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The effect of spent bleaching earth ageing process on its physicochemical and microbial composition and its potential use as a source of fatty acids and triterpenes

This study was aimed at investigating the physicochemical and microbiological changes that took place during the ageing process of spent bleaching earth in the presence of autochthonous microorganisms. Research material included fresh spent bleaching earth (SBE(0)) and the same material after 3 years of storage at the constant temperature of 20 °C, without aeration and moistening (SBE(3)). Changes in the chemical composition of analysed waste material were observed during its ageing process point to a spontaneous bioconversion of fat substance towards formation and/or release of free saturated fatty acids C16:0 and C18:0 (14.3 g 100 g(−1) D.M.), triterpenes (8.48 g 100 g(−1) D.M.), cholesterol (3.29 g 100 g(−1) D.M.), small quantities of carbohydrates and esters (0.80 g 100 g(−1) D.M.). This process was accompanied by other changes in physicochemical parameters of the waste material, such as colour, odour and viscosity, decrease in fat content from 28.27 to 24.6 % and that of soluble forms of metals (Mo, Cu, Fe, Zn, Ni, Cr and Mn), ranging from 25 to 75 %, and an increase in pH, from 3.85 to 4.2. At the same time, changes in the microbial consortium were observed.

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A Smart Card-Based Electronic School Absenteeism System for Influenza-Like Illness Surveillance in Hong Kong: Design, Implementation, and Feasibility Assessment

BACKGROUND: School-aged children have the highest incidence of respiratory virus infections each year, and transmission of respiratory viruses such as influenza virus can be a major concern in school settings. School absenteeism data have been employed as a component of influenza surveillance systems in some locations. Data timeliness and system acceptance remain as key determinants affecting the usefulness of a prospective surveillance system. OBJECTIVE: The aim of this study was to assess the feasibility of implementing an electronic school absenteeism surveillance system using smart card–based technology for influenza-like illness (ILI) surveillance among a representative network of local primary and secondary schools in Hong Kong. METHODS: We designed and implemented a surveillance system according to the Protocol for a Standardized information infrastructure for Pandemic and Emerging infectious disease Response (PROSPER). We employed an existing smart card–based education and school administration platform for data capture, customized the user interface, and used additional back end systems built for other downstream surveillance steps. We invited local schools to participate and collected absenteeism data by the implemented system. We compared temporal trend of the absenteeism data with data from existing community sentinel and laboratory surveillance data. RESULTS: We designed and implemented an ILI surveillance system utilizing smart card–based attendance tracking approach for data capture. We implemented the surveillance system in a total of 107 schools (including 66 primary schools and 41 secondary schools), covering a total of 75,052 children. The system successfully captured information on absences for 2 consecutive academic years (2012-2013 and 2013-2014). The absenteeism data we collected from the system reflected ILI activity in the community, with an upsurge in disease activity detected up to 1 to 2 weeks preceding other existing surveillance systems. CONCLUSIONS: We designed and implemented a novel smart card technology–based school absenteeism surveillance system. Our study demonstrated the feasibility of building a large-scale surveillance system riding on a routinely adopted data collection approach and the use of simple system enhancement to minimize workload implication and enhance system acceptability. Data from this system have potential value in supplementing existing sentinel influenza surveillance for situational awareness of influenza activity in the community.

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COVID-19 and off label use of drugs: an ethical viewpoint

BACKGROUND: The COVID-19 outbreak is rapidly spread over the world and kills infected patients. There is no proven medication for its treatment, so, all of the medications used for treatment are considered to be off-label. Off-label uses are not under regulation in the outbreak because there is no specific regulation for this condition. OBJECTIVES: In this short communication we aim at describing two ways of off-label use as clinical practice or investigational use. Further, we will describe the third way of off-label use, we named it pseudo-research and then we will state the most possible ethical challenges of off-label use for better perceptions and responsibility. RESULTS: The WHO considers off-label uses as country-specific. All international regulatory bodies consider off-label prescription as the physician’s responsibility and legal by necessitating some requirements. There is no international guideline for regulating investigational off-label uses as clinical practice. CONCLUSION: There are different types of approaches, none of them is comprehensive and conclusive. Furthermore, respecting the four ethical principles necessitates codification and strict regulation of off-label uses either as clinical practice or investigational. Besides, compilation of a special guideline based on ethical principles especially non-maleficence and autonomy for investigational off-label uses in disasters is highly recommended.

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Improving communication about COVID‐19 and emerging infectious diseases

John Ioannidis writes about the harm caused by misinformation about COVID-19.1 We draw from communication research to offer best practices for reducing misinformation, disseminating accurate health information, and promoting prevention and control recommendations. We recommend three strategies that medical, public health, and scientific professionals working with government officials, clinicians, media commentators, and in other contexts around the world can use to improve communication about outbreaks.

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Topical preparations to reduce SARS‐CoV‐2 aerosolization in head and neck mucosal surgery

AIM: The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has put health care workers at risk when exposed to aerosolized viral particles during upper airway mucosal surgery. The objective of this review was to discuss topical preparations that could be utilized preoperatively to help to decrease viral load and potentially reduce the risks of viral transmission. METHODS: A PubMed/MEDLINE database review of articles was performed querying topical preparations with virucidal activity against coronaviruses. RESULTS: Povidone‐iodine (PVP‐I) solutions ranging from 0.23% to 7% have been found to demonstrate highly effective virucidal activity against a broad range of viruses including several coronaviruses responsible for recent epidemics including SARS‐CoV‐1 and MERS‐CoV. CONCLUSIONS: While specific evidence regarding SARS‐CoV‐2 is lacking, PVP‐I‐based preparations have been successfully demonstrated to reduce viral loads of coronaviruses. They are relatively safe to use in the upper airway and may reduce risk of SARS‐CoV‐2 aerosolization during upper airway mucosal surgery.

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Recent developments and contributions from Chinese scientists in multidimensional separations for proteomics and traditional Chinese medicines

The most basic task in proteomics remains the detection and identification of proteins from a biological sample, and the most traditional way to achieve this goal consists in protein separations performed by two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE). Yet the 2‐D PAGE‐mass spectrometry (MS) approach has its drawbacks with regard to automation, sensitivity, and throughput. Consequently, considerable effort has been devoted to the development of non‐gel‐based proteome separation technologies in an effort to alleviate the shortcomings of 2‐D PAGE. In addition, traditional Chinese medicines (TCMs), due to their long period of clinical testing and reliable therapeutic efficacy, are attracting increased global attention. However, hundreds or even thousands of components are usually present in TCMs, which results in great difficulties of separation. As a mainstream separation tool, multidimensional liquid separation systems have shown powerful separation ability, high peak capacity, and excellent detectability in the analysis of complex samples including biological samples and TCMs, etc. Therefore, this review emphasizes the most recent advances in multidimensional liquid chromatography and capillary electrophoresis‐based separation techniques, and the corresponding applications in proteomics and TCMs. In view of the significant contributions from Chinese scientists, this review focuses mainly on the work of Chinese scientists in the above fields.

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Law, and Public Health Policy

Two of the most important tools that assist states in protecting their populations against threats to health are public health policy and public health law. Policy can exist without recourse to law, but where policy has been designed for a long-term purpose, and where voluntary compliance has not proved successful, policy may need the heavier hand of law for implementation. However, law is not always an appropriate mechanism for achieving public health objectives. This article explores the boundaries of public health policy and public health law, and examines how they might work as dual mechanisms for public health.

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High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection

Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

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Analyzing Vaccine Trials in Epidemics With Mild and Asymptomatic Infection

Vaccine efficacy against susceptibility to infection (VE(S)), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, because such infections may contribute to onward transmission and long-term sequelae, such as congenital Zika syndrome. However, estimating VE(S) is resource-intensive. We aimed to identify approaches for accurately estimating VE(S) when limited information is available and resources are constrained. We modeled an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history followed a “susceptible-exposed-infectious/symptomatic (or infectious/asymptomatic)-recovered” model. We then used 7 approaches to estimate VE(S), and we also estimated vaccine efficacy against progression to symptoms (VE(P)). A corrected relative risk and an interval-censored Cox model accurately estimate VE(S) and only require serological testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VE(S) estimates across values of the basic reproduction number (R(0)) and accurate estimates of VE(P) for higher R(0) values. Identifying resource-preserving methods for accurately estimating VE(S) and VE(P) is important in designing trials for diseases with a high proportion of asymptomatic infection.

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Tourism companies' risk exposures on text disclosure

Tourism is a risk-prone industry. But most studies focus on tourist risk perception while ignoring company risk exposure. As service providers, the companies play an important role in tourism activities, and systematically identifying the risks they face is vital to the development of the tourism industry. This paper attempts to identify tourism companies' risk exposures based on textual risk disclosure of financial statements. Using 51,008 risk headings of 255 public companies, we adopt Sentence-Latent Dirichlet Allocation (Sent-LDA) method to discover 30 risk exposures of the tourism industry. Further, we discuss the universality and industry representativeness of these risk exposures, as well as risk differences between different sub-industries and years. Findings can help stakeholders develop reasonable and timely risk management strategies.

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A Definition Framework for Building Adaptation Projects

Building adaptation encompasses a range of construction activities that improve existing building conditions and extend the effective lives of buildings. The scopes of building adaptation projects vary, and may include rehabilitating failing structures, improving environmental performances, and changing functional uses. In order to address multiple aspects of building adaptation, different terminologies are used in the literature and in practice, including refurbishment, retrofitting, rehabilitation, renovation, restoration, modernization, conversion, adaptive reuse, material reuse, conservation, and preservation, amongst others. These terminologies are often used interchangeably with overlapping definitions, causing a lack of clarity in the addressed scope of work. An extensive literature review of terminologies related to building adaptation was conducted and the most common and applicable terminologies were identified. Recent definitions, applications, and scope for the identified terminologies are reviewed. Based on this classification, a definition framework is developed enabling precise categorization of building adaptation projects, and application is demonstrated in multiple case studies. The proposed definition framework is a valuable reference for future researchers and practitioners to clearly and consistently define the scope of work in their building adaption projects, and thus avoid the high costs arising from codes, specifications, and project descriptions that confuse these definitions.

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HHS/CDC Legal Response to SARS Outbreak

Before the severe acute respiratory syndrome (SARS) outbreak, the Centers for Disease Control and Prevention’s (CDC) legal authority to apprehend, detain, or conditionally release persons was limited to seven listed diseases, not including SARS, and could only be changed using a two-step process: 1) executive order of the President of the United States on recommendation by the Secretary, U.S. Department of Health and Human Services (HHS), and 2) amendment to CDC quarantine regulations (42 CFR Parts 70 and 71). In April 2003, in response to the SARS outbreak, the federal executive branch acted rapidly to add SARS to the list of quarantinable communicable diseases. At the same time, HHS amended the regulations to streamline the process of adding future emerging infectious diseases. Since the emergence of SARS, CDC has increased legal preparedness for future public health emergencies by establishing a multistate teleconference program for public health lawyers and a Web-based clearinghouse of legal documents.

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The rise and fall of infectious diseases: Australian perspectives, 1914‐2014

Australia has been fortunate in its experience with infectious diseases over the past century. By the 1960s, many communicable diseases were controlled through a combination of high living standards, progressive adoption of vaccines and antimicrobial treatment. Australian medical scientists have made substantial contributions to the understanding of many historically significant communicable diseases and global initiatives for control. New challenges have emerged as previously unrecognised viral infections have emerged, and microbial resistance to antibiotics has developed in many old pathogens. Ongoing evolutionary forces, both environmental and social, change the balance between humans and microbes. The effects of these forces are most sorely felt in poor countries and communities.

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Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2

Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 ± 12.0 vs. 58.4 ± 18.0, years, P < 0.001) and with higher platelet count (215 ± 100 vs. 188 ± 98, ×10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 μg/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

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Strengthening National Disease Surveillance and Response—Haiti, 2010–2015

Haiti’s health system has faced many challenges over the years, with competing health priorities in the context of chronic financial and human resource limitations. As a result, the existing notifiable disease surveillance system was unable to provide the most basic epidemiologic data for public health decision-making and action. In the wake of the January 2010 earthquake, the Haitian Ministry of Public Health and Population collaborated with the U.S. Centers for Disease Control and Prevention, the Pan American Health Organization, and other local and international partners to implement a functional national surveillance system. More than 7 years later, it is important to take the opportunity to reflect on progress made on surveillance and response in Haiti, including disease detection, reporting, outbreak investigation, and response. The national epidemiologic surveillance network that started with 51 sites in 2010 has been expanded to 357 sites as of December 2015. Disease outbreaks identified via the surveillance system, or other surveillance approaches, are investigated by epidemiologists trained by the Ministry of Health’s Field Epidemiology Training Program. Other related surveillance modules have been developed on the same model and electronic platform, allowing the country to document the impact of interventions, track progress, and monitor health problems. Sustainability remains the greatest challenge since most of the funding for surveillance come from external sources.

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LUNG ULTRASOUND IN THE COVID-19 PANDEMIC: A PRACTICAL GUIDE FOR OBSTETRICIANS AND GYNECOLOGISTS

ABSTRACT The current COVID-19 pandemic is a challenge to every health system over the globe. Unfortunately, it is likely that this emergency will not disappear soon. No health system, with its present resources and work flow is ready to deal with a full-blown wave of this pandemic. Rapid acquisition of specific new skills may be fundamental in delivering appropriate health care for our patients. COVID-19 infection is classically diagnosed by real time reverse transcription polymerase chain reaction and radiological investigations (X-ray or high-resolution computerized tomography). These techniques are not without limitations. Ultrasound has been suggested as a reliable and accurate tool for assessing the lungs in patients with suspected pneumonia. Obstetricians and gynecologists are usually familiar with the use of ultrasound. Lung ultrasound can show specific signs of interstitial pneumonia, which is characteristic of COVID-19 pulmonary infection. We believe that extensive and rapid training of healthcare providers on the application of ultrasound in the detection of characteristic pulmonary signs of COVID-19 infection, in addition to proper care and handling of their ultrasound machines, is feasible and may be critical in order to provide appropriate management especially of the obstetric patient in the coming period. We present a systematic approach to lung examination, simplified to encourage its adoption by obstetricians and gynecologists, together with an example of a recent pregnant woman with COVID-19 infection, in which lung ultrasound was useful in the management.

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Reducing the Fatality Rate of COVID-19 by Applying Clinical Insights From Immuno-Oncology and Lung Transplantation

There is an urgent need to identify effective strategies that can stop or reverse the inflammatory process that causes acute lung injury, ARDS, and multi-organ failure in COVID-19. Adaptive clinical trials with parallel enrollment to different arms each evaluating a rationally designed combination modality could provide the foundation for the accelerated identification of effective and safe multi-modality treatment algorithms for COVID-19 pneumonia. This article summarizes the insights and lessons learned from clinical immune-oncology trials as well as lung transplantation that are informing the clinical development of promising new strategies aimed at reducing the fatality rate in COVID-19.

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Fluorinated Derivatives of Benz[4,5]imidazo[1,2-b][1,3] thiazole—Inhibitors of Reproduction of Measles Virus

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IDBD: Infectious Disease Biomarker Database

Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.

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Molecular Diagnosis of COVID-19: Challenges and Research Needs

[Image: see text] Molecular diagnosis of COVID-19 primarily relies on the detection of RNA of the SARS-CoV-2 virus, the causative infectious agent of the pandemic. Reverse transcription polymerase chain reaction (RT-PCR) enables sensitive detection of specific sequences of genes that encode the RNA dependent RNA polymerase (RdRP), nucleocapsid (N), envelope (E), and spike (S) proteins of the virus. Although RT-PCR tests have been widely used and many alternative assays have been developed, the current testing capacity and availability cannot meet the unprecedented global demands for rapid, reliable, and widely accessible molecular diagnosis. Challenges remain throughout the entire analytical process, from the collection and treatment of specimens to the amplification and detection of viral RNA and the validation of clinical sensitivity and specificity. We highlight the main issues surrounding molecular diagnosis of COVID-19, including false negatives from the detection of viral RNA, temporal variations of viral loads, selection and treatment of specimens, and limiting factors in detecting viral proteins. We discuss critical research needs, such as improvements in RT-PCR, development of alternative nucleic acid amplification techniques, incorporating CRISPR technology for point-of-care (POC) applications, validation of POC tests, and sequencing of viral RNA and its mutations. Improved assays are also needed for environmental surveillance or wastewater-based epidemiology, which gauges infection on the community level through analyses of viral components in the community’s wastewater. Public health surveillance benefits from large-scale analyses of antibodies in serum, although the current serological tests do not quantify neutralizing antibodies. Further advances in analytical technology and research through multidisciplinary collaboration will contribute to the development of mitigation strategies, therapeutics, and vaccines. Lessons learned from molecular diagnosis of COVID-19 are valuable for better preparedness in response to other infectious diseases.

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6th International Conference on Emerging Zoonoses

The 6th International Conference on Emerging Zoonoses, held at Cancun, Mexico, 24–27 February 2011, offered 84 participants from 18 countries, a snapshot of current research in numerous zoonoses caused by viruses, bacteria or prions. Co‐chaired by Professors Heinz Feldmann and Jürgen Richt, the conference explored 10 topics: (i) The ecology of emerging zoonotic diseases; (ii) The role of wildlife in emerging zoonoses; (iii) Cross‐species transmission of zoonotic pathogens; (iv) Emerging and neglected influenza viruses; (v) Haemorrhagic fever viruses; (vi) Emerging bacterial diseases; (vii) Outbreak responses to zoonotic diseases; (viii) Food‐borne zoonotic diseases; (ix) Prion diseases; and (x) Modelling and prediction of emergence of zoonoses. Human medicine, veterinary medicine and environmental challenges are viewed as a unity, which must be considered under the umbrella of ‘One Health’. Several presentations attempted to integrate the insights gained from field data with mathematical models in the search for effective control measures of specific zoonoses. The overriding objective of the research presentations was to create, improve and use the tools essential to address the risk of contagions in a globalized society. In seeking to fulfil this objective, a three‐step approach has often been applied: (i) use cultured cells, model and natural animal hosts and human clinical models to study infection; (ii) combine traditional histopathological and biochemical approaches with functional genomics, proteomics and computational biology; and (iii) obtain signatures of virulence and insights into mechanisms of host defense response, immune evasion and pathogenesis. This meeting review summarizes 39 of the conference presentations and mentions briefly the 16 articles in this Special Supplement, most of which were presented at the conference in earlier versions. The full affiliations of all presenters and many colleagues have been included to facilitate further inquiries from readers.

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The v-sis oncoprotein loses transforming activity when targeted to the early Golgi complex

The location of autocrine interactions between the v-sis protein and PDGF receptors remains uncertain and controversial. To examine whether receptor-ligand interactions can occur intracellularly, we have constructed fusion proteins that anchor v-sis to specific intracellular membranes. Fusion of a cis-Golgi retention signal from a coronavirus E1 glycoprotein to v-sis protein completely abolished its transforming ability when transfected into NIH3T3 cells. Fusion proteins incorporating mutations in this retention signal were not retained within the Golgi complex but instead were transported to the cell surface, resulting in efficient transformation. All chimeric proteins were shown to dimerize properly. Derivatives of some of these constructs were also constructed bearing the cytoplasmic tail from the glycoprotein of vesicular stomatitis virus (VSV-G). These constructs allowed examination of subcellular localization by double-label immunofluorescence, using antibodies that distinguish between the extracellular PDGF-related domain and the VSV-G cytoplasmic tail. Colocalization of sis-E1-G with Golgi markers confirmed its targeting to the early Golgi complex. The sis-E1 constructs, targeted to the early Golgi complex, exhibited no proteolytic processing whereas the mutant forms of sis-E1 exhibited normal proteolytic processing. Treatment with suramin, a polyanionic compound that disrupts ligand/receptor interactions at the cell surface, was able to revert the transformed phenotype induced by the mutant sis-E1 constructs described here. Our results demonstrate that autocrine interactions between the v-sis oncoprotein and PDGF receptors within the early Golgi complex do not result in functional signal transduction. Another v-sis fusion protein was constructed by attaching the transmembrane domain and COOH-terminus of TGN38, a protein that localizes to the trans-Golgi network (TGN). This construct was primarily retained intracellularly, although some of the fusion protein reached the surface. Deletion of the COOH-terminal region of the TGN38 retention signal abrogated the TGN-localization, as evidenced by very prominent cell surface localization, and resulted in increased transforming activity. The behavior of the sis-TGN38 derivatives is discussed within the context of the properties of TGN38 itself, which is known to recycle from the cell surface to the TGN.

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Declining Public Health Protections within Autocratic Regimes: Impact on Global Public Health Security, Infectious Disease Outbreaks, Epidemics, and Pandemics

Public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the worldʼs population. Management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. Unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. Autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. This is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. All autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. Autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. A cross section of autocratic nations currently experiencing the impact of COVID-19 (coronavirus disease 2019) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. It is time to re-address the pre-SARS (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under World Health Organization (WHO) leadership granted by an International Health Regulations Treaty. Treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. “Honesty is worth a lot more than hope…” The Economist, February 17, 2020.

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The usefulness of pre-employment and pre-deployment psychological screening for disaster relief workers: a systematic review

BACKGROUND: Individuals who conduct disaster relief work overseas are exposed to a variety of traumatic events that can cause distress and trigger psychological illnesses. Identification of which disaster relief workers may be at risk of experiencing psychological distress or mental health disorders is frequently carried out through pre-employment or pre-deployment psychological screening. The primary objective of our review was to assess the evidence for pre-employment and pre-deployment psychological screening of relief workers who work in disaster situations. We aimed to identify specific pre-employment and pre-deployment characteristics that predict impaired wellbeing of an individual following engaging in disaster-related work. METHODS: A combined list of search terms was composed relating to disaster-related occupations, screening methods, psychological disorders, and study design. The databases used were PsycINFO, MEDLINE, EMBASE, and GlobalHealth. We included studies that used cross-sectional or longitudinal study designs; were published in the English language in peer-reviewed academic journals; reported on the association between pre-employment and pre-deployment features and post-deployment psychological disorders or distress; considered any occupational groups responding to a specified, discrete crisis; and used at least one validated measure of distress or disorder. We extracted data on the author; year of publication; disaster description; country of study; study design; population sample; disorder(s) outcome and the measures used; and results. RESULTS: Sixty-two, high-quality studies were included in the review. Forty-one potential predictors were identified. Of these, only volunteer status and previous history of mental illness and life stressors emerged as reliable predictors of distress or disorder. CONCLUSION: The results suggest that whilst it is attractive to screen for pre-employment and pre-deployment indicators of resilience, the evidence base for doing so is weak. At best, this sort of screening can only weakly suggest vulnerability and at worst may result in discrimination. Until better evidence about its usefulness becomes available, employers should exercise caution over its use.

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Focal status epilepticus as unique clinical feature of COVID-19: a case report

Abstract SARS-CoV-2, a novel zoonotic coronavirus, is currently spreading all over the world, causing a pandemic disease defined coronavirus disease 2019 (COVID-19). The spectrum of COVID-19 ranges from asymptomatic or mild infection to rapidly progressive, acute respiratory distress syndrome and death 1 .To the best of our knowledge, status epilepticus has never been described as initial presentation of COVID-19. We report a patient affected by COVID-19 whose primary presentation was a focal status epilepticus.

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Hiding in Plain Sight: Conceptualizing the Creeping Crisis

The COVID‐19 crisis is a stark reminder that modern society is vulnerable to a special species of trouble: the creeping crisis. The creeping crisis poses a deep challenge to both academics and practitioners. In the crisis literature, it remains ill‐defined and understudied. It is even harder to manage. As a threat, it carries a potential for societal disruption—but that potential is not fully understood. An accumulation of these creeping crises can erode public trust in institutions. This paper proposes a definition of a creeping crisis, formulates research questions, and identifies the most relevant theoretical approaches. It provides the building blocks for the systematic study of creeping crises.

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The clinical significance of filmarray pneumonia panel plus in diagnosing pneumonia due to MDRO

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Haemoglobin Oxygen Affinity in Patients with Severe COVID‐19 Infection

During critical care, at least until the late stage of the disease, severely ill COVID‐19 patients may have relatively well preserved lung compliance but remain severely hypoxaemic. A recent theoretical study suggested a direct interaction between COVID‐19 viral proteins and haemoglobin (Hb) that could lead to a loss of oxygen carrying capacity. As national guidelines strongly support a restrictive transfusion strategy in the critically ill, any right‐shift in the Hb O(2) affinity curve could contribute to the hypoxaemia and be potentially harmful. We have measured Hb O(2) affinity curves from severely ill COVID‐19 patients and, in comparison to age‐ and sex‐matched controls, find no evidence for a shift in O(2) affinity that would support any change in clinical management.

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Tocilizumab for the treatment of severe coronavirus disease 2019

Tocilizumab, an interleukin‐6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID‐19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory‐confirmed severe COVID‐19 who received tocilizumab and completed 14 days of follow up. Twenty‐five patients were included, median age was 58 years (interquartile range, 50‐63) and the majority were males (92%). Co‐morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C‐reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID‐19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.

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“This is our next problem”: cleaning up from the covid-19 response

Abstract The purpose of this discussion is to highlight the essential role that solid waste management must play in a humanitarian response towards disasters, in particular the ongoing Covid-19 pandemic. We highlight a number of potential avenues for scholarly investigation into the waste impacts of our response to Covid-19, but in particular, briefly unpacks the relationship between disasters, consumption and disposability as one potential research topic. The discussion is intended to start a conversation that is, at the moment, critically relevant, and to contribute to a more inclusive, and less normatively Western waste management studies discourse

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Lectins: production and practical applications

Lectins are proteins found in a diversity of organisms. They possess the ability to agglutinate erythrocytes with known carbohydrate specificity since they have at least one non-catalytic domain that binds reversibly to specific monosaccharides or oligosaccharides. This articles aims to review the production and practical applications of lectins. Lectins are isolated from their natural sources by chromatographic procedures or produced by recombinant DNA technology. The yields of animal lectins are usually low compared with the yields of plant lectins such as legume lectins. Lectins manifest a diversity of activities including antitumor, immunomodulatory, antifungal, HIV-1 reverse transcriptase inhibitory, and anti-insect activities, which may find practical applications. A small number of lectins demonstrate antibacterial and anti-nematode activities.

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An update on enterovirus 71 infection and interferon type I response

Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Hand, foot, and mouth disease (HFMD) is a serious disease which is usually seen in the Asia‐Pacific region in children. Enterovirus 71 and coxsackievirus A16 are two important viruses responsible for HFMD which are members of group A enterovirus. IFN α and β are two cytokines, which have a major activity in the innate immune system against viral infections. Most of the viruses have some weapons against these cytokines. EV71 has two main proteases called 2A and 3C, which are important for polyprotein processing and virus maturation. Several studies have indicated that they have a significant effect on different cellular pathways such as interferon production and signaling pathway. The aim of this study was to investigate the latest findings about the interaction of 2A and 3C protease of EV71 and IFN production/signaling pathway and their inhibitory effects on this pathway.

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Corrigendum to “Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single centre, observational cohort study” (Br J Anaesth 2020;124: 670-5)

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Computational Resources in Infectious Disease: Limitations and Challenges

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Detection of asymptomatic SARS-CoV-2 exposed individuals by a sensitive S-based ELISA.

To assess the current coronavirus pandemic, there is a pressing need to determine the exposure and seroconversion to SARS-CoV-2 on a local and global level. Here, we demonstrate a sensitive and specific S-protein based assay that is well suited for detection of weak SARS- CoV-2-directed IgG responses, and that could identify exposed individuals with asymptomatic infection without the requirement of PCR diagnostics. Our results raise the possibility that on- going population-based studies using less sensitive state-of-the-art serological assays may significantly underestimate the frequency of exposure and seroconversion to SARS-CoV-2.

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Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China

Infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry. Here, we report the complete genome analysis results for a new natural recombination nephropathogenic IBV strain named SAIBK, which was isolated in the Sichuan province of China in 2005.

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Are Statins Safe in Patients With COVID-19?

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TRAQUEOTOMÍA EN PACIENTES COVID-19: UN PROCEDIMIENTO NECESARIO DE ALTO RIESGO. EXPERIENCIA DE DOS CENTROS

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Reply to the Letter to the Editor: Comment on “COVID-19 infection control protocol inside computed tomography suites”

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Characteristics of human parainfluenza virus type 4 infection in hospitalized children in Korea

BACKGROUND: The characteristics of human parainfluenza virus type 4 (hPIV4) infection are not thoroughly understood. We therefore clarified the characteristics of hPIV4 in Korea. METHOD: From January 2013 to December 2017, children admitted with respiratory tract infection at the Department of Pediatrics in Chung‐Ang University Hospital were enrolled in the study. Nasopharyngeal aspirate specimens were obtained from patients and tested for hPIV types by multiplex reverse transcription polymerase chain reaction. We retrospectively reviewed subject medical records, focusing on epidemiological and clinical characteristics. RESULTS: Of the 12 423 NPA specimens, 8,406 were positive by multiplex reverse transcription polymerase chain reaction for nine respiratory viruses, and 1,018 were positive for one of the four types of hPIV: 1,018 specimens led to the detection of 1,029 hPIVs; 3ss (31.3%) were positive for hPIV1, 120 (11.7%) were positive for hPIV2, 356 (34.6%) were positive for hPIV3, and 231 (22.4%) were positive for hPIV4. Of the hPIV‐positive patients, the mean age was 2.3 years (range, 0.1–12.7 years), 225 (97.4%) had no underlying disease, and 178 (77.1%) had a fever with a duration of 4.1 ± 2.3 days and a peak temperature of 39.0 ± 0.7 ℃. The most common diagnosis in hPIV4 infection was pneumonia (44.2%), followed by bronchiolitis (26.0%) and upper respiratory tract infection (24.3%). Only 2.2% of patients were diagnosed with croup. Although the most prevalent overall type of hPIV was hPIV3, hPIV4 generally caused acute respiratory tract infection in summer and early fall in an irregular annual pattern. CONCLUSIONS: Human parainfluenza virus type 4 is an important common pathogen of respiratory tract infections in pediatric patients in Korea.

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A new twenty-first century science for effective epidemic response

With rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems, epidemics will become more frequent, more complex and harder to prevent and contain. Here we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world—especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow’s leaders in epidemic prevention and response.

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Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types

BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.

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COVID-19 outbreaks in U.S. immigrant detention centers: the urgent need to adopt CDC guidelines for prevention and evaluation

There have been several significant outbreaks of COVID-19 in federal immigrant detention centers, which lack clear and consistent guidelines across Department of Homeland Security (DHS) agencies to limit the spread of COVID-19. The Centers for Disease Control and Prevention (CDC) has issued detailed guidelines for the control, prevention, and evaluation of COVID-19 in detention facilities. While the DHS’s Immigration and Customs Enforcement agency has stated that it complies with CDC recommendations, its policies significantly differ from these CDC guidelines, placing detainees at risk for contracting COVID-19. This submission urges the adoption of CDC guidelines across DHS-associated facilities. Such a policy change has the potential to protect and save the lives of the most vulnerable populations under the auspices of the federal government.

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Novel Coronavirus Disease (COVID-19)

The present outbreak of the novel coronavirus initially called as “2019 novel coronavirus” or “2019-nCoV” by the World Health Organization (WHO), is also known as “Wuhan coronavirus” or “Wuhan pneumonia”, as it started in the Wuhan city of China in early December of 2019. This new coronavirus-associated acute respiratory deadly disease is now officially named as Corona Virus Disease-19 (COVID-19) by the WHO. From China, this epidemic has now spread to all over the world. On 11 March 2020, the WHO recognised COVID-19 as a pandemic. A pandemic refers to a disease that has spread to several countries, continents, if not worldwide. While the information available on this newly identified virus is limited and evolving, here is a quick run-down of what has been figured out so far.

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Unmasking psychological reasons of delay in acute coronary syndromes presentation during the COVID‐19 pandemic

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Genetic restriction of murine hepatitis virus type 3 expression in liver and brain: comparative study in BALB/c and C3H mice by immunochemistry and hybridization in situ

To study the host-dependent genetic variations in murine hepatitis virus type 3 (MHV 3) induced diseases, we localized the sites of MHV 3 (Mill Hill strain) expression within liver and brain by immunohistochemistry or hybridization in situ. Two strains of mice were studied: BALB/c mice, which develop an acute and lethal hepatitis and C3H mice which develop a chronic brain infection. In BALB/c mice, viral RNA and antigens appeared during the first 24 h post infection (p.i.) in liver, whereas viral RNA was barely detectable in brain, up until death at day 3 p.i. In C3H mice, viral RNA and antigens were detected simultaneously in liver and brain only at day 2 p.i. In brain, the virus was detected in meningeal and ependymal cells and in perivascular cortical areas (days 5 and 7 p.i.). After day 49, the virus was no longer detected in brain parenchyma, but persisted in meningeal cells. Two host-dependent genetic differences in viral processing were observed in the liver: (1) the virus was first detected in Kupffer cells in BALB/c mice and mostly in hepatocytes in C3H mice; (2) in BALB/c mice, the 180 kDa S viral glycoprotein appeared more frequently cleaved in 90 kDa form than in C3H mice.

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Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines

There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.

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The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages

Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc γ R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc γ R on feline macrophage.

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Exaggerated information and COVID‐19 outbreak

We read the article on "Coronavirus disease 2019: the harms of exaggerated information and non-evidence-based measures" with a great interest [1]. Ioannidis noted that "It is important to differentiate promptly the true epidemic from an epidemic of false claims and potentially harmful actions [1]."

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Clinical Impact of Infection with Pandemic Influenza (H1N1) 2009 Virus in Naïve Nucleus and Multiplier Pig Herds in Norway

The Norwegian pig population has been free from influenza viruses until 2009. The pandemic influenza outbreak during the autumn 2009 provided an opportunity to study the clinical impact of this infection in an entirely naïve pig population. This paper describes the results of a case-control study on the clinical impact of pandemic influenza (H1N1) 2009 infection in the nucleus and multiplier herds in Norway. The infection spread readily and led to seroconversion of 42% of the Norwegian nucleus and multiplier herds within a year. Positive and negative herds were identified based on surveillance data from the Norwegian Veterinary Institute. Telephone interviews were conducted with pig herd owners or managers between November 2010 and January 2011. Pigs with clinical signs were reported from 40% of the case herds with varying morbidity and duration of respiratory disease and reduced reproductive performance. Clinical signs were reported in all age groups.

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ICU beds: less is more? Yes

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A binning tool to reconstruct viral haplotypes from assembled contigs

Infections by RNA viruses such as Influenza, HIV still pose a serious threat to human health despite extensive research on viral diseases. One challenge for producing effective prevention and treatment strategies is high intra-species genetic diversity. As different strains may have different biological properties, characterizing the genetic diversity is thus important to vaccine and drug design. Next-generation sequencing technology enables comprehensive characterization of both known and novel strains and has been widely adopted for sequencing viral populations. However, genome-scale reconstruction of haplotypes is still a challenging problem. In particular, haplotype assembly programs often produce contigs rather than full genomes. As a mutation in one gene can mask the phenotypic effects of a mutation at another locus, clustering these contigs into genome-scale haplotypes is still needed. We developed a contig binning tool, VirBin, which clusters contigs into different groups so that each group represents a haplotype. Commonly used features based on sequence composition and contig coverage cannot effectively distinguish viral haplotypes because of their high sequence similarity and heterogeneous sequencing coverage for RNA viruses. VirBin applied prototype-based clustering to cluster regions that are more likely to contain mutations specific to a haplotype. The tool was tested on multiple simulated sequencing data with different haplotype abundance distributions and contig sizes, and also on mock quasispecies sequencing data. The benchmark results with other contig binning tools demonstrated the superior sensitivity and precision of VirBin in contig binning for viral haplotype reconstruction. https://github.com/chjiao/VirBin yannisun@cityu.edu.hk

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Accidental Chlorine Gas Intoxication: Evaluation of 39 Patients

BACKGROUND: Chlorine is a known pulmonary irritant gas that may cause acute damage in the respiratory system. In this paper, the socio-demographic and clinical characteristics of 39 accidentally exposed patients to chlorine gas are reported and different emergency treatment modalities are also discussed. METHODS: Two emergency departments applications were retrospectively analyzed for evaluation of accidental chlorine gas exposure for year 2007. Patients were classified into 3 groups according to severity of clinical and laboratory findings based on the literature and duration of land of stay in the emergency department. The first group was slightly exposed (discharged within 6 hours), second group moderately exposed (treated and observed for 24 hours), and third group was severely exposed (hospitalized). Most of the patients were initially treated with a combination of humidified oxygen, corticosteroids, and bronchodilators. RESULTS: The average age was 17.03 ± 16.01 years (95% CI). Seven (17.9%) of them were female and 29 (74.4%) were children. Twenty-four patients (61.5%) were included in the first, nine (23.1%) were in second and six (15.4%) were in the third group. The presenting symptoms were cough, nausea, and vomiting and conjunctiva hyperemia for the first group, first groups symptoms plus dyspnea for the second group. Second groups symptoms plus palpitation, weakness and chest tightness were for the third group. Cough and dyspnea were seen in 64.1% and 30.8% of the patients respectively. No patients died. CONCLUSIONS: The authors recommend that non symptomatic or slightly exposed patients do not need any specific treatment or symptomatic treatment is sufficient. KEYWORDS: Accidental; Chlorine exposure; Chlorine gas; Chlorine intoxication; Emergency department

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Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19

In December 2019, a new and highly contagious infectious disease emerged in Wuhan, China. The etiologic agent was identified as a novel coronavirus, now known as Severe Acute Syndrome Coronavirus-2 (SARS-CoV-2). Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-α and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II). Both TNF-α and AT-II have been implicated in promoting overexpression of tissue factor (TF) in platelets and macrophages. Additionally, the generation of antiphospholipid antibodies associated with COVID-19 may also promote an increase in TF. TF may be a critical mediator associated with the development of thrombotic phenomena in COVID-19, and should be a target for future study.

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Selected veterinary concerns of geriatric rats, mice, hamsters and gerbils

Improved husbandry and better knowledge of exotic pets have led to a gradual increase in the lifespan of pets such as rats, mice, hamsters, and gerbils. Much of the information we have on these senior patients is derived from the laboratory animal studies and anecdotal practitioner information. While the small size of some of the patients makes blood collection problematic for hematology and organ function testing, the advent of polymerase chain reaction (PCR) testing and other molecular diagnostics is allowing the practitioner testing of specific etiologies with the very small biologic samples available. Both radiology and ultrasonography are also very valuable diagnostic modalities.

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Coordinated Response to SARS, Vancouver, Canada

Two Canadian urban areas received travelers with severe acute respiratory syndrome (SARS) before the World Health Organization issued its alert. By July 2003, Vancouver had identified 5 cases (4 imported); Toronto reported 247 cases (3 imported) and 43 deaths. Baseline preparedness for pandemic threats may account for the absence of sustained transmission and fewer cases of SARS in Vancouver.

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The Early Effects of Social Distancing Resultant From COVID-19 on Admissions To a Level I Trauma Center

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Burden of exposure to infectious bursal disease virus, infectious bronchitis virus, Newcastle disease virus, Mycoplasma gallisepticum, and intestinal parasites in introduced broiler chickens on the Galapagos

Diseases in introduced broilers can possibly spill over to wild birds on the Galapagos. Knowledge about the current burden of exposure to pathogens in broilers on the Galapagos is very limited. The objective of the study reported here was to measure the burden of exposure to infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), Mycoplasma gallisepticum (MG), and intestinal parasites in a sample of broiler chickens on 13 farms on Santa Cruz Island and San Cristobal Island in July 2017. Blood serum samples were tested for detection of antibodies to IBDV, IBV, NDV, and MG by using an IDEXX Enzyme-linked Immunosorbent Assay. In addition, fecal samples and pen bedding environmental samples were processed and analyzed for diagnosis of intestinal parasite eggs under a compound light microscope. The frequency of seropositive broilers to IBDV was 74/130 or 56% (95% CI = 48, 65%), to IBV was 27/130 or 20% (14, 28%), and to NDV was 1/130 or 0.7% (0.1, 4%). All broilers tested negative to MG antibodies. Eimeria spp. infection was common in study broilers. Finally, we observed interaction between broiler chickens and wild birds (finches) inside broiler pens, as well as the presence of backyard chickens inside property limits of study farms. This study produced evidence that exposure to IBDV, IBV, and intestinal parasites in broilers on Santa Cruz Island and San Cristobal Island is important. Study results are relevant because (i) they provide new baseline data on the burden of exposure to avian pathogens in broiler farms, (ii) justify the need to verify standard operating procedures in hatcheries that supply (non-vaccinated) day-old chicks to the Galapagos and (iii) to implement enhanced biosecurity standards on broiler chicken farms to mitigate risk of disease transmission between broilers, backyard poultry, and wild birds on the Galapagos.

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The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek

With 40% of the world population at risk, infections with dengue virus (DENV) constitute a serious threat to public health. While there is no antiviral therapy available against this potentially lethal disease, the efficacy of the only approved vaccine is not optimal and its safety has been recently questioned. In order to develop better vaccines based on attenuated and/or chimeric viruses, one must consider how the human immune system is engaged during DENV infection. The activation of the innate immunity through the detection of viruses by cellular sensors is the first line of defence against those pathogens. This triggers a cascade of events which establishes an antiviral state at the cell level and leads to a global immunological response. However, DENV has evolved to interfere with the innate immune signalling at multiple levels, hence dampening antiviral responses and favouring viral replication and dissemination. This review elaborates on the interplay between DENV and the innate immune system. A special focus is given on the viral countermeasure mechanisms reported over the last decade which should be taken into consideration during vaccine development.

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COVID-19 poses novel challenges for global primary care

COVID-19 is presenting novel challenges for global primary care, and its response has been inspiring, varied, and also troubling.

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Packaging of porcine reproductive and respiratory syndrome virus replicon RNA by a stable cell line expressing its nucleocapsid protein

Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, is one of the most common and economically important swine pathogens. Although both live-attenuated and killed-inactivated vaccines against the virus have been available for a decade, PRRSV is still a major problem in the swine industry worldwide. To explore the possibility of producing single-round infectious PRRSV replicon particles as a potential vaccine strategy, we have now generated two necessary components: 1) a stable cell line (BHK/Sinrepl9/PRRSV-N) that constitutively expresses the viral nucleocapsid (N) protein localized to the cytoplasm and the nucleolus and 2) a PRRSV replicon vector (pBAC/PRRSV/Replicon-AN) with a 177-nucleotide deletion, removing the 3′-half portion of ORF7 in the viral genome, from which the self-replicating propagation-defective replicon RNAs were synthesized in vitro by SP6 polymerase run-off transcription. Transfection of this replicon RNA into N protein-expressing BHK-21 cells led to the secretion of infectious particles that packaged the replicon RNA, albeit with a low production efficiency of 0.4 × 10(2) to 1.1 × 10(2) infectious units/ml; the produced particles had only single-round infectivity with no cell-to-cell spread. This trans-complementation system for PRRSV provides a useful platform for studies to define the packaging signals and motifs present within the viral genome and N protein, respectively, and to develop viral replicon-based antiviral vaccines that will stop the infection and spread of this pathogen.

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Could the D614 G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?

Increasing number of deaths due to COVID-19 pandemic has raised serious global concerns. Higher testing capacity and ample intensive care availability could explain lower mortality in some countries compared to others. Nevertheless, it is also plausible that the SARS-CoV-2 mutations giving rise to different phylogenetic clades are responsible for the obvious death disparities around the world. Current research literature linking the genetic make-up of SARS-CoV-2 with fatality is lacking. Here, we suggest that this disparity in fatality rates may be attributed to SARS-CoV-2 evolving mutations and urge the international community to begin addressing the phylogenetic clade classification of SARS-CoV-2 in relation to clinical outcomes.

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Homology Models and Molecular Dynamics Simulations of Main Proteinase from Coronavirus Associated with Severe Acute Respiratory Syndrome (SARS)

In this study, two structural models (denoted as M(pro)ST and M(pro)SH) of the main proteinase (M(pro)) from the novel coronavirus associated with severe acute respiratory syndrome (SARS‐CoV) were constructed based on the crystallographic structures of M(pro) from transmissible gastroenteritis coronavirus (TGEV) (M(pro)T) and human coronavirus HcoV‐229E (M(pro)H), respectively. Various 200 ps molecular dynamics simulations were subsequently performed to investigate the dynamics behaviors of several structural features. Both M(pro)ST and M(pro)SH exhibit similar folds as their respective template proteins. These structural models reveal three distinct functional domains as well as an intervening loop connecting domains II and III as found in both template proteins. In addition, domain III of these structures exhibits the least secondary structural conservation. A catalytic cleft containing the substrate binding subsites S1 and the S2 between domains I and II are also observed in these structural models. Although these structures share many common features, the most significant difference occurs at the S2 subsite, where the amino acid residues lining up this subsite are least conserved. It may be a critical challenge for designing anti‐SARS drugs by simply screening the known database of proteinase inhibitors.

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Bibliometric analysis of Severe Acute Respiratory Syndrome-related research in the beginning stage

Severe Acute Respiratory Syndrome (SARS) has become the major of health issues since its outbreak early 2003. No analyses by bibliometric technique that have examined this topic exist in the literature. The objective of this study is to conduct a bibliometric analysis of all SARS-related publications in Science Citation Index (SCI) in the early stage. A systematic search was performed using the SCI for publications since SARS outbreak early 2003. Selected documents included 'severe acute respiratory syndrome' or 'SARS' as a part of its title, abstract, or keyword from the beginning stage of SARS outbreak, March till July 8, 2003. Analysis parameters included authorship, patterns of international collaboration, journals, language, document type, research institutional address, times cited, and reprint address. Citation analysis was mainly based on impact factor as defined by Journal Citation Reports(JCR) issued in 2002 and on the actual citation impact (ACI), which has been used to assess the impact relative to the whole field and has been defined as the ratio between individual citation per publication value and the total citation per publication value. Thirty-two percent of total share was published as news features, 25% as editorial materials, 22% as articles, 13% as letters, and the remaining being biographic items, corrections, meeting abstracts, and reprints. The US dominated the production by 30% of the total share followed closely by Hong Kong with 24%. Sixty-three percent of publication was published by the mainstream countries. The SARS publication pattern in the past few months suggests immediate citation, low collaboration rate, and English and mainstream country domination in production. We observed no associations of research indexes with the number of cases.

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Neue und seltene pneumotrope Viren

While acute viral respiratory tract infections are one of the major reasons for the loss of productivity among the general population in industrialized nations, they are one of the top killers among infants worldwide, in particular in low-income countries. With the advances in molecular diagnostics and the introduction of high-throughput screening techniques a variety of novel, so far unknown viruses have been discovered from respiratory secretions. However, the clinical significance is often difficult to determine. This review article provides an introduction to those novel viruses which have been described since the beginning of the millennium and discusses the clinical relevance in the light of current scientific evidence. The viruses covered by the present review are human metapneumovirus, human bocavirus, human coronaviruses OC43, 229E, NL63, HKU1, SARS and MERS, human polyomaviruses KI, MC and WU and human parechoviruses.

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One health: the importance of companion animal vector-borne diseases

The international prominence accorded the 'One Health' concept of co-ordinated activity of those involved in human and animal health is a modern incarnation of a long tradition of comparative medicine, with roots in the ancient civilizations and a golden era during the 19(th )century explosion of knowledge in the field of infectious disease research. Modern One Health tends to focus on zoonotic pathogens emerging from wildlife and production animal species, but one of the most significant One Health challenges is rabies for which there is a canine reservoir. This review considers the role of small companion animals in One Health and specifically addresses the major vector-borne infectious diseases that are shared by man, dogs and cats. The most significant of these are leishmaniosis, borreliosis, bartonellosis, ehrlichiosis, rickettsiosis and anaplasmosis. The challenges that lie ahead in this field of One Health are discussed, together with the role of the newly formed World Small Animal Veterinary Association One Health Committee.

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Mechanisms that determine plasma cell lifespan and the duration of humoral immunity

Summary: Humoral immunity following vaccination or infection is mainly derived from two types of cells: memory B cells and plasma cells. Memory B cells do not actively secrete antibody but instead maintain their immunoglobulin in the membrane‐bound form that serves as the antigen‐specific B‐cell receptor. In contrast, plasma cells are terminally differentiated cells that no longer express surface‐bound immunoglobulin but continuously secrete antibody without requiring further antigenic stimulation. Pre‐existing serum or mucosal antibody elicited by plasma cells (or other intermediate antibody‐secreting cells) represents the first line of defense against reinfection and is critical for protection against many microbial diseases. However, the mechanisms involved with maintaining long‐term antibody production are not fully understood. Here, we examine several models of long‐term humoral immunity and present a new model, described as the ‘Imprinted Lifespan’ model of plasma cell longevity. The foundation of this model is that plasma cells are imprinted with a predetermined lifespan based on the magnitude of B‐cell signaling that occurs during the induction of an antigen‐specific humoral immune response. This represents a testable hypothesis and may explain why some antigen‐specific antibody responses fade over time whereas others are maintained essentially for life.

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COVID‐19 pneumonia in kidney transplant recipients—Where we are?

In late December 2019, China reported cases of respiratory illness in humans that involved a novel coronavirus SARS‐CoV‐2. On March 20, 2020, the first coronavirus disease 2019 (COVID‐19) in Brazil was diagnosed, and by now, we present the report on the first case of COVID among transplant recipients in our country. A liver and kidney transplant patient with SARS‐CoV‐2 pneumonia without respiratory failure was treated in a clinical multimodal strategy consisting of symptomatic support therapy, immunosuppression reduction, use of anti‐coronavirus drugs and heparin leading to a progressive improvement of patient symptoms till discharge. The authors also present a comprehensive review of published cases.

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COVID-19 preventive measures showing an unintended decline in infectious diseases in Taiwan

Abstract Many communicable diseases may have contact, airborne, and/or droplets transmission. Following the COVID-19 outbreak, Taiwan government implemented the use of masks and sanitizer and other prevention measures, like social distancing for prevention. This public response may have likely contributed significantly to the decline in the outbreak of other infectious diseases.

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Defining the spectrum of genome policy

Many achievements in the genome sciences have been facilitated by policies that have prioritized genome research, secured funding and raised public and health-professional awareness. Such policies should address ethical, legal and social concerns, and are as important to the scientific and commercial development of the field as the science itself. On occasion, policy issues take precedence over science, particularly when impasses are encountered or when public health or money is at stake. Here we discuss the spectrum of current issues and debates in genome policy, and how to actively engage all affected stakeholders to promote effective policy making.

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OPV-like poliovirus type 1 detection in patients with severe acute respiratory syndrome

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Management of asthma during the Coronavirus disease 2019 outbreak

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Care of Asymptomatic SARS‐CoV‐2 positive Kidney Transplant Recipients

Sharing of experience amongst transplant community through various platforms and rapid publications has proven invaluable during the COVID‐19 pandemic (1‐3). The general consensus seemed to be that most kidney transplant recipients would have a moderate or mild course, although some may progress to a more severe disease. It was recommended to stop or decrease the dose of anti‐proliferative agents and continue with calcineurin inhibitors (CNIs) and maintenance steroids (4).

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Healthy people 2100: modeling population health impacts of climate change

Quantitatively estimating the potential health impacts of climate change is facilitated by multi-determinant models that integrate micro- to macro-level exposures and processes that influence disease occurrence, including the public health responses, in order to identify regions and population groups that may be more vulnerable. Although progress has been made in constructing systems-based models, considerable work is required to address key issues of quantification of the climate-health associations and the factors that affect those associations; specification of model(s) appropriate to incorporate climate change, adaptation, and mitigation policies; incorporation of thresholds; incorporation of pathways of public health development; and quantification of uncertainties.

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Re: Toward a consensus view in the management of acute facial injuries during the Covid-19 pandemic

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Growing networks with communities: A distributive link model

Evolution and popularity are two keys of the Barabasi–Albert model, which generates a power law distribution of network degrees. Evolving network generation models are important as they offer an explanation of both how and why complex networks (and scale-free networks, in particular) are ubiquitous. We adopt the evolution principle and then propose a very simple and intuitive new model for network growth, which naturally evolves modular networks with multiple communities. The number and size of the communities evolve over time and are primarily subjected to a single free parameter. Surprisingly, under some circumstances, our framework can construct a tree-like network with clear community structures—branches and leaves of a tree. Results also show that new communities will absorb a link resource to weaken the degree growth of hub nodes. Our models have a common explanation for the community of regular and tree-like networks and also breaks the tyranny of the early adopter; unlike the standard popularity principle, newer nodes and communities will come to dominance over time. Importantly, our model can fit well with the construction of the SARS-Cov-2 haplotype evolutionary network.

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A natural reassortant and mutant serotype 3 reovirus from mink in China

Mammalian orthoreoviruses (MRVs) are widespread and infect virtually all mammals. We report here the first case of a natural mutant and reassortant serotype 3 reovirus from mink in China, known as MRV3 SD-14. Whole-genome sequence analysis showed that the MRV3 SD-14 may have resulted from a reassortment involving MRVs that infected swine, humans and mink. Interestingly, the S1 segment, which encodes the viral attachment protein σ1, which influences viral virulence and cell tropism in the host, had a stop codon mutation at amino acid 246. Surveillance of the virulence and evolution of MRVs in humans and other animals deserves more attention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-015-2670-1) contains supplementary material, which is available to authorized users.

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Human bocavirus types 1, 2 and 3 in acute gastroenteritis of childhood

Aim: Recently identified human bocavirus (HBoV) types 2 and 3 have been associated with acute gastroenteritis in children. We studied 878 stool specimens from children with acute gastroenteritis and 112 controls (43 children with unspecified fever, 33 with respiratory tract infection and 36 healthy children) for known HBoVs. The same specimens were previously studied for rotaviruses, noroviruses, sapoviruses, adenoviruses, coronaviruses and aichivirus. Methods: HBoVs were detected by PCR and positive amplicons were sequenced to identify HBoV1, HBoV2, HBoV3 and HBoV4. Results: HBoV of any type was found in 85 (9.7%) cases of acute gastroenteritis and in 6 (5.4%) controls. HBoV1 was detected in 49 (5.6%) cases and 2 (1.8%) controls, HBoV2 in 29 (3.3%) cases and 2 (1.8%) controls and HBoV3 in 8 (0.9%) cases and 2 (1.8%) controls. No HBoV4 was found. HBoV as a single infection was found in 16 (1.8%) cases and in 6 (5.4%) controls; in the remaining cases, a known gastroenteritis virus was also found. Among the single HBoV infections, HBoV2 was the most common type with 8 (50%) cases. Conclusion: HBoVs are rarely found alone in children with acute gastroenteritis. Further studies are warranted to confirm a possible specific association of HBoV2 with gastroenteritis.

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Zoonotic disease research in East Africa

BACKGROUND: The East African region is endemic with multiple zoonotic diseases and is one of the hotspots for emerging infectious zoonotic diseases with reported multiple outbreaks of epidemic diseases such as Ebola, Marburg and Rift Valley Fever. Here we present a systematic assessment of published research on zoonotic diseases in the region and thesis research in Kenya to understand the regional research focus and trends in publications, and estimate proportion of theses research transitioning to peer-reviewed journal publications. METHODS: We searched PubMed, Google Scholar and African Journals Online databases for publications on 36 zoonotic diseases identified to have occurred in the East Africa countries of Burundi, Ethiopia, Kenya, Tanzania, Rwanda and Uganda, for the period between 1920 and 2017. We searched libraries and queried online repositories for masters and PhD theses on these diseases produced between 1970 and 2016 in five universities and two research institutions in Kenya. RESULTS: We identified 771 journal articles on 22, and 168 theses on 21 of the 36 zoonotic diseases investigated. Research on zoonotic diseases increased exponentially with the last 10 years of our study period contributing more than half of all publications 460 (60%) and theses 102 (61%) retrieved. Endemic diseases were the most studied accounting for 656 (85%) and 150 (89%) of the publication and theses studies respectively, with publications on epidemic diseases associated with outbreaks reported in the region or elsewhere. Epidemiological studies were the most common study types but limited to cross-sectional studies while socio-economics were the least studied. Only 11% of the theses research transitioned to peer-review publications, taking an average of 2.5 years from theses production to manuscript publication. CONCLUSION: Our findings demonstrate increased attention to zoonotic diseases in East Africa but reveal the need to expand the scope, focus and quality of studies to adequately address the public health, social and economic threats posed by zoonoses.

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Health-protective behaviour, social media usage and conspiracy belief during the COVID-19 public health emergency

BACKGROUND: Social media platforms have long been recognised as major disseminators of health misinformation. Many previous studies have found a negative association between health-protective behaviours and belief in the specific form of misinformation popularly known as ‘conspiracy theory’. Concerns have arisen regarding the spread of COVID-19 conspiracy theories on social media. METHODS: Three questionnaire surveys of social media use, conspiracy beliefs and health-protective behaviours with regard to COVID-19 among UK residents were carried out online, one using a self-selecting sample (N = 949) and two using stratified random samples from a recruited panel (N = 2250, N = 2254). RESULTS: All three studies found a negative relationship between COVID-19 conspiracy beliefs and COVID-19 health-protective behaviours, and a positive relationship between COVID-19 conspiracy beliefs and use of social media as a source of information about COVID-19. Studies 2 and 3 also found a negative relationship between COVID-19 health-protective behaviours and use of social media as a source of information, and Study 3 found a positive relationship between health-protective behaviours and use of broadcast media as a source of information. CONCLUSIONS: When used as an information source, unregulated social media may present a health risk that is partly but not wholly reducible to their role as disseminators of health-related conspiracy beliefs.

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Orthopaedic resident management during the COVID-19 pandemic – AIIMS model

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Equine Arteritis Virus Does Not Induce Interferon Production in Equine Endothelial Cells: Identification of Nonstructural Protein 1 as a Main Interferon Antagonist

The objective of this study was to investigate the effect of equine arteritis virus (EAV) on type I interferon (IFN) production. Equine endothelial cells (EECs) were infected with the virulent Bucyrus strain (VBS) of EAV and expression of IFN-β was measured at mRNA and protein levels by quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP), respectively. Quantitative RT-PCR results showed that IFN-β mRNA levels in EECs infected with EAV VBS were not increased compared to those in mock-infected cells. Consistent with quantitative RT-PCR, Sendai virus- (SeV-) induced type I IFN production was inhibited by EAV infection. Using an IFN-β promoter-luciferase reporter assay, we subsequently demonstrated that EAV nsps 1, 2, and 11 had the capability to inhibit type I IFN activation. Of these three nsps, nsp1 exhibited the strongest inhibitory effect. Taken together, these data demonstrate that EAV has the ability to suppress the type I IFN production in EECs and nsp1 may play a critical role to subvert the equine innate immune response.

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Chapter 13 Transmission of Infectious Diseases Through Breast Milk and Breastfeeding

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Viral Diarrhea

Abstract Viral gastroenteritis is among the most common illnesses affecting humans and has greatest impact at the extremes of age. The spectrum of disease can range from asymptomatic infections to severe disease with dehydration. In contrast to bacterial pathogens, enteric viruses cannot multiply outside their host; hence, the original inoculum into the common source determines infectivity. Prevention of contamination of food and water control primary cases, whereas careful nursing and handwashing prevent secondary cases. Effective vaccines are available and widely used to prevent rotaviral gastroenteritis, but vaccines for other causes of viral gastroenteritis are not yet available.

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IFNL4 Genotypes Predict Clearance of RNA Viruses in Rwandan Children With Upper Respiratory Tract Infections

Polymorphisms in the interferon lambda gene locus (IFNL) such as the IFNL4 genetic variants rs12979860 and rs368234815 are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of IFNL4 variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, n = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell IFNL4 genotype at rs12979860 and rs368234815. Approximately 1/3 of the children were homozygous for the rs12979860 T allele and the rs368234815 ΔG allele, which are overrepresented in subjects of African descent. These IFNL4 variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that IFNL4 genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract.

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Update on the neurology of COVID‐19

Though infection with the SARS-CoV2 virus predominantly manifests in the lung as an interstitial pneumonia ("ground glass opacities"), there is increasing evidence that the virus invades all compartments of the body, particularly the eyes, heart, skin, kidneys, and the central nervous system(CNS).1 This article is protected by copyright. All rights reserved.

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Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study

BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

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A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein

Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.

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Effect of COVID‐19 pandemic on stroke admission rates in a Norwegian population

OBJECTIVES: There are concerns that public anxiety around COVID‐19 discourages patients from seeking medical help. The aim of this study was to see how lockdown due to the pandemic affected the number of admissions of acute stroke. METHODS: All patients discharged from Akershus University Hospital with a diagnosis of transient ischemic attack (TIA) or acute stroke were identified by hospital chart review. January 3 to March 12 was defined as before, and March 13 to April 30 as during lockdown. RESULTS: There were 21.8 admissions/week before and 15.0 admissions/week during the lockdown (P < .01). Patients had on average higher NIHSS during the lockdown than before (5.9 vs. 4.2, P = .041). In the multivariable logistic regression model for ischemic stroke (adjusted for sex, age, living alone and NIHSS ≤ 5), there was an increased OR of 2.05 (95% CI 1.10‐3.83, P = .024) for not reaching hospital within 4.5 hours during the lockdown as compared to the period before the lockdown. CONCLUSION: There was a significant reduction in number of admissions for stroke and TIAs during the lockdown due to the COVID‐19 pandemic in Norway.

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Rapid and sensitive detection of multiple genes from the SARS‐Coronavirus using quantitative RT‐PCR with dual systems

The outbreak of severe acute respiratory syndrome (SARS) was caused by a newly identified coronavirus (SARS‐CoV) in 2003. To detect early SARS‐CoV infection, a one‐step, real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) assay was developed that could simultaneously detect nucleocapsid (N), membrane (M), and spike (S) genes of SARS‐CoV with the same PCR condition using either Applied Biosystems (ABI) Prism 7700 Sequence Detection System or Roche LightCycler. The sensitivity of this assay was evaluated using cell culture‐derived viruses, in vitro transcribed viral RNA, and clinical specimens. The SARS‐S, ‐M, and ‐N primer/probe sets described in this paper could detect one to ten copies of in vitro transcribed S, M, and N RNA per test using both the ABI and Roche assay systems. The relative sensitivities for detecting cell culture‐derived SARS‐CoV were 0.01, 0.01, and 0.001 PFU/test, respectively. It showed that SARS‐N has comparable detection efficiencies to SARS2 and SARS3 which are primers sets designed by Centers for Disease Control and Prevention. In addition, SARS‐S and SARS‐M also demonstrated equivalent sensitivity to the commercially available RealArt HPA‐Coronavirus reagents (Artus). The relative sensitivity of these primer/probe sets was also examined using human sera spiked viruses and clinical specimens from four confirmed SARS patients. Similar results as above were obtained. Specificity tests and sequence alignment showed that these primer/probe sets annealed perfectly to 31 isolates of SARS‐CoV; and there was no cross detection with other coronaviruses and human respiratory tract‐associated viruses. Therefore, not only is it compatible with the ABI and Roche systems, this multiple‐gene detection assay also has the merit of being a rapid, safe, sensitive, and specific tool for accurate diagnosis of SARS‐CoV infection. J. Med. Virol. 77:151–158, 2005. © 2005 Wiley‐Liss, Inc.

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Potential Role of Platelets in COVID‐19: Implications for Thrombosis

For the past 150 years, platelets have been recognized as the major blood component that mediates hemostasis and thrombosis. In more recent years, however, we have come to appreciate that platelets also perform profound immune functions during infection with various pathogens. We now recognize that platelets can also mediate a response to various RNA viruses such as influenza and that many viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can affect platelet count. Thrombocytopenia and increased coagulation have been independently associated with increased mortality. This article provides a perspective on the potential roles of platelets during COVID‐19.

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A Randomized Clinical Trial Evaluating Metabolism of Colostral and Plasma Derived Immunoglobulin G in Jersey Bull Calves

BACKGROUND: Intravenous plasma administration has been recommended in healthy or sick calves with failure of passive immunity. HYPOTHESIS: IV administered plasma‐derived immunoglobulin G (IgG) undergoes increased catabolism as reflected by a rapid decrease in serum IgG concentration with an increase in fecal IgG concentrations within 48 h. ANIMALS: Thirty newborn Jersey calves. Fifteen were fed colostrum (CL group) and 15 were given bovine plasma IV (PL group). MATERIALS AND METHODS: Randomized clinical trial. Calves in the CL group were fed 3 L of colostrum once, by oroesophageal tubing. Calves in the PL group were given plasma IV at a dosage of 34 mL/kg. Serum and fecal samples were collected at 0 h, 6 h, 12 h, 48 h, 5 d, and 7 d. Serum and fecal IgG concentrations were determined by radial immunodiffusion. RESULTS: Calves in the CL group maintained serum IgG concentrations consistent with adequate transfer of immunity (≥1,000 mg/dL) throughout the study period. Calves in the PL group achieved median IgG concentrations of ≥1,000 mg/dL at 6 h but the concentrations were <1,000 mg/dL by 12 h. Calves in the PL group were 5 times more likely to experience mortality compared to the CL group (hazard ratio = 5.01). Fecal IgG concentrations were not different between the 2 groups during the first 48 h (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Catabolism of plasma derived IgG occurs rapidly during the first 12 h after transfusion. Fecal excretion did not explain the fate of the plasma derived IgG.

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Taxon-specific aerosolization of bacteria and viruses in an experimental ocean-atmosphere mesocosm

Ocean-derived, airborne microbes play important roles in Earth’s climate system and human health, yet little is known about factors controlling their transfer from the ocean to the atmosphere. Here, we study microbiomes of isolated sea spray aerosol (SSA) collected in a unique ocean–atmosphere facility and demonstrate taxon-specific aerosolization of bacteria and viruses. These trends are conserved within taxonomic orders and classes, and temporal variation in aerosolization is similarly shared by related taxa. We observe enhanced transfer into SSA of Actinobacteria, certain Gammaproteobacteria, and lipid-enveloped viruses; conversely, Flavobacteriia, some Alphaproteobacteria, and Caudovirales are generally under-represented in SSA. Viruses do not transfer to SSA as efficiently as bacteria. The enrichment of mycolic acid-coated Corynebacteriales and lipid-enveloped viruses (inferred from genomic comparisons) suggests that hydrophobic properties increase transport to the sea surface and SSA. Our results identify taxa relevant to atmospheric processes and a framework to further elucidate aerosolization mechanisms influencing microbial and viral transport pathways.

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The Many Mechanisms of Viral Membrane Fusion Proteins

Every enveloped virus fuses its membrane with a host cell membrane, thereby releasing its genome into the cytoplasm and initiating the viral replication cycle. In each case, one or a small set of viral surface transmembrane glycoproteins mediates fusion. Viral fusion proteins vary in their mode of activation and in structural class. These features combine to yield many different fusion mechanisms. Despite their differences, common principles for how fusion proteins function are emerging: In response to an activating trigger, the metastable fusion protein converts to an extended, in some cases rodlike structure, which inserts into the target membrane via its fusion peptide. A subsequent conformational change causes the fusion protein to fold back upon itself, thereby bringing its fusion peptide and its transmembrane domain—and their attached target and viral membranes—into intimate contact. Fusion ensues as the initial lipid stalk progresses through local hemifusion, and then opening and enlargement of a fusion pore. Here we review recent advances in our understanding of how fusion proteins are activated, how fusion proteins change conformation during fusion, and what is happening to the lipids during fusion. We also briefly discuss the therapeutic potential of fusion inhibitors in treating viral infections.

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Model of a Putative Pore: The Pentameric α-Helical Bundle of SARS Coronavirus E Protein in Lipid Bilayers

The coronavirus responsible for the severe acute respiratory syndrome contains a small envelope protein, E, with putative involvement in host apoptosis and virus morphogenesis. To perform these functions, it has been suggested that protein E can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a TM pore. Indeed, in a recent study we reported that the α-helical putative transmembrane domain of E protein (ETM) forms several SDS-resistant TM interactions: a dimer, a trimer, and two pentameric forms. Further, these interactions were found to be evolutionarily conserved. Herein, we have studied multiple isotopically labeled ETM peptides reconstituted in model lipid bilayers, using the orientational parameters derived from infrared dichroic data. We show that the topology of ETM is consistent with a regular TM α-helix. Further, the orientational parameters obtained unequivocally correspond to a homopentameric model, by comparison with previous predictions. We have independently confirmed that the full polypeptide of E protein can also aggregate as pentamers after expression in Escherichia coli. This interaction must be stabilized, at least partially, at the TM domain. The model we report for this pentameric α-helical bundle may explain some of the permabilizing properties of protein E, and should be the basis of mutagenesis efforts in future functional studies.

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Pediatric Coronavirus Disease-2019–Associated Multisystem Inflammatory Syndrome

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Recent and future developments in the epidemiology of the infectious diseases

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Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury

STUDY DESIGN: Cohort study of patients with spinal cord injury (SCI). OBJECTIVES: To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures. SETTING: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). METHODS: A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered. RESULTS: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1–10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually. CONCLUSION: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

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Favourable outcome of coronavirus disease 2019 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced immunosuppression

Since the beginning of coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.1 Few cases of infection in children with cancer are described; also in these patients, except for one reported case,2 the disease was largely asymptomatic.3 Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimize the clinical approach to these cases.

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Learning at home during COVID‐19: A multi‐institutional virtual learning collaboration

Given the cancellation of all elective procedures with the COVID-19 crisis, many anesthesiology learners are assigned to stay at home, limiting opportunities to learn in the clinical environment. We report on a novel use of existing resources to structure a daily nationwide learning experience, using Kotter's change management model (KCMM) to drive the process.