covid-19 Pneumonia: fact and fiction”


title: Evaluation of admissions to the Major Incident Hospital based on a standardized protocol

text: INTRODUCTION: The Major Incident Hospital (MIH) is a unique facility strictly reserved to provide immediate large-scale emergency care for victims of disasters and major incidents. We evaluated the implemented organization to identify strengths and weaknesses, and provide knowledge essential for further improvement of preparedness. METHOD: According to the Protocol for Reports from Major accidents and Disasters (PRMD) and along with our five scenarios for activation, we analyzed all the data from evaluation reports of all our deployments since the MIH was founded in 1991. RESULTS: The MIH was able to provide group-wise emergency care to military (29 admissions) as well as civilian victims of major incidents and disasters, both national (260) and international (226). Group-wise treatment was advantageous for quarantine, logistics, registration, emotional support and (pre)arrangements for family, media and security. Strong points are preparedness and availability of a dedicated facility, including ICU, X-ray and OR facilities, irrespective of MRSA status and prearranged cooperation, e.g., with a trauma centre, poison centre and the military. Evaluation, research and training resulted in a barcode registration system and continuous adaptations to improve preparedness. Shortage of resources did not occur; use of the MIH’s available resources for national incidents though, could be further optimized. CONCLUSIONS: Recommendations for the future are: improvement of imbedding in regional and national procedures, continued dedicated time and staff for training, research and development, improvement of nuclear/biological/chemical decontamination facilities and preparedness, implementation of standardized scoring systems and expansion of registration systems to the prehospital setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00068-010-0067-0) contains supplementary material, which is available to authorized users.


title: VereFlu™: an integrated multiplex RT-PCR and microarray assay for rapid detection and identification of human influenza A and B viruses using lab-on-chip technology

text: Threatening sporadic outbreaks of avian influenza and the H1N1 pandemic of 2009 highlight the need for rapid and accurate detection and typing of influenza viruses. In this paper, we describe the validation of the VereFlu™ Lab-on-Chip Influenza Assay, which is based on the integration of two technologies: multiplex reverse transcription (RT)-PCR followed by microarray amplicon detection. This assay simultaneously detects five influenza virus subtypes, including the 2009 pandemic influenza A (H1N1), seasonal H1N1, H3N2, H5N1 and influenza B virus. The VereFlu™ assay was clinically validated in Singapore and compared against reference methods of real-time PCR, virus detection by immunofluorescence of cell cultures and sequencing. A sensitivity and specificity of 96.8% and 92.8%, respectively, was demonstrated for pandemic H1N1; 95.7% and 100%, respectively, for seasonal H1N1; 91.2% and 97.6%, respectively, for seasonal H3N2; 95.2% and 100%, respectively, for influenza B. Additional evaluations carried out at the World Health Organization (WHO) Collaborating Centre, Melbourne, Australia, confirmed that the test was able to reliably detect H5N1. This portable, fast time-to-answer (3 hours) device is particularly suited for diagnostic applications of detection, differentiation and identification of human influenza virus subtypes.


title: Current evidence on possible oral manifestations of SARS‐CoV‐2 infection

text: The recently published article entitled "Oral vesiculobullous lesions associated with SARS-CoV-2 infection", by Carreras-Presas et al. (2020), has been widely discussed among the dentistry community. This is the first description presented in the scientific literature aimed exclusively at oral lesions associated with the new coronavirus (SARS-CoV-2), the infectious agent responsible for the COVID-19 pandemic.


title: Virus Metagenomics in Farm Animals: A Systematic Review

text: A majority of emerging infectious diseases are of zoonotic origin. Metagenomic Next-Generation Sequencing (mNGS) has been employed to identify uncommon and novel infectious etiologies and characterize virus diversity in human, animal, and environmental samples. Here, we systematically reviewed studies that performed viral mNGS in common livestock (cattle, small ruminants, poultry, and pigs). We identified 2481 records and 120 records were ultimately included after a first and second screening. Pigs were the most frequently studied livestock and the virus diversity found in samples from poultry was the highest. Known animal viruses, zoonotic viruses, and novel viruses were reported in available literature, demonstrating the capacity of mNGS to identify both known and novel viruses. However, the coverage of metagenomic studies was patchy, with few data on the virome of small ruminants and respiratory virome of studied livestock. Essential metadata such as age of livestock and farm types were rarely mentioned in available literature, and only 10.8% of the datasets were publicly available. Developing a deeper understanding of livestock virome is crucial for detection of potential zoonotic and animal pathogens and One Health preparedness. Metagenomic studies can provide this background but only when combined with essential metadata and following the “FAIR” (Findable, Accessible, Interoperable, and Reusable) data principles.


title: One Country's Transformation to Spa Destination: The Case of Canada

text: Interest in all aspects of health and wellness tourism has been growing in every part of the world. Businesses have responded with aggressive growth in the quantity and diversity of supply offered, especially in North America. Yet few countries have systematically assessed their supply and linked it to the changes in motivation and behaviour towards spas, health and wellness in their own population. This article brings together a number of secondary sources as well as research conducted by the author with the leading spa association in Ontario, Canada, in an effort to present an overview of the characteristics of the supply of and demand for spa, and the forces that continue to shape both aspects in that country.


title: Predictors of Mortality for Patients with COVID-19 Pneumonia Caused by SARS-CoV-2: A Prospective Cohort Study

text: To identify factors associated with the death for patients with COVID-19 pneumonia caused by a novel coronavirus SARS-CoV-2. All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital, Wuhan City, Hubei Province, China, between December 25, 2019 and February 7, 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk for death of COVID-19 pneumonia patients. A total of 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (odd ratio, 3.765; 95% confidence interval, 1.146‒17.394; p=0.023), preexisting concurrent cardiovascular or cerebrovascular diseases (2.464; 0.755‒8.044; p=0.007), CD3(+)CD8(+) T cells ≤75 cell·μL(−1) (3.982; 1.132‒14.006; p<0.001), and cardiac troponin I≥0.05 ng·mL(−1) (4.077; 1.166‒14.253; p<0.001) were associated with an increase in risk of mortality of COVID-19 pneumonia. In the sex‒, age‒, and comorbid illness-matched case study, CD3(+)CD8(+) T cells ≤75 cell·μL(−1) and cardiac troponin I≥0.05 ng·mL(−1) remained to be the predictors for high mortality of COVID-19 pneumonia. We identified four risk factors, age ≥65 years, preexisting concurrent cardiovascular or cerebrovascular diseases, CD3(+)CD8(+) T cells ≤75 cell·μL(−1), and cardiac troponin I≥0.05 ng·mL(−1), especially the latter two factors, were predictors for mortality of COVID-19 pneumonia patients.


title: Oxidation reactions using polymer-supported 2-benzenesulfonyl-3-(4-nitrophenyl)oxaziridine

text: A thermally stable polymer-supported oxidant has been developed. Polymer-supported 2-benzenesulfonyl-3-(4-nitrophenyl)oxaziridine was applied to microwave-assisted reactions that occurred at high temperatures and was shown to oxidize alkenes, silyl enol ethers, and pyridines to the corresponding epoxides and pyridine N-oxides in excellent to good yields and with much shorter reaction times. It also enabled tetrahydrobenzimidazoles to be oxidatively rearranged to spiro fused 5-imidazolones in a more efficient manner. Recycling of the polymer-supported oxidant is also possible with minimal loss of activity after several reoxidations.


title: Nested and teleconnected vulnerabilities to environmental change

text: The vulnerability of distant peoples and places to global change in environment and society is nested and teleconnected. Here, we argue that such vulnerabilities are linked through environmental change process feedbacks, economic market linkages, and flows of resources, people, and information. We illustrate these linkages through the examples of the global transmission of severe acute respiratory syndrome (SARS) and the interdependent vulnerabilities and adaptations of coffee farmers in Vietnam and Mexico. These cases demonstrate that the vulnerability of specific individuals and communities is not geographically bounded but, rather, is connected at different scales, so that the drivers of their exposure and sensitivity are inseparable from large‐scale processes of sociocultural change and market integration. Aggregate outcomes of government policies, trends in global commodity markets, and even decisions by individuals to improve livelihood security can have negative repercussions, not only locally, through transformations of ecological systems and social relations, but also at larger scales.


title: Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: Results from a claims analysis

text: INTRODUCTION|: Antibiotic treatment failure contributes to the economic and humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity, mortality, and healthcare costs. This study compared treatment failure rates of levofloxacin with those of other antibiotics in a large US sample. METHODS|: Medical and pharmacy claims in the nationally representative SDI database were used to identify adults with a new outpatient diagnosis of CAP receiving a study antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin) between September 1, 2005 and March 31, 2008. Treatment failure was defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. Cohorts were propensity score matched for demographic and clinical characteristics. Treatment failure rates were compared between pairs of cohorts for the full sample and for high-risk patients (age ≥65 and/or on Medicaid). RESULTS|: Among the 3994 study patients, the numbers of dispensed index prescriptions were 268 for amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657 for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8% for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and 19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment failure rates were significantly lower with levofloxacin than azithromycin (19.8% vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67), a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI: 1.22, 2.13). No significant differences were observed for other paired comparisons. CONCLUSION|: In a large US sample, treatment failure in CAP appeared to be less likely with quinolones (such as levofloxacin) than azithromycin, an effect particularly marked in high-risk patients (age ≥65 and/or on Medicaid).


title: Clinical manifestations of human coronavirus NL63 infection in children in Taiwan

text: Human coronavirus NL63 (HCoV-NL63) is a global respiratory tract pathogen; however, the epidemiology of this virus in subtropical area is not well known. To evaluate the epidemics and disease spectrum of HCoV-NL63 infection in children in Taiwan, we prospectively screened children admitted to the hospital with respiratory tract infection from May 2004 to April 2005. Every enrolled child had a nasopharyngeal aspirate (NPA) sample taken. Quantitative RT-PCR was used to detect 1b gene of HCoV-NL63. A total of 539 NPAs were collected. Seven (1.3%) were positive for HCoV-NL63. All cases were boys younger than 3 years of age and most cases occurred in autumn. Co-infection with other pathogens was observed in three cases. The most common symptoms/signs of HCoV-NL63 infection were cough, fever, and inspiratory stridor. HCoV-NL63 was the most common pathogen (14.7%) in children with croup and was the cause of three cases of croup in October. The odds ratio of croup in children infected with HCoV-NL63 was 43.4 (95% CI 8.1∼233.1). In conclusion, HCoV-NL63 is an important respiratory tract pathogen as the main cause in children admitted to the hospital in Taiwan.


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title: Human Avian Influenza: How Ready Are We?

text: Three influenza pandemics emerged in the 20th century, and scientists are concerned that the currently circulating, highly pathogenic A (H5N1) avian influenza virus could lead to the next pandemic, one as deadly as the 1918 influenza pandemic. Not since the identification of HIV and AIDS will the duty to care among health care providers be tested as during such an event. Nonetheless, the expertise of health care providers is an integral part of the response to a pandemic. In the fight against flu, forewarned is forearmed. This report provides an overview of avian influenza (a.k.a. bird flu) and phases of pandemic influenza, with an emphasis on what health care providers should know to be prepared for a human avian influenza outbreak and the next pandemic.


title: Papel de las enfermedades infecciosas en el desarrollo de la esclerosis múltiple: evidencia científica

text: Resumen Introducción La esclerosis múltiple (EM) es el trastorno inflamatorio más común del sistema nervioso central (SNC) y la causa principal de discapacidad neurológica en adultos jóvenes. Los factores ambientales e infecciosos han sido fuertemente asociados al incremento de la ocurrencia de la enfermedad, hasta más del doble, en los últimos 10 años. En este artículo de revisión se describen los principales hallazgos reportados sobre la relación entre ciertas infecciones virales y bacterianas con la aparición y progresión de la EM. Métodos Se realizó un plan metodológico de búsqueda de artículos científicos relacionados con infección y EM, mediante la búsqueda de artículos científicos, principalmente publicados en inglés, en las plataformas virtuales de Pubmed, Medline y Cochrane. Para la búsqueda se utilizaron como palabras claves (términos MeSH): «virus, bacteria, autoimmune disease of the nervous system, multiple sclerosis». Se eligieron artículos publicados en revistas indexadas durante los últimos 15 años. Resultados Estudios epidemiológicos sugieren que la EM tiene un componente etiológico infeccioso que origina un proceso inflamatorio que puede contribuir a la iniciación o exacerbación de la enfermedad. Particularmente, la infección viral y los eventos de desmielinización en el SNC puede deberse a la penetración de un virus como el virus Epstein-Barr (EBV), a través del torrente sanguíneo, específicamente hacia el SNC. Por otro lado, las infecciones bacterianas crónicas pueden causar procesos de desmielinización en el SNC que agravan la enfermedad de EM. Conclusiones Este estudio contribuye a aportar evidencia científica donde se demuestra la multicausalidad implicada en la ocurrencia de la EM. Aún falta desarrollar más estudios epidemiológicos que demuestren y comprueben la relación y la implicación de agentes virales y bacterianos en el origen, el desarrollo y la severidad de la enfermedad. Abstract Introduction Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS) and the leading cause of neurological disability in young adults. Environmental and infectious factors had been strongly associated and involved in the increased occurrence of MS, to more than twice, in the last 10 years. In this review, we describe the main findings on the relationship between viral and bacterial infections and the onset and progression of MS. Methods The research involved a systematic review of scientific literature regarding infection and MS. Our search was performed using and consulting specialized websites like PubMed, Medline and Cochrane. The keywords (MeSH terms) employed for the digital search were: “virus, bacteria, autoimmune disease of the nervous system, and multiple sclerosis.” Articles published in English indexed journals during the past 15 years were used for the study. Results Epidemiological studies suggest that MS has an infectious etiologic component causing an inflammatory process that may contribute to the initiation and/or exacerbation of the disease. Particularly, viral infections and demyelination events in the CNS may be due to the penetration of viruses such as the Epstein-Barr virus (EBV) through the bloodstream to the CNS, specifically. On the other hand, chronic bacterial infections may cause demyelination processes that trigger or increase the complications of the disease in MS. Conclusions This study shows the multiple factors involved in the occurrence of MS. More epidemiological studies are necessary to support the relationship and involvement of viral and bacterial infections in the onset, development and severity of the disease.


title: Use of chimeric influenza viruses as a novel internal control for diagnostic rRT-PCR assays

text: Real-time quantitative reverse transcriptase polymerase chain reaction (rRT-PCR) is now widely used to detect viral pathogens in various human specimens. The application of internal controls to validate the entire process of these assays is necessary to prevent false-negative results caused by unexpected inhibition or inefficient extraction. In the present study, we describe a strategy to produce a stable internal control for rRT-PCR by packaging foreign RNA into influenza virions using plasmid-based reverse genetics technology. The envelope structure of influenza virus can effectively protect RNA segments from RNase digestion, which provides an advantage for its routine use as an internal control. Utilizing this approach, we successfully generated a recombinant influenza virus (rPR8-HCV) containing the 5′ untranslated region (5′ UTR) of the hepatitis C virus (HCV) RNA genome. After inactivation and purification, the rPR8-HCV particles were demonstrated to be RNase resistant and stable at 4 °C for at least 252 days in human plasma, with no degradation even after being frozen and thawed multiple times. These results were reproducible in the COBAS TaqMan HCV test for 164 days. Moreover, the chimeric influenza virus particles could be easily produced in embryonated eggs and were noninfectious after inactivation treatment. Additionally, this strategy could also be adapted for real-time clinical applications of other RNA targets, providing a universal approach with broad clinical applications in rRT-PCR assays.


title: Should Contact Bans Have Been Lifted More in Germany?: A Quantitative Prediction of Its Effects

text: Many countries consider the lifting of restrictions of social contacts (RSC). We quantify the effects of RSC for Germany. We initially employ a purely statistical approach to predicting prevalence of Covid-19 if RSC had been upheld after 20 April. We employ these findings and feed them into our theoretical model. We find that the peak of the number of sick individuals would have been reached already end of April. The number of sick individuals would have fallen below 1000 at the beginning of July. If restrictions had been lifted completely on April 20, the number of sick should have risen quickly again from around 27 April. A balance between economic and individual costs of RSC and public health objectives consists in lifting RSC for activities that have high economic benefits but low health costs. In the absence of large-scale representative testing of CoV-2 infections, these activities can most easily be identified if federal states of Germany adopted exit strategies that differ across states.


Response letter to Eosinophil count in severe coronavirus disease 2019 (COVID-19)


title: From Bedside to Webside: a neurological clinical teaching experience

text: This was followed by an interactive discussion of investigation and management plan. Appropriate radiological imaging such as an MRI brain scan was shown to the group using the “share‐screen” function. Other clinical information such as laboratory results can likewise be displayed. The session was completed after thorough discussion on the appropriate treatment plan with respect to the patient’s scenario.


title: The N-formyl peptide receptors and the anaphylatoxin C5a receptors: An overview

text: Abstract Leukocyte recruitment to sites of inflammation and infection is dependent on the presence of a gradient of locally produced chemotactic factors. This review is focused on current knowledge about the activation and regulation of chemoattractant receptors. Emphasis is placed on the members of the N-formyl peptide receptor family, namely FPR (N-formyl peptide receptor), FPRL1 (FPR like-1) and FPRL2 (FPR like-2), and the complement fragment C5a receptors (C5aR and C5L2). Upon chemoattractant binding, the receptors transduce an activation signal through a G protein-dependent pathway, leading to biochemical responses that contribute to physiological defense against bacterial infection and tissue damage. C5aR, and the members of the FPR family that were previously thought to be restricted to phagocytes proved to have a much broader spectrum of cell expression. In addition to N-formylated peptides, numerous unrelated ligands were recently found to interact with FPR and FPRL1. Novel agonists include both pathogen- and host-derived components, and synthetic peptides. Antagonistic molecules have been identified that exhibit limited receptor specificity. How distinct ligands can both induce different biological responses and produce different modes of receptor activation and unique sets of cellular responses are discussed. Cell responses to chemoattractants are tightly regulated at the level of the receptors. This review describes in detail the regulation of receptor signalling and the multi-step process of receptor inactivation. New concepts, such as receptor oligomerization and receptor clustering, are considered. Although FPR, FPRL1 and C5aR trigger similar biological functions and undergo a rapid chemoattractant-mediated phosphorylation, they appear to be differentially regulated and experience different intracellular fates.


title: Specificity in PDZ-peptide interaction networks: Computational analysis and review

text: Abstract Globular PDZ domains typically serve as protein–protein interaction modules that regulate a wide variety of cellular functions via recognition of short linear motifs (SLiMs). Often, PDZ mediated-interactions are essential components of macromolecular complexes, and disruption affects the entire scaffold. Due to their roles as linchpins in trafficking and signaling pathways, PDZ domains are attractive targets: both for controlling viral pathogens, which bind PDZ domains and hijack cellular machinery, as well as for developing therapies to combat human disease. However, successful therapeutic interventions that avoid off-target effects are a challenge, because each PDZ domain interacts with a number of cellular targets, and specific binding preferences can be difficult to decipher. Over twenty-five years of research has produced a wealth of data on the stereochemical preferences of individual PDZ proteins and their binding partners. Currently the field lacks a central repository for this information. Here, we provide this important resource and provide a manually curated, comprehensive list of the 271 human PDZ domains. We use individual domain, as well as recent genomic and proteomic, data in order to gain a holistic view of PDZ domains and interaction networks, arguing this knowledge is critical to optimize targeting selectivity and to benefit human health.


title: Harnessed viruses in the age of metagenomics and synthetic biology: an update on infectious clone assembly and biotechnologies of plant viruses

text: Recent metagenomic studies have provided an unprecedented wealth of data, which are revolutionizing our understanding of virus diversity. A redrawn landscape highlights viruses as active players in the phytobiome, and surveys have uncovered their positive roles in environmental stress tolerance of plants. Viral infectious clones are key tools for functional characterization of known and newly identified viruses. Knowledge of viruses and their components has been instrumental for the development of modern plant molecular biology and biotechnology. In this review, we provide extensive guidelines built on current synthetic biology advances that streamline infectious clone assembly, thus lessening a major technical constraint of plant virology. The focus is on generation of infectious clones in binary T‐DNA vectors, which are delivered efficiently to plants by Agrobacterium. We then summarize recent applications of plant viruses and explore emerging trends in microbiology, bacterial and human virology that, once translated to plant virology, could lead to the development of virus‐based gene therapies for ad hoc engineering of plant traits. The systematic characterization of plant virus roles in the phytobiome and next‐generation virus‐based tools will be indispensable landmarks in the synthetic biology roadmap to better crops.


title: Repurposing 0.5% povidone iodine solution in otorhinolaryngology practice in Covid 19 pandemic

text: SARS CoV 2 is very much homologous in structure to SARS CoV. Review of literature suggests the in-vitro virucidal action of povidone iodine in SARS CoV and MERS. The oropharynx and nasopharynx are target sites of SARS CoV 2. A significant proportion of COVID 19 sufferers are asymptomatic, but shedding these viral particles, PVP-I has been shown to be a safe therapy when used as a mouthwash or taken nasally or used during ophthalmic surgeries. AIMS: 1. To propose the use of 0.5% Povidone iodine gargles and nasal drops as prerequisite for office based nose and throat examination and procedures during COVID 19 pandemic. 2. To assess tolerability of 0.5% PVP-I in patients and in healthcare workers. MATERIALS AND METHODS: 0.5% PVP-I solution is prepared from commercially available 10% PVP-I solution. Patients were instructed to put 0.5% PVP-I drops in nose and rinse mouth with gargle prior examinations for 30 s. For endoscopic procedure (nasal and throat) nasal douching and gargling to be started one day prior. Douching and rinsing to be repeated just before procedures. Nasal packing with 0.5% PVP-I along with 4% xylocaine/adrenaline solution, tolerability and any allergic reaction noted. RESULTS: The patient and health care workers tolerated the 0.5%. No allergy was noted. CONCLUSION: We propose the use of 0.5% PVP-I in healthcare workers and their patients to minimise the risk of spread of the disease in addition to the recommended PPE.


title: Reactivity of antibodies in human serum with antigens of an enteropathogenic bovine coronavirus

text: Antibodies in human serum against an enteropathogenic bovine coronavirus were detected by double immunodiffusion (DID), neutralization of infectivity, indirect immunofluorescence, and immune electron microscopy. Human sera reacting in the DID test neutralized the infectivity of the bovine coronaviruses to indices of 2.5 to > 5. Nineteen of 40 DID-negative, heat-inactivated sera had neutralizing indices of 1 to 3.0. Human serum with neutralizing and DID antibodies produced juxtanuclear and cytoplasmic fluorescence identical to that of bovine immune serum in cells infected with the bovine coronavirus. Antibodies in human and bovine sera interacted with the peplomeres of the bovine coronavirus, matting and bridging them, when present in excess, and facilitated formation of large viral aggregates when present in equivalent concentrations. Complement added to the virus-antibody complexes did not alter specifically the morphology of single, antibody-laden viral particles or viral particles in aggregates. Evidence of the transmission of coronavirus from experimentally inoculated calves to man, with ensuing gastroenteritis, was found by electron microscopic tracing of the coronavirus and its virus-antibody complexes.


Ventilacion mecanica no invasiva y covid-19. Minimizando la dispersion


Infectious Diseases Continued to be the World's Core Challenge


docid: fiyvdrto

title: Interferon-λ in the Context of Viral Infections: Production, Response and Therapeutic Implications

text: Interferon (IFN)-λ forms the type III IFN family. Although they signal through distinct receptors, type I (IFN-α/β) and type III IFNs elicit remarkably similar responses in cells. However, in vivo, type III and type I IFN responses are not fully redundant as their respective contribution to the antiviral defense highly depends on virus species. IFN-λ is much more potent than IFN-α/β at controlling rotavirus infection. In contrast, clearance of several other viruses, such as influenza virus, mostly depends on IFN-α/β. The IFN-λ receptor was reported to be preferentially expressed on epithelial cells. Cells responsible for IFN-λ production are still poorly characterized but seem to overlap only partly IFN-α/β-producing cells. Accumulating data suggest that epithelial cells are also important IFN-λ producers. Thus, IFN-λ may primarily act as a protection of mucosal entities, such as the lung, skin or digestive tract. Type I and type III IFN signal transduction pathways largely overlap, and cross talk between these IFN systems occurs. Finally, this review addresses the potential benefit of IFN-λ use for therapeutic purposes and summarizes recent results of genome-wide association studies that identified polymorphisms in the region of the IFN-λ3 gene impacting on the outcome of treatments against hepatitis C virus infection.


title: Coronavirus Disease 2019 (COVID-19) in Kenya: Preparedness, response and transmissibility

text: Abstract The world and Kenya face a potential pandemic as the respiratory virus Coronavirus Disease 2019 (COVID-19) affects world populations. Nations have been forced to intervene and issue directions under executive orders to ensure the pandemic is contained. Kenya has reported 110 confirmed COVID-19 cases (as at 2nd April, 2020), three persons have succumbed and 2 people have fully recovered. Most of the affected people had entered/returned to Kenya from different parts of the world. Most of the people who have contracted COVID 19 are between the 16–74 years of age. As a result, since February 2020, Kenya put in place several precautionary measures to mitigate the pandemic in its early stages. However, the economic status of the population of country won't be simple to control COVID 19, if government won't integrate the realistic feasible timely plans. This article highlights the preparedness, response, transmissibility of Covid-19 and proposes intuitions to manage COVID-19 in Kenya. Currently it is clear that since first confirmation to current, the transmission of the COVID-19 is exponentially increasing in Kenya.


El test rápido de inmunoglobulinas confirma un caso sospechoso de COVID-19


title: Drug repositioning: a brief overview

text: OBJECTIVES: Drug repositioning, that is, the use of a drug in an indication other than the one for which it was initially marketed, is a growing trend. Its origins lie mainly in the attrition experienced in recent years in the field of new drug discovery. KEY FINDINGS: Despite some regulatory and economic challenges, drug repositioning offers many advantages, and a number of recent successes have confirmed both its public health benefits and its commercial value. The first examples of successful drug repositioning mainly came about through serendipity like acetylsalicylic acid, thalidomide, sildenafil or dimethylfumarate. CONCLUSION: The history of great‐repositioned drugs has given some solutions to various pathologies. Serendipity is not yet useful to find repositioning drugs. Drug repositioning is of growing interest. Nowadays, a more rational approach to the identification of drug candidates for repositioning is possible, especially using data mining.


title: An assessment on the role of endophytic microbes in the therapeutic potential of Fagonia indica

text: BACKGROUND: Natural products of animals, plants and microbes are potential source of important chemical compounds, with diverse applications including therapeutics. Endophytic bacteria that are especially associated with medicinal plants presents a reservoir of therapeutic compounds. Fagonia indica has been recently investigated by numerous researchers because of its striking therapeutic potential especially in cancer. It is also reported that endophytes play a vital role in the biosynthesis of various metabolites; therefore we believe that endophytes associated with F. indica are of crucial importance in this regard. The present study aims successful isolation, molecular identification of endophytic bacteria and their screening for bioactive metabolites quantification and in vitro pharmacological activities. METHODS: 16S rRNA gene sequencing was used for the identification of isolated endophytic bacteria. Methanolic extracts were evaluated for total phenolic contents (TPC), total flavonoids contents (TFC), DPPH free radical scavenging activity, reducing power and total anti-oxidant assays were performed. And also screened for antibacterial and antifungal activities by disc diffusion method and their MIC were calculated by broth dilution method using microplate reader. Further, standard protocols were followed for antileishmanial activity and protein kinase inhibition. Analysis and statistics were performed using SPSS, Table curve and Origin 8.5 for graphs. RESULTS: Bacterial strains belonging to various genera (Bacillus, Enterobacter, Pantoea, Erwinia and Stenotrophomonas) were isolated and identified. Total phenolic contents and total flavonoids contents varies among all the bacterial extracts respectively in which Bacillus subtilis showed high phenolic contents 243 µg/mg of gallic acid equivalents (GAE) and Stenotrophomonas maltophilia showed high flavonoids contents 15.9 µg/mg quercitin equivalents (QA), total antioxidant capacity (TAC) 37.6 µg/mg of extract, reducing power (RP) 206 µg/mg of extract and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with 98.7 μg/mL IC(50) value. Although all the extracts tested were active to inhibit growth of selected pathogenic microbes (bacteria and fungi), but significant antibacterial activity was observed against Klebsiella pneumonia and B. subtilis. An Enterobacter cloaca was active against Leishmania tropica with IC(50) value of 1.4 µg/mg extracts. B. subtilis and Bacillus tequilensis correspondingly exhibit significant protein kinase inhibition of 47 ± 0.72 and 42 ± 1.21 mm bald zones, indicating anti-infective and antitumor potential. CONCLUSIONS: Our findings revealed that crude extracts of selected endophytic bacteria from F. indica possess excellent biological activities indicating their potential as an important source of antibiotics (antifungal, antibacterial) compounds.


title: A Fusion Peptide in the Spike Protein of MERS Coronavirus

text: Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.


title: Adapting lessons from SARS for the COVID-19 pandemic - Perspectives from Radiology Nursing in Singapore

text: Abstract When SARS hit Singapore in 2003, we began to formulate rigorous protocols and reconfigure our facilities to prevent in-hospital transmission. This became the foundation of our practices in COVID-19. However, some adaptations were made to suit the current needs of the department, and technology has been employed for communication. This paper describes the preparation and response of nursing in Radiology Department in Singapore in Severe Acute Respiratory Syndrome (SARS) and Corona virus 2019 (COVID-19) outbreak. Protocols and measures taken during SARS and COVID-19 were described.Stringent infection control and prevention measures, detailed standard operating protocols for handling SARS and COVID-19 patients coming for radiological examinations and interventions, team segregation, safe distancing, efficient communication and rigorous staff surveillance are paramount to ensure patient and staff safety.Our SARS experience has shaped our preparations and response towards the COVID-19 pandemic. To date, there have been zero healthcare worker transmission in the department. The crisis has also enhanced the cohesiveness among staff due to the camaraderie and shared experience.The response and measures taken by the Radiology Department in a large acute care teaching hospital could be practiced in other similar healthcare settings.


title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome

text: Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1β secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus (SARS-CoV) activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1β secretion. While cells uninfected or infected with a lentivirus expressing a 3a protein defective in ion channel activity expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells infected with a lentivirus expressing the 3a protein. K(+) efflux and mitochondrial reactive oxygen species were important for SARS-CoV 3a-induced NLRP3 inflammasome activation. These results highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.


docid: vypynhfl

title: Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities

text: Pyridoacridines are a class of strictly marine‐derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti‐HIV, and anti‐parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assignment.


title: Chapter Two −1 Programmed Ribosomal Frameshifting as a Force-Dependent Process

text: Abstract −1 Programmed ribosomal frameshifting is a translational recoding event in which ribosomes slip backward along messenger RNA presumably due to increased tension disrupting the codon–anticodon interaction at the ribosome's coding site. Single-molecule physical methods and recent experiments characterizing the physical properties of mRNA's slippery sequence as well as the mechanical stability of downstream mRNA structure motifs that give rise to frameshifting are discussed. Progress in technology, experimental assays, and data analysis methods hold promise for accurate physical modeling and quantitative understanding of −1 programmed ribosomal frameshifting.


docid: bmskalsa

title: Exosomes: Nanoparticulate tools for RNA interference and drug delivery

text: Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell‐cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules.


title: An inventory model for a three-stage supply chain with random capacities considering disruptions and supplier reliability

text: This study develops an inventory model to solve the problems of supply uncertainty in response to demand which follows a Poisson distribution. A positive aspect of this model is the consideration of random inventory, delivery capacities and supplier’s reliability. Additionally, we assume supplier capacity follows an exponential distribution. This inventory model addresses the problem of a manufacturer having an imperfect production system with single supplier and single retailer and considers the quantity of product (Q), reorder points (r) and reliability factors (n) as the decision variables. The main contribution of our study is that we consider supplier may not be able to deliver the exact amount all the time a manufacturer needed. We also consider that the demand and the time interval between successive availability and unavailability of supplier and retailer follows a probability distribution. We use a genetic algorithm to find the optimal solution and compare the results with those obtained from simulated annealing algorithm. Findings reveal the optimal value of the decision variables to maximize the average profit in each cycle. Moreover, a sensitivity analysis was carried out to increase the understanding of the developed model. The methodology used in this study will help manufacturers to have a better understanding of the situation through the joint consideration of disruption of both the supplier and retailer integrated with random capacity and reliability.