title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection

text: Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed.


title: Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to almost every region and country in the world, leading to widespread travel restrictions and national lockdowns. Currently, there are limited epidemiological and clinical data on COVID-19 patients from low and middle-income countries. We conducted a retrospective single-center study of the first 100 individuals with suspected COVID-19 (between Jan. 25 and Mar. 29, 2020) admitted to San Lazaro Hospital (SLH), the national infectious diseases referral hospital in Manila, Philippines. RESULTS: Demographic data, travel history, clinical features, and outcomes were summarized and compared between COVID-19 confirmed and non-confirmed cases. The first two confirmed cases were Chinese nationals, admitted on Jan. 25. The third confirmed case was a Filipino, admitted on Mar. 8. Trends toward confirmed COVID-19 cases not reporting international travel and being admitted to SLH from the densely populated area of Manila city were observed during Mar. 8-29. All 42 of the 100 confirmed COVID-19 cases were adults, 40% were aged 60 years and above and 55% were male. Three were health workers. Among individuals with suspected COVID-19, confirmed cases were more likely to be older, Filipino, not report international travel history and have at least one underlying disease, particularly diabetes, report difficulty in breathing, and a longer duration of symptoms. In over 90% of non-COVID-19 cases, the alternative diagnosis was respiratory. Nine (21%) confirmed cases died. The median duration from symptoms onset to death was 11.5 (range: 8–18) days. CONCLUSIONS: Imported COVID-19 cases have reduced but local transmission persists and there is a trend toward cases being admitted to SLH from densely populated areas. This study highlights the difficulty in diagnosing COVID-19 on clinical grounds and the importance of diagnostic capacity in all settings. Difficulty of breathing was the only symptom associated with COVID-19 infection and should alert clinicians to the possibility of COVID-19. Clinical characteristics of confirmed COVID-19 cases and a hospital case fatality rate of 21% are comparable with other settings.


title: Summary of the World Small Animal Veterinary Association Standardization Committee Guide to Classification of Liver Disease in Dogs and Cats

text: Liver disease is a frequently encountered problem in small animal practice. The World Small Animal Veterinary Association has formed a group of experienced clinicians and pathologists to develop a standardized format for diagnostic terminology. This is hoped to lead to greater uniformity in diagnoses and better communication between clinicians and pathologists alike. The aim is to find a sound scientific basis of diagnostic and treatment protocols for hepatobiliary diseases. This article provides an overview of that monograph.


docid: wiosxjew

title: HCoV-Oc43–Induced Apoptosis of Murine Neuronal Cells


title: Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar)

text: Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.


title: Upper airway viral infections

text: Abstract Upper airway viral infections (URI) are a major cause of absence from school and work. Although morbidity is low in most of the subjects, the complications of URI, including otitis media, sinusitis and exacerbations of asthma and chronic obstructive pulmonary disease (COPD) have an enormous health impact. Despite the major health care consequences associated with these complications, our understanding of how URI trigger upper airway symptoms and cause exacerbations of lower airway diseases remains limited. This article reviews our current understanding of the pathogenesis of URI, and of viral exacerbations of asthma and COPD, and considers host defense parameters that may regulate susceptibility to disease exacerbations. We will also consider current and potential therapeutic approaches for the treatment of URI and their lower airway complications.


title: The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease—A systematic review

text: Abstract Background Despite the increasing knowledge on the role of viruses in exacerbations of COPD (AECOPD), it is less clear which viruses are involved and to what extent they contribute to exacerbations. This review aims to systematically combine and evaluate the available literature of the prevalence of respiratory viruses in patients with AECOPD, detected by PCR. Methods An electronic search strategy was performed on PubMed and Embase and reference lists were screened for eligible studies. Cross-sectional, prospective studies and case-control studies were included. The primary outcome measure was the prevalence of respiratory viruses (adenovirus, bocavirus, coronavirus, EBV, hMPV, influenza, parainfluenza, rhino-/enterovirus, RSV) in respiratory secretions of patients during an AECOPD. Secondary outcomes were the odds of the presence of the viruses in different respiratory secretions and the odds of the presence of viruses in upper and lower respiratory tract (URT/LRT) samples. Results Nineteen studies with 1728 patients were included. Rhino-/enteroviruses (16.39%), RSV (9.90%) and influenza (7.83%) were the most prevalent viruses detected with lower detection rates of coronaviruses (4.08%) and parainfluenza (3.35%). Adenovirus (2.07%), hMPV (2.78%) and bocaviruses (0.56%) appear to be rare causative agents of AECOPD. Definitive conclusions regarding the role of EBV cannot be made. Seven of the eight analyzed viruses had a higher prevalence in LRT samples. Coronaviruses were detected more frequently in the URT. Conclusions Respiratory viruses are frequently detected in both URT and LRT samples in AECOPD with rhino-/enteroviruses, RSV and influenza viruses the most prevalent viruses. Detection rates vary between the two sites for different viruses.


Reply to “COVID-19 can present with a rash and be mistaken for Dengue”: Petechial rash in a patient with COVID-19 infection


title: Chapter 5 Physical and Chemical Methods for the Reduction of Biological Hazards in Animal Feeds

text: Abstract Feed for livestock animals have been under increased scrutiny as a vector for pathogenic bacteria leading to human illnesses. Control of these pathogenic bacteria in animal feeds can be controlled via physical and chemical means. Physical methods can include thermal processing, including irradiation, pelleting, and extrusion. Chemical mitigation can be accomplished through the inclusion of various additives, including formaldehyde, organic acids, essential oils, or medium chain fatty acids. While physical and chemical interventions can help mitigate risk of pathogens contaminating finished animal feeds, the implementation of a biosecurity plan at the feed mill can help prevent pathogens from entering or spreading throughout the facility.


title: A G1-lineage H9N2 virus with oviduct tropism causes chronic pathological changes in the infundibulum and a long-lasting drop in egg production

text: Since 1997, G1-lineage H9N2 avian influenza viruses have been circulating in Asia and later on in the Middle East, and they have been associated to mild respiratory disease, drops in egg production and moderate mortality in chickens, in particular in the presence of concurrent infections. In this study, we investigated the importance of the G1-lineage H9N2 A/chicken/Israel/1163/2011 virus as a primary pathogen in layers, analyzing its tropism and binding affinity for the oviduct tissues, and investigating the long-term impact on egg production. Besides causing a mild respiratory infection, the virus replicated in the oviduct of 60% of the hens causing different degrees of salpingitis throughout the organ, in particular at the level of the infundibulum, where the detection of the virus was associated with severe heterophilic infiltrate, and necrosis of the epithelium. Binding affinity assays confirmed that the infundibulum was the most receptive region of the oviduct. The drop in egg production was at its peek at 2 weeks post-infection (pi) (60% decrease) and continued up to 80 days pi (35% decrease). On day 80 pi, non-laying birds showed egg yolk peritonitis, and histopathological analyses described profound alteration of the infundibulum architecture, duct ectasia and thinning of the epithelium, while the rest of the oviduct and ovary appeared normal. Our results show that this H9N2 virus is a primary pathogen in layer hens, and that its replication in the infundibulum is responsible for acute and chronic lesions that limits the effective functionality of the oviduct, compromising the commercial life of birds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13567-018-0575-1) contains supplementary material, which is available to authorized users.


Hospital preparedness for knowledge-based response to Ebola and other emerging infectious diseases: A continuous challenge


title: Adolescents’ Motivations to Engage in Social Distancing during the COVID-19 Pandemic: Associations with Mental and Social Health

text: Abstract Purpose Reducing the spread of infection during the COVID-19 pandemic prompted recommendations for individuals to socially distance. Little is known about the extent to which youth are socially distancing, what motivations underlie their social distancing, and how these motivations are connected with amount of social distancing, mental health, and social health. Using a large sample of adolescents from across the US, this study examined adolescents’ motivations for social distancing, their engagement in social distancing, and their mental and social health. Methods Data were collected March 29th and 30th 2020, two-weeks after COVID-19 was declared a national emergency in the US. The sample consisted of 683 adolescents recruited using social media. A series of multiple linear regressions examined unique associations among adolescents’ motivations to engage in social distancing, perceived amount of social distancing, anxiety symptoms, depressive symptoms, burdensomeness, and belongingness. Results Almost all respondents (98.1%) reported engaging in at least a little social distancing. The most commonly reported motivations for social distancing concerned social responsibility and not wanting others to get sick. Motivations concerning state or city lockdowns, parental rules, and social responsibility were associated with greater social distancing, whereas motivations concerning no alternatives were associated with less social distancing. Specific motivations for social distancing were differentially associated with adolescents’ anxiety symptoms, depressive symptoms, burdensomeness, and belongingness. Conclusions Understanding adolescents’ motivations to engage in social distancing may inform strategies to increase social distancing engagement, reduce pathogen transmission, and identify individual differences in mental and social health during the COVID-19 pandemic.


title: The Ambient Ozone and COVID-19 Transmissibility in China: A Data-Driven Ecological Study of 154 Cities

text: • We quantified the COVID-19 transmissibility by the basic reproductive number. • The COVID-19 transmissibility could be negatively associated with ambient ozone. • The daily 1-h maximum ozone might cover 7.6% of the transmissibility variability. • It echoes a previous study of negative effects of ozone on the flu transmission. • The ground-level ozone may be a “double-edged sword” to public health.


title: Approaches to Management and Care of the Neonatal Nondomestic Ruminant

text: Management and care of the nondomestic ruminant neonate are similar in principle to domestic animal practice. Housing of the dam, conditions for birth, preparation for intervention, and plans for treatment and hand-rearing of sick neonates must all be considered carefully before undertaking nondomestic ruminant breeding. Unfortunately, neonatal losses tend to be much higher in nondomestic calves before weaning than in domestic cattle, sheep, and goat herds.1 With continued habitat and population declines in wild species, successful captive breeding of nondomestic herds becomes more important to species sustainability and potential reintroduction programs. The primary challenges contributing to neonatal losses in nondomestic ruminants are often animal temperament and adaptation to captivity. Only through experience can some of these challenges be overcome. However, by understanding some species-specific behavioral tendencies and the fractious nature of nondomestic ruminants in general, we can improve our success in managing and maintaining healthy populations of nondomestic ruminants in captivity.


docid: kzshcrwx

title: Programmed –1 Frameshifting by Kinetic Partitioning during Impeded Translocation

text: Programmed –1 ribosomal frameshifting (−1PRF) is an mRNA recoding event utilized by cells to enhance the information content of the genome and to regulate gene expression. The mechanism of –1PRF and its timing during translation elongation are unclear. Here, we identified the steps that govern –1PRF by following the stepwise movement of the ribosome through the frameshifting site of a model mRNA derived from the IBV 1a/1b gene in a reconstituted in vitro translation system from Escherichia coli. Frameshifting occurs at a late stage of translocation when the two tRNAs are bound to adjacent slippery sequence codons of the mRNA. The downstream pseudoknot in the mRNA impairs the closing movement of the 30S subunit head, the dissociation of EF-G, and the release of tRNA from the ribosome. The slippage of the ribosome into the –1 frame accelerates the completion of translocation, thereby further favoring translation in the new reading frame.


title: Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

text: Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC(50)) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC(50). The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same in vitro resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.


title: Meeting report: 31st International Conference on Antiviral Research

text: Abstract The 31st International Conference on Antiviral Research (ICAR) was held in Porto, Portugal from June 11–15, 2018. In this report, volunteer rapporteurs provide their summaries of scientific presentations, hoping to effectively convey the speakers' goals and the results and conclusions of their talks. This report provides an overview of the invited keynote and award lectures and highlights of short oral presentations, from the perspective of experts in antiviral research. Of note, a session on human cytomegalovirus included an update on the introduction to the clinic of letermovir for the prevention of CMV infection and disease. The 31st ICAR successfully promoted new discoveries in antiviral research and drug development. The 32nd ICAR will be held in Baltimore, Maryland, USA, May 6–10, 2019.


title: Stem-loop structure of Cocksfoot mottle virus RNA is indispensable for programmed −1 ribosomal frameshifting

text: Abstract The −1 programmed ribosomal frameshifting (−1 PRF) mechanism utilized by many viruses is dependent on a heptanucleotide slippery sequence and a downstream secondary structure element. In the current study, the RNA structure downstream from the slippery site of cocksfoot mottle sobemovirus (CfMV) was proven to be a 12bp stem-loop with a single bulge and a tetranucleotide loop. Several deletion and insertion mutants with altered stem-loop structures were tested in wheat germ extract (WGE) for frameshifting efficiency. The impact of the same mutations on virus infectivity was tested in oat plants. Mutations shortening or destabilizing the stem region reduced significantly but did not abolish −1 PRF in WGE. The same mutations proved to be deleterious for virus infection. However, extending the loop region to seven nucleotides had no significant effect on frameshifting efficiency in WGE and did not hamper virus replication in infected leaves. This is the first report about the experimentally proven RNA secondary structure directing −1 PRF of sobemoviruses.


title: Psychosocial factors, respiratory viruses and exacerbation of asthma

text: Abstract The aim of this research was study the role of psychosocial factors in exacerbations of asthma in adults induced by upper respiratory tract infections (URTIs). It involved a longitudinal study (one year) of 92 adults with asthma. The volunteers were 27 men and 65 women 19–46 years of age with a mean duration of wheeze of 19 years. The main outcome measure was symptomatic colds producing asthma exacerbations (infections confirmed by laboratory assays and exacerbation of asthma confirmed by objective changes in peak expiratory flow rate). The results showed that about 20% of the sample did not report an episode. This sub-group had a high proportion of males, low negative affectivity scores and consumed more alcohol. When volunteers with at least one episode were considered it was found that those who reported more negative life events and had low levels of social support had more episodes. Smokers were more likely to have to visit their doctor when they developed a cold-induced exacerbation of asthma. Overall, these results show that health-related behaviours, demographic and psychosocial factors influence susceptibility to and severity of exacerbations of asthma by URTIs.


title: Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID‐19

text: CONTEXT: No studies evaluated the prospective association between hyperglycemia assessed by laboratory measurements and the risk of mortality among patients with coronavirus disease 2019 (COVID‐19). OBJECTIVE: We aimed to evaluate the association between different degrees of hyperglycemia and the risk of all‐cause mortality among hospitalized patients with COVID‐19. DESIGN: A retrospective study. SETTING: Union Hospital in Wuhan, China. PARTICIPANTS: 453 patients were admitted to the hospital with laboratory‐confirmed SARS‐Cov‐2 infection from January 22, 2020 to March 17, 2020. MAIN OUTCOMES AND MEASURES: Patients were classified into four categories: normal glucose, hyperglycemia (fasting glucose 5.6–6.9 mmol/L and/or HbA1c 5.7–6.4%), newly diagnosed diabetes (fasting glucose ≥7 mmol/L and/or HbA1c ≥6.5%), and known diabetes. The major outcomes included in‐hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV). RESULTS: Patients with newly diagnosed diabetes had the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable‐adjusted hazard ratios of mortality among COVID‐19 patients with normal glucose, hyperglycemia, newly diagnosed diabetes, and known diabetes were 1.00, 3.29 (95% confidence interval [CI] 0.65–16.6), 9.42 (95% CI 2.18–40.7), and 4.63 (95% CI 1.02–21.0), respectively. CONCLUSION: We firstly showed that COVID‐19 patients with newly diagnosed diabetes had the highest risk of all‐cause mortality compared with COVID‐19 patients with known diabetes, hyperglycemia and normal glucose. Patients with COVID‐19 need to be under surveillance for blood glucose screening. This article is protected by copyright. All rights reserved.


title: Chapter 11 Nanotechnology and sialic acid biology

text: Abstract Nanotechnology is the science of matter at size in a scale of 1/1,000,000,000 of a meter. In the last century, considerable progress has been made in the field of nanotechnology and its finds application in major spheres of human life encompassing personal products, medicines, biosensors, disease diagnosis, food, chemicals, energy, agriculture, and industry with application in human health and environment. Nanotechnology application to glycobiology is a considerable new development. In the recent times, nanotechnology finds promising applications in the study and targeting of sialic acid encompassing (i) detection of sialic acids in minute quantities and (ii) enabling their targeting in diseases. We discuss in this chapter the recent advances in the application of nanotechnology to sialic acid biology as (i) imaging agents, (ii) spectroscopic tools for their detection, (iii) monitoring of cellular systems, and (iv) application in drug delivery.


title: Engaging and retaining customers with AI and employee service

text: Abstract Artificial intelligence (AI) permeates in service organisations as a tool to enhance operational efficiency and improve customer experience. Reports show that most consumers prefer human interactions with service employees. Drawing on this observation, the current study examines how customers' service experiences with employees and AI influence customer engagement and loyalty. Customers’ emotional intelligence is proposed as a moderator between service experience and customer engagement. The study was conducted with hotel customers in Australia. The results show that whilst both service experience with employees and AI are significantly related to customer engagement and loyalty, only certain dimensions make significant unique variances in the outcome variables. The findings indicate that customers prefer employee service. These service experiences also have significant partial mediation effects on customer loyalty. Emotional intelligence has a significant moderation effect on customer engagement. Discussion of these findings and implications derived from this study concludes this paper.


title: Systemic or biologic treatment in psoriasis patients does not increase the risk of a severe form of COVID‐19

text: Some systemic and biologic psoriasis treatments [SBT] have been associated with an increased risk of infection.(1) To date, more and more data regarding the risk of COVID‐19 infection in patients receiving SBT becomes available.(2‐5) To enrich these data, we evaluated the frequency of severe COVID‐19 infections, defined as hospitalisation or death, in psoriasis patients receiving SBT, especially during the 4 months following SBT initiation.


The role of ACEIs/ARBs in COVID-19: friend or foe?


title: Pitfalls in interpretation of CT-values of RT-PCR in children with acute respiratory tract infections

text: Abstract Background The relation between viral load and disease severity in childhood acute respiratory tract infections (ARI) is not fully understood. Objectives To assess the clinical relevance of the relation between viral load, determined by cycle threshold (CT) value of real-time reverse transcription-polymerase chain reaction assays and disease severity in children with single- and multiple viral ARI. Study design 582 children with ARI were prospectively followed and tested for 15 viruses. Correlations were calculated between CT values and clinical parameters. Results In single viral ARI, statistically significant correlations were found between viral loads of Respiratory Syncytial Virus (RSV) and hospitalization and between viral loads of Human Coronavirus (HCoV) and a disease severity score. In multiple-viral ARI, statistically significant correlations between viral load and clinical parameters were found. In RSV-Rhinovirus (RV) multiple infections, a low viral load of RV was correlated with a high length of hospital stay and a high duration of extra oxygen use. The mean CT value for RV, HCoV and Parainfluenza virus was significantly lower in single- versus multiple infections. Conclusion Although correlations between CT values and clinical parameters in patients with single and multiple viral infection were found, the clinical importance of these findings is limited because individual differences in host-, viral and laboratory factors complicate the interpretation of statistically significant findings. In multiple infections, viral load cannot be used to differentiate between disease causing virus and innocent bystanders.


title: Evolutional insights on uncharacterized SARS coronavirus genes

text: The complete genome of the severe acute respiratory syndrome coronavirus (SARS-CoV) and many of its variants has been determined by several laboratories. The genome contains fourteen predicted open reading frames (ORFs). However, a function had been clearly assigned for only six of these ORFs, in the viral replication, transcription and structural constituents. The others are herein referred to as uncharacterized ORFs (UC-ORFs). Here, we try to provide a relational insight on those UC-ORFs, suggesting that a number of them are remotely related to structural proteins of coronaviruses and other viruses infecting mammalian hosts. Surprisingly, several of the UC-ORFs exhibit considerable similarity with other SARS-CoV ORFs. These observations may provide clues on the evolution and genome dynamics of the SARS-CoV.


Telemedicine and the challenge of epilepsy management at the time of COVID-19 pandemic()


docid: iiahpjod

title: The rise of artificial intelligence in healthcare applications

text: Big data and machine learning are having an impact on most aspects of modern life, from entertainment, commerce, and healthcare. Netflix knows which films and series people prefer to watch, Amazon knows which items people like to buy when and where, and Google knows which symptoms and conditions people are searching for. All this data can be used for very detailed personal profiling, which may be of great value for behavioral understanding and targeting but also has potential for predicting healthcare trends. There is great optimism that the application of artificial intelligence (AI) can provide substantial improvements in all areas of healthcare from diagnostics to treatment. It is generally believed that AI tools will facilitate and enhance human work and not replace the work of physicians and other healthcare staff as such. AI is ready to support healthcare personnel with a variety of tasks from administrative workflow to clinical documentation and patient outreach as well as specialized support such as in image analysis, medical device automation, and patient monitoring. In this chapter, some of the major applications of AI in healthcare will be discussed covering both the applications that are directly associated with healthcare and those in the healthcare value chain such as drug development and ambient assisted living.


title: Recurrent positive SARS‐CoV‐2: Immune certificate may not be valid

text: Currently, coronavirus disease in 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1 has become a global pandemic. The presence of SARS-CoV-2 in COVID-19 patients is usually confirmed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) method.2 This article is protected by copyright. All rights reserved.


Laboratory Exposure to Influenza A H2N2, Germany, 2004–2005


Excess out‐of‐hospital deaths during COVID‐19 outbreak: evidence of pulmonary embolism as a main determinant


title: Quantification of the sensitivity of early detection surveillance

text: Early detection surveillance is used for various purposes, including the early detection of non‐communicable diseases (e.g. cancer screening), of unusual increases of disease frequency (e.g. influenza or pertussis outbreaks), and the first occurrence of a disease in a previously free population. This latter purpose is particularly important due to the high consequences and cost of delayed detection of a disease moving to a new population. Quantifying the sensitivity of early detection surveillance allows important aspects of the performance of different systems, approaches and authorities to be evaluated, compared and improved. While quantitative evaluation of the sensitivity of other branches of surveillance has been available for many years, development has lagged in the area of early detection, arguably one of the most important purposes of surveillance. This paper, using mostly animal health examples, develops a simple approach to quantifying the sensitivity of early detection surveillance, in terms of population coverage, temporal coverage and detection sensitivity. This approach is extended to quantify the benefits of risk‐based approaches to early detection surveillance. Population‐based clinical surveillance (based on either farmers and their veterinarians, or patients and their local health services) provides the best combination of sensitivity, practicality and cost‐effectiveness. These systems can be significantly enhanced by removing disincentives to reporting, for instance by implementing effective strategies to improve farmer awareness and engagement with health services and addressing the challenges of well‐intentioned disease notification policies that inadvertently impose barriers to reporting.


title: Use of machine learning and artificial intelligence to predict SARS-CoV-2 infection from full blood counts in a population

text: Since December 2019 the novel coronavirus SARS-CoV-2 has been identified as the cause of the pandemic Covid 19. Early symptoms overlap with other common conditions such as common cold and Influenza, making early screening and diagnosis are crucial goals for health practitioners. The aim of the study was to use machine learning, an artificial neural network (ANN) and a simple statistical test to identify SARS-CoV-2 positive patients from full blood counts without knowledge of symptoms or history of the individuals. The dataset included in the analysis and training contains anonymized full blood count results from patients seen at the Hospital Israelita Albert Einstein, at São Paulo, Brazil, and who had samples collected to perform the SARS-CoV-2 rt-PCR test during a visit to the hospital. Patient data was anonymised by the hospital, clinical data was standardized to have a mean of zero and a unit standard deviation. This data was made public with the aim to allow researchers to develop ways to enable the hospital to rapidly predict and potentially identify SARS-CoV-2 positive patients. We find that with full blood counts random forest, shallow learning and a flexible ANN model predict SARS-CoV-2 patients with high accuracy between populations on regular wards (AUC = 93-94%) and those not admitted to hospital or in the community (AUC = 80-86%). Here AUC is the Area Under the receiver operating characteristics Curve and a measure for model performance. Moreover, a simple linear combination of 4 blood counts can be used to have an AUC of 85% for patients within the community. The normalised data of different blood parameters from SARS-CoV-2 positive patients exhibit a decrease in platelets, leukocytes, eosinophils, basophils and lymphocytes, and an increase in monocytes. SARS-CoV-2 positive patients exhibit a characteristic immune response profile pattern and changes in different parameters measured in the full blood count that are detected from simple and rapid blood tests. While symptoms at an early stage of infection are known to overlap with other common conditions, parameters of the full blood count can be analysed to distinguish the viral type at an earlier stage than current rt-PCR tests for SARS-CoV-2 allow at present. This new methodology has potential to greatly improve initial screening for patients where PCR based diagnostic tools are limited.


title: Far-UVC light (222 nm) efficiently and safely inactivates airborne human coronaviruses

text: A direct approach to limit airborne viral transmissions is to inactivate them within a short time of their production. Germicidal ultraviolet light, typically at 254 nm, is effective in this context but, used directly, can be a health hazard to skin and eyes. By contrast, far-UVC light (207–222 nm) efficiently kills pathogens potentially without harm to exposed human tissues. We previously demonstrated that 222-nm far-UVC light efficiently kills airborne influenza virus and we extend those studies to explore far-UVC efficacy against airborne human coronaviruses alpha HCoV-229E and beta HCoV-OC43. Low doses of 1.7 and 1.2 mJ/cm(2) inactivated 99.9% of aerosolized coronavirus 229E and OC43, respectively. As all human coronaviruses have similar genomic sizes, far-UVC light would be expected to show similar inactivation efficiency against other human coronaviruses including SARS-CoV-2. Based on the beta-HCoV-OC43 results, continuous far-UVC exposure in occupied public locations at the current regulatory exposure limit (~3 mJ/cm(2)/hour) would result in ~90% viral inactivation in ~8 minutes, 95% in ~11 minutes, 99% in ~16 minutes and 99.9% inactivation in ~25 minutes. Thus while staying within current regulatory dose limits, low-dose-rate far-UVC exposure can potentially safely provide a major reduction in the ambient level of airborne coronaviruses in occupied public locations.


title: Ear, nose and throat manifestation of viral systemic infections in pediatric patients

text: Abstract Objective/Methods An exhaustive review of literature was performed to investigate available data and evidences regarding pediatric otolaryngologic manifestations of viral systemic infections. Results/Conclusions Modern otolaryngologists should be familiar with viral systemic infections since many have head and neck manifestations. Cooperation between otolaryngologist, paediatrician and virologist can be considered and excellent tool in diagnosis and treatment of these diseases in particular when complications occur.


Zika virus and microcephaly: why is this situation a PHEIC?


Cutaneous hyperesthesia: a novel manifestation of COVID-19


title: Diagnóstico de virus respiratorios utilizando un sistema automatizado de PCR múltiples (FilmArray) y su comparación con métodos convencionales

text: Resumen Las infecciones respiratorias agudas producen una importante morbimortalidad y comúnmente son causadas por virus. En Argentina, los programas de vigilancia epidemiológica se basan en la detección de antígenos virales por inmunofluorescencia (IF), aunque es bien conocido que los métodos moleculares son más sensibles. El panel respiratorio (PR) FilmArray (PR-FilmArray) es un equipo comercial automatizado de PCR múltiples que detecta 17 virus respiratorios y 3 bacterias, en un sistema cerrado que requiere 5min de procesamiento y una 1h de instrumentación. Se evaluó un total de 315 muestras respiratorias de niños menores de 6 años con infecciones respiratorias agudas por IF para 8 virus respiratorios y por RT-PCR para rinovirus. Posteriormente, estas muestras se estudiaron con el PR-FilmArray. La frecuencia de positividad al considerar los 9 virus estudiados por IF y RT-PCR fue del 75%; por PR-FilmArray fue del 92%. El porcentaje de acuerdo positivo entre ambas metodologías fue del 70,5% y el de acuerdo negativo fue del 99,6% (intervalo de confianza 95%: 65,5-75,1 y 99,2-99,8, respectivamente). El PR-FilmArray permitió obtener un mayor diagnóstico positivo (97%) y detectó otros virus, como los coronavirus NL63, 229E, OC43 y HKU1 (10%) y los bocavirus (18%). Además, permitió identificar coinfecciones múltiples (39%) con 2, 3, 4 y hasta 5 virus. Actualmente, la IF continúa siendo el método más utilizado en los países latinoamericanos para el diagnóstico de virus respiratorios por su bajo costo, por su capacidad para procesar un alto número de muestras simultáneamente y porque los resultados de los virus más frecuentes están disponibles en 5h. Sin embargo, la futura incorporación de métodos moleculares aumentaría notablemente la capacidad diagnóstica. Abstract Acute respiratory infections, which are commonly caused by viruses, are an important cause of morbidity and mortality in children. In Argentina, national surveillance programs for the detection of respiratory viruses are usually performed by using immunofluorescence (IF) assays, although it is well known that molecular methods are more sensitive. An automated multiplex PCR device, the FilmArray-Respiratory Panel (FilmArray-RP), can detect 17 viral and 3 bacterial pathogens in a closed system that requires only 5min of hands-on time and 1h of instrumentation time. A total of 315 respiratory samples from children under 6 years of age suffering from acute respiratory infections, were studied by IF for 8 respiratory viruses and by RT-PCR for rhinoviruses. Later, these samples were tested by the FilmArray-RP. The positivity frequency obtained for the 9 viruses tested was 75% by IF/RT-PCR and 92% by the FilmArray-RP. The positive and negative percent agreement between both methods was 70.5% whereas the negative percent agreement was 99.6% (95% confidence interval:65.5-75.1 and 99.2-99.8 respectively). The FilmArray-RP allowed a higher positive diagnosis (97%) and detected other viruses such as coronavirus NL63, 229E, OC43, HKU1 (10%) and bocavirus (18%). In addition, this method identified multiple coinfections (39%) with 2, 3, 4 and up to 5 different viruses. At present, IF is still the most frequently used method in most Latin American countries for respiratory viruses diagnosis due to its low cost, its capability to process a high number of samples simultaneously and the fast determination of results for the most frequent viruses, which are available within 5h. However, the coming incorporation of molecular methods in routine procedures will significantly increase the diagnostic yield of these infections.


title: Epidemiological Characteristics of Coronavirus Disease 2019 (COVID-19) Patients in IRAN: A single Center Study

text: • The majority of cases were in the age group of 50 to 60 years of old. • A total of 2964 cases of COVID-19 were investigated. • The male-to-female ratio was 1.93:1. • A significant effect of age, gender and comorbidities on the mortality. • The Case Fatality Rate among understudy cases was 8.06%.


title: Isolation and molecular characterization of Brazilian turkey reovirus from immunosuppressed young poults

text: In this study, we investigated turkey reovirus (TReoV) in tissue samples from young birds, aged 15 days. RT-PCR for TReoV detected 3.3 % positive samples and TReoV was successfully isolated in Vero cells. Histological analysis of positive bursa of Fabricius (BF) revealed atrophied follicles and lymphocyte depletion. The number of CD8+, CD4+ and IgM+ cells was lower in infected BF. Phylogenetic analysis based on S3 gene showed that the Brazilian TReoV isolates clustered in a single group with 98-100 % similarity to TReoV strains circulating in the United States. This is the first indication that TReoV infection may be a contributing factor to immunosuppression in young birds.


title: Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

text: Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.


title: Collecting Data To Assess SARS Interventions

text: With cases of severe acute respiratory syndrome (SARS) occurring across geographic regions, data collection on the effectiveness of intervention strategies should be standardized to facilitate analysis. We propose a minimum dataset to capture data needed to examine the basic reproduction rate, case status and criteria, symptoms, and outcomes of SARS.


title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.

text: BACKGROUND: : SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: : To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: : Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm appears to contribute to the damage in ARDS. IMPLICATIONS: : In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.


title: Dispositif d’urgence en situation de crise sanitaire: application d’un régime dérogatoire au pharmacien d’officine

text: Abstract The coronavirus pandemic is an unprecedented health crisis (in the XXIth Century). France has declared a “state of health emergency”. In order to tackle the spread of the virus and to prevent the risk of overwhelming the health care system, the French government has implemented extraordinary measures all over the country. In accordance with the public health code, the Minister of Health has implemented the provisions that are deemed necessary to avoid jeopardizing the therapeutic follow-up of patients. The mandatory medical prescriptions dispensing system is being transformed for a limited period. Therefore, the pharmacist’s liability is disrupted.


title: Asthme et usage d’héroïne

text: Résumé Introduction L’usage d’héroïne peut être responsable de complications pulmonaires parmi lesquelles figure l’asthme. Objectifs Revue systématique de la littérature sur les données concernant l’asthme chez les consommateurs d’héroïne. Sources documentaires Medline® sur la période 1980–2017 avec pour mots-clés : « asthma » ou « bronchospasm » et « heroin » ou « opiate » ou « opiates », avec les limites « Title/Abstract » ; les langues retenues étaient l’anglais et le français. Parmi 97 articles, 67 résumés sélectionnés ont donné lieu à une double lecture aboutissant à retenir 23 études. Résultats Les sept rapports de cas incluaient 21 patients (âge moyen : 28 ans [19 à 46 ans] ; sex-ratio : 2,5 [71,5 % d’hommes]). L’héroïne était inhalée (71,4 %), sniffée (19,0 %) ou injectée par voie intraveineuse (9,5 %). Les substances addictives associées étaient le tabac (81 %), le cannabis (38 %), l’alcool (4,7 %) et la cocaïne (4,7 %). L’évolution était fatale chez 3 sujets (14,3 %). Les autres études incluaient une étude transversale, 3 études cas-témoins et 12 études longitudinales (11 études rétrospectives et une étude prospective). La proportion de consommateurs d’héroïne était plus importante chez les sujets asthmatiques et la prévalence de l’asthme et de l’hyperréactivité bronchique était plus élevée chez les consommateurs d’héroïne. La consommation d’héroïne peut favoriser le développement de l’asthme, avec une relation temporelle entre le début de l’usage d’héroïne et l’apparition de l’asthme chez 28 % à 31 % des sujets. Une association positive entre l’usage d’héroïne inhalée et l’exacerbation de l’asthme a été notée. L’observance du traitement de l’asthme est moins bonne chez les consommateurs d’héroïne. En cas d’exacerbation d’asthme, les consommateurs d’héroïne s’adressent plus souvent aux services d’urgences, sont plus souvent admis en soins intensifs et plus souvent intubés avec un recours plus fréquent à une ventilation invasive. Les décès par asthme provoqués par l’héroïne surviennent principalement après une injection intraveineuse (notamment en cas de surdose), mais aussi après une utilisation d’héroïne par voie nasale (sniff) ou pulmonaire. Conclusion La consommation d’héroïne peut favoriser le développement d’un asthme et provoquer des exacerbations aiguës d’asthme (pouvant nécessiter une intubation et une ventilation invasive), voire des décès par asthme. Une consommation d’héroïne doit être recherchée devant une exacerbation d’asthme survenant chez des sujets jeunes et les praticiens doivent aider les usagers d’héroïne à arrêter leur consommation. Summary Introduction Heroin use can be responsible for many respiratory complications including asthma. Objectives Systematic literature review of data on asthma in heroin users. Documentary sources Medline®, on the period 1980-2017 with the following keywords: keywords: “asthma” or “bronchospasm” and “heroin” or “opiate” or “opiates”, limits “title/abstract”; the selected languages were English or French. Among 97 articles, 67 abstracts have given use to a dual reading to select 23 studies. Results The seven case reports included 21 patients (mean age: 28 years [19–46 years]; sex-ratio: 2.5 [males: 71.5%]). Heroin was inhaled (71.4%), sniffed (19%) or injected by intravenous route (9.5%). Associated addictive substances were tobacco (81%), cannabis (38%), alcohol (4.7%) and cocaine (4.7%). Outcome was fatal in 3 subjects (14.3%). Other studies included one cross-sectional study, 3 case-control studies and 12 longitudinal studies (11 retrospective studies and one prospective study). The proportion of heroin users was higher in asthmatic subjects and the prevalence of asthma and bronchial hyperreactivity was higher in heroin users. Heroin use can be responsible for asthma onset, with a temporal relationship between the onset of heroin use and asthma onset in 28 to 31% of subjects. A positive association between inhaled heroin use and acute asthma exacerbation was observed. Asthma treatment observance was lower in heroin users. In case of asthma exacerbation, heroin users were more likely to seek care in the emergency department, to be admitted in intensive care units and to require intubation and invasive ventilation. Asthma deaths related to heroin use mainly occurred following an intravenous injection (especially in the case of overdose), but also following heroin use by nasal (sniff) or pulmonary route. Conclusion Heroin use may be responsible for asthma onset, acute asthma exacerbations (which may require intubation and invasive ventilation) or deaths related to asthma. Heroin use must be sought in case of asthma exacerbation in young persons and practitioners must help heroin users to stop their consumption.


title: Detection of SARS Coronavirus in Patients with Suspected SARS

text: Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.


Ethical considerations for paediatrics during the COVID‐19 pandemic: A discussion paper from the Australian Paediatric Clinical Ethics Collaboration


The COVID-19 Pandemic Personal Reflections on Editorial Responsibility


title: NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV)

text: The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. Intense research has shown that macro domains bind ADP-ribose and other derivatives, but it still remains intangible about their exact function. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function.


title: 3-D Printed Protective Equipment during COVID-19 Pandemic

text: While the number of coronavirus cases from 2019 continues to grow, hospitals are reporting shortages of personal protective equipment (PPE) for frontline healthcare workers. Furthermore, PPE for the eyes and mouth, such as face shields, allow for additional protection when working with aerosols. 3-D printing enables the easy and rapid production of lightweight plastic frameworks based on open-source data. The practicality and clinical suitability of four face shields printed using a fused deposition modeling printer were examined. The weight, printing time, and required tools for assembly were evaluated. To assess the clinical suitability, each face shield was worn for one hour by 10 clinicians and rated using a visual analogue scale. The filament weight (21–42 g) and printing time (1:40–3:17 h) differed significantly between the four frames. Likewise, the fit, wearing comfort, space for additional PPE, and protection varied between the designs. For clinical suitability, a chosen design should allow sufficient space for goggles and N95 respirators as well as maximum coverage of the facial area. Consequently, two datasets are recommended. For the final selection of the ideal dataset to be used for printing, scalability and economic efficiency need to be carefully balanced with an acceptable degree of protection.


title: Novel Human Rhinoviruses and Exacerbation of Asthma in Children

text: To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C.


title: Rapid detection of human immunodeficiency virus type 1 group M by a reverse transcription-loop-mediated isothermal amplification assay

text: Abstract A rapid one-step reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the pol-integrase gene was developed to detect human immunodeficiency virus type 1 (HIV-1) group M. This HIV-1 RT-LAMP assay is simple and rapid, and amplification can be completed within 35min under isothermal conditions at 60°C. The 100% detection limit of HIV-1 RT-LAMP was determined using a standard strain (WHO HIV-1 [97/656]) in octuplicate and found to be 120 copies/ml. The RT-LAMP assay was evaluated for use for clinical diagnosis using plasma samples collected from 57 HIV-1-infected and 40 uninfected individuals in Cameroon, where highly divergent HIV-1 strains are prevalent. Of the 57 samples from infected individuals, 56 harbored group-M HIV-1 strains, such as subtypes A, B, G, F2, and circulating recombinant forms (CRFs) _01, _02, _09, _11, _13; all were RT-LAMP positive. One sample harboring group-O HIV-1 and the 40 HIV-1-uninfected samples were RT-LAMP negative. These findings indicate that HIV-1 RT-LAMP can detect HIV-1 group-M RNA from plasma samples rapidly and with high sensitivity and specificity. These data also suggest that this RT-LAMP assay can be useful for confirming HIV diagnosis, particularly in resource-limited settings.


Chapter 6 Transport and Destination Development


docid: nwtwtfmr

title: COVID-19 and Transplant Research from China: an ethical dilemma


title: Global COVID-19 fatality analysis reveals Hubei-like countries potentially with severe outbreaks

text: • CFR in Iran in the early stage of the outbreak is highest among all the countries. • CFRs in the USA and Italy are similar to Hubei Province in the early stage. • CFRs in South Korea are similar to outside Hubei, indicating less severity. • Our findings highlight the severity of outbreaks globally, particular in the USA.


title: MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

text: While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.


docid: siwzjeea

title: Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV

text: Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity.


title: COVID-19 infection in a patient with severe chronic rhinosinusitis with nasal polyps during therapy with dupilumab

text: A patient with severe CRSwNP, asthma, and NSAIDS received dupilumab treatment. Three weeks after therapy onset, the patient was diagnosed with Covid-19, had a mild course of the disease, and fully recovered from the infection.


title: Ethacrynic and α-lipoic acids inhibit vaccinia virus late gene expression

text: Abstract Smallpox was declared eradicated in 1980. However recently, the need of agents effective against poxvirus infection has emerged again. In this paper, we report an original finding that two redox-modulating agents, the ethacrynic and α-lipoic acids (EA, LA), inhibit growth of vaccinia virus (VACV) in vitro. The effect of EA and LA was compared with those of β-mercaptoethanol, DTT and ascorbic acid, but these agents increased VACV growth in HeLa G cells. The inhibitory effects of EA and LA on the growth of VACV were further confirmed in several cell lines of different embryonic origin, in epithelial cells, fibroblasts, macrophages and T-lymphocytes. Finally, we have analyzed the mechanism of action of the two agents. They both decreased expression of VACV late genes, as demonstrated by western blot analysis and activity of luciferase expressed under control of different VACV promoters. In contrast, they did not inhibit virus entry into the cell, expression of VACV early genes or VACV DNA synthesis. The results suggest new directions in development of drugs effective against poxvirus infection.


The impact of covid-19 on midwives’ practice in Kenya, Uganda and Tanzania: A reflective account


title: Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia

text: Background The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. Objective We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. Methods Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. Results During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. Conclusions Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged.


title: Weather: driving force behind the transmission of severe acute respiratory syndrome in China?

text: Background: The association between weather and severe acute respiratory syndrome (SARS) transmission in Beijing and Hong Kong in the 2003 epidemic was studied to examine the effect of weather on SARS transmission. Methods: Pearson’s correlation analyses and negative binomial regression analyses were used to quantify the correlations between the daily newly reported number of SARS cases and weather variables, using daily disease notification data and meteorological data from the two locations. Results: The results indicate that there were inverse association between the number of daily cases and maximum and/or minimum temperatures whereas air pressure was found to be positively associated with SARS transmission. Conclusion: The study suggests that weather might be a contributory factor in the 2003 SARS epidemic, in particular in the transmission among the community members.


title: Anti‐bacterial IgE in the antibody responses of house dust mite allergic children convalescent from asthma exacerbation

text: Background Atopic sensitization to the house dust mite (HDM) is associated with altered antibody responses to the nasopharyngeal colonizing bacterium Haemophilus influenzae and children admitted to the emergency department for asthma exacerbation have reduced IgG responses to HDM allergens. Objective To investigate anti‐bacterial and anti‐allergen antibody responses during convalescence from asthma exacerbation and differences found in exacerbations associated with and without viral infection. Results IgE antibodies to the P6 bacterial antigen increased in 60% of sera during convalescence and for many children achieved titres as high as IgE titres to allergens. In contrast IgE anti‐HDM titres declined during convalescence. The anti‐bacterial IgE titres were the same in subjects with and without virus infection while the anti‐HDM IgE declined more rapidly in virus‐infected subjects. IgG titres to the major HDM allergens showed no consistent increase and the overall IgG anti‐HDM titres even declined in subjects without a virus infection. Anti‐bacterial IgG antibodies in contrast to IgE did not change. Patients with frequent episodic or persistent asthma had similar IgE anti‐bacterial titres to patients with infrequent asthma during the acute phase, although they had reduced IgG titres to both the bacteria and the HDM. Conclusions During the period following an acute exacerbation of asthma there was a marked and specific increase in anti‐bacterial IgE compared with a reduced IgE response to HDM. This provides further support for the concept of T‐helper type 2 responses to bacterial antigens playing a role in asthma pathogenesis.


docid: geqkvkat

title: Transient Renal Tubular Syndromes Associated with Acute COVID-19 Disease


title: Metagenomics and future perspectives in virus discovery

text: Monitoring the emergence and re-emergence of viral diseases with the goal of containing the spread of viral agents requires both adequate preparedness and quick response. Identifying the causative agent of a new epidemic is one of the most important steps for effective response to disease outbreaks. Traditionally, virus discovery required propagation of the virus in cell culture, a proven technique responsible for the identification of the vast majority of viruses known to date. However, many viruses cannot be easily propagated in cell culture, thus limiting our knowledge of viruses. Viral metagenomic analyses of environmental samples suggest that the field of virology has explored less than 1% of the extant viral diversity. In the last decade, the culture-independent and sequence-independent metagenomic approach has permitted the discovery of many viruses in a wide range of samples. Phylogenetically, some of these viruses are distantly related to previously discovered viruses. In addition, 60–99% of the sequences generated in different viral metagenomic studies are not homologous to known viruses. In this review, we discuss the advances in the area of viral metagenomics during the last decade and their relevance to virus discovery, clinical microbiology and public health. We discuss the potential of metagenomics for characterization of the normal viral population in a healthy community and identification of viruses that could pose a threat to humans through zoonosis. In addition, we propose a new model of the Koch's postulates named the ‘Metagenomic Koch's Postulates’. Unlike the original Koch's postulates and the Molecular Koch's postulates as formulated by Falkow, the metagenomic Koch's postulates focus on the identification of metagenomic traits in disease cases. The metagenomic traits that can be traced after healthy individuals have been exposed to the source of the suspected pathogen.


docid: yvrlgquv

title: Approaches to Aggregation and Decision Making—A Health Economics Approach: An ISPOR Special Task Force Report [5]

text: Abstract The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted life-years. For example, we describe a recently developed extended cost-effectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features—measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach—augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing “hedonic” value frameworks, and conclude with some recommendations in this area.


docid: weoxwksv

title: Spatial and Temporal Algorithm Evaluation for Detecting Over-The-Counter Thermometer Sale Increases during 2009 H1N1 Pandemic

text: BACKGROUND: Spatial outbreak detection algorithms using routinely collected healthcare data have been developed since the late 90s to identify and locate disease outbreaks. However, current well-received spatial algorithms assume only one outbreak cluster present at the same point of time which may not be valid during a pandemic when several clusters of geographic areas concurrently occur. Based on a retrospective evaluation on time-series and spatial algorithms, this paper suggests that time series analysis in detection of pandemics is still a desirable process, which may achieve more sensitive performance with better timeliness. METHODS: In this paper, we first prove in theory that two existing spatial models, the likelihood ratio and the Bayesian spatial scan statistics, are not useful if multiple clusters occur at the same point of time in different geographic regions. Then we conduct a comparison between a spatial algorithm, the Bayesian Spatial Scan Statistic (BSS), and a time series algorithm, the wavelet anomaly detector (WAD), on the performance of detecting the increase of the over-the-counter (OTC) medicine sales during 2009 H1N1 pandemic. RESULTS: The experiments demonstrated that the Bayesian spatial algorithm responded to the increase of thermometer sales about 3 days later than the time series algorithm. CONCLUSION: Time-series algorithms demonstrated an advantage for early outbreak detection, especially when multiple clusters occur at the same time in different geographic regions. Given spatial-temporal algorithms for outbreak detection are widely used, this paper suggests that epidemiologists or public health officials would benefit by applying time series algorithms as a complement to spatial algorithms for public health surveillance.


title: Two cases of cutaneous eruptions due to CoVID‐19 infection in Singapore: new insights into the spectrum of clinical presentation and histopathology

text: The dermatological manifestations of CoVID-19 infection (CI) are variable, including livedo/necrosis, pseudochillblains, vesicular (monomorphic vesicles unlike varicella), urticarial and maculopapular subtypes1 . We report the cutaneous manifestations of two Han-Chinese patients in Singapore with CI and highlight their instructive features. Case 1 is a 43-year-old male with CI who developed truncal and limb rashes 12 days after onset of respiratory symptoms.


title: Chapter 2 Virion Structure, Genome Organization, and Taxonomy of Viruses

text: Summary Although the classification of viruses follows the traditional, albeit, restricted hierarchical system of orders, families, subfamilies, genera, and species, viruses do not neatly fit into the established biological classification used for cellular organisms. First of all, there is no universally common ancestor of viruses. That is, viruses are polyphyletic and, so far, it has not been possible to construct a tree of viruses or to include them in the tree of life. Yet we classify and study viruses in the realm of biological sciences for a number of reasons. Viruses have exploited the nucleic acid and sequence space to their limits; they have also managed to create strategies of encoding information and expressing it in a unique manner that is foreign to cellular organisms; they vary in shape and form, infect only one host or a myriad of hosts, and some insert themselves into the genome of their host, changing its real-time performance or even its evolutionary history, sometimes benefiting the host or causing its death. In this chapter we briefly review the diversity in virus structure, genome organization, and features of virus replication in cells or organisms they infect; essentially we examine the ways viruses have become conspicuously present in our lives and how we seek to organize and make sense of their diversity.


title: Equine arteritis virus-infected cells contain six polyadenylated virus-specific RNAs

text: Abstract The kinetics of equine arteritis virus growth and virus-specific RNA synthesis at 40° were determined in BHK-21 cells. Maximum titers of infectious virus (∼107 PFU/ml) were observed at 12 hr p.i., while incorporation of [3H]uridine into virus-specific RNA became detectable at 4 hr p.i. and increased to reach a maximum rate at 8 hr p.i. This RNA was labeled between 2.5 and 7 hr p.i. and isolated from infected cells. About 44% bound to oligo(dT)-cellulose; this material was denatured using glyoxal and dimethyl sulfoxide and analyzed by electrophoresis in a 1% agarose-urea gel. Six virus-specific RNA species were found having the following molecular weights: 4.3 × 106 (RNA1), 1.3 × 106 (RNA2), 0.9 × 106 (RNA3), 0.7 × 106 (RNA4), 0.3 × 106 (RNA5), and 0.2 × 106 (RNA6). RNA1 comigrated with the viral genome. Artifacts caused by defective interfering particles or breakdown of RNA were excluded. Subsequently, the target sizes of the templates for the synthesis of the genome-sized RNA and the five subgenomic RNAs were determined by uv transcription mapping. Infected cells were irradiated at 6.5 hr p.i. The effect o of reasing uv doses on the RNA synthesis was determined by quantitation of the individual RNAs after separation by agarose gel electrophoresis. The uv target sizes calculated for the templates for RNAs 2–5 were very close to the physical size of RNA1. The target size of the template of RNA6 was smaller (2.8 × 106 daltons), although much greater than its physical size. The data are consistent with a model in which the individual RNAs are derived from a larger precursor RNA molecule. The consequences of these findings for the taxonomy of Togaviridae are discussed.


title: Antimicrobial resistance is a global problem – a UK perspective

text: Increasingly we are reaching a situation where current antimicrobial medicines are no longer effective for common infections, and antimicrobial resistance (AMR) is becoming a global public health crisis. The reliance on antimicrobials such as antibiotics has become a major issue for both medicine and agriculture, particularly given the slow development of new medicines and pharmaceutical industry investment. The UK government has been working with other international bodies in the search for solutions to the many challenges AMR poses. Herbal medicines may provide a useful modality in the fight against AMR and can work solely or in tandem with current antimicrobial approaches. Recommendations for herbal medicine use during the COVID-19 outbreak have featured in Chinese national guidelines and policies, but UK strategies have no such guidance. More research is urgently needed to explore the biological plausibility and safety of herbal medicines to manage AMR. AMR is universal, affecting anyone and everyone, at any age and in any country. Investigating how such approaches can be integrated into western medicine will be important to elucidate.


title: Identification of critical active‐site residues in angiotensin‐converting enzyme‐2 (ACE2) by site‐directed mutagenesis

text: Angiotensin‐converting enzyme‐2 (ACE2) may play an important role in cardiorenal disease and it has also been implicated as a cellular receptor for the severe acute respiratory syndrome (SARS) virus. The ACE2 active‐site model and its crystal structure, which was solved recently, highlighted key differences between ACE2 and its counterpart angiotensin‐converting enzyme (ACE), which are responsible for their differing substrate and inhibitor sensitivities. In this study the role of ACE2 active‐site residues was explored by site‐directed mutagenesis. Arg273 was found to be critical for substrate binding such that its replacement causes enzyme activity to be abolished. Although both His505 and His345 are involved in catalysis, it is His345 and not His505 that acts as the hydrogen bond donor/acceptor in the formation of the tetrahedral peptide intermediate. The difference in chloride sensitivity between ACE2 and ACE was investigated, and the absence of a second chloride‐binding site (CL2) in ACE2 confirmed. Thus ACE2 has only one chloride‐binding site (CL1) whereas ACE has two sites. This is the first study to address the differences that exist between ACE2 and ACE at the molecular level. The results can be applied to future studies aimed at unravelling the role of ACE2, relative to ACE, in vivo.


title: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Kinetics of Infection in Lymphatic Organs and Lung

text: Pigs were infected by the oronasal route with European isolates of the porcine reproductive and respiratory syndrome virus (PRRSV; I10 and Cobbelsdorf). The kinetics of infection in lymphatic organs and the lung were analysed by immunofluorescence detection of virus antigen, re‐isolation of the virus and reverse transcription‐polymerase chain reaction (RT‐PCR) for PRRSV‐specific RNA. The kinetics of PRRSV infection proceeded in three phases, irrespective of the varying infestation of lymphatic organs within the first days post‐infection (p.i.). First, an early acute infection of lymphatic organs developed within the first week and was characterized by a high number of antigen‐positive macrophages. Second, a delayed acute infection of the lung was observed, which was most pronounced during the second and third week p.i. when a high number of infected alveolar macrophages was observed. The acute infection of lymphatic organs had resolved at this time. Infected cells in the lung were predominantly located in pneumonic lesions. Third, a persistent infection was demonstrated by RT‐PCR and immunohistology when the experiments were terminated at day 49 p.i. The virus persisted in lymphatic organs, especially in the tonsils, and in the lung. At this stage, indications for a re‐occurrence of acute infection were observed in restricted areas of the lung.


title: Study on release suppression of cinnamaldehyde from κ-carrageenan gel by HR-MASNMR and pulsed field gradient NMR (PFG-NMR)

text: Aiming toward the production and characterization of delicious and functional gel foods, this communication studies the flavor release from cinnamon-containing κ-carrageenan gel. Cinnamaldehyde, which provides the flavor of cinnamon, was released in a trace amount from the gel and detected by flame ionization detector gas chromatography. The retention of cinnamaldehyde in κ-carrageenan gel and the interaction between flavor and polysaccharide were investigated by high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) and pulsed-field gradient NMR (PFG NMR). The intact cinnamaldehyde in the gel was also observed by HR-MAS NMR. The relative mobility difference of the flavor and polysaccharide molecules was observed from the diffusion-ordered NMR spectrum of PFG NMR.


title: Immunization of Puppies in the Presence of Maternally Derived Antibodies Against Canine Distemper Virus

text: Summary Vaccination of dams with modified-live canine distemper virus (CDV) vaccines will elicit high concentrations of colostral antibody, that although vital for protection of the pup during the first weeks of life, can interfere with active vaccination against the virus. In the present study, 12 pups, 7–9 weeks of age, with maternally derived immunity to CDV, were vaccinated with a canarypox-vectored CDV vaccine. These pups were protected against intravenous challenge with CDV. Three littermate pups that were unvaccinated all developed clinical signs of infection after challenge, and two of these control pups died.


title: Epitope selection and their placement for increased virus neutralization in a novel vaccination strategy for porcine epidemic diarrhea virus utilizing the Hepatitis B virus core antigen

text: Abstract Porcine epidemic diarrhea virus (PEDV) is a member of the Alphacoronaviridae genus within the Coronaviridae family. It is the causative agent of porcine epidemic diarrhea, a disease that can have mortality rates as high as 100% in suckling piglets. PEDV causes severe economic loss, and has been in existence for decades. A panzootic starting in 2010 renewed interest in the development of a universal vaccine toward PEDV. This report details several design changes made to a Hepatitis B virus core antigen (HBcAg)-based recombinant vaccine strategy, and their effect in vivo. Initially, several multi-antigen vaccine candidates were able to elicit antibodies specific to three out of four B-cell epitopes inserted into the chimeric proteins. However, a lack of virus neutralization led to a redesign of the vaccines. The focus of the newly redesigned vaccines was to elicit a strong immune response to the YSNIGVCK amino acid motif from PEDV. Genetically modified new vaccine candidates were able to elicit a strong antibody (Ab) response to the YSNIGVCK epitope, which correlated with an increased ability to neutralize the CO strain of PEDV. Additionally, the location of the inserted PEDV epitopes within the vector protein was shown to affect the immune recognition toward the native HBcAg during vaccination.


title: Evaluation of the efficacy of a commercial inactivated genogroup 2b-based porcine epidemic diarrhea virus (PEDV) vaccine and experimental live genogroup 1b exposure against 2b challenge

text: Porcine epidemic diarrhea virus strains from the G1b cluster are considered less pathogenic compared to the G2b cluster. The aim of this study was to compare the ability of G1b-based live virus exposure against use of a commercial G2b–based inactivated vaccine to protect growing pigs against G2b challenge. Thirty-nine PEDV naïve pigs were randomly divided into five groups: EXP-IM-1b (intramuscular G1b exposure; G2b challenge), EXP-ORAL-1b (oral G1b exposure; G2b challenge), VAC-IM-2b (intramuscular commercial inactivated G2b vaccination; G2b challenge), POS-CONTROL (sham-vaccination; G2b challenge) and NEG-CONTROL (sham-vaccination; sham-challenge). Pigs were vaccinated/exposed at 3 weeks of age (day post-vaccination 0, dpv 0), VAC-IM-2b pigs were revaccinated at dpv 14, and the pigs were challenged at dpv 28. Among all groups, VAC-IM-2b pigs had significantly higher anti-PEDV IgG levels on dpv 21 and 28 while EXP-ORAL-1b pigs had significantly higher anti-PEDV IgA levels on dpv 14, 21, 28 and 35. EXP-ORAL-1b also had detectable IgA in feces. Intramuscular PEDV exposure did not result in a detectable antibody response in EXP-IM-1b pigs. The fecal PEDV RNA levels in VAC-IM-2b pigs were significantly lower 5–7 days after challenge compared to the POS-CONTROL group. Under the study conditions a commercial inactivated G2b-based vaccine protected pigs against G2b challenge, as evidenced by reduction of PEDV RNA in feces for 3–4 logs during peak shedding and a shorter viral shedding duration. The oral, but not the intramuscular, experimental G1b-based live virus exposure induced a high anti-PEDV IgA response prior to challenge, which apparently did not impact PEDV shedding compared to POS-CONTROL pigs.


title: Coupled disease–behavior dynamics on complex networks: A review

text: Abstract It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease–behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease–behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.


First impressions of performing bedside cognitive assessment of COVID‐19 inpatients.


title: The status of training in new technologies in advanced endoscopy: from defining competence to credentialing and privileging

text: Abstract The landscape of advanced endoscopy continues to evolve as new technologies and techniques become available. Although postgraduate advanced endoscopy fellowships have traditionally centered on ERCP and diagnostic EUS, the breadth of training has increased over the years in response to the ever-growing demand for therapeutic endoscopy. The increasing diversity and complexity of emerging endoscopic techniques accompanied by the shift in focus toward competency-based medical education requires innovative changes to the curriculum that will ensure adequate training yet without compromising best patient practices. The purpose of this review is to highlight the expansive array of advanced endoscopic procedures and the challenges of both defining and measuring competence during training. All authors are interventional endoscopists at their respective institutions performing these complex procedures, as well as training fellows in these techniques. We share our perspectives based on our experience navigating through these issues at our institutions and discuss strategies to standardize training and how to potentially incorporate these measures toward the process of credentialing and privileging in endoscopy.


title: Monoclonal antibody-based therapies for microbial diseases

text: The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases.


title: CEACAM1: Expression and Role in Melanocyte Transformation

text: Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.


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title: A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L

text: The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.


title: The practice of infection control and applied epidemiology: A historical perspective

text: The United States health care system and patient populations have changed substantially over the past several decades. The practice of infection control also has evolved since the landmark Study on the Efficacy of Nosocomial Infection Control project, and infection control professionals (ICPs) must continue to develop the knowledge and skills necessary to practice infection prevention and control. Practice analyses of infection control conducted between 1982 and 2001 were analyzed to determine changes in practice. These data reflect a 145% increase in infection control activities over a 20-year period. However, resources for infection control and prevention have not kept pace with this increased activity. In addition, the current trend toward mandatory reporting of health care-associated infections (HAIs) among several states will add more tasks for ICPs with limited resources, at the risk of spending less time on prevention and control activities. In keeping with its philosophy of quality health care and responsible public reporting, the Association of Professionals in Infection Control and Epidemiology, Inc, continues to explore the issue of mandatory reporting of HAIs.


title: Differential response of porcine immature monocyte-derived dendritic cells to virulent and inactivated transmissible gastroenteritis virus

text: Abstract Exposure of piglets less than 2 weeks of age to virulent transmissible gastroenteritis virus (TGEV) gives rise to mortality as high as 100%, and adult pigs recovering from its infection often become TGEV carriers. These facts suggest an evasion of the immune system by virulent TGEV. In this study, we showed that a virulent TGEV SHXB strain could infect porcine immature monocyte-derived dendritic cells (Mo-DCs), and down-regulate cell surface markers (SLA-II-DR, CD1a and CD80/86). Moreover, SHXB-infected immature Mo-DCs showed low expression of IL-12 and IFN-γ, and also lost the ability to stimulate T cell proliferation. Finally, SHXB inhibited the activation of nuclear factor kappa B (NF-κB) in these cells. Instead, UV-inactivated SHXB (UV-SHXB) had the opposite effects in immature Mo-DCs. In conclusion, the virulent SHXB could severely impair immature Mo-DCs, which might be involved in the pathogenesis of virulent TGEV in vivo.


title: Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome—Associated Coronavirus and Human Coronaviruses 229E and OC43

text: Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ⩾4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E.


COVID-19 and Racial Disparities


Abstracts der 54. Jahrestagung der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde


title: A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV Genome

text: The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.


title: Postponed ICOM 2020 is now taking place in December

text: The 12th International Congress on Membranes & Membrane Processes (ICOM 2020) is now scheduled to be held on 6–11 December 2020 instead of 12–17 July 2020. It is still set to be held at the Excel Convention Centre in London, UK.


COVID-19 is Out of Proportion in African Americans. This Will Come as No Surprise…