title: Tobacco, a highly efficient green bioreactor for production of therapeutic proteins

text: Abstract Molecular farming of pharmaceuticals in plants has the potential to provide almost unlimited amounts of recombinant proteins for use in disease diagnosis, prevention or treatment. Tobacco has been and will continue to be a major crop for molecular farming and offers several practical advantages over other crops. It produces significant leaf biomass, has high soluble protein content and is a non-food crop, minimizing the risk of food-chain contamination. This, combined with its flexibility and highly-efficient genetic transformation/regeneration, has made tobacco particularly well suited for plant-based production of biopharmaceutical products. The goal of this review is to provide an update on the use of tobacco for molecular farming of biopharmaceuticals as well the technologies developed to enhance protein production/purification/efficacy. We show that tobacco is a robust biological reactor with a multitude of applications and may hold the key to success in plant molecular farming.


title: Medical Education During the COVID-19 Pandemic: Learning From A Distance

text: Abstract As paradigms of clinical care delivery have been significantly impacted by the novel coronavirus disease 2019 (COVID-19) pandemic, so has the structure, delivery, and future of medical education. Both undergraduate and graduate medical education have seen disruptions ranging from fully virtual delivery of educational content and limited clinical care for medical students to increased clinical demands with redeployment for residents and fellows. Adherence to social distancing has led to the adoption and implementation of already available technologies in medical education, including video conferencing softwares and social media platforms. Efficient and effective use of these technologies requires an understanding not only of these platforms and their features, but also of their inherent limitations. During a time of uncertainty and increased clinical demands, the approach to medical education must be thoughtful with attention to wellness of both the educator and learner. In this review, we discuss the influence of the pandemic on the existing medical education landscape, outline existing and proposed adaptations to social distancing, and describe challenges that lie ahead.


title: Macrophage Polarization in Inflammatory Diseases

text: Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.


title: The re‐emerging of SADS‐CoV infection in pig herds in Southern China

text: A new highly virulent swine acute diarrhoea syndrome coronavirus (SADS‐CoV) emerged in Guangdong province in 2017 followed by fatal diarrhoea that involved the death of 24,693 piglets. And yet from May 2017 to January 2019, there were no new SADS cases arising in pig herds in Guangdong. In this study, we reported the recent diarrhoea outbreak of SADS‐CoV in Southern China on February 2019. Intestinal samples collected from diarrhoeal piglets were detected for common swine virus and confirmed that SADS‐CoV was responsible for the diarrhoea case. Meanwhile, serological investigation of sows’ sera implied that SADS‐CoV has existed in the farm and PEDV antibody may not directly contribute to the amplification of SADS‐CoV. Homology and phylogenetic analysis of the whole genome showed that the re‐emerging SADS‐CoV strain shared high sequence identities with existing SADS‐CoV strains and all strains clustered together in Alpha coronavirus. All in all, the report herein emphasized the re‐emerging of SADS‐CoV and highlights continuous monitoring for this virus.


title: The role of toll-like receptors in acute and chronic lung inflammation

text: By virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections.


title: Aspects of inflammatory bowel disease during the COVID-19 pandemic and general considerations

text: Abstract So far, available evidence suggests that patients with inflammatory bowel disease (IBD) are not at greater risk for developing COVID-19 infection. In regard to patients with IBD remission: 5-aminosalycylates (5-ASAs) do not increase the risk for infection and should be continued. There is no need to suspend them or lower the dose. Immunomodulating drugs, such as thiopurines and methotrexate, should be continued, without modifying doses (even in patients with positive SARS-CoV-2 infection). No type of biologic therapy should be suspended, unless there are signs of COVID-19. Regarding patients with IBD activity: the oral and/or topical 5-ASA dose should be optimized in cases of disease relapse. Budesonide MMX should be considered in cases of mild-to-moderate activity, to avoid systemic steroid use. Systemic steroids should be avoided whenever possible because doses above 20 mg per day have an immunosuppressive effect, which could increase susceptibility to any type of infection, including COVID-19. The combined use of thiopurines with steroids and/or tumor necrosis factor (TNF) monoclonal antibodies should also be avoided because those combinations can increase the risk for infections, including COVID-19. Finally, biologic treatment with anti-TNF-alpha agents or any other mechanism of action, such as anti-integrins or anti-interleukins, should be suspended if patients become infected with SARS-CoV-2. The drugs can be restarted once the infectious process is resolved.


title: Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays

text: Abstract Rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. Non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. Such libraries can be constructed from a variety of sources e.g. B cell cDNA or synthetically generated, and use a variety of antibody formats, typically scFv or Fab. However, antibody source and format can impact on the quality of antibodies generated and hence the effectiveness of this methodology for the timely production of antibodies. We have carried out a comparative screening of two antibody libraries, a semi-synthetic scFv library and a human-derived Fab library against the protective antigen toxin component of Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown that while the synthetic library produced a diverse collection of specific scFv-phage, these contained a high frequency of unnatural amber stops and glycosylation sites which limited their conversion to IgG, and also a high number which lost specificity when expressed as IgG. In contrast, these limitations were overcome by the use of a natural human library. Antibodies from both libraries could be used to develop sandwich ELISA assays with similar sensitivity. However, the ease and speed with which full-length IgG could be generated from the human-derived Fab library makes screening this type of library the preferable method for rapid antibody generation for diagnostic assay development.


title: The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

text: The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.


title: Development of a tiered framework for public health capacity in Canada

text: • Select SARS reports were qualitatively analyzed for usage of “capacity”/“capacities”. • Public health capacity can be sub-divided into 17 individual capacity components. • These components can be organized into five tiers to build a capacity framework. • This framework can be used to guide capacity assessment and building efforts.


title: Research on COVID-19 Based on ARIMA Model(Δ)—Taking Hubei, China as an example to see the epidemic in Italy

text: COVID-19 has spread throughout the world; various forecast models have been used to predict the development of the pandemic. The number of new cases from the outbreak to zero has gone through a complete cycle in Hubei, China, on lockdown over coronavirus. So, the time series ARIMA models for new cases and new deaths daily during this period could be created. Moreover, these models have been used in Italy, which has the same population conditions and on lockdown as Hubei, in order to predict the epidemic in Italy in the next ten days and provide a theoretical basis for the development of pandemics in some countries in the future.


title: Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan

text: Summary This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.


title: The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children

text: The relationship between exacerbations of wheezing and infection of the respiratory tract was studied prospectively in 32 young hospitalized asthmatic children. Of 139 episodes of wheezing, 58 (42 per cent) were associated with identifiable viral infections. There were 25 respiratory syncytial virus infections; wheezing occurred in 24 of these and pneumonia in 13. Parainfluenza type 2 infection appeared to be next most likely to be associated with wheezing, followed by coronavirus infection. Influenza A. (Hong Kong) was not associated with wheezing in any of the children. Infection with “pathogenic” bacteria was not statistically associated with wheezing.


title: Localization of extensive deletions in the structural genes of two neurotropic variants of murine coronavirus JHM

text: Abstract The intracellular RNA of two neurotropic variants of the JHM strain of mouse hepatitis virus (MHV) independently isolated from the brain and spinal cord of an infected Wistar Furth rat were compared with that of the parental virus. The mRNAs corresponding to the genes encoding the peplomer (S) and the hemagglutinin-esterase (HE) proteins of the variant viruses were found to be smaller in size. The possible sequence changes were studied by oligonucleotide fingerprinting and direct RNA sequencing. Both variants have a large deletion of 246 amino acids in the carboxy-terminal end of the HE protein. However, this truncated protein was not detected in the infected cells, suggesting either a translational regulation or rapid degradation of the truncated protein in these cells. The variant virus isolated from the spinal cord has a second deletion of 147 amino acids in the amino-terminal half of the S protein. This deletion site corresponds to a hypervariable region where deletions have been frequently noted among MHV variants with different biological properties. These findings suggest that the changes in pathogenic properties of the two neural isolates are associated with drastic alterations of the viral structural glycoproteins.


title: Clinical manifestations of respiratory adenoviral infection among hospitalized children in Korea

text: BACKGROUND: The objective of our study was to understand the epidemiological and clinical features of respiratory adenoviral infections among children at a single institution over the course of several years. METHODS: From January 2005 to April 2009, 1836 children (≤15 years old) who had been admitted to Korea University Ansan Hospital were tested for acute respiratory infection. The patients who were positive for an adenovirus infection were enrolled in this study, and their medical records were retrospectively reviewed. RESULTS: Adenoviruses were isolated from 310 patients. The male to female ratio was 1.6:1 and mean age was 32 ± 24 months. Children under 5 years of age had the highest prevalence. In 2007, adenovirus infections occurred endemically throughout the year. The clinical diagnoses were primarily upper respiratory tract infections (45.4%), lower respiratory tract infections (48.1%), and neurologic disease (5.2%). Associated symptoms, signs and laboratory findings included fever (91.9%), cough (83.9%), pharyngeal injection (62.3%), rale (32.6%) and elevated C‐reactive protein (93.9%). The most common radiologic findings were perihilar and peribronchial infiltrates (42.6%). Co‐infections were observed in 29 cases. The mean durations of hospitalization and fever were 6.2 ± 6.5 and 4.8 ± 3.1 days, respectively. The lengths of hospitalization were similar for patients admitted for upper respiratory tract infections with severe morbidity and those admitted for lower respiratory tract infections. No children in the study died. CONCLUSION: Our study demonstrates that respiratory adenovirus infections are an important cause of hospitalization in young children, and contribute to a significant morbidity.


title: Mechanisms of transmissible gastroenteritis coronavirus neutralization

text: Abstract Transmissible gastroenteritis virus (TGEV) was neutralized more than 109-fold with antibodies of a single specificity [monoclonal antibodies (MAbs)]. Most of the virus was neutralized in the first 2–3 min of a reversible reaction, which was followed by a second phase with a decreased neutralization rate and, in some cases, by a persistent fraction, which was a function of the MAb and of the antibody-to-virus ratio. Neutralization of TGEV is a specific event that requires the location of the epitope involved in the neutralization in the appropriate structural context, which is present in the wild-type virus but not in certain MAb escaping mutants. In neutralization of TGEV by binary combinations of MAbs specific for the same or for different antigenic sites, either no cooperation or a synergistic effect, respectively, was observed. Mechanisms of TGEV neutralization by MAbs were characterized at high, intermediate, and low antibody-to-virus ratios. Under these conditions, mainly three steps of the replication cycle were inhibited: binding of virus to the cell, internalization, and a step that takes place after internalization. In addition, virus aggregation could be responsible for the neutralization of 10 to 20% of virus infectivity.


title: Evolution of Canine Parvovirus in Argentina between years 2003 and 2010: CPV2c has become the predominant variant affecting the domestic dog population

text: Abstract The current frequency of Canine Parvovirus variants (CPV2a, CPV2b and CPV2c) in the Argentine dog population was investigated by PCR amplification of a 583bp fragment in the VP2 gene. From a total of 79 rectal swab samples that have been submitted to our laboratory since 2008, 55 (69.6%) resulted positive and were further analyzed by direct DNA sequencing. Fifty positives samples (91%) were characterized as CPV2c variant, which appeared in Argentina in the year 2003 and has been the prevalent type since 2008, whereas CPV2a and CPV2b, still found in Argentine dogs, were represented in 3.6% and 5.4% of the population, respectively. Considering that CPV2c is spreading worldwide, and that this variant is also affecting vaccinated dogs, efforts should be made towards the development of new matched CPV vaccines.


title: Long non-coding RNAs in the regulation of the immune response

text: It is increasingly clear that long non-coding RNAs (lncRNAs) regulate a variety biological responses, and that they do so by a diverse range of mechanisms. In the field of immunology, recent publications have shown widespread changes in the expression of lncRNAs during the activation of the innate immune response and T cell development, differentiation, and activation. These lncRNAs control important aspects of immunity such as production of inflammatory mediators, differentiation, and cell migration through regulating protein–protein interactions or via their ability to basepair with RNA and DNA. We review the current understanding of the mechanism of action of these immune-related lncRNAs, discuss their impact on physiological and pathological processes, and highlight important areas of inquiry at the intersection between immunology and lncRNA biology.


title: Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations

text: Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.


title: Clinical perspectives of emerging pathogens in bleeding disorders

text: Summary As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.


title: Severe acute respiratory syndrome (SARS): chest radiographic features in children

text: BACKGROUND: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. OBJECTIVE: The goal of this study was to characterize the radiographic presentation of children with SARS. MATERIALS AND METHODS: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. RESULTS: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 °C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age≥10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. CONCLUSION: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.


title: Physical multimorbidity, health service use, and catastrophic health expenditure by socioeconomic groups in China: an analysis of population-based panel data

text: BACKGROUND: Multimorbidity, the presence of two or more mental or physical chronic non-communicable diseases, is a major challenge for the health system in China, which faces unprecedented ageing of its population. Here we examined the distribution of physical multimorbidity in relation to socioeconomic status; the association between physical multimorbidity, health-care service use, and catastrophic health expenditures; and whether these associations varied by socioeconomic group and social health insurance schemes. METHODS: In this population-based, panel data analysis, we used data from three waves of the nationally representative China Health and Retirement Longitudinal Study (CHARLS) for 2011, 2013, and 2015. We included participants aged 50 years and older in 2015, who had complete follow-up for the three waves. We used 11 physical non-communicable diseases to measure physical multimorbidity and annual per-capita household consumption spending as a proxy for socioeconomic status. FINDINGS: Of 17 708 participants in CHARLS, 11 817 were eligible for inclusion in our analysis. The median age of participants was 62 years (IQR 56–69) in 2015, and 5766 (48·8%) participants were male. 7320 (61·9%) eligible participants had physical multimorbidity in China in 2015. The prevalence of physical multimorbidity was increased with older age (odds ratio 2·93, 95% CI 2·71–3·15), among women (2·70, 2·04–3·57), within a higher socioeconomic group (for quartile 4 [highest group] 1·50, 1·24–1·82), and higher educational level (5·17, 3·02–8·83); however, physical multimorbidity was more common in poorer regions than in the more affluent regions. An additional chronic non-communicable disease was associated with an increase in the number of outpatient visits (incidence rate ratio 1·29, 95% CI 1·27–1·31), and number of days spent in hospital as an inpatient (1·38, 1·35–1·41). We saw similar effects in health service use of an additional chronic non-communicable disease in different socioeconomic groups and among those covered by different social health insurance programmes. Overall, physical multimorbidity was associated with a significantly increased likelihood of catastrophic health expenditure (for the overall population: odds ratio 1·29, 95% CI 1·26–1·32, adjusted for sociodemographic variables). The effect of physical multimorbidity on catastrophic health expenditures persisted even among the higher socioeconomic groups and across all health insurance programmes. INTERPRETATION: Concerted efforts are needed to reduce health inequalities that are due to physical multimorbidity, and its adverse economic effect in population groups in China. Social health insurance reforms must place emphasis on reducing out-of-pocket spending for patients with multimorbidity to provide greater financial risk protection. FUNDING: None.


title: Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

text: INTRODUCTION. Severe acute respiratory syndrome due to novel Coronavirus (SARS-CoV-2) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for COVID-19. Nitric oxide is a selective pulmonary vasodilator gas used as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In has also shown invitro and clinical evidence that inhaled nitric oxide gas (iNO) has antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic COVID-19. This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients will be blinded to the treatment. METHODS AND ANALYSIS. Intubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not (control group). Treatment will be stopped when patients are free from hypoxemia for more than 24 hours. The primary outcome evaluates levels of oxygenation between the two groups at 48 hours. Secondary outcomes include rate of survival rate at 28 and 90 days in the two groups, time to resolution of severe hypoxemia, time to achieve negativity of SARS-CoV-2 RT-PCR tests. ETHICS AND DISSEMINATION. The study protocol has been approved by the Investigational Review Board of Xijing Hospital (Xi’an, China) and by the Partners Human Research Committee (Boston, USA). Recruitment will start after approval of both IRBs and local IRBs at other enrolling centers. Results of this study will be published in scientific journals, presented at scientific meetings, reported through flyers and posters, and published on related website or media in combating against this widespread contagious disease. TRIAL REGISTRATION. Clinicaltrials.gov. NCT04306393


title: Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

text: The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-Le(X) identified in a previous glycan microarray screen.


title: When health professionals look death in the eye: the mental health of professionals who deal daily with the 2019 coronavirus outbreak

text: Abstract Background : The fact that COVID-19 is transmissible from human to human and associated with high morbidity and potentially fatality can intensify the perception of personal danger. In addition, the foreseeable shortage of supplies and an increasing flow of suspected and real cases of COVID-19 contribute to the pressures and concerns of health professionals. Method : The studies were identified in well-known international journals found in two electronic databases: Scopus and Embase. The data were cross-checked with information from the main international newspapers. Results : Work-related stress is a potential cause of concern for health professionals. It has been associated with anxiety including multiple clinical activities, depression in the face of the coexistence of countless deaths, long work shifts with the most diverse unknowns and demands in the treatment with patients with COVID-19. Therefore, it is an important indicator of psychic exhaustion. Conclusions : As coronavirus cases increase and deaths surge in Italy, new figures show an "enormous" level of contagion among the country's medical personnel. At least 2,629 health workers have been infected with coronavirus since the outbreak onset in February, representing 8.3% of total cases. The percentage of infected health workers has almost doubled the number registered in China throughout the epidemic. Intensive care unit physicians are on their stress limit, especially when dealing with older patients and with death prospects. Doctors, not a relative, are inevitably the last people a dying COVID-19 patient will see.


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title: Atrial fibrillation: a risk factor for unfavourable outcome in COVID-19? A case report

text: BACKGROUND: Fulminant cardiac involvement in COVID-19 patients has been reported; the underlying suspected mechanisms include myocarditis, arrhythmia, and cardiac tamponade. In parallel, atrial fibrillation is common in the elderly population which is at particularly high risk for COVID-19 morbidity and mortality. CASE SUMMARY: A 72-year-old male SARS-CoV2-positive patient was admitted to the intensive care unit due to delirium and acute respiratory failure. Atrial fibrillation known from history was exacerbated, and made complex rate and rhythm control necessary. Progressive heart failure with haemodynamic deterioration and acute kidney injury with the need for continuous renal replacement therapy were further aggravated by pericardial tamponade. DISCUSSION: Treatment of acute heart failure in COVID-19 patients with a cytokine storm complicated by tachycardic atrial fibrillation should include adequate rate or rhythm control, and potentially immunomodulation.


title: Literature‐guided recommendations for otolaryngologists during the COVID‐19 pandemic: A contemporary review

text: OBJECTIVE: The objective of this study was to review the current literature and guidelines on management of the novel coronavirus 2019 (COVID‐19 or 2019nCoV) with respect to the field of Otolaryngology. DESIGN: Contemporary literature review. METHODS: Systematic literature review of global medical literature databases and communications were queried to find all available literature recommendations, research, and guidelines applicable to otolaryngologists in the COVID‐19 pandemic. RESULTS: Guidance on personal protective equipment, office visits, and surgical scheduling, as well as recommendations for safe airway management and tracheotomy performance during the COVID‐19 pandemic were compiled and interpreted. CONCLUSIONS: Little guidance exists for otolaryngologists who are among the highest risk groups during the rapidly evolving COVID‐19 pandemic. This synthesis and compilation of global resources serve as a building block for further guidance during the epidemic. LEVEL OF EVIDENCE: NA.


title: Recombinant porcine rotavirus VP4 and VP4-LTB expressed in Lactobacillus casei induced mucosal and systemic antibody responses in mice

text: BACKGROUND: Porcine rotavirus infection is a significant cause of morbidity and mortality in the swine industry necessitating the development of effective vaccines for the prevention of infection. Immune responses associated with protection are primarily mucosal in nature and induction of mucosal immunity is important for preventing porcine rotavirus infection. RESULTS: Lactobacillus casei expressing the major protective antigen VP4 of porcine rotavirus (pPG612.1-VP4) or VP4-LTB (heat-labile toxin B subunit from Echerichia coli) (pPG612.1-VP4-LTB) fusion protein was used to immunize mice orally. The expression of recombinant pPG612.1-VP4 and pPG612.1-VP4-LTB was confirmed by SDS-PAGE and Western blot analysis and surface-displayed expression on L. casei was verified by immunofluorescence. Mice orally immunized with recombinant protein-expressing L. casei produced high levels of serum immunoglobulin G (IgG) and mucosal IgA. The IgA titters from mice immunized with pPG612.1-VP4-LTB were higher than titters from pPG612.1-VP4-immunized mice. The induced antibodies demonstrated neutralizing effects on RV infection. CONCLUSION: These results demonstrated that VP4 administered in the context of an L. casei expression system is an effective method for stimulating mucosal immunity and that LTB served to further stimulate mucosal immunity suggesting that this strategy can be adapted for use in pigs.


title: Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19

text: Resumen La infección por el coronavirus SARS-CoV-2, causante de la enfermedad denominada COVID-19, provoca alteraciones fundamentalmente en el sistema respiratorio. En los pacientes graves, con frecuencia la enfermedad evoluciona a un síndrome de distrés respiratorio agudo que puede predisponer a los pacientes a un estado de hipercoagulabilidad, con trombosis tanto a nivel venoso como arterial. Esta predisposición presenta una fisiopatología multifactorial, relacionada tanto con la hipoxia como con el grave proceso inflamatorio ligado a esta patología, además de los factores trombóticos adicionales presentes en muchos de los pacientes. Ante la necesidad de optimizar el manejo de la hipercoagulabilidad, los grupos de trabajo de las Sociedades Científicas de Anestesiología-Reanimación y Terapéutica del Dolor (SEDAR) y de Medicina Intensiva, Crítica y de Unidades Coronarias (SEMICYUC), han desarrollado un consenso para establecer unas pautas de actuación frente a las alteraciones de la hemostasia observadas en los pacientes graves con infección por COVID-19. Estas recomendaciones incluyen la profilaxis de la enfermedad tromboembólica venosa en pacientes graves y en el periparto, el manejo de los pacientes en tratamiento crónico con fármacos antiagregantes o anticoagulantes, de las complicaciones hemorrágicas en la evolución de la enfermedad y de la interpretación de las alteraciones generales de la hemostasia. Abstract The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19 infection. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.


title: Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon

text: OBJECTIVE: Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBoV in Gabon. Two first studies was conducted to determine the prevalence of respiratory and enteric viruses in children under 5 years old who visited health centers for influenza-like illness (ILI) or diarrhea in Gabon from March 2010 to June 2011. However, HBoV was not included in the screening. The aim of this retrospective study was to evaluate the prevalence and the HBoV genotype in children under 5 years old with ILI or diarrhea in Gabon. RESULTS: A total of 810 nasal swabs and 317 feces samples collected during the two first study were analyzed among which 32 (4.4%) and 7 (2.2%) were positive for HBoV respectively. While there were no significant differences in prevalence between age groups in children with ILI, all children with diarrhea were under 12 months of age. Moreover, 84.4 and 42.8% were diagnosed in co-infections with at least one other respiratory virus, or enteric viruses respectively. Finally, HBoV subtype 1 has been detected in both respiratory and gastrointestinal tracts with very low variability.


title: Lower respiratory infections and potential complications in athletes

text: A review and synthesis of recently published literature regarding lower respiratory infections in athletes was conducted. Diagnosis and treatment of common etiologies, specifically acute bronchitis, pneumonia, and influenza, are examined and discussed. In addition, potential complications, including spontaneous pneumothorax, bronchiectasis, hemoptysis, and acute respiratory failure that may result from inadequate diagnosis and treatment, are addressed. Criteria for allowing athletes to return to play were reviewed and current accepted guidelines for return to activity are discussed.


title: A 12-year follow-up study of combined treatment of post-severe acute respiratory syndrome patients with femoral head necrosis

text: OBJECTIVE: To investigate the long-term efficacy of a combination treatment of alendronate, extracorporeal shock and hyperbaric oxygen for osteonecrosis of the femoral head (ONFH) of post-severe acute respiratory syndrome (SARS) patients. PATIENTS AND METHODS: The retrospective study was performed including a total of 37 post-SARS ONFH patients (66 hip joints) in the Department of Orthopedics of the General Hospital of Tianjin Medical University between November 2003 and November 2015, consisting of 6 males (11 hip joints) and 31 females (55 hip joints), with age between 19 and 47 years (average 29.9 years). Visual analog scale (VAS) score, Harris score and Association Research Circulation Osseous (ARCO) stage of imaging examination were compared among those before treatment, and at 1, 3, 6, 9 and 12 years after treatment. Paired t-test was used for statistical analysis of VAS and Harris score before and after treatment. Difference of effective rate on all stages was analyzed with Chi-square test. RESULTS: With 12-year follow-up, significant improvements on VAS (6.81 of pre-treatment vs 3.94 of 12-year post-treatment) and Harris score (74.54 of pre-treatment vs 80.14 of 12-year post-treatment) were observed (all p<0.05). Effective rate showed statistical significance among three stages of ARCO (p<0.05). The combined treatment showed different efficacies on different ARCO stages; the best was on ARCO Phase I. CONCLUSION: The combined treatment may delay or discontinue the development of ONFH in post-SARS patients.


title: COVID-19 pneumonia patient without clear epidemiological history outside Wuhan: An analysis of the radiographic and clinical features

text: Abstract The purpose of this case report is to describe the CT and clinical features of a COVID-19 pneumonia patient without clear epidemiological history outside Wuhan, China.


title: Evaluation of 2 different treatment procedures after calving to improve harvesting of high-quantity and high-quality colostrum

text: ABSTRACT The objective of this study was to evaluate 2 different treatment procedures at the first milking after calving to increase colostrum quantity and to improve colostrum quality in dairy cows. We hypothesized that either exogenous treatment with oxytocin or the presence of the calf at first milking would lead to higher colostrum quantity and higher IgG concentration. The study was conducted from October to December 2017 on a commercial dairy farm in Germany. A total of 567 cows at the time of calving were enrolled, but for the final analyses only 521 animals were considered. The cows were randomly assigned on a daily basis into 1 of 3 groups: (1) control group (n = 177), (2) application of 20 IU of oxytocin i.m. (OXY; n = 163), and (3) presence of the calf (CA; n = 181) before and during milking. Cows in the control and oxytocin group had no contact with their calves after calving and were milked in a separate milking parlor. Cows in the oxytocin group were injected with 20 IU of oxytocin i.m. 3 min before manual stimulation. For cows in the third group, the calf was placed into a calf cart and located in front of the cow 3 min before manipulation of the cow. Colostrum quantity was determined by a digital hanging scale. The colostrum quality was assessed with digital Brix refractometry and ELISA. To evaluate the effect of 2 different treatment procedures, a generalized linear mixed model was constructed using SPSS (SPSS Inc., IBM, Ehningen, Germany). The mean (±SE) colostrum quantity was 4.17 ± 0.30 kg. The treatment procedures and the harvesting time after calving had no effect on colostrum quantity. Parity, calf birth weight, and calving time affected colostrum quantity. Cows in second parity had the lowest quantity of colostrum (3.74 ± 0.37 kg) compared with cows in parity 1 (4.75 ± 0.34 kg) and cows in parity 3 or greater (4.75 ± 0.38 kg). Cows calving during the night (2200 until 0600 h; 4.93 ± 0.37 kg) had the highest quantity of colostrum compared with cows calving in the morning (0600 until 1400 h; 4.17 ± 0.38 kg) or afternoon (1400 until 2200 h; 4.14 ± 0.34 kg). Regarding colostrum quality, 48% of the colostrum samples contained ≥50 mg of IgG/mL. The mean IgG concentration was 54.6 ± 2.80 mg of IgG/mL. Colostrum quality was affected by the treatment procedures, colostrum quantity, parity, calving time, harvesting time after calving, and the calving day during the week. Both treatment procedures (i.e., OXY with mean IgG concentration results of 57.0 mg of IgG/mL and CA with 56.0 mg of IgG/mL) resulted in higher IgG concentrations in colostrum compared with the control group (50.7 mg of IgG/mL). With increasing colostrum quantity, the colostrum quality decreased in primiparous and multiparous cows. A longer time lag between calving and milking negatively affected the colostrum quality. Concentration of IgG was higher for cows in parity 3 or greater (64.6 ± 2.59 mg of IgG/mL) compared with cows in parity 1 (48.5 ± 2.86 mg of IgG/mL) and cows in parity 2 (50.7 ± 2.89 mg of IgG/mL). Cows calving during the night had greater IgG concentrations (60.4 ± 2.92 mg of IgG/mL) compared with cows calving in the morning (51.9 ± 2.98 mg of IgG/mL) or afternoon (51.3 ± 2.71 mg of IgG/mL). Harvesting colostrum on quieter days, such as Sundays, resulted in higher IgG concentrations (61.4 ± 3.70 mg of IgG/mL). The assessment by Brix refractometry resulted in a mean result of 26.0 ± 0.20% Brix. Treatment procedures and the harvesting time after calving had no effect on colostrum quality. A negative association was observed between colostrum quantity and quality in primiparous and multiparous cows determined by Brix refractometry. Brix readings were greater for cows in parity 3 or higher (27.7 ± 0.26% Brix) compared with cows in parity 1 (25.3 ± 0.30% Brix) and cows in parity 2 (25.0 ± 0.32% Brix). In conclusion, the treatment procedure for the first milking is irrelevant to improve the quantity of colostrum. Both treatment procedures, however, increased IgG concentrations as determined by ELISA.


title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2

text: Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐CoVs and Middle East Respiratory Syndrome coronavirus (MERS‐CoVs), the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high‐throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS‐CoV‐2 proteins and structures. Here we report two high‐resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.


title: Multiple Ensemble Neural Network Models with Fuzzy Response Aggregation for Predicting COVID-19 Time Series: The Case of Mexico.

text: In this paper, a multiple ensemble neural network model with fuzzy response aggregation for the COVID-19 time series is presented. Ensemble neural networks are composed of a set of modules, which are used to produce several predictions under different conditions. The modules are simple neural networks. Fuzzy logic is then used to aggregate the responses of several predictor modules, in this way, improving the final prediction by combining the outputs of the modules in an intelligent way. Fuzzy logic handles the uncertainty in the process of making a final decision about the prediction. The complete model was tested for the case of predicting the COVID-19 time series in Mexico, at the level of the states and the whole country. The simulation results of the multiple ensemble neural network models with fuzzy response integration show very good predicted values in the validation data set. In fact, the prediction errors of the multiple ensemble neural networks are significantly lower than using traditional monolithic neural networks, in this way showing the advantages of the proposed approach.


docid: jitkxtdg

title: From Pasteur to genomics: progress and challenges in infectious diseases

text: Over the past decade, microbiology and infectious disease research have undergone the most profound revolution since the times of Pasteur. Genomic sequencing has revealed the much-awaited blueprint of most pathogens. Screening blood for the nucleic acids of infectious agents has blunted the spread of pathogens by transfusion, the field of antiviral therapeutics has exploded and technologies for the development of novel and safer vaccines have become available. The quantum jump in our ability to detect, prevent and treat infectious diseases resulting from improved technologies and genomics was moderated during this period by the greatest emergence of new infectious agents ever recorded and a worrisome increase in resistance to existing therapies. Dozens of new infectious diseases are expected to emerge in the coming decades. Controlling these diseases will require a better understanding of the worldwide threat and economic burden of infectious diseases and a global agenda.


title: Imported infectious diseases and surveillance in Japan

text: Summary Surveillance of imported infectious diseases is important because of the need for early detection of outbreaks of international concern as well as information of risk to the travelers. This paper attempts to review how the Japanese surveillance system deals with imported infectious diseases and reviews the trend of these diseases. The cases of acquired infection overseas were extracted from the surveillance data in 1999–2008. The incidence and rate of imported cases of a series of infectious diseases with more than one imported case were observed by the year of diagnosis and place of acquired infection. During the period 10,030 cases that could be considered to be imported infectious diseases were identified. Shigellosis ranked as the most common imported disease, followed by amebiasis, malaria, enterohemorrhagic Escherichia coli infection and the acquired immunodeficiency syndrome, typhoid fever, dengue fever, hepatitis A, giardiasis, cholera, and paratyphoid fever. The annual trends of these diseases always fluctuated but not every change was investigated. The study reveals that the situation of imported infectious diseases can be identified in the current Japanese surveillance system with epidemiologic features of both temporal and geographic distribution of cases of imported infectious diseases. However, further timely investigation for unusual increase in infectious diseases is needed.


title: Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia

text: Abstract Background The main symptoms of primary ciliary dyskinesia (PCD) are nasal rhinorrhea or blockage and moist-sounding cough. Diagnosis can be difficult and is based on an abnormal ciliary beat frequency, accompanied by specific abnormalities of the ciliary axoneme. It is unknown whether determining ciliary beat pattern related to specific ultrastructural ciliary defects might help in the diagnosis of PCD. Objective We sought to determine ciliary beat pattern and beat frequency (CBF) associated with the 5 common ultrastructural defects responsible for PCD. Methods Nasal brushings were performed on 56 children with PCD. Ciliary movement was recorded using digital high-speed video imaging to assess beat frequency and pattern. Electron microscopy was performed. Results In patients with an isolated outer dynein arm or with an outer and inner dynein arm defect, 55% and 80% of cilia were immotile, respectively. Cilia that moved were only flickering. Mean CBF (± 95% CI) was 2.3 Hz (± 1.2) and 0.8 Hz(± 0.8), respectively. Cilia with an isolated inner dynein arm or a radial spoke defect had similar beat patterns. Cilia appeared stiff, had a reduced amplitude, and failed to bend along their length. Immotile cilia were present in 10% of cilia with an inner dynein arm defect and in 30% of radial spoke defects. Mean CBF was 9.3 Hz (± 2.6) and 6.0 Hz (± 3.1), respectively. The ciliary transposition defect produced a large circular beat pattern (mean CBF, 10.7 Hz [± 1.1]). No cilia were immotile. Conclusions Different ultrastructural defects responsible for PCD result in predictable beat patterns. Recognition of these might help in the diagnostic evaluation of patients suspected of having PCD.


docid: qvhwypjt

title: Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China

text: Abstract Objectives This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.


title: Establishment of Hairy Root Cultures by Agrobacterium Rhizogenes Mediated Transformation of Isatis Tinctoria L. for the Efficient Production of Flavonoids and Evaluation of Antioxidant Activities

text: In this work, Isatis tinctoria hairy root cultures (ITHRCs) were established as an alternative source for flavonoids (FL) production. I. tinctoria hairy root line V was found to be the most efficient line and was further confirmed by the PCR amplification of rolB, rolC and aux1 genes. Culture parameters of ITHRCs were optimized by Box-Behnken design (BBD), and eight bioactive FL constituents (rutin, neohesperidin, buddleoside, liquiritigenin, quercetin, isorhamnetin, kaempferol and isoliquiritigenin) were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total FL accumulation of ITHRCs (24 day-old) achieved was 438.10 μg/g dry weight (DW), which exhibited significant superiority as against that of 2 year-old field grown roots (341.73 μg/g DW). Additionally, in vitro antioxidant assays demonstrated that ITHRCs extracts exhibited better antioxidant activities with lower IC(50) values (0.41 and 0.39, mg/mL) as compared to those of field grown roots (0.56 and 0.48, mg/mL). To the best of our knowledge, this is the first report describing FL production and antioxidant activities from ITHRCs.


title: Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis

text: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface.


title: SOPORTE TELEFÓNICO AL PACIENTE CON EPOC EN TIEMPOS DEL COVID-19

text: Abstract The state of alarm declared by the Spanish government as the main measure for preventing contagion has involved a change in the clinical management of chronic patients. Although new communication technologies offer us many ways to establish direct but remote contact, the peculiarities of the COPD patient often mean that their healthcare is reduced to telephone calls. The challenge of caring for COPD patients is made even more complex when it has to be delivered over the phone. The interview must be conducted without examining the patient, without performing additional tests, and without checking their inhalation technique. Therefore, healthcare providers who conduct these interviews must be trained to perform them properly in order to make the right decisions. This document is aimed at healthcare professionals who need to provide some form of telephone care to COPD patients during the SARS-CoV-2 pandemic and is based on the authors' experience in telephone interviews conducted during this period. It summarizes essential aspects of how this interview should be approached, how to conduct it, what factors should be kept in mind, how to organize the interview, and how to keep patients informed. It is very likely that from now on this type of interview will be common practice in the care of our patients, so we need to learn how to structure a new model of healthcare for many of the clinical visits that have until now been conducted face-to-face.


title: Preference among 7 bait flavors delivered to domestic dogs in Arizona: Implications for oral rabies vaccination on the Navajo Nation

text: Abstract Less than 20% of the domestic dogs on tribal lands in the United States are vaccinated against rabies. One method to increase vaccination rates may be the distribution of oral rabies vaccines (ORVs). ONRAB® (Artemis Technologies, Inc., Ontario, Canada) is the primary ORV used in Canada to vaccinate striped skunks and raccoons. To investigate the potential use of ONRAB® ORV baits to vaccinate feral domestic dogs against rabies on tribal lands and beyond, we performed a flavor preference study. A total of 7 bait flavors (bacon, cheese, dog food, hazelnut, sugar-vanilla, peanut butter, and sardine) were offered in pairs to 13 domestic dogs. Each dog was offered all possible combinations of bait pairs over a period of 10 days, with each bait offered 6 times. The proportion of times each bait was consumed first by individual dogs was calculated and comparisons among dogs were conducted using the MIXED procedure in SAS (SAS Institute, Cary, NC). Pairwise comparisons between baits were performed using “contrast” statements with sugar-vanilla flavor as the default for comparison. Type 3 tests of fixed effects showed a significant treatment effect (F 6,72 =9.74, P <0.0001). Sugar-vanilla was selected first during 14% of the offerings and exhibited the least preference among all bait types (F 1,72 =22.46, P <0.0001). Dog food was selected first 56% of the time, and more frequently than all other bait types (F 1,72 =13.09, P =0.0005).


docid: wizlpkrk

title: Diabetes is a risk factor for the progression and prognosis of COVID‐19

text: BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID‐19). METHODS: A total of 174 consecutive patients confirmed with COVID‐19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID‐19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury‐related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation‐related biomarkers such as IL‐6, C‐reactive protein, serum ferritin and coagulation index, D‐dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID‐19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID‐19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.


title: Tracheostomy guidelines developed at a large academic medical center during the COVID‐19 pandemic

text: BACKGROUND: During the SARS‐CoV‐2 pandemic, tracheostomy may be required for COVID‐19 patients requiring long‐term ventilation in addition to other conditions such as airway compromise from head and neck cancer. As an aerosol‐generating procedure, tracheostomy increases the exposure of health care workers to COVID‐19 infection. Performing surgical tracheostomy and tracheostomy care requires a strategy that mitigates these risks and maintains the quality of patient care. METHODS: This study is a multidisciplinary review of institutional tracheostomy guidelines and clinical pathways. Modifications to support clinical decision making in the context of COVID‐19 were derived by consensus and available evidence. RESULTS: Modified guidelines for all phases of tracheostomy care at an academic tertiary care center in the setting of COVID‐19 are presented. DISCUSSION: During the various phases of the COVID‐19 pandemic, clinicians must carefully consider the indications, procedural precautions, and postoperative care for tracheostomies. We present guidelines to mitigate risk to health care workers while preserving the quality of care.


title: Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

text: BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C(50)).


title: Coronavirus disease 19 in minority populations of Newark, New Jersey

text: BACKGROUND: The purpose of this study is to report the clinical features and outcomes of Black/African American (AA) and Latino Hispanic patients with Coronavirus disease 2019 (COVID-19) hospitalized in an inter-city hospital in the state of New Jersey. METHODS: This is a retrospective cohort study of AA and Latino Hispanic patients with COVID-19 admitted to a 665-bed quaternary care, teaching hospital located in Newark, New Jersey. The study included patients who had completed hospitalization between March 10, 2020, and April 10, 2020. We reviewed demographics, socioeconomic variables and incidence of in-hospital mortality and morbidity. Logistic regression was used to identify predictor of in-hospital death. RESULTS: Out of 416 patients, 251 (60%) had completed hospitalization as of April 10, 2020. The incidence of In-hospital mortality was 38.6% (n = 97). Most common symptoms at initial presentation were dyspnea 39% (n = 162) followed by cough 38%(n = 156) and fever 34% (n = 143). Patients were in the highest quartile for population’s density, number of housing units and disproportionately fell into the lowest median income quartile for the state of New Jersey. The incidence of septic shock, acute kidney injury (AKI) requiring hemodialysis and admission to an intensive care unit (ICU) was 24% (n = 59), 21% (n = 52), 33% (n = 82) respectively. Independent predictors of in-hospital mortality were older age, lower serum Hemoglobin < 10 mg/dl, elevated serum Ferritin and Creatinine phosphokinase levels > 1200 U/L and > 1000 U/L. CONCLUSIONS: Findings from an inter-city hospital’s experience with COVID-19 among underserved minority populations showed that, more than one of every three patients were at risk for in-hospital death or morbidity. Older age and elevated inflammatory markers at presentation were associated with in-hospital death.


title: TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway

text: We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK–STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK–STAT signaling pathway.


title: Middle East respiratory syndrome coronavirus: review of the current situation in the world

text: This article reviews the current epidemiology and clinical presentation of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and describes the preparedness plan of several countries. The MERS-CoV was first reported in 2012 and has since infected more than 1600 patients in 26 countries, mostly in Saudi Arabia and the Middle East. The epidemiology of the infection is compatible with multiple introductions of the virus into humans from an animal reservoir, probably dromedary camels. The clinical presentation ranges from no symptoms to severe pneumonitis and respiratory failure. Most confirmed cases so far were part of MERS-CoV clusters in hospital settings, affecting mainly middle-aged men and patients with a chronic disease or immuno-suppressed status. There is no vaccine or anti-viral medication available. Viral epidemics can occur anywhere in today’s “global village”. MERS-CoV is a relatively new virus, and this work is intended to add to the still-sparse data on its epidemiology, modes of transmission, natural history, and clinical features as well as to describe the preparedness plan for MERS-CoV infection in several countries. Effective national and international preparedness plans are essential to predict and control outbreaks, improve patient management, and ensure global health security.


title: LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens

text: BACKGROUND: Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. RESULTS: In this paper, we study how the efficiency of random PCR amplification affects hybridization signals. We describe a model that predicts the amplification efficiency of a given random primer on a target viral genome. The prediction allows us to filter false-negative probes of the genome that lie in regions of poor random PCR amplification and improves the accuracy of pathogen detection. Subsequently, we propose LOMA, an algorithm to generate random primers that have good amplification efficiency. Wet-lab validation showed that the generated random primers improve the amplification efficiency significantly. CONCLUSION: The blind use of a random primer with attached universal tag (random-tagged primer) in a PCR reaction on a pathogen sample may not lead to a successful amplification. Thus, the design of random-tagged primers is an important consideration when performing PCR.


title: Genotyping of avian infectious bronchitis virus in Iran: Detection of D274 and changing in the genotypes rate

text: Abstract The coronavirus avian Infectious bronchitis virus (IBV) poses economic threats to poultry farms worldwide, affecting the performance of both meat-type and egg-laying birds. To define the evolution of recent IBVs in Iran, a genetic analysis based on hypervariable nucleotide sequences of S1 gene was carried out. Tracheal swab samples were collected from 170 Broiler flocks during 2017. Ten tracheal swabs from each flock pooled. From a total number of 170 flocks tested, 84.71% found to be positive. Phylogenetic tree analysis revealed the presence of D274 as a first time in Iran. IS/1494/06 was showed to be dominant IBV type circulating in broiler farms with a significantly higher prevalence than other four genotypes. Considering fluctuations in QX-type prevalence in recent years, continuous monitoring is necessary to reduce economic consequences in layer and broiler farms. The findings highlight the importance of using modified vaccination strategies that are adapted to the changing disease scenario.


title: Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020

text: Abstract Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.


title: Recent Evolutionary History of Human Immunodeficiency Virus Type 1 Subtype B: Reconstruction of Epidemic Onset Based on Sequence Distances to the Common Ancestor

text: We obtained and studied HIV-1 sequences with a known sampling year from three outbreaks of the HIV-1 epidemic: 141 env V3 (270 nt) sampled between 1984 and 1992 and 117 pol prot/RT (804 nt) sequences sampled between 1986 and 1999 from Dutch homosexual men and injecting drug users (IDUs), as well as 77 env V3 sequences sampled between 1983 and 1994 in the United States. Since retrospective serological and/or epidemiological data on these populations are available, providing estimates of the dates of the onset of the HIV-1 epidemics, we had the opportunity to test different phylogenetic models for their accuracy in deriving the recent evolutionary history of HIV-1 subtype B and the onset date of the HIV-1 epidemic. We observed that, in any given year, individual sequences vary widely in their distances to the common ancestor, and sequences close to the ancestors were found decades after the onset of the epidemic. Nevertheless, the mean evolutionary distances of virus strains to ancestors were increasing significantly during the course of the studied epidemics, which indicates that the molecular clock is operational in the recent evolution of HIV-1. When the relationship between the sampling years of sequences and their nucleotide distances to the common ancestor was extrapolated to the past, analysis of pol sequences provided accurate estimates of the onset years of the epidemics, whereas analysis of V3 sequences by the maximum-likelihood or neighbor-joining methods led to an overestimation of the age of the epidemics. Separate analysis of nonsynonymous and synonymous distances revealed that this overestimation results from nonsynonymous substitutions, whose numbers were not increasing significantly in all three virus populations over the observation period. In contrast, analysis of synonymous env V3 distances provided accurate estimates of the onset years for the outbreaks we studied.


title: Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature

text: Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factors.


title: Preparedness of Our Emergency Department During Novel Coronavirus Pneumonia from the Nurses’ Perspectives: A Qualitative Research Study

text: INTRODUCTION: This in-depth study explores the preparedness of our emergency department (ED) during the novel coronavirus pneumonia (NCP) outbreak from nurses’ perspectives, providing reference and a basis for our ED’s response to public health emergencies. METHODS: Using qualitative research methods, semi-structured interviews were conducted with 12 ED nurses who met the inclusion criteria, and Colaizzi analysis was used for data analysis, summary, and induction. RESULTS: Four themes that involved preparedness of the ED during the NCP outbreak were extracted: organizational preparedness, personal preparedness, patient and family preparedness, and deficiencies and challenges. DISCUSSION: The organizations, individuals, patients, and family members were actively prepared to respond to NCP in the ED. The ED nurses said that the trusted organization guaranteed personal preparedness, and the active cooperation from patients and families was a motivator for personal preparedness. In addition, our study showed that there were deficiencies in both multidisciplinary collaboration efforts and efforts to rapidly diagnose and treat patients with fever in critical condition.


title: The phylogeny of SARS coronavirus

text: Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.


title: Ultrasonographic Examination of the Equine Neonate Thorax and Abdomen

text: Diagnostic imaging can substantially augment physical examination findings in neonatal foals. Used in combination with radiography or as a stand-alone imaging modality, ultrasound evaluation of the thoracic and abdominal body cavities can be a high-yield diagnostic undertaking. Many of the conditions that afflict neonatal foals are highly amenable to sonographic interrogation, including pneumonia and other changes in the lungs associated with sepsis, systemic inflammatory response syndrome, multiple organ dysfunction, and prematurity; colic arising from medical and surgical causes; and urinary tract disorders. Sonographic imaging is not affected by intracavitary fluid accumulation and reveals abnormalities of soft tissue and bony origin.


The ailing anaesthetist


title: One World – One Health: The Threat of Emerging Swine Diseases. An Asian Perspective

text: Owing to the expanding globalization, the trans‐boundary spread of an epizootic can easily result from uncontrolled animal movements and human traffic. Foot and mouth disease (FMD) is a major trans‐boundary disease in most Asian countries. Its sporadic re‐emergence suggests that collaborative FMD control strategies should be uniformly implemented in endemic countries to ensure the overall national herd vaccination coverage, biocontainment when outbreaks occur, and strict biosecurity control of animal movement between countries. Sustained commitments from governments, cooperative diplomatic relationships, and public awareness campaigns are critical to FMD control, to ensure collaboration among veterinarians, traders and farmers throughout Southeast Asia (SEA). Recently, highly pathogenic porcine reproductive and respiratory syndrome (HP‐PRRS) and porcine epidemic diarrhoea (PED) spread from China to Southeast Asian countries, causing major economic losses. Foot and mouth disease, HP‐PRRS, and PED currently remain endemic and may continue to sporadically re‐emerge, owing to inadequate public health management and/or biosecurity failures. Therefore, the risk factors must be identified to better understand the epidemiology of these diseases in an effort to develop effective control measures. International coordination through the establishment of a collaborative network supported by the World Organization for Animal Health (OIE) and the Food and Agriculture Organization (FAO) should be implemented to prevent trans‐boundary transmission among countries. This review discusses trans‐boundary swine diseases of particular importance to SEA, including FMD, HP‐PRRS and PED, with a primary focus on major factors contributing to the spread of these diseases and important control measures, reflecting the impact of globalization on disease control and surveillance.


title: Expanding the size limit of RNA viruses: Evidence of a novel divergent nidovirus in California sea hare, with a ~35.9 kb virus genome

text: While RNA viruses thrive with massive structural and functional diversity, their genomes size variation is particularly low, ranging only from ~2-to-33 kb. Here, I present the characterization of RNA sequences corresponding to the first virus associated with Aplysia californica. Genome structure and domain architecture suggest that the identified virus is a novel member of Nidovirales. The proposed aplysia californica nido-like virus (AcNV), with a genome sequence of ca.35,906 nt, represents the longest ever recorded RNA virus yet. Phylogenetic insights indicate that AcNV clusters in a major phylloclade of unclassified invertebrate nidoviruses, Roniviridae, and Mesoniviridae. Basal branching in this emerging cluster could indicate that AcNV is a member of a novel divergent clade within Nidovirales. Further, virus RNA detection in multiple independent studies suggests that AcNV is neurotropic with a broad cell/tissue/organ tropism, supported by AcNV occurrence in diverse organs, including the first detection of a Nidovirales in single specific neurons. Highlights -RNA virus genomes reported in the literature are limited at ca. 33.4 kb -A novel nidovirus was identified in the gastropod mollusk Aplysia californica -The aplysia californica nido-like virus (AcNV) presents a 35.9 kb RNA genome -AcNV has a broad tropism, is enriched in the CNS, and accumulates in neurons -The unique features of A. californica enables single-neuron virus dynamics of AcNV


title: Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality

text: Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-α/β-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection.


docid: ddhylzid

title: Ritter reaction-mediated syntheses of 2-oxaadamantan-5-amine, a novel amantadine analog

text: Two alternative syntheses of 2-oxaadamantan-5-amine, a novel analog of the clinically approved drug amantadine, are reported. The compound has been tested as an anti-influenza A virus agent and as an NMDA receptor antagonist. While the compound was not antivirally active, it displayed moderate activity as an NMDA receptor antagonist.


docid: jwglalgx

title: IL-15 INDEPENDENT MAINTENANCE OF VIRUS-SPECIFIC CD8(+) T CELLS IN THE CNS DURING CHRONIC INFECTION

text: The role of IL-15 in T cell survival was examined during chronic CNS coronavirus infection. Similar numbers of virus-specific CD8(+) T cells were retained in the CNS of IL-15(−/−)and wt mice, consistent with loss of IL-2/15 receptor (CD122) expression. IL-15 deficiency also had no affect on IL-7 receptor (CD127) expression, Bcl-2 upregulation, granzyme B expression, or IFN-γ secretion in CNS persisting CD8(+) T cells. Furthermore, CD8(+) T cell division in the CNS was reduced compared to spleen. CD8(+) T cells in the persistently infected CNS are thus characterized by IL-15 independent, low level proliferation and an activated/memory phenotype.


Invasive pulmonary aspergillosis in severe COVID-19 pneumonia


title: Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2

text: BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro. RESULTS: PAMs were successfully infected by PCV2-WH strain, as evidenced quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assay (IFA) results. Infection-related differential gene expression was investigated using pig microarrays from the US Pig Genome Coordination Program and validated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Microarray analysis at 24 and 48 hours post-infection (HPI) revealed 266 and 175 unique genes, respectively, that were differentially expressed (false discovery rate <0.05; fold-change >2). Only six genes were differentially expressed between 24 and 48 HPI. The up-regulated genes were principally related to immune response, cytokine activity, locomotion, regulation of cell proliferation, apoptosis, cell growth arrest, and antigen procession and presentation. The down-regulated genes were mainly involved in terpenoid biosynthesis, carbohydrate metabolism, translation, proteasome degradation, signal transducer activity, and ribosomal proteins, which were representative of the reduced vital activity of PCV2-infected cells. CONCLUSIONS: PCV2 infection of PAMs causes up-regulation of genes related to inflammation, indicating that PCV2 may induce systematic inflammation. PCV2 persistently induced cytokines, mainly through the Toll-like receptor (TLR) 1 and TLR9 pathways, which may promote high levels of cytokine secretion. PCV2 may prevent apoptosis in PAMs by up-regulating SERPINB9 expression, possibly to lengthen the duration of PCV2 replication-permissive conditions. The observed gene expression profile may provide insights into the underlying immunological response and pathological changes that occur in pigs following PCV2 infection.


title: 3D-printed contact-free devices designed and dispatched against the COVID19 pandemic: the 3D COVID initiative

text: Abstract Contacts with public devices such as elevator buttons, beepers, telephones, computer mice and keyboards can contribute to spread viral diseases. Here we report our experience in designing, producing and dispatching three 3D-printed objected intending to lower the risks of COVID19 contamination by limiting direct contacts: (1) fixed hand-free door openers, (2) door hooks and (3) button pushers. These devices were produced in industrial quantities and made available for free for Greater Paris University Hospitals and various state institutions as part of the 3D COVID project. In this short technical note, we describe the sequential organisation of the design and production and highlight the advantages of additive manufacturing in dealing with specific aspects of sanitary crises.


title: Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

text: Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis.


title: Can vitamins and/or supplements provide hope against coronavirus?

text: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) quickly became a global pandemic and has been responsible, so far, for infecting 5.8 million and claiming the lives of more than 350,000. While certain medications initially garnered attention as potential treatment options, further studies failed to demonstrate great promise but did demonstrate the need to reduce the cytokine storm experienced by patients with this potentially life-threatening virus. Unfortunately, there is no cure on the horizon, but members of the medical community are beginning to evaluate the potential role of vitamins and supplements as potential treatment options or addition to other treatments. The goal of this narrative review is to evaluate current and ongoing clinical trials of vitamins and supplements, alone or in combination with each other or other therapies, for the treatment of coronavirus disease-2019 (COVID-19).


title: In-hospital Use of Statins is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

text: Summary Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a Cox model with time-varying exposure, as well as a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with a hazard ratio 0.58. These results imply the potential benefits of statin therapy in hospitalized subjects with COVID-19. Further, they give support for the completion of on-going prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.