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The coronavirus SARS-CoV-2 is the causative agent for the COVID-19 pandemic. Its proteome is typically separated into three classes of proteins: (1) Structural proteins which facilitate the transport and host cell infiltration of the viral RNA, (2) non-structural proteins which are thought to be essential for the viral life cycle and are all produced from open reading frame 1ab (ORF1ab) on the RNA, and (3) everything else, called accessory proteins. Although it was originally thought that these accessory proteins are non-essential for viral replication, a growing body of evidence suggests that these diverse proteins have crucial roles in virus-host interactions, in particular in the way they interfere with the signalling pathways that modulate the host cell's response to infection and viral pathogenicity. Here, we summarize efforts to structurally characterize the accessory proteins from SARS-CoV-2.
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Background: The health consequences of the SARS-CoV-2 pandemic are dominating the international healthcare systems. More than 15% of patients with supposedly mild SARS-CoV-II disease develop persisting symptoms (Sudre et al., 2021). In addition to known internal limitations, such as respiratory distress or tachycardia, severe neurological deficits are prominent. For example, fatigue persisting for months, cognitive impairment, and a marked increase in daytime sleepiness, sometimes accompanied by an inability to work, are described (Taquet et al., 2021). Previous research indicates that hospitalized patients suffering from COVID-19 often develop fatigue or muscle weakness (63%), difficulties in sleep (26%) and psychiatric disorders, such as anxiety and depression (23%) (Taquet et al., 2021). This constellation of symptoms can lead to severe limitations in the everyday lives of the people concerned. The pathophysiology of this multifaceted neurological and dysautonomic symptom complex is not yet understood but now becoming the focus of interdisciplinary research in the context of the global pandemic. A similar disease is chronic fatigue syndrome (CFS). Affected patients suffer from very comparable limitations, especially persistent fatigue. Evidence suggests an alteration of the specific cerebral reward system in CFS, an important modulator of learning processes involved in various homeostatic regulatory processes (Wylie and Flashman, 2017). Objective(s): Based on the similarity of symptoms in CFS and Post-COVID fatigue this study aims to investigate whether a reduced sensitivity of the reward system in the context of postviral fatigue syndrome is present. We hypothesize that the sensitivity of the reward system in patients with Post-COVID syndrome is reduced compared to healthy adults. Method(s): 24 subjects with a diagnosed Post-COVID syndrome and 20 healthy individuals between the age of 18-55 without relevant neurological or psychiatric disorders in the medical record participated in the study. Magnetoencephalography and electroencephalography were used for the characterization of the reward system during the monetary incentive delay task, a classic paradigm used in existing publications (Frank et al., 2004;Opitz et al., 2022). In addition, standardized questionnaires were used to obtain further information about the included individuals' living conditions and the severity of symptoms. Result(s) and Conclusion(s): Results of the study will help to better characterize reward network changes in the context of fatigue symptoms to open up therapeutic options for medication or psychotherapeutic interventions. Data analysis will be completed by the start of the conference.Copyright © 2023
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Objective To describe clinical and paraclinical features of non-paraneoplastic NIFmediated disease associated with concurrent SARS-CoV-2 infection. Background Neurologic syndromes associated with neuronal intermediate filament (NIF) immunoglobulin G (IgG) most often are characterized by encephalopathy, cerebellar ataxia, or myelopathy. NIF-IgG has been strongly correlated with the presence of an underlying malignancy, with neuroendocrine tumors being most prevalent. Despite the intracellular target of this antibody, patients with NIF-IgG mediated disease tend to improve clinically with immunotherapy. While some cases have been described in a parainfectious context, this is the first such case in the context of a SARS-CoV-2 infection. Design/Methods NA. Results We reported a case of non-paraneoplastic NIF-mediated disease in the setting of SARS-CoV-2 infection. The patient presented with first time seizure. He was found to have frequent left temporal lobe spikes then two left temporal lobe seizures on neurotelemetry. Brain MRI displayed abnormal signal throughout the left hippocampus and mesial temporal lobe, without contrast enhancement. LP was subsequently performed. CSF showed elevated protein, 14-3-3, T-tau, interleukin 13, interleukin 2 receptor, and interleukin 6. The meningitis/encephalitis panel, and HSV-1/2 IgG were negative. Serum autoimmune encephalitis panel revealed a high-positive titer for anti-NIF 1:960, with concurrent NIF heavy chain cell-based assay positive. He improved with three days of IV steroids and treatment with levetiracetam and lacosamide. He has since been seizure free. Conclusions NIF-mediated diseases usually present with encephalopathy, cerebellar ataxia, or myelopathy and are generally seen in the setting of malignancy. Our case illustrated an example of NIF-mediated disease presenting as seizure in the setting of infection. This highlights the importance of consideration of parainfectious autoimmunity.
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Background A large proportion of the European population seeks information about the COVID-19 vaccination on the internet. The population seems to split into those with positive stance on the vaccination and those with negative stance, but there are still individuals who do not have a final position yet. By now, there is a lack of understanding about the online information seeking behavior in these three groups. The current analysis sheds light on differences in internet usage and requested qualities of online information regarding the COVID-19 vaccination. Methods An online survey with N = 1,000 people (18-74 years) living in Germany was conducted between November 26 and December 8, 2021. The questionnaire included closed questions about frequency, information channels, formats and reasons of online information seeking, as well as one open question about requested qualities of online content. We conducted bivariate analysis for differences in information seeking behavior and content analysis for the requests. Results Information seeking behavior differed significantly by attitude towards the vaccination regarding frequency, almost all types of formats, three of ten listed information channels, and three of six reasons for online information seeking. Undecided participants and those who support COVID-19 vaccination used the internet more often than participants who are against the vaccination. Individuals supporting vaccination preferred reading text contributions (e.g. online articles). Informative videos were more often consumed by those who are undecided or against vaccination. Those who have not decided yet preferred online resources providing full information about side-effects and showing reliable facts by credible sources. Conclusions Our findings support an online vaccination communication that is tailored to target groups with different attitudes towards the vaccination. Overall, online campaigns should focus on transparent, reliable and complete information. Key messages • Online information seeking behavior regarding COVID-19 vaccination varies between individuals with different attitudes towards the vaccination. • Online information about the COVID-19 vaccination should focus on transparency and reliable information.
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BACKGROUND: Lack of transparency around manufacturing costs, who bears the bulk of research and development costs and how total costs relate to the pricing of products, continue to fuel debates. This paper considers the case of olaparib (Lynparza®), recently indicated for use among BRCA-mutant breast cancer patients, and estimates the extent of public and philanthropic R&D funding. METHODS: We know from previous work that attempting to ascertain the amount of public and philanthropic funding using purely bibliographic sources (i.e., authors' declarations of funding sources and amounts traced through funders) is limited. Since we knew that a publically funded research unit was pivotal in developing olaparib, we decided to supplement bibliographic data with a Freedom of Information request for administrative records on research funding data from this research centre. RESEARCH: In terms of stages of product development, work conducted in the pre-clinical research stage was the most likely to report non-industry funding (> 90% of pre-clinical projects received public or philanthropic funding). Clinical trials were least likely to be funded through non-industry sources-although even here, contrary to the popular assertion that this is wholly industry-financed, we found public or philanthropic funding declared by 23% of clinical trials. Using information reported in the publications, we identified approximately £128 million of public and philanthropic funding that may have contributed to the development of olaparib. However, this amount was less than one-third of the total amount received by one research institute playing a pivotal role in product discovery. The Institute of Cancer Research reported receiving 38 funding awards to support olaparib work for BRCA-mutant breast cancer totalling over £400 million. CONCLUSIONS: Government or charitable funding of pharmaceutical product development is difficult to trace using publicly available sources, due to incomplete information provided by authors and/or a lack of consistency in funding information made available by funders. This study has shown that a Freedom of Information request, in countries where such requests are supported, can provide information to help build the picture of financial support. In the example of olaparib, the funding amounts directly reported considerably exceeded amounts that could be ascertained using publically available bibliographic sources.
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Purpose: The COVID-19 pandemic has accelerated demand for home delivery services for alcohol and cannabis-products traditionally accessed through brick-and-mortar outlets. Many governments have relaxed long-standing public health regulations to permit expanded online ordering, takeout, and home delivery. This evolving landscape of availability could have important implications for the epidemiology of alcohol and cannabis consumption and related problems. However, research on the home delivery of commercially available intoxicants remains alarmingly sparse, in part due to a lack of data. Prior research demonstrated that crowdsourced websites can be used to validly enumerate brick-and-mortar cannabis outlets. We piloted an extension of this method to measure availability of cannabis home delivery in California. Methods and data: We webscraped data from Weedmaps, the largest crowdsourced website for commercial cannabis, to quantify the number of cannabis retailers delivering to specific locations across California. We counted retailers reporting to offer home delivery to the geographical centroid of each Census block group, and compared these to counts of the number of brick-and-mortar outlets within each block group. To shed further light on data quality, we conducted follow-up telephone calls with a subsample of cannabis delivery retailers. Results: Of the 23,212 block groups assessed, 22,730 (98%) were served by at least one cannabis delivery business. In contrast, only 461 block groups (2%) contained at least one brick-and-mortar cannabis outlet. Telephone interviews raised questions about how physical availability should be defined for home delivery businesses. Whereas physical proximity from a brick-and-mortar outlet to a residential address is fixed in space and time, the availability of home delivery varied dynamically as a function of staffing levels, order sizes, time of day, competition, and demand. Conclusions: Webscraping crowdsourced websites could be a viable method for quantifying the availability of cannabis and alcohol home delivery. However, key practical and conceptual challenges must be overcome to proceed with a full-scale validation and methodological standards. Despite limitations, our pilot data suggest that cannabis home delivery is now nearly universal in California, while access to brick-and-mortar outlets is relatively limited, underscoring the need for research on home delivery.
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Objetivo: Validar o Ensaio da Monocamada de Monócitos (MMA) na Central de Imuno-Hematologia da Fundação Hemominas, Belo Horizonte/MG, de forma a contribuir para elevar ainda mais a segurança transfusional no estado. Material e métodos: A validação do ensaio de MMA foi realizada tendo como base estudos de referência na área. Em síntese, as etapas do ensaio incluem: isolamento dos monócitos a partir de bolsas de sangue total (ST), adsorção do anticorpo à hemácia do concentrado de hemácias (CHM) selecionado, indução da fagocitose, pelos monócitos, das hemácias opsonizadas, fixação e coloração das células e leitura da lâmina em microscópio óptico. O resultado do ensaio é obtido pelo cálculo do Índice de Monócitos (MI) e a interpretação é a seguinte: MI ≤ 5,0%: anticorpo clinicamente não significante (baixo risco de hemólise);MI = 5,1–20,0%: risco de 33% do receptor apresentar hemólise pós-transfusional;MI > 20,0%: risco de 64% do receptor apresentar hemólise pós-transfusional. A validação do ensaio foi realizada testando-se controles positivos (CP) e controles negativos (CN), além da testagem de amostras de soro de pacientes que continham anticorpos da classe IgG de reconhecido significado clínico. Resultados: A validação do ensaio abrangeu a definição da infraestrutura necessária: espaço físico, equipamentos, aquisição de insumos/reagentes e elaboração de Procedimento Operacional Padrão. Foram realizadas testagens múltiplas de CP (hemácias comerciais sensibilizadas com anticorpos da classe IgG) e CN (hemácias da bolsa de ST). Foram testadas amostras de soro de pacientes com anticorpos direcionados a antígenos dos sistemas Rh (D, E), Kell (K) e Kidd (Jka/Jkb). Os resultados dos MI para os CP e CN foram superiores a 20,0% e zero, respectivamente, enquanto que para os anticorpos testados foram inferiores a 5,0%. Discussão: Foram validadas bolsas de ST de baixo volume, que seriam descartadas, para o isolamento dos monócitos. Dessa forma, evitou-se o uso de bolsas viáveis para transfusão, considerando-se a expressiva redução do número de doações devido, principalmente, à atual pandemia pelo novo coronavírus. Foram incluídas bolsas de doadores e doadoras, com idades inferiores a 45 anos, sendo satisfatório o número de monócitos isolados para ambos os sexos. As etapas de lavagem das células com solução fisiológica foram delicadamente executadas para não gerar o seu desprendimento e perda. Os tempos ideais para fixação e coloração das células foram cuidadosamente padronizados. A lavagem das hemácias pós-adsorção dos anticorpos, com salina aquecida a 37°C, foi essencial para evitar a dissociação desses. Os resultados de MI obtidos para os controles foram 100% satisfatórios. Com relação aos resultados de MI inferiores a 5,0% para os anticorpos testados, a literatura apresenta casos em que anticorpos clinicamente importantes estão associados a MI inferiores a 5,0%. Não foram avaliadas as subclasses das imunoglobulinas IgG testadas. Conclusão: A validação do MMA na Fundação Hemominas constitui um passo importante para elevar ainda mais a segurança transfusional dos receptores de CHM em Minas Gerais.
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We analyze the supply-side disruptions associated with COVID-19. We find that sectors in which a higher fraction of the workforce is not able to work remotely experienced greater declines in employment and expected revenue growth, worse stock market performance, and higher likelihood of default. The stock market overweights low-exposure industries. Thus, our findings cast light on the disconnect between stock market indices and aggregate outcomes. We combine these ex ante heterogeneous industry exposures with daily financial market data to create a stock return portfolio that tracks news about the supply-side disruptions resulting from the pandemic. (JEL G12, D22, H25, J20, E00) © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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After mixed results in emergency virtual and remote learning during the 2020 COVID pandemic, content assessment may have felt the greatest negative impacts. Even for in-person classroom settings, digital application literacy provides the opportunity for teachers to orient students to the nuances of digital applications so that novice experiences do not impact test performance. Digital Application Literacy (DAppLit) refers to the nimble use of a web-based app or software-based application for academic purposes, including assessment. Steps of DAppLit include: 1) Identifying goals and consequences outside the testing environment;2) Modeling assessment to build digital application literacy skills;3) Providing low-stakes experience before a high-stakes assessment;and 4) Reflecting and diagnosing the process for improvement. With impacts on assessment of virtual and remote learning, digital comprehension skills, and challenges to adaptive assessment, digital application literacy is a standard needed to properly equip all students for success in the assessment process. © 2021, Springer Nature Switzerland AG.
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Portuguese-speaking countries are at different levels in the process of promoting environmental education and sustainability. In recognition of the political and cultural ties within a considerable diversity of socio-economic conditions, a pioneering study was developed in 2017 to map and establish a diagnostic of Environmental Education’s (EE) realities and “sustainability norms legislation” in the Lusophone nations. Three years later, the EE2CPLP survey, implemented in 2020, builds upon and streamlines the first edition, considering the current context marked by Agenda 2030 and the impacts and concerns regarding the COVID-19 pandemic. Thus, the survey was divided into three main sections: (1) Contexts and EE approaches in the CPLP countries;(2) Place and role of children and youth in the field of EE and (3) Coronavirus pandemic environment, against the backdrop of Agenda 2030. In the following chapter, we will address EE’s cross-cutting nature, its selective traditions (i.e., positivist, normative, and pluralist) and its role for sustainable development and the 2030 Agenda. Looking for the perspective of stakeholders and experts in Environmental Education (EE) and sustainability, we will assess the perceived impact of the current health crisis, which compounds the climate crisis, exacerbating the socio-economic issues within Portuguese-speaking countries. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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Background An OECD benchmark (2020) shows that Germany has, in effect, an above-average healthcare infrastructure to face COVID-19. Nevertheless, at the beginning of the pandemic, there were restrictions and uncertainties in the use of health-related services. The following analysis examines the subjective perception of respondents with their healthcare provision whether there were sociodemographic differences. Methods Data from an online cross-sectional survey conducted between 29 April and 8 May 2020 were used (N = 1,570;18-74 years). Bivariate test methods were used for analysis, stratified by age group, subjective social status (SSS) and chronic illness. The subjective perception was assessed via subjects' subjectively perceived worries, fears and difficulties of not receiving an adequate healthcare provision during the COVID-19 pandemic. Thus, an index was constructed with a range of values from 3 to 12 (Cronbach's α = 0.886). A higher index implies a poorer perception of the healthcare provision. Results Compared to the groups 50-59-year-olds and 60 years and older the 18-29-year-olds (MRank 431.1) had a significantly (p < 0.05) poorer perception of their healthcare provision during COVID-19. In addition, probands with low SSS were found to have a significantly (p < 0.05) worse perception (MRank 423.0) than subjects with medium SSS (MRank 374.1). Chronically ill subjects suffered significantly poorer perception (MRank 406.1;p < 0.05) compared to healthy subjects (MRank 366.0). Conclusions Vulnerable groups with poorer perceptions of their health care provision during COVID-19 can be identified. More investigation is needed to identify subjective or COVID-19 related predictors that cause this subjective perception. Reference OECD (2020). Beyond Containment: Health systems responses to COVID-19 in the OECD. Available: https://read.oecd-ilibrary.org/view/?ref=119_119689-ud5comtf84&title=Beyond_Containment:Health_systems_responses_to_COVID-19_in_the_OECD (Accessed: 14.04.2021) Key messages It was found that respondents perceived their subjective healthcare provision during COVID-19 differently, according to sociodemographic stratification. Especially younger, chronically ill, and socioeconomically deprived respondents experienced a poorer perception of their healthcare provision during the first wave of the COVID-19 pandemic.
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BACKGROUND: We considered the extent of the contribution of publicly funded research to the late-stage clinical development of pharmaceuticals and medicinal products, based on the European Commission (EC) FP7 research funding programme. Using two EC FP7-HEALTH case study examples-representing two types of outcomes-we then estimated wider public and charitable research funding contributions. METHODS: Using the publicly available database of FP7-HEALTH funded projects, we identified awards relating to late-stage clinical development according to the systematic application of inclusion and exclusion criteria, classified them according to product type and clinical indication, and calculated total EC funding amounts. We then identified two case studies representing extreme outcomes: failure to proceed with the product (hepatitis C vaccine) and successful market authorisation (Orfadin® for alkaptonuria). Total public and philanthropic research funding contributions to these products were then estimated using publicly available information on funding. RESULTS: 12.3% (120/977) of all EC FP7-HEALTH awards related to the funding of late-stage clinical research, totalling 686,871,399. Pharmaceutical products and vaccines together accounted for 84% of these late-stage clinical development research awards and 70% of its funding. The hepatitis C vaccine received total European Community (FP7 and its predecessor, EC Framework VI) funding of 13,183,813; total public and charitable research funding for this product development was estimated at 77,060,102. The industry sponsor does not consider further development of this product viable; this now represents public risk investment. FP7 funding for the late-stage development of Orfadin® for alkaptonuria was so important that the trials it funded formed the basis for market authorisation, but it is not clear whether the price of the treatment (over 20,000 per patient per year) adequately reflects the substantial public funding contribution. CONCLUSIONS: Public and charitable research funding plays an essential role, not just in early stage basic research, but also in the late-stage clinical development of products prior to market authorisation. In addition, it provides risk capital for failed products. Within this context, we consider further discussions about a public return on investment and its reflection in pricing policies and decisions justified.
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Historically, medical imaging programs have consisted of traditional learning styles including face-to-face didactic instruction with hands-on learning in simulation laboratories, where imaging equipment and phantoms are used to mimic patient procedures. However, COVID-19 has helped to expedite the transition to supplement or replace traditional learning styles with computer-based learning.1 Many medical imaging and radiation therapy educational programs are transitioning to distance learning and simulated laboratories for a variety of reasons. Wertz et al argued that traditional pedagogical techniques are not suited for modern adult learners in the radiologic sciences because today’s adult learners have experienced some form of higher education through self-paced learning environments. A selfpaced learning environment consists of feedback that is learner-controlled and given in real-time.2 Educators are using pedagogical innovation in the profession as well as adapting to modern learning theories by transforming traditional programs into hybrid programs consisting of face-to-face and distance learning methods.1 With this progression in radiologic science education methods, the Joint Review Committee on Education in Radiologic Technology (JRCERT) provided guidelines for programs implementing distance learning methods that require programs to have procedures for maintaining the integrity of distance education courses.3 In addition, JRCERT encourages innovation in education, including the delivery of distance education.3 A distance education checklist in accordance with the 2021 JRCERT Standards for an Accredited Educational Program is available for program faculty and site visitors. © 2021, Radiologic Technology. All Rights Reserved.
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Emerging infectious diseases like Covid-19 cause a major threat to global health. When confronted with new pathogens, individuals generate several beliefs about the epidemic phenomenon. Many studies have shown that individual protective behaviors largely depend on these beliefs. Due to the absence of treatment and vaccine against these emerging pathogens, the relation between these beliefs and these behaviors represents a crucial issue for public health policies. In the premises of the Covid-19 pandemic, several preliminary studies have highlighted a delay in the perception of risk by individuals, which potentially holds back the implementing of the necessary precautionary measures: people underestimated the risks associated with the virus, and therefore also the importance of complying with sanitary guidelines. During the peak of the pandemic, the salience of the threat and of the risk of mortality could then have transformed the way people generate their beliefs. This potentially leads to upheavals in the way they understand the world. Here, we propose to explore the evolution of beliefs and behaviors during the Covid-19 crisis, using the theory of predictive coding and the theory of terror management, two influential frameworks in cognitive science and in social psychology.