title: Infectious bronchitis virus Mass-type (GI-1) and QX-like (GI-19) genotyping and vaccine differentiation using SYBR green RT-qPCR paired with melting curve analysis

text: Abstract Infectious Bronchitis Virus (IBV) is a highly contagious virus of chicken, causing huge economic losses in the poultry industry. Many genotypes circulate in a given area, and optimal protection relies on vaccination with live attenuated vaccines of the same genotype. As these live vaccines are derived from field viruses and circulate, understanding the prevalence of different IBV genotypes in any area is complex. In a recent study, the genome comparison of an IBV QX vaccine and its progenitor field strain led to the identification of vaccine markers. Here we developed a simplex SYBRgreen RT-qPCR assay for differentiation between QX-like field and vaccine strains and a multiplex SYBRgreen RT-qPCR assay for IBV genotyping with melting curve analysis, as each virus produced distinct and reliable melting peaks. Both the simplex and the multiplex assays showed excellent efficiency, sensitivity and specificity representing a low cost diagnostic tool for IBV genotyping and vaccine differentiation.


title: Outcome of a patient with refractory Hodgkin lymphoma on pembrolizumab, infected with SARS‐CoV‐2

text: A 22-year-old female presented the Emergency Department on the 14th March 2020 with a 3 day history of cough, pyrexia, sore throat, chills and rigors. Dyspnoea, myalgia, anosmia did not feature at presentation. The patient had a history of early-stage unfavourable-risk, classical Hodgkin Lymphoma (HL) for which she was diagnosed in May 2017. She underwent two cycles of adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) with escalation to bleomycin/etoposide/adriamycin/cyclophosphamide/vincristine/procarbazine/prednisolone (escBEACOPP) for four cycles due to a suboptimal response on interval positron emission tomography (PET) scan.


docid: yjzysztp

title: Back to BAC: The Use of Infectious Clone Technologies for Viral Mutagenesis

text: Bacterial artificial chromosome (BAC) vectors were first developed to facilitate the propagation and manipulation of large DNA fragments in molecular biology studies for uses such as genome sequencing projects and genetic disease models. To facilitate these studies, methodologies have been developed to introduce specific mutations that can be directly applied to the mutagenesis of infectious clones (icBAC) using BAC technologies. This has resulted in rapid identification of gene function and expression at unprecedented rates. Here we review the major developments in BAC mutagenesis in vitro. This review summarises the technologies used to construct and introduce mutations into herpesvirus icBAC. It also explores developing technologies likely to provide the next leap in understanding these important viruses.


title: Oral mucosal lesions in a COVID-19 patient: new signs or secondary manifestations?

text: Some oral manifestations have been observed in patients with coronavirus disease in 2019 (COVID-19). However, there is still a question about whether these lesions are due to coronavirus infection or secondary manifestations resulting from the patient's systemic condition. Thus, this article aims to report an additional case of the oral conditions in a patient diagnosed with COVID-19. Our patient, a sixty-seven-year-old Caucasian man, tested positive to coronavirus and presented oral manifestations such as recurrent herpes simplex, candidiasis, and geographic tongue. We support the argument that some oral conditions could be secondary to the deterioration of systemic health or due to treatments for COVID-19. The present case report highlights the importance of including dentists in the intensive care unit multi-professional team to improve oral health in critical patients not only COVID-19 patients. Also, to contribute to evidence-based and decision-making in managing infectious diseases.


title: Quality of Evidence Supporting Surviving Sepsis Campaign Recommendations

text: Abstract Introduction: The Surviving Sepsis Campaign (SSC) guidelines, released in 2017, are a combination of expert opinion and evidence-based medicine, adopted by many institutions as a standard of practice. The aim was to analyse the quality of evidence supporting recommendations on the management of sepsis. Methods: The strength and quality of evidence (high, moderate, low-very low and best practice statements) of each recommendation were extracted. Randomised controlled trials were required to qualify as high-quality evidence. Results: A total of 96 recommendations were formulated, and 87 were included. Among thirty-one (43%) strong recommendations, only 15.2% were supported by high-quality evidence. Overall, thirty-seven (42.5%) recommendations were based on low-quality evidence, followed by 28 (32.2%) based on moderate-quality, 15 (17.2%) were best practice statements and only seven (8.0%) were supported by high-quality evidence. Randomised controlled trials supported 21.4%, 9.5% and 8.6% recommendations on mechanical ventilation, resuscitation, and management/adjuvant therapy, respectively. In contrast, none high-quality evidence recommendation supported antimicrobial/source control (82.4% were low-very low evidence or best practice statements), and nutrition. Conclusions: In the SSC guidelines most recommendations were informed by indirect evidence and non-systematic observations. While awaiting trials results, Delphi-like approaches or multi-criteria decision analyses should guide recommendations.


title: Chloroquine paradox may cause more damage than help fight COVID-19

text: Abstract Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.


docid: qorwfuqk

title: COVID-19 and careers: On the futility of generational explanations

text: Abstract It is common to broadly group people of different ages into “generations” and to speak of distinctions between such groups in terms of “generational differences.” The problem with this practice, is that there exists no credible scientific evidence that (a) generations exist, (b) that people can be reliably classified into generational groups, and (c) that there are demonstrable differences between such groups. We have already noted an emerging generationalized rhetoric that has characterized how people of different ages have been affected by and reacted to the COVID-19 pandemic. These narratives have been especially present in discussions of how work and careers will be affected by this crisis. In this essay, we outline problems with applying the concept of generations, especially for researchers seeking explanations for how COVID-19 will affect careers and career development. We urge researchers to eschew the notion of generations and generational differences and consider alternative lifespan development theoretical frameworks that better capture age-graded processes.


title: Disease management with ARIMA model in time series

text: The evaluation of infectious and noninfectious disease management can be done through the use of a time series analysis. In this study, we expect to measure the results and prevent intervention effects on the disease. Clinical studies have benefited from the use of these techniques, particularly for the wide applicability of the ARIMA model. This study briefly presents the process of using the ARIMA model. This analytical tool offers a great contribution for researchers and healthcare managers in the evaluation of healthcare interventions in specific populations.


title: COVID-ABS: An Agent-Based Model of COVID-19 Epidemic to Simulate Health and Economic Effects of Social Distancing Interventions

text: The COVID-19 pandemic due to the SARS-CoV-2 coronavirus has directly impacted the public health and economy worldwide. To overcome this problem, countries have adopted different policies and non-pharmaceutical interventions for controlling the spread of the virus. This paper proposes the COVID-ABS, a new SEIR (Susceptible-Exposed-Infected-Recovered) agent-based model that aims to simulate the pandemic dynamics using a society of agents emulating people, business and government. Seven different scenarios of social distancing interventions were analyzed, with varying epidemiological and economic effects: (1) do nothing, (2) lockdown, (3) conditional lockdown, (4) vertical isolation, (5) partial isolation, (6) use of face masks, and (7) use of face masks together with 50% of adhesion to social isolation. In the impossibility of implementing scenarios with lockdown, which present the lowest number of deaths and highest impact on the economy, scenarios combining the use of face masks and partial isolation can be the more realistic for implementation in terms of social cooperation. The COVID-ABS model was implemented in Python programming language, with source code publicly available. The model can be easily extended to other societies by changing the input parameters, as well as allowing the creation of a multitude of other scenarios. Therefore, it is a useful tool to assist politicians and health authorities to plan their actions against the COVID-19 epidemic.


title: Health Status of Visitors and Temporary Residents, United States

text: Human mobility has always been associated with the spread of infection, and mobility of nonimmigrant visitors and temporary residents to the United States is increasing, from ≈12 million in 1987 to ≈37 million in 2007. Lack of information about the health status of these populations upon arrival and their need for and use of medical services in the United States hinders development of public health policy, education, and provision of adequate clinical care. After these issues and needs are clarified, intervention programs should be developed to increase access and decrease the disparities of care experienced by these populations.


title: External Surface Disinfection of the Lesser Mealworm (Coleoptera: Tenebrionidae)

text: Understanding the dynamics of movement of bacteria within the environment and between species is crucial to unraveling the epidemiology of bacterial diseases and to developing biosecurity measures to prevent dissemination. Many arthropods, some beneficial and some detrimental, inhabit poultry houses. The lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), is a pest commonly found in poultry litter that can harbor pathogens involved in both human and animal health issues. Current farm management practices perpetuate persistent infestations contributing to the dispersal of beetles and pathogens. To study the dissemination of bacteria by this beetle, we require the ability to differentiate internal from external sources of bacteria carried by the beetle. In this study, we tested previously described methods to externally disinfect beetles and found disinfectant efficacies between 40 and 98%. The irregular surface of the insect posed a challenge to cleansing procedures because the surface offered many recesses able to sequester bacteria. Complete bacterial disinfection was achieved with a serial treatment of ethanol and hydrogen peroxide or hydrogen peroxide/peracetic acid.


title: A Peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019 (COVID-19)

text: SARS-CoV-2, a novel ß-coronavirus, cause severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named COVID-19. To date, real-time RT-PCR is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. Here, we developed a peptide-based luminescent immunoassay that detected immunoglobulin G (IgG) and IgM. The assay cut-off value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.


title: Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

text: Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (10(5) TCID(50)) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.


title: Long-term prediction of dynamic distribution of passive contaminant in complex recirculating ventilation system

text: Abstract Recirculating ventilation systems may act as carriers of hazardous substances. The long-term prediction of the dynamic distribution of contaminants in this type of system is crucial for the evaluation of pollution and further design of more efficient ventilation systems. However, few convenient methods can predict the dynamic distribution of contaminants, because the dynamic supply air concentrations resulting from air recirculation are unknown, especially over long time periods, such as months or years. In this study, a novel method is proposed to predict the dynamic distribution of contaminants over a long time period in a complex recirculating ventilation system, where an algebraic expression based on the indices of the response coefficient is applied to account for the relationship between the contaminant distribution inside the room and various boundary conditions. The method is established by obtaining comprehensive mathematical descriptions of the relationships between concentrations of contaminants in the air handling units, supply air inlets, return air outlets, and fresh air. Hourly supply air concentrations can be easily obtained by solving a matrix, and the dynamic distribution of contaminants is then calculated using an expression based on the response coefficient. The reliability of the proposed method is analyzed by both experimental and numerical methods. A simplified method is suggested to accelerate the time-consuming calculation of the response coefficient. The proposed method is beneficial for predicting three-dimensional dynamic distribution of contaminants in complex ventilation systems with an acceptable accuracy and time cost.


title: Correction to: Heparin resistance in COVID‑19 patients in the intensive care unit

text: In the original publication of this article, one of the co-author name "D. de Monteverde-Robb" was inadvertently mentioned as "R. de Monteverde-Robb". The correct author name is "D. de Monteverde-Robb". This error has been corrected with this erratum.


title: Recommandations pour une reprise progressive et contrôlée de l’électroconvulsivothérapie en France en période de levée du confinement et de pandémie COVID-19 liée au SARS-CoV-2

text: The COVID-19 pandemic has had major consequences for the organization of care. In France and around the world, centers practicing electroconvulsive therapy (ECT) have seen their activity decrease, or even stop for many reasons. In this context, maintaining or resuming this essential therapeutic activity for many patients suffering from psychiatric disorders requires material, human and logistical adaptations that should be supervised. The objective of this collective and national work is to offer simple recommendations that can be applied immediately by any healthcare establishment, public or private, practicing ECT. They are the result of feedback from multiprofessional and inter-establishment experiences. Declined in three stages, these recommendations are accompanied by a practical sheet which describes in detail the necessary conditions and prerequisites for any resumption of ECT activity.


title: Prevention of Experimental Coronavirus Colds with Intranasal α-2b Interferon

text: Fifty-five volunteers treated with either intranasal recombinant interferon (rIFN; 2 × 10(6) IU/day) or placebo for 15 days were exposed to coronavirus by direct intranasal inoculation on the eighth day of treatment. Symptom scores were recorded, and cultures of virus were taken daily for all volunteers for seven days after inoculation. Nineteen (73%) of the 26 placebo recipients met symptom-score criteria for a cold, compared with 12 (41%) of the IFN recipients (P = .02). The mean nasal symptom scores in the placebo and IFN groups were 9.2 and 5.4, respectively (P = .03), and the mean total symptom scores in the two groups were 23.2 and 9.4, respectively (P = .003). The mean number of days with a total symptom score >4 was 1.6 in the placebo recipients and 0.5 in the rIFN recipients (P = .02). Prophylactic intranasal rIFN effectively shortened the duration and reduced the severity of coronavirus cold symptoms.


title: Structural and genetic basis for development of broadly neutralizing influenza antibodies

text: Influenza viruses take a yearly toll on human life despite efforts to contain them with seasonal vaccines. These viruses evade human immunity through the evolution of variants that resist neutralization. The identification of antibodies that recognize invariant structures on the influenza haemagglutinin (HA) protein have invigorated efforts to develop universal influenza vaccines. Specifically, antibodies to the highly conserved stem region of HA neutralize diverse viral subtypes. These antibodies largely derive from a specific antibody gene, heavy-chain variable region IGHV1-69, after limited affinity maturation from their germline ancestors(1,2), but how HA stimulates naive B cells to mature and induce protective immunity is unknown. To address this question, we analysed the structural and genetic basis for their engagement and maturation into broadly neutralizing antibodies. Here we show that the germline-encoded precursors of these antibodies act as functional B-cell antigen receptors (BCRs) that initiate subsequent affinity maturation. Neither the germline precursor of a prototypic antibody, CR6261 (ref. 3), nor those of two other natural human IGHV1-69 antibodies, bound HA as soluble immunoglobulin-G (IgG). However, all three IGHV1-69 precursors engaged HA when the antibody was expressed as cell surface IgM. HA triggered BCR-associated tyrosine kinase signalling by germline transmembrane IgM. Recognition and virus neutralization was dependent solely on the heavy chain, and affinity maturation of CR6261 required only seven amino acids in the complementarity-determining region (CDR) H1 and framework region 3 (FR3) to restore full activity. These findings provide insight into the initial events that lead to the generation of broadly neutralizing antibodies to influenza, informing the rational design of vaccines to elicit such antibodies and providing a model relevant to other infectious diseases, including human immunodeficiency virus/AIDS. The data further suggest that selected immunoglobulin genes recognize specific protein structural ‘patterns’ that provide a substrate for further affinity maturation. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature11371) contains supplementary material, which is available to authorized users.


title: Inequality in Learning Opportunities during Covid-19: Evidence from Library Takeout

text: Research shows that Covid-19 enhanced inequality in families’ learning environments. We use register data from Denmark to analyze inequality in families’ takeout of digital children’s books from public libraries. Our register data, which include more than 55 million observations of families’ daily library takeout, show that the socioeconomic gradient in library takeout (by parents’ education and income) that existed before the Covid-19 lockdown increased after the lockdown. We also find that the increase in the socioeconomic gradient during Covid-19 was weaker in immigrant than in native families, stronger in families with recent experience in taking out digital materials from the library, and stronger in families with children in the early stages of elementary school. Overall, our results suggest that Covid-19 increased inequality in learning opportunities because better off families were more successful at using libraries during the pandemic than worse off families.


title: Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department

text: The 2019 coronavirus disease (COVID-19) has not appeared to affect children as severely as adults. However, approximately 1 month after the COVID-19 peak in New York City in April 2020, cases of children with prolonged fevers abruptly developing inflammatory shock-like states have been reported in Western Europe and the United States. This case series describes four previously healthy children with COVID-19 infection confirmed by serologic antibody testing, but negative by nasopharyngeal RT-PCR swab, presenting to the Pediatric Emergency Department (PED) with prolonged fever (5 or more days) and abrupt onset of hemodynamic instability with elevated serologic inflammatory markers and cytokine levels (IL-6, IL-8 and TNF-α). Emergency physicians must maintain a high clinical suspicion for this COVID-19 associated post-infectious cytokine release syndrome, with features that overlap with Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) in children with recent or current COVID-19 infection, as patients can decompensate quickly.


title: Estimate of the Basic Reproduction Number for COVID-19: A Systematic Review and Meta-analysis

text: OBJECTIVES: The outbreak of coronavirus disease 2019 (COVID-19) is one of the main public health challenges currently facing the world. Because of its high transmissibility, COVID-19 has already caused extensive morbidity and mortality in many countries throughout the world. An accurate estimation of the basic reproduction number (R(0)) of COVID-19 would be beneficial for prevention programs. In light of discrepancies in original research on this issue, this systematic review and meta-analysis aimed to estimate the pooled R(0) for COVID-19 in the current outbreak. METHODS: International databases (including Google Scholar, Science Direct, PubMed, and Scopus) were searched to identify studies conducted regarding the R(0) of COVID-19. Articles were searched using the following keywords: “COVID-19” and “basic reproduction number” or “R(0).” The heterogeneity among studies was assessed using the I(2) index, the Cochran Q test, and T(2). A random-effects model was used to estimate R(0) in this study. RESULTS: The mean reported R(0) in the identified articles was 3.38±1.40, with a range of 1.90 to 6.49. According to the results of the random-effects model, the pooled R(0) for COVID-19 was estimated as 3.32 (95% confidence interval, 2.81 to 3.82). According to the results of the meta-regression analysis, the type of model used to estimate R(0) did not have a significant effect on heterogeneity among studies (p=0.81). CONCLUSIONS: Considering the estimated R(0) for COVID-19, reducing the number of contacts within the population is a necessary step to control the epidemic. The estimated overall R(0) was higher than the World Health Organization estimate.


Mental health participation in the fight against the COVID‐19 pandemic


title: Management of patients with ovarian cancer in the COVID‐19 era

text: At the beginning of 2020, coronavirus disease 2019 (COVID‐19) spreads worldwide. Patients with ovarian cancer should be considered at high‐risk of developing severe morbidity related to COVID‐19. Most of them are diagnosed in advanced stages of disease, and they are fragile. Here, we evaluated the major impact of COVID‐19 on patients with ovarian cancer, discussing the effect of the outbreak on medical and surgical treatment.


title: Prospective study of Human Bocavirus (HBoV) infection in a pediatric university hospital in Germany 2005/2006

text: Abstract Background Human Bocavirus (HBoV), a new species of the genus parvovirus newly detected in 2005, seems to be a worldwide distributed pathogen among children with respiratory tract infection (prevalence 2%–18%). Recently published retrospective studies and one prospective birth cohort study suggest that HBoV-primary infection occurs in infants. Methods Prospective single center study over one winter season (November 2005–May 2006) with hospitalized children without age restriction using PCR-based diagnostic methods. Results HBoV DNA was detected in 11 (2.8%) of 389 nasopharyngeal aspirates from symptomatic hospitalized children (median age 9.0 months; range: 3–17 months). RSV, HMPV, HCoV, and Influenza B were detected in 13.9% (n =54), 5.1% (n =20), 2.6% (n =10), and 1.8% (n =7), respectively. There was no influenza A DNA detected in any of the specimens. The clinical diagnoses were acute wheezing (bronchitis) in four patients, radiologically confirmed pneumonia in six patients (55%) and croup syndrome in one patient. In five to six patients with pneumonia, HBoV was the only pathogen detected. While no patient had to be mechanically ventilated, 73% needed oxygen supplementation. In four (36.4%) patients at least one other viral pathogen was found (plus RSV n =3; 27.3%; Norovirus n =1; 9.1%). Conclusion HBoV causes severe respiratory tract infections in infants and young children. Its role as a copathogen and many other open questions has to be defined in further prospective studies.


Simulation-based Training as Perceived by Young Anesthesiology and Intensive Care Residents


title: Operational protocol for donation of anti‐COVID‐19 convalescent plasma in Italy

text: Coronavirus Disease 19 (COVID-19) represents a public health threat worldwide and Italy at the present time is considered the epicenter of this severe infection in the western world. Unfortunately, no standardized therapy does exist for COVID-19 and a number of investigational drugs for use in patients with life-threatening COVID-19 infections have been tried. One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients.


title: Multi-triazole-resistant Aspergillus fumigatus and SARS-CoV-2 co-infection: A lethal combination

text: We report a case of severe COVID-19 pneumonia complicated by fatal co-infection with a multi-triazole resistant Aspergillus fumigatus and highlight the importance of recognising the significance of Aspergillus sp. isolation from respiratory samples. Early diagnosis and detection of triazole resistance are essential for appropriate antifungal therapy to improve outcome in patients with coronavirus associated invasive aspergillosis.


title: Understanding Haemophilus parasuis infection in porcine spleen through a transcriptomics approach

text: BACKGROUND: Haemophilus parasuis (HPS) is an important swine pathogen that causes Glässer's disease, which is characterized by fibrinous polyserositis, meningitis and arthritis. The molecular mechanisms that underlie the pathogenesis of the disease remain poorly understood, particularly the resistance of porcine immune system to HPS invasion. In this study, we investigated the global changes in gene expression in the spleen following HPS infection using the Affymetrix Porcine Genechip™. RESULTS: A total of 931 differentially expressed (DE) transcripts were identified in the porcine spleen 7 days after HPS infection; of these, 92 unique genes showed differential expression patterns based on analysis using BLASTX and Gene Ontology. The DE genes involved in the immune response included genes for inflammasomes (RETN, S100A8, S100A9, S100A12), adhesion molecules (CLDN3, CSPG2, CD44, LGALS8), transcription factors (ZBTB16, SLC39A14, CEBPD, CEBPB), acute-phase proteins and complement (SAA1, LTF, HP, C3), differentiation genes for epithelial cells and keratinocytes (TGM1, MS4A8B, CSTA), and genes related to antigen processing and presentation (HLA-B, HLA-DRB1). Further immunostimulation analyses indicated that mRNA levels of S100A8, S100A9, and S100A12 in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly(I:C) respectively. In addition, mapping of DE genes to porcine health traits QTL regions showed that 70 genes were distributed in 7 different known porcine QTL regions. Finally, 10 DE genes were validated by quantitative PCR. CONCLUSION: Our findings demonstrate previously unrecognized changes in gene transcription that are associated with HPS infection in vivo, and many potential cascades identified in the study clearly merit further investigation. Our data provide new clues to the nature of the immune response in mammals, and we have identified candidate genes that are related to resistance to HPS.


Neumomediastino y neumotórax espontáneo en neumonía bilateral por COVID- 19


title: MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape

text: Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ–dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV–mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.


title: Neutral Theory and Rapidly Evolving Viral Pathogens

text: The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.


title: Evaluation of an Electrostatic Spray Disinfectant Technology for Rapid Decontamination of Portable Equipment and Large Open Areas in the Era of SARS-CoV-2

text: In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual pre-cleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.


title: Differential host gene responses in mice infected with two highly pathogenic avian influenza viruses of subtype H5N1 isolated from wild birds in Thailand

text: Abstract In Thailand, highly pathogenic avian influenza (HPAI) viruses of subtype H5N1 had been isolated from various wild birds during the HPAI outbreak in poultries. In this study, we examined the pathogenicity of two wild bird isolates (A/Pigeon/Thailand/VSMU-7-NPT/2004; Pigeon04 and A/Tree sparrow/Ratchaburi/VSMU-16-RBR/2005; T.sparrow05) in mice. They showed similar replication in several organs and lethal outcome. However, on day 3 post-infection, Pigeon04 induced mRNA expression of proinflammatory cytokines (IL6 and TNFα) and MIP-2, neutrophil chemoattractant, in the lungs, resulting in severe pneumonia that was accompanied by neutrophil infiltration. In contrast, on day 7 post-infection, T.sparrow05 induced the expression of several cytokines to a greater extent than Pigeon04; it also potently induced mRNA expression of several cytokines in brains of the infected mice that triggered frequent inflammatory events. In sum, our study demonstrated that two HPAI viruses induced different host responses, despite having similar replications, resulting in lethal outcome in mice.


Artificial Lung in a Porcine Model: Using Peritoneal Perfusion With Perfluorocarbo


docid: pfsztifl

title: Chapter 100 Angiotensin-Converting Enzyme-2

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 850 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 100 is Angiotensin-Converting Enzyme-2. Keywords: Angiotensin, angiotensin-converting enzyme 2 (ACE2), apelin, bradykinin, carboxypeptidase, cardiovascular, collectrin, renin-angiotensin system, SARS virus, shedding, transmembrane, vasoactive, zinc-binding motif.


title: Preparation and evaluation of anti-SARS coronavirus IgY from yolks of immunized SPF chickens

text: Abstract Severe acute respiratory syndrome (SARS) is a recently discovered viral disease, characterized by fever, cough, acute fibrinous pneumonia and high infectivity. Specific pathogen-free (SPF) chickens were immunized with inactivated SARS coronavirus and their eggs were harvested at regular intervals. Yolk immunoglobulin (IgY) was extracted using the water dilution method, followed by further purification on a Sephadex G-75 column. SDS-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot and neutralization test results showed that the IgY obtained was of a high purity and had a strong reactive activity with a neutralization titer of 1:640. Lyophilization and stability tests showed that lyophilized anti-SARS coronavirus IgY had promising physical properties, with no significant reduction in reactive activity and good thermal stability. All these data suggest that the anti-SARS coronavirus IgY could be a new useful biological product for specific antiviral therapy against SARS.


title: Virus-like particles—universal molecular toolboxes

text: Virus-like particles (VLPs) are highly organised spheres that self-assemble from virus-derived structural antigens. These stable and versatile subviral particles possess excellent adjuvant properties capable of inducing innate and cognate immune responses. Commercialised VLP-based vaccines have been successful in protecting humans from hepatitis B virus (HBV) and human papillomavirus (HPV) infection and are currently explored for their potential to combat other infectious diseases and cancer. Much insight into VLP-mediated immune stimulation and optimised VLP design has been gained from human immunodeficiency virus (HIV)-derived VLPs presenting promising components of current AIDS vaccine approaches. Owing to their unique features, VLPs and virosomes, the in vitro-reconstituted VLP counterparts, have recently gained ground in the field of nanobiotechnology as organic templates for the development of new biomaterials.


title: Validation of a novel severe acute respiratory syndrome scoring system()

text: STUDY OBJECTIVE: In a pilot study conducted during March 14 to April 2, 2003, 2 severe acute respiratory syndrome (SARS) screening scores were developed for predicting SARS among febrile patients presenting to the emergency department (ED). The objective of this study is to validate these scoring systems with a different set of patients. METHODS: All adult patients with documented fever, measured at home or at the hospital, and presenting to the ED of National Taiwan University Hospital, a 2,400-bed tertiary care teaching hospital in northern Taiwan, were prospectively enrolled. Two previously developed SARS screening scores were applied to all patients. The final diagnosis of SARS was made by the Expert Committee of the Center for Disease Control Taiwan, Republic of China, according to the criteria of Centers for Disease Control and Prevention, Atlanta, GA. RESULTS: A total of 239 adult patients, including 117 men and 122 women, were enrolled. Eighty-two patients were finally diagnosed with SARS. Compared with the SARS patients in the derivation cohort, those in the validation cohort were older (44.5±15.9 versus 33.9±15.9 years), more likely to acquire the disease locally (76.8% versus 37.5%), and more likely to have cough before or during fever. For the non-SARS patients, cases in the validation cohort presented with less cough and coryza but more diarrhea. For the 4-item symptom score, the sensitivity reached 96.3% (95% confidence interval [CI] 89.7% to 98.7%) and the specificity 51.6% (95% CI 43.8% to 59.3%). For the 6-item clinical score, the sensitivity reached 92.6% (95% CI 84.8% to 96.6%) and the specificity 71.2% (95% CI 63.6% to 77.7%). When the clinical score was applied to patients with a positive symptom score, the combined sensitivity reached 90.2% (95% CI 82.0% to 95.0%), and the combined specificity reached 80.1% (95% CI 73.2% to 85.6%). CONCLUSION: This prospective study validated the scoring system previously developed by using a different cohort. The scoring systems could be applied to settings where mass screening of SARS is needed during future outbreaks.


docid: ggqupsck

title: Rapid preparation of plasma membranes from avian lymphoid cells and fibroblasts for virus binding studies

text: Abstract A simple and rapid protocol for the preparation of plasma membranes from chicken embryo fibroblasts and chicken lymphoid cells was developed. Characterization of the preparations by morphological, biochemical and serological methods indicated the specific enrichment of the plasma membranes as well as cell surface proteins. Binding of infectious bursal disease virus (IBDV) particles was demonstrated after immobilization of the plasma membranes, and cell type-specific differences were observed. Although the results of these studies reflect the interaction between IBDV and isolated cells only partially, the advantages of these plasma membrane preparations, the specific enrichment of cell surface proteins, their constant quality and the possibility to store aliquots over several months, make them a useful tool for virus binding studies with avian cells.


Shedding ultraviolet light on coronavirus


title: A vector expressing feline mature IL-18 fused to IL-1β antagonist protein signal sequence is an effective adjuvant to a DNA vaccine for feline leukaemia virus

text: DNA vaccination using vectors expressing the gag/pol and env genes of feline leukaemia virus (FeLV) and plasmids encoding feline interleukin-12 (IL-12) and IL-18 completely protected cats from viraemia following challenge [Hanlon L, Argyle D, Bain D, Nicolson L, Dunham S, Golder MC, et al. Feline leukaemia virus DNA vaccine efficacy is enhanced by coadministration with interleukin-12 (IL-12) and IL-18 expression vectors. J Virol 2001;75:8424–33]. However, the relative contribution of each cytokine gene towards protection is unknown. This study aimed to resolve this issue. IL-12 and IL-18 constructs were modified to ensure effective expression, and bioactivity was demonstrated using specific assays. Kittens were immunised intramuscularly with FeLV DNA and various cytokine constructs. Together with control kittens, these were challenged oronasally with FeLV and monitored for 15 weeks. All six kittens given FeLV, IL-12 and IL-18 were protected from the establishment of persistent viraemia and four from latent infection. Of six kittens immunised with FeLV DNA and IL-18, all were protected from viraemia and five from latent infection. In contrast, three of five kittens given FeLV DNA and IL-12 became persistently viraemic. Therefore, the adjuvant effect on the FeLV DNA vaccine appears to reside in the expression of IL-18.


title: Using online technologies to improve diversity and inclusion in cognitive interviews with young people

text: BACKGROUND: We aimed to assess the feasibility of using multiple technologies to recruit and conduct cognitive interviews among young people across the United States to test items measuring sexual and reproductive empowerment. We sought to understand whether these methods could achieve a diverse sample of participants. With more researchers turning to approaches that maintain social distancing in the context of COVID-19, it has become more pressing to refine these remote research methods. METHODS: We used several online sites to recruit for and conduct cognitive testing of survey items. To recruit potential participants we advertised the study on the free online bulletin board, Craigslist, and the free online social network, Reddit. Interested participants completed an online Qualtrics screening form. To maximize diversity, we purposefully selected individuals to invite for participation. We used the video meeting platform, Zoom, to conduct the cognitive interviews. The interviewer opened a document with the items to be tested, shared the screen with the participant, and gave them control of the mouse and keyboard. After the participant self-administered the survey, the interviewer asked about interpretation and comprehension. After completion of the interviews we sent participants a follow-up survey about their impressions of the research methods and technologies used. We describe the processes, the advantages and disadvantages, and offer recommendations for researchers. RESULTS: We recruited and interviewed 30 young people from a range of regions, gender identities, sexual orientations, ages, education, and experiences with sexual activity. These methods allowed us to recruit a purposefully selected diverse sample in terms of race/ethnicity and region. It also may have offered potential participants a feeling of safety and anonymity leading to greater participation from gay, lesbian, and transgender people who would not have agreed to participate in-person. Conducting the interviews using video chat may also have facilitated the inclusion of individuals who would not volunteer for in-person meetings. Disadvantages of video interviewing included participant challenges to finding a private space for the interview and problems with electronic devices. CONCLUSIONS: Online technologies can be used to achieve a diverse sample of research participants, contributing to research findings that better respond to young people’s unique identities and situations.


title: Influenza molecular diagnostic testing in a 1000-bed academic Italian hospital during the 2018–19 influenza season

text: AIM: The aims of this study were to examine the requests for influenza molecular tests processed by the Virology Laboratory of the University Hospital of Udine during the 2018–19 influenza season and to assess the test results and to estimate costs. SUBJECTS AND METHODS: We analyzed various administrative databases of the hospital health information system, which can be deterministically linked at the individual level through an anonymous stochastic key. Requests for influenza molecular tests from November 1, 2018, to April 15, 2019, and test results were described by week and, for hospitalized patients, hospital ward. Previous vaccination status of tested patients, outcomes and estimated test costs were assessed. RESULTS: In the 2018–19 influenza season, 979 influenza A and B virologic tests were processed by the laboratory, corresponding to 758 patients. Requests had more than doubled compared with the previous influenza season. Rapid real-time PCR tests, routinely available at the University Hospital of Udine since January 2019, represented 17% of requests. Six hundred forty-eight patients were hospitalized. Medical wards requested the test after a median of 1 day after admission, whereas requests were delayed for surgical and oncologic patients. The number of tests, proportion of positivity and consumption of rapid tests varied by medical specialty. Overall consumption of oseltamivir was similar to that of the previous influenza season. CONCLUSIONS: This analysis, benefiting from the availability of integrated health administrative databases, provided useful information to support public health decision-making and managing the supply and demand for diagnostic tests.


title: Improved Diagnostics Help to Identify Clinical Features and Biomarkers That Predict Mycoplasma pneumoniae Community-acquired Pneumonia in Children

text: BACKGROUND: There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. METHODS: This is a prospective cohort study of children, 3–18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. RESULTS: Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT <0.25 μg/L, were statistically associated with Mp infection. A combination of age >5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT <0.25 μg/L (AUC = 0.81) improved diagnostic performance (AUC = 0.90) (P = .05). CONCLUSIONS: A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.


title: Lymphangiosarcoma in two cats

text: Lymphangiosarcoma is a malignant neoplasm of the lymphatic endothelium that is rare in cats. This report describes two cases of feline lymphangiosarcoma that originated in the distal limb, causing intractable lymphoedema and serosanguineous discharge with ecchymoses in local and distant sites. In association with the neoplasia, one cat had cortical bone lysis of multiple metacarpal bones of the affected limb and the other had severe immune-mediated haemolytic anaemia (IMHA). The disease in both cases affected young cats and progressed rapidly. Persistent distal limb lymphoedema with serosanguineous discharge is suggestive of lymphangiosarcoma especially when local or distal ecchymoses are evident.


title: An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge

text: Abstract Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine respiratory disease (BRD), we sought to investigate the efficacy of an inactivated IDV vaccine. Vaccinated calves seroconverted with hemagglutination inhibition titers 137–169 following two doses. Non-vaccinated calves challenged with a homologous virus exhibited signs of mild respiratory disease from days four to ten post challenge which was significantly different than negative controls at days five and nine post challenge. Peak viral shedding of approximately 5 TCID50/mL was measured in nasal and tracheal swabs and bronchoalveolar lavage fluids four to six days post challenge. Viral titers were significantly (P <0.05) decreased 1.4 TCID50/mL, 3.6 TCID50/mL and 5.0 TCID50/mL, respectively, in the aforementioned samples collected from vaccinated animals compared to non-vaccinated controls at peak shedding. Viral antigen was detected in the respiratory epithelium of the nasal turbinates and trachea by immunohistochemistry from all unvaccinated calves but in significantly fewer vaccinates. Inflammation characterized by neutrophils was observed in the nasal turbinate and trachea but not appreciably in lungs. Together these results support an etiologic role for IDV in BRD and demonstrate that partial protection is afforded by an inactivated vaccine.


title: Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

text: Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC(50) as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection.


title: Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Viral Pathogens

text: Abstract Acute respiratory infection is a frequently transmitted illness of concern to doctors and patients. Considering its airborne transmission, early diagnosis of such disease is particularly important. This study explored respiratory viral infections with influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human bocavirus, coronavirus, and other early diagnostic substances as confirmed by literature resources. This study also used the corresponding monoclonal antibodies that were produced with the use of hybridoma technology, which were fixed on the chip after purification, for further serum detection. Using this method, a new technique to simultaneously detect 6 kinds of febrile respiratory viruses in a protein chip was developed. The accuracy rate of this method can be >99.65%. This product is inexpensive and capable of high-precision and high-throughput screening, which are prominent advantages.


title: Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective

text: There is no evidence on benefits or harms of inhaled steroids in COVID-19. It is essential that epidemiological studies of COVID-19 include detailed information on comorbidities and prior medication to help answer this question. https://bit.ly/2XVwIsa


title: Selection of staphylococcal enterotoxin B (SEB)-binding peptide using phage display technology

text: Abstract In this study, peptides were selected to recognize staphylococcal enterotoxin B (SEB) which cause food intoxication and can be used as a biological war agent. By using commercial M13 phage library, single plaque isolation of 38 phages was done and binding affinities were investigated with phage-ELISA. The specificities of the selected phage clones showing high affinity to SEB were checked by using different protein molecules which can be found in food samples. Furthermore, the affinities of three selected phage clones were determined by using surface plasmon resonance (SPR) sensors. Sequence analysis was realized for three peptides showing high binding affinity to SEB and WWRPLTPESPPA, MNLHDYHRLFWY, and QHPQINQTLYRM amino acid sequences were obtained. The peptide sequence with highest affinity to SEB was synthesized with solid phase peptide synthesis technique and thermodynamic constants of the peptide–SEB interaction were determined by using isothermal titration calorimetry (ITC) and compared with those of antibody–SEB interaction. The binding constant of the peptide was determined as 4.2±0.7×105 M−1 which indicates a strong binding close to that of antibody.


title: The impact of global budgeting in Taiwan on inpatients with unexplained fever

text: Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan. The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000–2001 were recruited; their 2000–2001 and 2004–2005 data were considered baseline and postintervention data, respectively. Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ± 0.35 days and 5.29 ± 0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ± NT$97.43, NT$3249.90 ± NT$1108.27, NT$421.03 ± NT$100.03, and NT$13,866.77 ± NT$2,114.95 before GB system implementation to NT$2224.34 ± NT$238.36, NT$4272.31 ± NT$1466.90, NT$2217.03 ± NT$672.20, and NT$22,856.41 ± NT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ± 2.7% and 8.3% ± 2.4% before implementation to 6.3% ± 2.2% and 4.0% ± 1.7% after implementation. GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.


Tomographic findings and thrombogenic effects of COVID-19


title: Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review

text: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.


title: Exposure to DPP‐4 inhibitors and COVID‐19 among people with type 2 diabetes. A case–control study

text: Because other coronaviruses enter the cells by binding to dipeptidyl‐peptidase‐4 (DPP‐4), it has been speculated that DPP‐4 inhibitors (DPP‐4i) may exert an activity against SARS‐CoV‐2. In the absence of clinical trial results, we analyzed epidemiological data to support or discard such hypothesis. We retrieved information on exposure to DPP‐4i among patients with type 2 diabetes (T2D) hospitalized for COVID‐19 at an outbreak hospital in Italy. As reference, we retrieved exposure to DPP‐4i among matched T2D patients in the same Region. Of 403 hospitalized COVID‐19 patients, 85 had T2D. The rate of exposure to DPP‐4i was similar between T2D patients with COVID‐19 (10.6%) and 14 857 matched patients in the Region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID‐19 pneumonia (11.3%) to 351 matched patients with pneumonia of other etiology (10.3%). T2D patients with COVID‐19 who were on DPP‐4i had a similar disease outcome as those who were not. In summary, we found no evidence that DPP‐4i might affect hospitalization for COVID‐19. This article is protected by copyright. All rights reserved.


Moratorium on Research Intended To Create Novel Potential Pandemic Pathogens


title: Medical student concerns relating to neurosurgery education during COVID-19

text: Abstract Background The Coronavirus Disease 2019 (COVID-19) pandemic has created significant obstacles within medical education. For medical students interested in pursuing neurosurgery as a specialty, educational policies surrounding COVID-19 present unique challenges. This study utilizes a nationwide survey to identify concerns held by students interested in pursuing neurosurgery during the COVID-19 pandemic. Methods Students who previously registered for the Medical Student Neurosurgery Training Camps were sent an online Qualtrics survey, requesting them to assess how the COVID-19 pandemic was affecting their neurosurgical education. The Pearson Chi-Square test and post-hoc pairwise Fisher’s exact test were used for analysis of categorical variables and the two-tailed paired Student’s t-test was utilized for continuous variables. Results The survey was distributed to 852 medical students with 127 complete responses. Concerns regarding conferences/networking opportunities (63%), clinical experience (59%), and board exam scores (42%) were most frequently cited. 76% of M3s reported at least one cancelled/postponed neurosurgery rotation. On average, students were more likely to take a year off from medical school after COVID-19 than before the start of the pandemic, measured from 0 to 100 (25.3 ± 36.0 vs 39.5 ± 37.5; p = 0.004). Virtual mentorship pairing was the highest rated educational intervention suggested by M1s and M2s, while M3s and M4s cited virtual surgical skills workshops most frequently. Conclusions This nationwide survey highlights the concerns of medical students in neurosurgery education during the COVID-19 pandemic. With these findings, neurosurgery organizations can consider targeted plans for students of each year to continue their development.


docid: vlpwhmui

title: Factors Associated with Urban Risk-Taking Behaviour during 2018 Typhoon Mangkhut: A Cross Sectional Study

text: Although much of the health emergency and disaster risk management (Health-EDRM) literature evaluates methods to protect health assets and mitigate health risks from disasters, there is a lack of research into those who have taken high-risk behaviour during extreme events. The study’s main objective is to examine the association between engaging in high-risk behaviour and factors including sociodemographic characteristics, disaster risk perception and household preparedness during a super typhoon. A computerized randomized digit dialling cross-sectional household survey was conducted in Hong Kong, an urban metropolis, two weeks after the landing of Typhoon Mangkhut. Telephone interviews were conducted in Cantonese with adult residents. The response rate was 23.8% and the sample was representative of the Hong Kong population. Multivariable logistic regressions of 521 respondents adjusted with age and gender found education, income, risk perception and disaster preparedness were insignificantly associated with risk-taking behaviour during typhoons. This suggests that other factors may be involved in driving this behaviour, such as a general tendency to underestimate risk or sensation seeking. Further Health-EDRM research into risk-taking and sensation seeking behaviour during extreme events is needed to identify policy measures.


title: Diverse Mechanisms of RNA Recombination

text: Recombination is widespread among RNA viruses, but many molecular mechanisms of this phenomenon are still poorly understood. It was believed until recently that the only possible mechanism of RNA recombination is replicative template switching, with synthesis of a complementary strand starting on one viral RNA molecule and being completed on another. The newly synthesized RNA is a primary recombinant molecule in this case. Recent studies have revealed other mechanisms of replicative RNA recombination. In addition, recombination between the genomes of RNA viruses can be nonreplicative, resulting from a joining of preexisting parental molecules. Recombination is a potent tool providing for both the variation and conservation of the genome in RNA viruses. Replicative and nonreplicative mechanisms may contribute differently to each of these evolutionary processes. In the form of trans splicing, nonreplicative recombination of cell RNAs plays an important role in at least some organisms. It is conceivable that RNA recombination continues to contribute to the evolution of DNA genomes.


title: Four Cultural Narratives for Managing Social-ecological Complexity in Public Natural Resource Management

text: Public Natural Resource Management (NRM) agencies operate in complex social-ecological domains. These complexities proliferate unpredictably therefore investigating and supporting the ability of public agencies to respond effectively is increasingly important. However, understanding how public NRM agencies innovate and restructure to negotiate the range of particular complexities they face is an under researched field. One particular conceptualisation of the social-ecological complexities facing NRM agencies that is of growing influence is the Water–Energy–Food (WEF) nexus. Yet, as a tool to frame and understand those complexities it has limitations. Specifically, it overlooks how NRMs respond institutionally to these social-ecological complexities in the context of economic and organisational challenges—thus creating a gap in the literature. Current debates in public administration can be brought to bear here. Using an organisational cultures approach, this paper reports on a case study with a national NRM agency to investigate how they are attempting to transform institutionally to respond to complexity in challenging times. The research involved 12 elite interviews with senior leaders from Natural Resources Wales, (NRW) and investigated how cultural narratives are being explicitly and implicitly constructed and mobilised to this end. The research identified four distinct and sequential cultural narratives: collaboration, communication, trust, and empowerment where each narrative supported the delivery of different dimensions of NRW’s social-ecological complexity mandate. Counter to the current managerialist approaches in public administration, these results suggest that the empowerment of expert bureaucrats is important in responding effectively to complexity.


title: The COVID-19 pandemic and health inequalities

text: This essay examines the implications of the COVID-19 pandemic for health inequalities. It outlines historical and contemporary evidence of inequalities in pandemics—drawing on international research into the Spanish influenza pandemic of 1918, the H1N1 outbreak of 2009 and the emerging international estimates of socio-economic, ethnic and geographical inequalities in COVID-19 infection and mortality rates. It then examines how these inequalities in COVID-19 are related to existing inequalities in chronic diseases and the social determinants of health, arguing that we are experiencing a syndemic pandemic. It then explores the potential consequences for health inequalities of the lockdown measures implemented internationally as a response to the COVID-19 pandemic, focusing on the likely unequal impacts of the economic crisis. The essay concludes by reflecting on the longer-term public health policy responses needed to ensure that the COVID-19 pandemic does not increase health inequalities for future generations.


title: Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels

text: Kawasaki's disease is a disease of unknown cause. The characteristic clinical features of Kawasaki's disease are fever≥102°F for≥5 days accompanied by a bilateral bulbar conjunctivitis/conjunctival suffusion, erythematous rash, cervical adenopathy, pharyngeal erythema, and swelling of the dorsum of the hands/feet. Kawasaki's disease primarily affects children and is rare in adults. In children, Kawasaki's disease is more likely to be associated with aseptic meningitis, coronary artery aneurysms, and thrombocytosis. In adult Kawasaki's disease, unilateral cervical adenopathy, arthritis, conjunctival suffusion/conjunctivitis, and elevated serum transaminases (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) are more likely. Kawasaki's disease in adults may be mimicked by other acute infections with fever and rash, that is, group A streptococcal scarlet fever, toxic shock syndrome (TSS), and Rocky Mountain Spotted Fever (RMSF). Because there are no specific tests for Kawasaki's disease, diagnosis is based on clinical criteria and the syndromic approach. In addition to rash and fever, scarlet fever is characterized by circumoral pallor, oropharyngeal edema, Pastia's lines, and peripheral eosinophilia, but not conjunctival suffusion, splenomegaly, swelling of the dorsum of the hands/feet, thrombocytosis, or an elevated SGOT/SGPT. In TSS, in addition to rash and fever, there is conjunctival suffusion, oropharyngeal erythema, and edema of the dorsum of the hands/feet, an elevated SGOT/SGPT, and thrombocytopenia. Patients with TSS do not have cervical adenopathy or splenomegaly. RMSF presents with fever and a maculopapular rash that becomes petechial, first appearing on the wrists/ankles after 3 to 5 days. RMSF is accompanied by a prominent headache, periorbital edema, conjunctival suffusion, splenomegaly, thrombocytopenia, an elevated SGOT/SGPT, swelling of the dorsum of the hands/feet, but not oropharyngeal erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasaki's disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasaki's disease. We conclude that Kawasaki's disease should be considered in the differential diagnosis in adult patients with rash/fever for≥5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels.


title: Binding specificity of influenza C-virus to variablyO-acetylated glycoconjugates and its use for histochemical detection ofN-acetyl-9-O-acetylneuraminic acid in mammalian tissues

text: The specificity of influenza C-virus binding to sialoglycoconjugates was tested with various naturallyO-acetylated gangliosides or syntheticallyO-acetylated sialic acid thioketosides, which revealed binding to 9-O-acetylatedN-acetylneuraminic acid. Binding was also observed with a sample of Neu5,7Ac(2)-GD3, however at a lower degree. Sialic acids with two or threeO-acetyl groups in the side chain of synthetic sialic acid derivatives are not recognized by the virus. In these experiments, bound viruses were detected with esterase substrates. Influenza C-virus was also used for the histological identification of mono-O-acetylated sialic acids in combination with an immunological visualization of the virus bound to thin-sections. The occurrence of these sialic acids was demonstrated in bovine submandibular gland, rat liver, human normal adult and fetal colon and diseased colon, as well as in human sweat gland. Submandibular gland and colon also contain significant amounts of glycoconjugates with two or three acetyl esters in the sialic acid side chain, demonstrating the value of the virus in discriminating between mono- and higherO-acetylation at the same site. The patterns of staining showed differences between healthy persons and patients with colon carcinoma, ulcerative colitis or Crohn's disease. Remarkably, some human colon samples did not showO-acetyl sialic acid-specific staining. The histochemical observations were controlled by chemical analysis of tissue sialic acids.


Richtlinien und Empfehlungen schnell in die Praxis bringen: Schutzmaßnahmen im Gesundheitsbereich anlässlich der COVID-19-Krise schulen


Viral etiology of Acute Respiratory Infections in Hospitalized Children in Novosibirsk City, Russia (2013 – 2017)


title: Comparative transcriptional analysis reveals distinct expression patterns of channel catfish genes after the first infection and re-infection with Aeromonas hydrophila

text: Abstract To determine whether transcriptional levels of channel catfish (Ictalurus punctatus) genes are differentially regulated between a first infection with Aeromonas hydrophila and a re-infection, suppression subtractive hybridization (SSH) was performed in this study using anterior kidney cDNA after the re-infection as tester. Of the 96 clones isolated from the SSH library, 28 unique expressed sequence tags (ESTs) were obtained, of which eight were confirmed to be slightly but significantly (P < 0.05) more up-regulated by the re-infection at 6 h post infection (hpi). Expression kinetics studies at 3, 6, 12, 24, and 48 hpi revealed that the eight ESTs were significantly (P = 0.016) more up-regulated by the first infection, with a major peak at 3 hpi. A total of 96 genes reported in literature to be up-regulated by bacterial infections were selected and subjected to expression analysis at 3 hpi. Of the 96 selected genes, 19 were found to be significantly (P < 0.05) induced by A. hydrophila after the first infection and the re-infection. The 19 genes belonged to the following five main categories: 1) toll-like receptor (TLR2, TLR3, TLR5, TLR21); 2) antimicrobial peptide (NK-lysin type 1, NK-lysin type 2, NK-lysin type 3, cathepsin D, transferrin, hepcidin); 3) cytokine or chemokine (interleukin-1β, interleukin-10, tumor necrosis factor α, chemokine CXCL-10); 4) signaling proteins (cadherin EGF LAG seven-pass G-type receptor 1, very large inducible GTPase 1, arginine deiminase type 2, lymphokine-activated killer T-cell originated protein kinase); 5) lysozyme (lysozyme c). Overall, the total 27 genes (8 ESTs plus the 19 selected genes) were significantly (P < 0.001) more induced by the first infection. Peaked expression of lysozyme c and serum lysozyme activity after the first infection were seen at 24 hpi, whereas that after the re-infection were seen at 12 hpi, suggesting that both innate and adaptive immunity were involved in the defense against the re-infection of A. hydrophila.


title: Prokaryotic and eukaryotic translational machineries respond differently to the frameshifting RNA signal from plant or animal virus

text: Abstract Many mutational and structural analyses of the RNA signals propose a hypothesis that programmed frameshifting occurs by a specific interaction between ribosome and frameshifting signals comprised of a shifty site and a downstream RNA structure, in which the exact nature of the interaction has not yet been proven. To address this question, we analyzed the frameshifting sequence elements from animal or plant virus in yeast and Escherichia coli. Frameshifting efficiencies varied in yeast, but not in E. coli, depending on the specific conformation of mouse mammary tumor virus (MMTV) RNA pseudoknot. Similar changes in frameshifting efficiencies were observed in yeast, but not in E. coli, for the mutations in frameshifting sequence elements from cereal yellow dwarf virus serotype RPV (CYDV-RPV). The differential response of MMTV or CYDV-RPV frameshifting signal to prokaryotic and eukaryotic translational machineries implies that ribosome pausing alone is insufficient to mediate frameshifting, and additional events including specific interaction between ribosome and RNA structural element are required for efficient frameshifting. These results supports the hypothesis that frameshifting occurs by a specific interaction between ribosome and frameshifting signal.


title: Is Hesperidin Essential for Prophylaxis and Treatment of COVID-19 Infection?

text: SARS-CoV-2 or COVID-19 is representing the major global burden that implicated more than 4.7 million infected cases and 310 thousand deaths worldwide in less than 6 months. The prevalence of this pandemic disease is expected to rise every day. The challenge is to control its rapid spread meanwhile looking for a specific treatment to improve patient outcomes. Hesperidin is a classical herbal medicine used worldwide for a long time with an excellent safety profile. Hesperidin is a well-known herbal medication used as an antioxidant and anti-inflammatory agent. Available shreds of evidence support the promising use of hesperidin in prophylaxis and treatment of COVID 19. Herein, we discuss the possible prophylactic and treatment mechanisms of hesperidin based on previous and recent findings. Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID- 19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.


title: Human and bovine viruses in the Milwaukee River watershed: Hydrologically relevant representation and relations with environmental variables

text: Abstract To examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n=63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300genomiccopies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11genomiccopies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing human exposure and disease transmission.


title: A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

text: BACKGROUND: Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. PRESENTATION OF THE HYPOTHESIS: Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. TESTING THE HYPOTHESIS: CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. IMPLICATIONS OF THE HYPOTHESIS: CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.


title: Mimicking microbial strategies for the design of mucus-permeating nanoparticles for oral immunization

text: Abstract Dealing with mucosal delivery systems means dealing with mucus. The name mucosa comes from mucus, a dense fluid enriched in glycoproteins, such as mucin, which main function is to protect the delicate mucosal epithelium. Mucus provides a barrier against physiological chemical and physical aggressors (i.e., host secreted digestive products such as bile acids and enzymes, food particles) but also against the potentially noxious microbiota and their products. Intestinal mucosa covers 400m2 in the human host, and, as a consequence, is the major portal of entry of the majority of known pathogens. But, in turn, some microorganisms have evolved many different approaches to circumvent this barrier, a direct consequence of natural co-evolution. The understanding of these mechanisms (known as virulence factors) used to interact and/or disrupt mucosal barriers should instruct us to a rational design of nanoparticulate delivery systems intended for oral vaccination and immunotherapy. This review deals with this mimetic approach to obtain nanocarriers capable to reach the epithelial cells after oral delivery and, in parallel, induce strong and long-lasting immune and protective responses.


title: Syphilis in China: the great comeback

text: China is currently witnessing a major resurgence of syphilis from the elimination of the disease in the 1960s to 5.3 per 100,000 people incidence in 2000–2005. The reasons for the elimination and subsequent resurgence of syphilis in China lie at the heart of much public health debate, highlighting both the relationship between politics and public health, and the role of government in controlling disease. Were the Draconian measures to control syphilis during the early Mao years a price worth paying for the effective control? Is the recent resurgence of syphilis an inevitable consequence of economic development and greater freedom for the individual, which will ultimately lead to better health for the majority of the population? Could tougher control measures such as those of the early Mao years be re-introduced in the current social and economic climate in China? In this review, we briefly chart the history of the syphilis epidemic in China, its elimination in the 1960s, and its gradual resurgence in the past two decades. We explore the reasons for this resurgence, and we conclude with a discussion on the options for control.


title: Coronavirus Disease 2019 (COVID-19): Forecast of an Emerging Urgency in Pakistan

text: Background/Aims Novel coronavirus disease 2019 (COVID-19) is a global challenge due to little available knowledge and treatment protocols. Thus, there is a great need for collecting data related to COVID-19 from all around the world. Hence, we conducted this study, collecting daily data on COVID-19, to map the epidemiology outbreak and forecast its trajectory for May 2020. Methodology The data was collected from the officially released reports of the National Institute of Health (NIH), Pakistan, and the World Health Organization (WHO). The analysis was done using Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY), and forecasting was done using a simple moving average in time series modeler/expert modeler. Results The purpose of this study is to draw the attention of international, as well as national, governing bodies to the rapidly rising number of COVID-19 cases in Pakistan, and the urgency of evaluating the efficacy of the currently implemented strategy against COVID-19. According to this study, there is now an alarming increase in the number of COVID-19 patients in Pakistan, despite a contained spread in the beginning. The predicted number of COVID-19 cases can go over 35,000 by the end of May 2020. Conclusion It is crucial for governing bodies, administrators, and researchers to re-evaluate the current situation, designed policies, and implemented strategies.


title: Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection

text: Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) is a concern for global public health, as there is a lack of efficacious vaccine platforms and antiviral therapeutic strategies. Previously, it was shown that MyD88, an adaptor protein necessary for signaling by multiple TLRs, is a required component of the innate immune response to mouse-adapted SARS-CoV infection in vivo. Here, we demonstrate that TLR3(−/−), TLR4(−/−), and TRAM(−/−) mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. In contrast, mice deficient in the TLR3/TLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers. Distinct alterations in inflammation were present in TRIF(−/−) mice infected with SARS-CoV, including excess infiltration of neutrophils and inflammatory cell types that correlate with increased pathology of other known causes of acute respiratory distress syndrome (ARDS), including influenza virus infections. Aberrant proinflammatory cytokine, chemokine, and interferon-stimulated gene (ISG) signaling programs were also noted following infection of TRIF(−/−) mice that were similar to those seen in human patients with poor disease outcome following SARS-CoV or MERS-CoV infection. These findings highlight the importance of TLR adaptor signaling in generating a balanced protective innate immune response to highly pathogenic coronavirus infections.


docid: ptmxkpae

title: Clinical Insights into the Gastrointestinal Manifestations of COVID-19

text: The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal–oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.


docid: shnpktxc

title: 38 Immune Deficiencies at the Extremes of Age

text: Abstract In early life as well as in late life, the immune system is dysfunctional. During early infancy, innate as well as adaptive immune cells are immature, immune memory has not been built, and regulatory pathways that maintain tolerance dominate. Throughout life, the adult human systems face the challenge of maintaining immune cell and population homeostasis while facing declining regenerative capacity and constant exogenous assaults. Failure of homeostatic mechanisms, together with age-acquired cellular defects, leads to the complex embodiment of immunosenescence that combines ineffective immune responses to infection and vaccination with constitutive production of inflammatory mediators and increased risk of autoimmunity.


title: Assessment of economic vulnerability to infectious disease crises

text: Infectious disease crises have substantial economic impact. Yet mainstream macroeconomic forecasting rarely takes account of the risk of potential pandemics. This oversight contributes to persistent underestimation of infectious disease risk and consequent underinvestment in preparedness and response to infectious disease crises. One reason why economists fail to include economic vulnerability to infectious disease threats in their assessments is the absence of readily available and digestible input data to inform such analysis. In this Viewpoint we suggest an approach by which the global health community can help to generate such inputs, and a framework to use these inputs to assess the economic vulnerability to infectious disease crises of individual countries and regions. We argue that incorporation of these risks in influential macroeconomic analyses such as the reports from the International Monetary Fund's Article IV consultations, rating agencies and risk consultancies would simultaneously improve the quality of economic risk forecasting and reinforce individual government and donor incentives to mitigate infectious disease risks.


title: Experimental models of demyelination and remyelination

text: Abstract Introduction Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. Development We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Conclusions Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study.


title: COVID-19 en residencias de mayores: una asignatura pendiente

text: Resumen Antecedentes: En un brote de Covid-19, las residencias geriátricas asistidas son entornos donde existe un riesgo elevado tener resultados graves. Ello se debe tanto a la edad avanzada de los residentes y a la frecuencia con que presentan problemas de salud crónicos como al movimiento del personal sanitario entre instalaciones de la zona. Métodos: Tras la identificación, el 28 de febrero de 2020, de un caso confirmado de Covid-19 en una residencia asistida en el condado de King, Washington. Salud Pública-Seattle y el condado de King, con la ayuda de los Centros para el Control y la Prevención de Enfermedades pusieron en marcha una investigación del caso, la localización de contactos, la cuarentena de las personas expuestas, el aislamiento de los casos confirmados y sospechosos y la mejora in situ de la prevención y el control de la infección. Resultados: El 18 de marzo, se determinó que un total de 167 casos confirmados de Covid-19 que afectaban a 101 residentes, 50 trabajadores sanitarios y 16 visitantes, estaban vinculados epidemiológicamente a la residencia. La mayoría de los residentes afectados presentaban enfermedades respiratorias compatibles con el Covid-19; sin embargo, en 7 residentes no se documentaron síntomas. Las tasas de hospitalización de los residentes, los visitantes y del personal fueron del 54,5%, 50,0% y 6,0%, respectivamente. La tasa de letalidad de los residentes fue del 33,7% (34 de 101). En esa misma fecha se había identificado al menos un caso confirmado de Covid-19 en un total de 30 centros asistidos en el condado de King. Conclusiones: En el contexto del rápido aumento de los brotes de Covid-19, se necesitan medidas proactivas por parte de las residencias geriátricas para identificar y excluir al personal y a los visitantes potencialmente infectados, vigilar activamente a los pacientes potencialmente infectados y aplicar medidas apropiadas de prevención y control de la infección para evitar la introducción del Covid-19.


title: Supplemental trace minerals (zinc, copper, and manganese) as sulfates, organic amino acid complexes, or hydroxy trace-mineral sources for shipping-stressed calves

text: ABSTRACT Crossbred calves (n=350; average BW 240±1kg) were obtained from regional livestock auctions. Within each set (block, n=4), calves were stratified by BW and arrival sex into 1 of 8, 0.42-ha pens (10 to 12 calves per pen). Pens were assigned randomly to 1 of 3 treatments consisting of supplemental Zn (360mg/d), Mn (200mg/d), and Cu (125mg/d) from inorganic (zinc sulfate, manganese sulfate, and copper sulfate; n=2 pens per block), organic (zinc amino acid complex, manganese amino acid complex, and copper amino acid complex; Availa-4, Zinpro Corp., Eden Prairie, MN; n=3 pens per block), and hydroxy (IntelliBond Z, IntelliBond C, and IntelliBond M; Micronutrients, Indianapolis, IN; n=3 pens per block) sources. During the 42- to 45-d backgrounding period calves had ad libitum access to bermudagrass hay and were fed corn and dried distillers grain–based supplements that served as carrier for the treatments. After removal of data for chronic (n=6) and deceased (n=1) calves, trace-mineral source had no effect on final or intermediate BW (P=0.86) or ADG (P≥0.24). With all data included in the analysis, dietary treatments had no effect on the number treated once (P=0.93), twice (P=0.71), or 3 times (P=0.53) for bovine respiratory disease or on the number of calves classified as chronic (P=0.55). Based on these results, trace-mineral source had no effect on total BW gain, ADG, or morbidity during the receiving phase in shipping-stressed cattle.


title: Attention-Deficit/Hyperactivity Disorder Patients May Have Undiagnosed Narcolepsy

text: Background Attention-deficit/hyperactivity disorder (ADHD) patients have many comorbidities. Narcoleptic patients have a big prevalence of ADHD (15%-30%). Both groups suffer from similar symptoms and benefit from the same class of medications. As such, narcolepsy could be masked in ADHD patients. Low serum ferritin has been found both in ADHD patients as well as in patients with narcolepsy. Materials & methods We enrolled 26 participants (14 ADHD patients and 12 controls). They answered several questionnaires, and blood samples were obtained from 20 participants. We had clear exclusion criteria. Results Using the Ullanlinna Narcolepsy Scale (UNS), we identified three possible narcolepsy patients within the ADHD group and no suspects in the control group. There was a statistically significant negative correlation between serum iron levels and ADHD symptom severity. No correlation was found measuring serum ferritin levels. Conclusions Narcolepsy may be more common within ADHD patients than in the general population. Some of these patients could benefit from a change in medication. Low serum iron and ferritin levels could be relevant in ADHD pathophysiology. This requires further exploratory research.