title: PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities

text: The Open Reading Frame 3 (ORF3), an accessory protein of porcine epidemic diarrhea virus (PEDV), has been shown to interact with a myriad of cellular proteins, among which include the IκB kinase β (IKBKB). Here, specific IKBKB domains responsible for ORF3–IKBKB interaction were identified. Dysregulation of NF-κB and Type I interferon (IFN) in the presence of ORF3 was also demonstrated. We showed that while ORF3 was capable of up-regulating IKBKB-meditated NF-κB promoter activity, it surprisingly down-regulated the activation of IKBKB-meditated IFN-β promoter and expression of IFN-β mRNA. When overexpressed, ORF3 could suppress Poly I:C mediated type I IFN production and induction. Finally, we demonstrated that IKBKB- and RIG-I-mediated type I IFN induction by ORF3 resulted in different outcomes. Our study is the first to demonstrate the potential and complex roles of ORF3 in the involvement of aberrant immune signaling as well as in the virus–host interaction.


Prise en charge des cancers oculaires en période épidémique de Covid-19[[[en]]]Management of ocular cancer during COVID-19 pandemic


Albert Camus’ ‘The COVID-19 Plague’ Revisited


title: Let’s emerge from the pandemic lockdown into a fairer academic world

text: King et al. argue that academic institutions need to better support employees who have faced disproportionate consequences of the pandemic and lockdown.


title: Chapter 8 Bioactive Coumarins and Xanthones From Calophyllum Genus and Analysis of Their Druglikeness and Toxicological Properties

text: Abstract Calophyllum spp. (Calophyllaceae) is a genus of tropical trees valued in the chemopharmacological industry as an important source of biogenetically related coumarins and xanthones, which can lead to the development of new drugs due to their relevant pharmacological activities and diversity of molecular structural. These compounds have relevant pharmacological activities, such as: cytotoxicity against human tumor cell lines (especially leukemia), parasites (Plasmodium, Leshmania, and Trypanosoma), retroviruses (e.g., HIV), and Mycobacterium tuberculosis. Chemoinformatic and toxicoinformatic tools were used here to perform a computational analysis of 70 coumarins and 70 xanthones isolated from this genus in order to explore their potential as new drugs. Most coumarins from this genus possess similar patterns of druglikeness with differences in its physicochemical properties. Xanthones, on the other hand, show quite similar physicochemical properties and druglikeness. It is interesting to note that the vast majority of these compounds (57 coumarins and 59 xanthones) are in compliance with Lipinski´s Rule of Five. Remarkably, two xanthones (2-hydroxyxanthone and caledonixanthone-B) have leadlikeness potential that accordingly with chemoinformatic analysis may target MAO A and B, respectively, and therefore may exhibit antidepressant potential. These compounds also target tyrosine-phosphorilation-regulated kinase 1A (DYRK1A) which is over-expressed in a variety of hematological and brain cancers, therefore they could act as anticancer compounds. Several toxicological predictions were also depicted. Coumarins could be an irritant and may affect the reproductive system, while xanthones may have mutagenic results. To our knowledge, this is the first chemoinformatic report on the main active compounds of this genus and its potential for drug development.


title: First detection of bovine coronavirus in Yak (Bos grunniens) and a bovine coronavirus genome with a recombinant HE gene

text: The yak (Bosgrunniens) is a unique domestic bovine species that plays an indispensable role for herdsmen in the Qinghai–Tibet Plateau. Here, 336 diarrhoeic samples were collected from yaks on 29 farms in the Qinghai–Tibet Plateau from 2015 to 2017. Approximately 69.05 % (232/336) of the diarrhoeic samples were assessed as bovine coronavirus (BCoV)-positive by RT-PCR assay, and most of the detected strains showed a unique evolution based on 40 spike (S), nucleocapsid (N) and haemagglutinin-esterase (HE) gene fragments. Notably, the 12 complete S genes detected shared 1 identical amino acid mutation (E121V) in the S1 subunit compared with the other 150 complete S genes in the GenBank database. Furthermore, a BCoV strain (designated YAK/HY24/CH/2017) was isolated from one diarrhoeic sample (virus titre : 10(8.17)TCID(50) ml(−1)), and a phylogenetic analysis based on complete genome sequences revealed that strain YAK/HY24/CH/2017 has the closest genetic relationship with the BCoV prototype strain Mebus. Interestingly, 2 significant characteristics were observed in the genome of strain YAK/HY24/CH/2017 : (1) the strain had 26 unique amino acid variations in the S gene compared with the other 150 BCoV S genes in the GenBank database and (2) a recombination event was identified between the esterase and lectin domains of the HE gene. In conclusion, this study revealed the high prevalence of BCoV in yaks in the Qinghai–Tibet Plateau. To the best of our knowledge, this is the first description of the molecular prevalence of BCoV in yaks and of a BCoV genome with an HE gene recombination.


title: Multicenter evaluation of the QIAstat Respiratory Panel—A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections

text: Acute respiratory tract infections (ARTI), including the common cold, pharyngitis, sinusitis, otitis media, bronchiolitis and pneumonia are the most common diagnoses among patients seeking medical care in western countries, and account for most antibiotic prescriptions. While a confirmed and fast ARTI diagnosis is key for antibiotic prescribing, empiric antimicrobial treatment remains common, because viral symptoms are often clinically similar and difficult to distinguish from those caused by bacteria. As a result, inappropriate antibiotic prescriptions are high and in certain settings likely higher than the commonly estimated 30%. The QIAstat Respiratory Panel(®) assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. We describe the first multicenter study of 445 respiratory samples, collected through the 2016–2017 and 2018 respiratory seasons, with performance compared against BioFire FilmArray RP v1.7 and discrepancy testing by Seegene Allplex RP. The QIAstat RP demonstrated a positive percentage of agreement of 98.0% (95% CI: 96.0–99.1%) and a negative percentage agreement of 99.8% (95% CI: 99.6–99.9%). With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship may potentially be achieved.


title: COVID-19 : caractéristiques cliniques, biologiques et radiologiques chez l’adulte, la femme enceinte et l’enfant. Une mise au point au cœur de la pandémie

text: The spread of the new coronavirus SARS-CoV-2, discovered in China in January 2020, led to a pandemic as early as March 2020, forcing every health care system in the affected countries to adapt quickly. In order to better address this major health crisis, which has given rise to numerous scientific publications, we have synthesized the main original clinical studies to facilitate the day-to-day management of patients with COVID-19. We detail the early signs and progression of the disease as well as the different clinical forms, including extra-pulmonary, as known at the beginning of this pandemic. We focus on clinical, biological and CT markers predictive of severity or mortality. Finally, we discuss the impact of SARS-CoV-2 infection in populations suspected to be at high risk of severe forms.


title: Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome

text: Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814‐7.630) and 2.047 (1.013‐4.138) in the training cohort and validation cohort, respectively. The AUC of 3‐year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high‐risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.


title: COVID‐19 infections and deaths among Connecticut nursing home residents: facility correlates

text: OBJECTIVE: To determine the associations of nursing home registered nurse (RN) staffing, overall quality of care, and concentration of Medicaid or racial and ethnic minority residents with COVID‐19 confirmed cases and deaths by April 16, 2020 among Connecticut nursing home residents. DESIGN: Cross‐sectional analysis on Connecticut nursing home (n=215) COVID‐19 report, linked to other nursing home files and county counts of confirmed cases and deaths. Multivariable two‐part models determined the associations of key nursing home characteristics with the likelihood of at least 1 confirmed case (or death) in the facility, and with the count of cases (deaths) among facilities with at least 1 confirmed case (death). RESULTS: The average number of confirmed cases was 8 per nursing home (zero in 107 facilities), and the average number of confirmed deaths was 1.7 per nursing home (zero in 131 facilities). Among facilities with at least 1 confirmed case, every 20 minutes (per resident day) increase in RN staffing was associated with 22% fewer confirmed cases (incidence rate ratio [IRR]=0.78, 95% confidence interval [CI] 0.68‐0.89, p<0.001); compared to 1‐ to 3‐star facilities, 4‐ or 5‐star facilities had 13% fewer confirmed cases (IRR=0.87, 95% CI 0.78‐0.97, p<0.015); and facilities with high concentration of Medicaid residents (IRR=1.16, 95% CI 1.02‐1.32, p=0.025) or racial/ethnic minority residents (IRR=1.15, 95% CI 1.03‐1.29, p=0.026) had 16% and 15% more confirmed cases, respectively, than their counterparts. Among facilities with at least 1 death, every 20 minutes increase in RN staffing significantly predicted 26% fewer COVID‐19 deaths (IRR=0.74, 95% CI 0.55‐1.00, p=0.047). Other focused characteristics did not show statistically significant associations with deaths. CONCLUSIONS: Nursing homes with higher RN staffing and quality ratings have the potential to better control the spread of the novel coronavirus and reduce deaths. Nursing homes caring predominantly for Medicaid or racial and ethnic minority residents tend to have more confirmed cases.


docid: vijzfbyj

title: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies

text: Abstract The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.


title: Application of deep learning technique to manage COVID-19 in routine clinical practice using CT images: Results of 10 convolutional neural networks

text: Abstract Fast diagnostic methods can control and prevent the spread of pandemic diseases like coronavirus disease 2019 (COVID-19) and assist physicians to better manage patients in high workload conditions. Although a laboratory test is the current routine diagnostic tool, it is time-consuming, imposing a high cost and requiring a well-equipped laboratory for analysis. Computed tomography (CT) has thus far become a fast method to diagnose patients with COVID-19. However, the performance of radiologists in diagnosis of COVID-19 was moderate. Accordingly, additional investigations are needed to improve the performance in diagnosing COVID-19. In this study is suggested a rapid and valid method for COVID-19 diagnosis using an artificial intelligence technique based. 1020 CT slices from 108 patients with laboratory proven COVID-19 (the COVID-19 group) and 86 patients with other atypical and viral pneumonia diseases (the non-COVID-19 group) were included. Ten well-known convolutional neural networks were used to distinguish infection of COVID-19 from non-COVID-19 groups: AlexNet, VGG-16, VGG-19, SqueezeNet, GoogleNet, MobileNet-V2, ResNet-18, ResNet-50, ResNet-101, and Xception. Among all networks, the best performance was achieved by ResNet-101 and Xception. ResNet-101 could distinguish COVID-19 from non-COVID-19 cases with an AUC of 0.994 (sensitivity, 100%; specificity, 99.02%; accuracy, 99.51%). Xception achieved an AUC of 0.994 (sensitivity, 98.04%; specificity, 100%; accuracy, 99.02%). However, the performance of the radiologist was moderate with an AUC of 0.873 (sensitivity, 89.21%; specificity, 83.33%; accuracy, 86.27%). ResNet-101 can be considered as a high sensitivity model to characterize and diagnose COVID-19 infections, and can be used as an adjuvant tool in radiology departments.


title: Viral antibodies in bovine fetuses in Argentina

text: Abstract In order to establish the prevalence of viral infections of the bovine fetus in Argentina, a serological survey for antibodies against viral agents currently affecting cattle in this country was conducted. Antibodies against foot-and-mouth disease virus (FMDV), bovine herpesvirus-1 (BHV-1), bovine leukaemia virus (BLV), bovine rotavirus (BRV), bovine coronavirus (BCV), bovine viral diarrhoea virus (BVDV) and parainfluenza-3 (PI-3) were investigated in a total of 315 fetal serum samples. Conventional techniques were used: indirect immunofluorescence (FMDV, BHV-1, BVDv and BCV), radial immunodiffusion (BLV), ELISA (BRV) and haemagglutination inhibition (PI-3). Antibodies against BHV-1, BVDV and PI-3 were detected in samples from fetuses in the second and third trimester of gestation, with a prevalence of 1·21 per cent (two of 165), 2·03 per cent (four of 197) and 5·08 per cent (nine of 177), respectively. Either antibodies or non-antibody factors able to bind to BRV and Bcv antigens were detected with a prevalence of 2·44 per cent (five of 205) and 4·54 per cent (five of 110), respectively. In addition, 14·68 per cent of non-specific inhibitors of PI-3 mediated haemagglutination were found. No seropositives against FMDV and BLV were detected.


title: Epidemiology, genome, and clinical features of the pandemic SARS-CoV-2: a recent view

text: Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, the number of globally confirmed cases according to World Health Organization statistics reached 292 124 in 189 countries by 22 March 2020. The number of deaths reached 12 784, with estimated case-fatality rates ranging from 0.5% to 5.7%. Children population seems to be the least affected by the disease, while the highest rate of death is among the elderly and people with comorbidities. Most infected individuals are asymptomatic or only exhibit mild symptoms. After the incubation period, the most common symptoms are fever, cough and fatigue. Asymptomatic carrier state is of paramount importance because of carriers' ability to spread the infection and to shed the virus into the air and surroundings. Although much is still unknown about SARS-CoV-2, the scientific research is moving at an unprecedented pace towards understanding the nature, effective control, prevention and treatment of SARS-CoV-2. Various reports have suggested an in vivo evolution of the virus, which may explain the rapid spread and changing epidemiology of SARS-CoV-2, but further evidence is needed. Unfortunately, no effective treatment or therapeutic drug is available for the disease; only supportive treatment and classical intervention measures are available for confronting the SARS-CoV-2 pandemic.


title: Evaluation of Two Dry Commercial Therapeutic Diets for the Management of Feline Chronic Gastroenteropathy

text: Management of feline chronic gastroenteropathies has included intervention with both veterinary therapeutic formulas designed to manage non-specific gastrointestinal disorders and those designed with limited novel or hydrolyzed ingredients for management of food-responsive enteropathies and steroid-responsive enteropathies (inflammatory bowel disease). There have been few studies evaluating the use of dietary intervention for the management of feline chronic gastroenteropathy. This prospective, multi-center study evaluated the use of two commercially available feline veterinary therapeutic dry diets designed to manage non-specific gastrointestinal disorders in 28 cats with a history of chronic vomiting and/or diarrhea. The majority of cats enrolled in the study had a history of vomiting (n = 25), with a smaller number having a history of concurrent diarrhea (n = 2) or diarrhea alone (n = 3). Cats were excluded if diagnostic tests identified any systemic or infectious disease that could be associated with the clinical signs of vomiting or diarrhea, and if they were panhypoproteinemic, hypoalbuminemic, hypocobalaminemic, or had a Spec fPL ≥5.4 µg/L. Cats were randomized to one of two veterinary therapeutic diets for 4 weeks. Feeding of both therapeutic diets resulted in a numeric reduction in the number of vomiting episodes over the 4-week period, but no significant differences were seen between dietary interventions. When looking within dietary groups, significant differences were seen in cats fed Diet A with reductions of 69.1, 73.3, and 63.2% (p values of 0.008, 0.003, and 0.029) in weeks 2, 3, and 4, respectively, when compared to week 0. The probability of vomiting also showed significant reductions in cats fed Diet A between weeks 0 and 2, 3, and 4, with odds ratios of 0.008, 0.005, and 0.005, respectively (p values of 0.038, 0.23, and 0.23). Results of this study demonstrate that a veterinary therapeutic gastrointestinal formula can be effective in the management of feline chronic vomiting. Cats that fail to respond to this dietary approach after a 2- to 4-week trial may benefit from a limited novel or hydrolyzed ingredient formula and may require additional diagnostics to better characterize the underlying disease.


title: Traffic-driven SIR epidemic spreading in networks

text: Abstract We study SIR epidemic spreading in networks driven by traffic dynamics, which are further governed by static routing protocols. We obtain the maximum instantaneous population of infected nodes and the maximum population of ever infected nodes through simulation. We find that generally more balanced load distribution leads to more intense and wide spread of an epidemic in networks. Increasing either average node degree or homogeneity of degree distribution will facilitate epidemic spreading. When packet generation rate ρ is small, increasing ρ favors epidemic spreading. However, when ρ is large enough, traffic congestion appears which inhibits epidemic spreading.


title: Sorting of progeny coronavirus from condensed secretory proteins at the exit from the trans-Golgi network of AtT20 cells

text: Murine hepatitis virus (strain A59), (MHV-A59) is a coronavirus that buds into pre-Golgi compartments and then exploits the exocytic pathway of the host cell to reach the exterior. The fibroblastic cells in which replication of this virus is usually studied have only a constitutive exocytic pathway that the virus uses. MHV-A59 also infects, albeit inefficiently, AtT20 cells, murine pituitary tumor cells with a regulated as well as a constitutive exocytic pathway. Here we examine AtT20 cells at early times after the infection, when the Golgi apparatus retains its morphological and biochemical integrity. We observe that progeny coronavirus and secretory protein destined for the secretory granules of the regulated exocytic pathway traverse the same Golgi stacks and accumulate in the trans-Golgi network. Their pathways diverge at this site, the condensed secretory proteins including the ACTH going to the secretory granules and the coronavirus to post-Golgi transport vesicles devoid of ACTH. On very rare occasions there is missorting such that aggregates of condensed secretory proteins and viruses occur together in post-Golgi vesicles. We conclude that the constitutive and regulated exocytic pathways, identified respectively by the progeny virions and the secretory protein ACTH, diverge at the exit from the trans-Golgi network.


title: Emerging Highly Virulent Porcine Epidemic Diarrhea Virus: Molecular Mechanisms of Attenuation and Rational Design of Live Attenuated Vaccines

text: The highly virulent porcine epidemic diarrhea virus (PEDV) emerged in China in 2010. It infects pigs of all ages, and causes severe diarrhea and high mortality rates in newborn pigs, leading to devastating economic losses in the pork industry worldwide. Effective and safe vaccines against highly virulent PEDV strains are still unavailable, hampering the further prevention, control and eradication of the disease in herds. Vaccination of pregnant sows with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows, which provides A passive protection of suckling piglets against PEDV via the colostrum (beestings, or first milk) and milk. Several LAV candidates have been developed via serially passaging the highly virulent PEDV isolates in non-porcine Vero cells. However, their efficacies in the induction of sufficient protection against virulent PEDV challenge vary in vivo. In this review, we summarize the current knowledge of the virulence-related mutations of PEDV and their potential roles in PEDV attenuation in vivo. With the successful development of reverse genetics systems for PEDV, we also discuss how to use them to generate promising LAV candidates that are safe, effective and genetically stable. This article provides timely insight into the rational design of effective and safe PEDV LAV candidates.


title: Multipurpose Instantaneous Microarray Detection of Acute Encephalitis Causing Viruses and Their Expression Profiles

text: Detection of multiple viruses is important for global analysis of gene or protein content and expression, opening up new prospects in terms of molecular and physiological systems for pathogenic diagnosis. Early diagnosis is crucial for disease treatment and control as it reduces inappropriate use of antiviral therapy and focuses surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay and the need for specific, accessible point-of-care diagnosis able to distinguish causative viruses and their subtypes. None of the available viral diagnostic assays combine a point-of-care format with the complex capability to identify a large range of human and animal viruses. Microarray detection provides a useful, labor-saving tool for detection of multiple viruses with several advantages, such as convenience and prevention of cross-contamination of polymerase chain reaction (PCR) products, which is of foremost importance in such applications. Recently, real-time PCR assays with the ability to confirm the amplification product and quantitate the target concentration have been developed. Furthermore, nucleotide sequence analysis of amplification products has facilitated epidemiological studies of infectious disease outbreaks and monitoring of treatment outcomes for infections, in particular for viruses that mutate at high frequency. This review discusses applications of microarray technology as a potential new tool for detection and identification of acute encephalitis-causing viruses in human serum, plasma, and cell cultures.


title: Community Mental Health Care Delivery During the COVID-19 Pandemic: Practical Strategies for Improving Care for People with Serious Mental Illness

text: The COVID-19 pandemic has presented a formidable challenge to care continuity for community mental health clients with serious mental illness and for providers who have had to quickly pivot the modes of delivering critical services. Despite these challenges, many of the changes implemented during the pandemic can and should be maintained. These include offering a spectrum of options for remote and in-person care, greater integration of behavioral and physical healthcare, prevention of viral exposure, increased collaborative decision-making related to long-acting injectable and clozapine use, modifying safety plans and psychiatric advance directives to include new technologies and broader support systems, leveraging natural supports, and integration of digital health interventions. This paper represents the authors’ collaborative attempt to both reflect the changes to clinical practice we have observed in CMHCs across the US during this pandemic and to suggest how these changes can align with best practices identified in the empirical literature.


title: Ability of device to collect bacteria from cough aerosols generated by adults with cystic fibrosis

text: Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR) molecular assays. Results: Twenty adult patients with CF and 10 healthy controls participated. CF related bacteria (CFRB) were detected in 13/20 (65%) cough specimens versus 15/15 (100%) sputum specimens. Commensal S. mitis was present in 0/17 (0%, p=0.0002) cough specimens and 13/14 (93%) sputum samples. In normal controls, no bacteria were collected in cough specimens but 4/10 (40%) oral specimens were positive for CFRB. Conclusions: Non-invasive cough aerosol collection may detect lower respiratory pathogens in CF patients, with similar specificity and sensitivity to rates detected by BAL, without contamination by oral CFRB or commensal bacteria.


title: Mental health in elderly Spanish people in times of COVID-19 outbreak

text: BACKGROUND: We aim to assess COVID-19 outbreak-related emotional symptoms, identify gender differences, and study the relationship between the emotional state and environmental features in the elderly. METHODS: We conducted a cross-sectional study starting on March 29 to April 5, 2020 based on a national online survey using snowball sampling techniques. Symptoms of anxiety (Hamilton Anxiety Scale), depression (Beck Depression Inventory) and acute stress (Acute Stress Disorder Inventory) were compared between people over and under 60 years old. Gender differences and the relationship of loneliness, regular exercise, economic losses and use of anxiolytics on the mental state were evaluated. RESULTS: 1639 [150 (9.2%) aged ≥60] participants completed the survey. The ≥60 group showed lower mean (SD) BDI levels than the <60 group [3.02 (3.28) vs. 4.30 (4.93)]; and lower mean (SD) ASDI scores than the <60 group [3.68 (3.20) vs. 4.45 (3.06)]. There were no gender differences in any of the clinical measures. The presence of economic losses as well as the increase in the use of anxiolytics was significantly associated with higher emotional distress in the elderly compared to the younger group. CONCLUSIONS: Older people has shown less emotional distress, with no differences between men and women. Economic loss and substance use should be monitored to guarantee the emotional well-being of the elderly.


title: Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan

text: Abstract We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.


title: The amino-terminal signal peptide on the porcine transmissible gastroenteritis coronavirus matrix protein is not an absolute requirement for membrane translocation and glycosylation

text: Abstract cDNA clones mapping within the first 2601 bases of the 3′ end of the porcine transmissible gastroenteritis coronavirus (TGEV) genome were sequenced by the method of Maxam and Gilbert and an open reading frame yielding a protein having properties of the matrix (M or E1) protein was identified. It is positioned at the 5′ side of the nucleocapsid (N) gene from which it is separated by an intergenic stretch of 12 bases. The deduced M protein comprises 262 amino acids, has a molecular weight of 29,544, is moderately hydrophobic, and has a net charge of +7 at neutral pH. Thirty-four percent of its amino acid sequence is homologous with the M protein of the bovine coronavirus (BCV), 32% with that of the mouse hepatitis coronavirus (MHV), and 19% with that of the avian infectious bronchitis coronavirus (IBV). Judging from alignment with the BCV, MHV, and IBV M proteins, the amino terminus of the TGEV M protein extends 54 amino acids from the virion envelope which compares with only 28 for BCV, 26 for MHV, and 21 for IBV. Eleven of the sixteen amino-terminal amino acids are hydrophobic and the positions of charged amino acids around this sequence suggest that the first 16 amino acids comprise a potentially cleavable signal peptide for membrane insertion. A similar sequence is not found in the M proteins of BCV, MHV, or IBV. When mRNA from infected cells, or RNA prepared by in vitro transcription of the reconstructed M gene, was translated in vitro in the presence of microsomes, the M protein became translocated and glycosylated. When a protein without the amino-terminal signal peptide was made by translating a truncated version of the M gene transcript, some translocation and glycosylation also occurred suggesting that the amino-terminal signal peptide on the TGEV M protein is not an absolute requirement for membrane translocation. Interestingly, the amino-terminal peptide did not appear to be cleaved during in vitro translation in the presence of microsomes suggesting that a step in virion assembly may be required for proper exposure of the cleavage site to the signal peptidase.


title: Risques viraux émergents en transfusion sanguine

text: During the last 20 years, the safety of blood products increased dramatically with regard to the infectious risk and notably to that represented by retroviruses (HIV and HTLV) and hepatitis B and C viruses. The aim of this review is to identify the residual and emergent viral threats that could be responsible for the occurring of new contaminations in the receivers of blood products. Beside many other viruses (HHV-8, erythrovirus B19, hepatitis A and E viruses…), a special attention has been paid to emerging arbovirus diseases (West Nile virus infection, dengue, chikungunya) that threaten to occur in the French metropolitan area following the implantation in Europe of the mosquito Aedes albopictus, the main vector of dengue and chikungunya in temperate regions. Another blood-linked risk, notably in United Kingdom and France, is the prion agent responsible for the variant form of the Creutzfeldt-Jakob disease. The review is concluded by a brief overview of the measures aimed to control these emergences, including the exclusion of at-risk donors, the diagnostic tests able to detect a specific agent, the leukocyte reduction of labile blood products, and the physical or chemical treatments aiming the nonspecific inactivation of infectious agents potentially present in blood without impairing significantly the physiological properties of blood compounds. The ability to control prospectively the new viral risks linked to blood products is a challenge for the preservation of the confidence of both clinicians and receivers in the safety of blood transfusion.


Propiedades antivirales y antiinflamatorias de ivermectina y su potencial uso en COVID-19


title: Globalization and advances in information and communication technologies: The impact on nursing and health

text: Globalization and information and communication technology (ICT) continue to change us and the world we live in. Nursing stands at an opportunity intersection where challenging global health issues, an international workforce shortage, and massive growth of ICT combine to create a very unique space for nursing leadership and nursing intervention. Learning from prior successes in the field can assist nurse leaders in planning and advancing strategies for global health using ICT. Attention to lessons learned will assist in combating the technological apartheid that is already present in many areas of the globe and will highlight opportunities for innovative applications in health. ICT has opened new channels of communication, creating the beginnings of a global information society that will facilitate access to isolated areas where health needs are extreme and where nursing can contribute significantly to the achievement of “Health for All.” The purpose of this article is to discuss the relationships between globalization, health, and ICT, and to illuminate opportunities for nursing in this flattening and increasingly interconnected world.


title: Prospective evaluation of a new automated nucleic acid extraction system using routine clinical respiratory specimens

text: The aim of the study was to evaluate the MagNA Pure 96™ nucleic acid extraction system using clinical respiratory specimens for identifying viruses by qualitative real‐time PCR assays. Three extraction methods were tested, that is, the MagNA Pure LC™, the COBAS Ampliprep™, and the MagNA Pure 96™ with 10‐fold dilutions of an influenza A(H1N1)pdm09 sample. Two hundred thirty‐nine respiratory specimens, 35 throat swabs, 164 nasopharyngeal specimens, and 40 broncho‐alveolar fluids, were extracted with the MagNA Pure 96™ and the COBAS Ampliprep™ instruments. Forty COBAS Ampliprep™ positive samples were also tested. Real‐time PCRs were used to identify influenza A and influenza A(H1N1)pdm09, rhinovirus, enterovirus, adenovirus, varicella zoster virus, cytomegalovirus, and herpes simplex virus. Similar results were obtained on RNA extracted from dilutions of influenza A(H1N1)pdm09 with the three systems: the MagNA Pure LC™, the COBAS Ampliprep™, and the MagNA Pure 96™. Data from clinical respiratory specimens extracted with the MagNA Pure 96™ and COBAS Ampliprep™ instruments were in 98.5% in agreement (P < 0.0001) for influenza A and influenza A(H1N1)pdm09. Data for rhinovirus were in 97.3% agreement (P < 0.0001) and in 96.8% agreement for enterovirus. They were in 100% agreement for adenovirus. Data for cytomegalovirus and HSV1‐2 were in 95.2% agreement (P < 0.0001). The MagNA Pure 96™ instrument is easy‐to‐use, reliable, and has a high throughput for extracting total nucleic acid from respiratory specimens. These extracts are suitable for molecular diagnosis with any type of real‐time PCR assay. J. Med. Virol. 84:906–911, 2012. © 2012 Wiley Periodicals, Inc.


title: Modeling the Heterogeneity of Dengue Transmission in a City

text: Dengue fever is one of the most important vector-borne diseases in the world, and modeling its transmission dynamics allows for determining the key influence factors and helps to perform interventions. The heterogeneity of mosquito bites of humans during the spread of dengue virus is an important factor that should be considered when modeling the dynamics. However, traditional models generally assumed homogeneous mixing between humans and vectors, which is inconsistent with reality. In this study, we proposed a compartmental model with negative binomial distribution transmission terms to model this heterogeneity at the population level. By including the aquatic stage of mosquitoes and incorporating the impacts of the environment and climate factors, an extended model was used to simulate the 2014 dengue outbreak in Guangzhou, China, and to simulate the spread of dengue in different scenarios. The results showed that a high level of heterogeneity can result in a small peak size in an outbreak. As the level of heterogeneity decreases, the transmission dynamics approximate the dynamics predicted by the corresponding homogeneous mixing model. The simulation results from different scenarios showed that performing interventions early and decreasing the carrying capacity for mosquitoes are necessary for preventing and controlling dengue epidemics. This study contributes to a better understanding of the impact of heterogeneity during the spread of dengue virus.


docid: rucfowvv

title: Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases

text: OBJECTIVES: To report methods and findings of 2 autopsies with molecular evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals. METHODS: Postmortem examination was completed following Centers for Disease Control and Prevention public guidelines. Numerous formalin-fixed paraffin-embedded (FFPE) tissue types from each case were surveyed for SARS-CoV-2 RNA by quantitative reverse transcription polymerase chain reaction (qRT-PCR). SARS-CoV-2 viral genome was sequenced by next-generation sequencing (NGS) from FFPE lung tissue blocks. RESULTS: Postmortem examinations revealed diffuse alveolar damage, while no viral-associated hepatic, cardiac, or renal damage was observed. Viral RNA was detected in lungs, bronchi, lymph nodes, and spleen in both cases using qRT-PCR method. RNA sequencing using NGS in case 1 revealed mutations most consistent with Western European Clade A2a with ORF1a L3606F mutation. CONCLUSIONS: SARS-CoV-2 testing and viral sequencing can be performed from FFPE tissue. Detection and sequencing of SARS-CoV-2 in combination with morphological findings from postmortem tissue examination can aid in gaining a better understanding of the virus’s pathophysiologic effects on human health.


title: Effect of inhaled azodicarbonamide on F344 N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures

text: Abstract Azodicarbonamide (ADA), a compound used in the baking and plastics industries, has been reported to cause pulmonary sensitization and dermatitis in people. Two-week repeated and 13-week subchronic inhalation exposures of F344 N rats and B6C3F1 mice to ADA were conducted to determine the toxicity of inhaled ADA. The mean air concentrations of ADA in the 2-week studies were 207, 102, 52, 9.4, or 2.0 mg/m3. No exposure-related mortality nor abnormal clinical signs were observed in rats or mice during or after exposure. The terminal body weights were slightly depressed in the highest exposure group. Liver weights were lower in male rats exposed to 200 mg ADA/m3. No significant lesions were noted on either gross or histologic evaluation of rats or mice. In the 13-week subchronic study, the mean air concentrations of ADA were 204, 100, or 50 mg/m3. No mortality or clinical signs related to exposure were observed. The terminal body weights of exposed rats were not significantly different from those of control rats but were significantly depressed in mice exposed to 100 or 200 mg ADA/m3. No histopathological lesions were noted in mice. Lung weights were increased and enlarged mediastinal and/or tracheobronchial lymph nodes were noted in rats exposed to 50 mg ADA/m3. No exposure-related lesions were observed microscopically in rats exposed to 100 or 200 mg ADA/m3. All rats in the 50 mg DNA/m3 exposure group only had lung lesions that consisted of perivascular cuffing with lymphocytes and a multifocal type II cell hyperplasia, suggesting a possible immune reaction to an antigen in the lung. Viral titers for rats exposed to 50 mg ADA/m3 were negative for Sendai virus and pneumonia virus of mice, which produce similar lesions. The possibility of an unknown viral antigen causing this lesion cannot be eliminated. Lung tissue from male rats was analyzed for ADA and biurea, the major metabolite of ADA. No ADA was detected. The amount of biurea in the lungs increased nonlinearly with increasing exposure concentration, suggesting that clearance was somewhat impaired with repeated exposures. However, even at the highest exposure concentration, this amount of biurea was less than 1% of the estimated total ADA deposited over the exposure period. In summary, ADA is rapidly cleared from the lungs, even when inhaled at concentrations up to 200 mg/m3. Exposure to ADA for up to 13 weeks did not appear to be toxic to rodents.


title: Mathematical model of infection kinetics and its analysis for COVID-19, SARS and MERS

text: Abstract The purpose of this paper is to reveal the spread rules of the three pneumonia: COVID-19, SARS and MERS. We compare the new spread characteristics of COVID-19 with those of SARS and MERS. By considering the growth rate and inhibition constant of infectious diseases, their propagation growth model is established. The parameters of the three coronavirus transmission growth models are obtained by nonlinear fitting. Parametric analysis shows that the growth rate of COVID-19 is about twice that of the SARS and MERS, and the COVID-19 doubling cycle is two to three days, suggesting that the number of COVID-19 patients would double in two to three days without human intervention. The infection inhibition constant in Hubei is two orders of magnitude lower than in other regions, which reasonably explains the situation of the COVID-19 outbreak in Hubei.


title: Comparative analysis of perceived stress in dermatologists and other physicians during home‐quarantine and COVID‐19 pandemic with exploration of possible risk factors‐ A web‐based cross‐sectional study from Eastern India

text: Since the declaration of COVID‐19 as global pandemic, several countries including India have enforced a national quarantine.We aimed to compare the perceived stress of Dermatologists and non‐dermatologists, due to quarantine and COVID‐19 pandemic and analyze the role of possible risk‐factors. We conducted a web‐based cross‐sectional study to determine the perceived stress of doctors using the Perceived stress scale‐10 and evaluate possible risk‐factors. Among 384 valid responders,we had 37.5% dermatologists and 62.5% non‐dermatologists. Perceived stress was more in non‐dermatologists compared to dermatologists, but not statistically significant (P = 0.1). Degree of stress was also comparable (P = 0.5). Higher stress was significantly associated with females and unmarried individuals in both groups. Risk of infecting self or colleagues or family members and lack of protective gear at work‐place were top causes of stress. Perceived stress is increased in all doctors due to COVID‐19 pandemic and quarantine. Even dermatologists have developed high‐stress due to current situation, comparable to non‐dermatologists, despite being traditionally considered an out‐patient speciality with minimum stress. Thus, proper mental health care policies should be adopted for all doctors, including dermatologists. This article is protected by copyright. All rights reserved.


nBreastfeeding Risk from Detectable Severe Acute Respiratory Syndrome Coronavirus 2 in Breastmilk


title: Oncological Surgery During the COVID‐19 Pandemic: The Need for Deep and Lasting Measures

text: The COVID‐19 pandemic has overwhelmed health system capacity and affected cancer centers worldwide. This letter to the editor proposes the need to prepare for a long‐lasting battle.


title: Regulation of aminopeptidase N (EC 3.4.11.2; APN; CD13) by interferon-γ on the HL-60 cell line

text: Abstract Membrane-bound peptidases play important roles in the regulation of local concentrations of various signalling peptides such as the growth factors, hormones, chemokines and cytokines. That is accomplished by means of their enzyme activity. Recently, membrane-bound peptidases have also been shown to act as receptors, receiving signals from as yet undefined ligands and transducing them into the cell interior. By using either or both of these mechanisms, peptidases interact with fundamental cellular functions: growth, differentiation, activation and death. This study addressed the effects of a T-cell derived cytokine, interferon-gamma (IFN-γ) on the activity of aminopeptidase N (APN), an ectoenzyme processing several signal peptides. Cells of a myelo-monocytic cell line HL-60 were used as a model system, and APN was assayed at the levels of mRNA, its membrane marker CD13, and the enzyme activity. Regulation of CD13/APN by IFN-γ was found at all three levels. The direction of regulation was time-dependent: an initial down-regulation seen 24 and 48 hrs after the onset of treatment with IFN-γ was replaced by an up-regulation after 72 and/or 96 hrs. Up-regulation of CD13/APN observed after 96 hrs was preceded by an up-regulation of APN mRNA reaching its maximum after 72 hrs. The IFN-γ-induced regulation of APN was due to membrane aminopeptidase N, since it could be completely abrogated by an APN blocking antibody WM-15. The delayed up-regulation of CD13/APN (observed after 72 and/or 96 hrs), required de novo protein synthesis as it could be abrogated by cycloheximide, an inhibitor of protein synthesis. Possible role of endogenous (IFN-γ-induced) TGF-β in mediating CD13/APN up-regulation could be excluded, since no TGF-β was found in supernatants of IFN-γ treated HL-60 cells. Thus, our data show regulation of CD13/APN on cells of myelo-monocytic origin by a T-cell derived cytokine, IFN-γ. A similar mechanism might play a role in inflammation.


title: Le syndrome respiratoire aigu sévère (SRAS) existe aussi chez l’enfant et semble d’autant moins agressif que l’enfant est plus jeune K.L.E. Hon

text: Unknown


title: The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators

text: SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus’ pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC(50) values ranging from 2.0 to 13 μM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19.


title: Origination and consequences of bovine viral diarrhea virus diversity

text: The potential consequences of BVDV genetic and antigenic diversity are far ranging. The complexity of clinical presentations associated with BVDV likely arises from factors encoded by the virus genome. More importantly,prevention and control of BVDV may be complicated by diagnostic and immunization failure resulting from virus diversity. Evolutionary pressures will continue to drive further diversity, making control of BVDV challenging. Current and the potential for future BVDV strain diversity should be considered when designing BVDV control programs both at the individual farm and national herd level.


title: Containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings: a scoping review

text: BACKGROUND: The emergence and re-emergence of vector-borne and other infectious diseases of poverty pose a threat to the health of populations living in urban and low-income settings. A detailed understanding of intervention strategies, including effectiveness of past outbreak containment, is necessary to improve future practices. The objective was to determine what is known about the effectiveness of containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings and identify research gaps and implications for public health practice. MAIN BODY: We conducted a scoping review and systematically searched peer-reviewed and grey literature published between 2000 and 2016. Different data extraction tools were used for data coding and extraction, and data on implementation process and transferability were extracted from all studies. A quality assessment was conducted for each included study. We screened 205 full-text articles and reports for a total of 31 articles included in the review. The quality of the studies was generally low to moderate. The largest body of evidence concerned control activities for Ebola virus and dengue fever. The majority of interventions (87%) relied on multiple types of measures, which were grouped into four categories: 1) healthcare provision; 2) epidemiological investigation and/or surveillance; 3) environmental or sanitary interventions; and 4) community-based interventions. The quality of the majority of studies (90%) was poor or moderate, and one-third of the studies did not provide a clear description of the outcomes and of the procedures and/or tools used for the intervention. CONCLUSIONS: Our results highlight the difficulty of establishing causation when assessing the effect of containment measures. Studies that extend beyond solely reporting on effectiveness and take into account the complexity of real-world settings are urgently needed. We recommend the allocation of research efforts to the evaluation of the implementation processes of interventions as well as their comprehensive and systematic description using validated checklists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0478-4) contains supplementary material, which is available to authorized users.


title: Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection

text: INTRODUCTION: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial. METHODS: Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry. RESULTS: Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1–4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1–7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7–2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0–4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed. CONCLUSIONS: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.


docid: kvvxmvqo

title: MultiBac: from protein complex structures to synthetic viral nanosystems

text: The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. We review some of these developments, including the ongoing rewiring of the MultiBac system for mammalian applications, notably CRISPR/Cas9-mediated gene editing.


title: Contributions of pediatrics and pediatric pathology to the body of knowledge regarding human disease

text: Summary A century or so ago, pediatrics and pediatric pathology did not exist. Then, many fetuses/newborns died in utero or shortly after birth. With time, the issue of sepsis was addressed, and a greater number of newborns survived. Gradually, in this soil, the disciplines of pediatrics and pediatric nursing arose, as some recognized that infants were not merely small adults but were, in fact, quite different. Years later, pediatric pathology developed as a field of exploration. Today, pediatric pathology is a specialty, as witnessed by training programs, societies devoted to research and education, an expanding number of textbooks and innovative research. Pediatric pathology is distinct from adult pathology, as seen by the diversity of malformations and metabolic diseases stemming from mutations, the immaturity of the newborn's immune system, and the types of neoplasms germane to infants and children. Much of the progress in these areas was facilitated by the simultaneous emergence of cytogenetics and molecular biology and their powerful tools of investigation. The latter were applied in a synergistic fashion to a major extent in maternity clinics and children's hospitals by, among others, molecular biologists, clinical geneticists, cytogeneticists, pediatricians, and pediatric pathologists. This article describes a select but small number of the many contributions of pediatrics and pediatric pathology to the current body of medical knowledge.


title: SARS‐CoV‐2 Testing and Outcomes in the First 30 Days after the First Case of COVID‐19 at an Australian Children’s Hospital

text: OBJECTIVE: International studies describing COVID‐19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS‐CoV‐2 at a large Australian tertiary children’s hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children’s Hospital, Melbourne, Australia. It included all paediatric patients (aged 0–18 years) who presented to the Emergency Department (ED) or the Respiratory Infection Clinic (RIC) and were tested for SARS‐CoV‐2. The 30‐day study period commenced after the first confirmed positive case was detected at the hospital on 21(st) March 2020, until 19(th) April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS‐CoV‐2 testing was performed in ED (331 (76%)) or RIC (102 (24%)). There were 4 (0.9%) who had positive SARS‐CoV‐2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS‐CoV‐2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS‐CoV‐2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID‐19 were identified in 4/4 SARS‐CoV‐2 positive patients and 47/429 (11%) SARS‐CoV‐2 negative patients. CONCLUSIONS: Our study identified a very low rate of SARS‐CoV‐2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS‐CoV‐2 negative had comorbidities.


Can concomitant use of zinc and curcumin with other immunity‐boosting nutraceuticals be the arsenal against COVID‐19?


title: Intragastric immunization with recombinant Lactobacillus casei expressing flagellar antigen confers antibody-independent protective immunity against Salmonella enterica serovar Enteritidis

text: A recombinant Lactobacillus casei expressing a flagellar antigen from Salmonella enterica serovar Enteritidis was constructed and evaluated as a mucosal vaccine. Intragastric immunization of the recombinant strain conferred protective immunity against Salmonella infection in mice. This immunization did not result in antigen-specific antibody in either feces or sera but induced the release of IFN-γ on restimulation of primed lymphocytes ex vivo. The results suggested that the protective efficacy provided by flagellin-expressing L. casei is mainly attributable to cell-mediated immune responses. In addition, an adjuvant-type effect of the antigen delivery system with L. casei was also observed.


title: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore

text: Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R(0)) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.


title: A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike

text: SARS-CoV-2 has emerged as a global pathogen(1,2), sparking urgent vaccine development efforts with the trimeric spike(3,4). However, the inability of antibodies like CR3022(5), which binds a cryptic spike epitope with nanomolar affinity(6), to neutralize virus, suggests a spike-based means of neutralization escape. Here, we show the SARS-CoV-2 spike to have 10% the unfolding enthalpy of a globular protein at physiological pH, where it is recognized by antibodies like CR3022, and up to 10-times more unfolding enthalpy at endosomal pH, where it sheds such antibodies, suggesting that the spike evades potentially neutralizing antibody through a pH-dependent mechanism of conformational masking. To understand the compatibility of this mechanism with ACE2-receptor interactions, we carried out binding measurements and determined cryo-EM structures of the spike recognizing up to three ACE2 molecules at both physiological and endosomal pH. In the absence of ACE2, cryo-EM analyses indicated lower pH to reduce conformational heterogeneity. Single-receptor binding domain (RBD)-up conformations dominated at pH 5.5, resolving into a locked all-down conformation at lower pH through lowering of RBD and refolding of a pH-dependent switch. Notably, the emerging Asp614Gly strain(7) partially destabilizes the switch that locks RBD down, thereby enhancing functional interactions with ACE2 while reducing evasion by conformational masking.


title: WU polyomavirus detected in respiratory tract specimens from young children in Japan

text: Polyomaviruses (PyV) WU and KI are reportedly associated with respiratory tract disease (RTD) worldwide but their incidence is unclear in Japan. In a 2 year prospective study, WU/KIPyV were detected in 48 (13.9%) and in five (1.4%) of 345 children hospitalized with lower RTD, respectively. The seasonal distribution was observed in spring and early summer. Other respiratory viruses were co‐detected in 51% of PyV‐positive patients, but eight (2.3%) of the WUPyV‐positive patients were negative for other known pathogens.


title: Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis

text: Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host–apoptosis–virus triangle.


title: Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013

text: Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious, acute enteric viral disease of swine characterized by vomiting, watery diarrhea, dehydration and death. To identify and characterize the field PEDVs associated with the outbreaks of severe diarrhea in piglets in Jiangxi, 2013, the complete genome sequences of two representative strains of PEDV, designated CH/JX-1/2013 and CH/JX-2/2013, were determined and analyzed. The genome sequences of both emergent Jiangxi PEDV strains, CH/JX-1/2013 and CH/JX-2/2013, were 28,038 nucleotides in length excluding 3’ poly (A) tail. Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5´-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. The nucleotide identity between the two Jiangxi strains (CH/JX-1/2013 and CH/JX-2/2013) and 30 strains of PEDV identified ante-2010 and post-2010 ranged from 96.3–97.0% and 97.3–99.7%, respectively. Multiple nucleotide and deduced amino acid mutations were observed in the ORF1a/b, S, ORF3, E, M and N genes among the current field PEDV strains when compared to the CV777 strain. Some of the mutations altered the amino acid charge and hydrophilicity, and notably, there was an amino acid substitution in the middle of one neutralizing epitope (L1371I) of the S gene of both CH/JX-1/2013 and CH/JX-2/2013. Taken together, the accumulated genetic variations of the current field PEDV strains might have led to antigenic changes of the viruses, which might confer the less effectiveness or failure of the CV777-based vaccines currently being widely used in Jiangxi, China.


docid: pvjvmzcf

title: Three Novel COVID-19 Pneumonia Cases Successfully Treated With Lopinavir/Ritonavir

text: Following the first case of Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2), in Wuhan, China, in December 2019, it has spread worldwide. An outbreak in Japan occurred on a cruise ship, and this was followed by community-acquired COVID-19. Herein, we report three cases of COVID-19 that presented pneumonia following admission to Kitasato University Hospital. Patients were admitted based on the positive result of real-time reverse transcriptase–polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid. All patients were diagnosed as suffering from non-severe COVID-19 pneumonia and were successfully treated with Lopinavir/Ritonavir (LPV/r). LPV/r could be an option for treating non-severe COVID-19 pneumonia in general and even in elderly patients.


title: État actuel de la prise en charge des infections rhinosinusiennes aiguës de l'enfant en France

text: Résumé Un groupe de médecins généralistes et multidisciplinaire de spécialistes contribue à définir les différentes formes de sinusites ou rhinosinusites aiguës de l'enfant à partir des principaux symptômes et signes cliniques. Le rôle des pathologies associées telles que l'allergie, les troubles immunitaires est envisagé. L'incidence, la présentation clinique et la prise en charge des complications sont présentées. Les indications des examens radiologiques et biologiques sont analysées. La prise en charge médicale en particulier, la place et le type des antibiotiques sont discutés. Des propositions de prise en charge selon des situations cliniques rencontrées en pratique sont présentées. Abstract A multidisciplinary panel of specialists and general practitioners provided definitions for the different forms of acute pediatric rhinosinusitis, with a description of the main symptoms and signs. They emphasized the role of concomitant systemic diseases, such as allergy and immunological disorders. Incidence, description, and management of complications are presented. They also provided the indications for radiological examination and microbiological investigations. The adequate medical management, particularly the place and the type of antibiotics, is analyzed and discussed, and guidelines for practical situations are suggested.


Apnea neonatal como manifestación inicial de infección por sars-cov2


title: Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients

text: Abstract Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.


title: What caused lymphopenia in SARS and how reliable is the lymphokine status in glucocorticoid-treated patients?

text: Severe Acute Respiratory Syndrome (SARS) outbreak in 2002–03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. Lymphopenia along with neutrophilia was a feature of SARS, as it is in respiratory syncytial virus (RSV) and Ebola infections, to name a few. Direct infestation of lymphocytes, neutrophils and macrophages by SARS coronavirus (CoV) has been debated as a cause of lymphopenia, but there is no convincing data. Lymphopenia can be caused by glucocorticoids, and thus any debilitating condition has the potential to induce lymphopenia via stress mechanism involving the hypothalamic–pituitary–adrenal axis. Cortisol levels are elevated in patients with RSV and Ebola, and cortisol was higher in SARS patients with lymphopenia before any steroid therapy. Glucocorticoids also down-regulate the production of proinflammatory lymphokines. Because of the insidious presentation, SARS was treated with antibacterial, antiviral and supra-physiological doses of glucocorticoids. Treatment with glucocorticoids complicated the issue regarding lymphopenia, and certainly calls into question the status of lymphokines and their prognostic implications in SARS.


title: Rapid De-Escalation and Triaging Patients in Community-Based Palliative Care

text: Abstract Context The COVID-19 pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? Measures The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment (PPE) resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. Conclusions/Lessons Learned We recommend active triaging, communication, frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.


title: Study on the resistance of severe acute respiratory syndrome-associated coronavirus

text: Abstract In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20°C. However, at 4°C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5mg/L for chlorine or 2.19mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.


title: A public antibody lineage that potently inhibits malaria infection by dual binding to the circumsporozoite protein

text: Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZ) has been shown to be protective, but the features of the antibody response induced by this treatment remain unclear. To investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. All IgG monoclonals isolated bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in the N-terminus, NANP repeat region, and C-terminus. Strikingly, the most effective antibodies, as assessed in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and used VH3-30 or VH3-33 alleles carrying tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.


title: Genome analysis of a G9P[23] group A rotavirus isolated from a dog with diarrhea in China

text: Abstract Genotype G9 is an emerging genotype among species A rotavirus (RVA) circulating in humans and pigs worldwide. In this study, an RVA strain designated RVA/Dog-tc/CHN/SCCD-A/2017/G9P[23] was isolated in cell culture from a pet dog stool sample with acute diarrhea, and its whole genome was sequenced. The genotype constellation of SCCD-A was G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. All genome segments except the VP1 gene were closely related to the genes from porcine RVA strains or porcine-like human RVA strains. On the other hand, the VP1 gene clustered in a distinct lineage only with that of a G5P[6] porcine-like human RVA, preventing the identification of the exact host species origin, but very unlikely to be originated from human RVA. In addition, phylogenetic analysis showed that the G9 VP7 gene of SCCD-A clustered into a novel sublineage within the lineage III of G9. This first isolation of a G9P[23] RVA from a pet dog may justify the exploration of the role dogs play in the interaction of RVA circulating in pigs and humans.


title: Subgenomic RNAs with nucleotide sequences derived from RNAs 1 and 2 of cucumber mosaic virus can act as messenger RNAsin Vitro

text: Abstract Encapsidated RNAs of cucumber mosaic virus (CMV) were analyzed by hybridization to specific probes after gel electrophoresis. [32P]-complementary DNA (cDNA) probes were prepared by transcription of genomic RNA 1 and RNA 2 nucleotide sequences that had been cloned in a bacteriophage M13 vector. Probes that correspond to unique sequences near the 3′ ends of RNA 1 and RNA 2 revealed over 20 smaller RNAs. The subgenomic RNAs derived from each genomic RNA were analyzed more definitively by hybrid selection from total encapsidated RNA, using minus DNA clones derived from sequences in either RNA 1 or RNA 2, and a cDNA probe for the 3′ sequence conserved among all the genomic RNAs. Different patterns of over 20 minor RNA species, which were 3′-coterminal with RNAs 1 and 2, were detected, and they were reproducible irrespective of the host, cucumber orNicotiana clevelandii, from which the virus was isolated. The same RNA patterns were found in RNA extracted from the particulate fraction of CMV-infected cucumber orN. clevelandii. In order to determine whether the subgenomic RNAs could function as messenger RNAs, hybrid-selected RNAs were tested byin vitro translation, using the rabbit reticulocyte lysate. The subgenomic RNAs from RNA 1 produced over 10 major polypeptides from Mr 27,000 to Mr 90,000 all of which could be translated from a few RNA species over about 2,300 nucleotides long. The 3′-coterminal subgenomic RNAs derived from RNA 2 gave less than 10 products from Mr , 17,000 toMr 85,000. The smallest product (Mr 17,000) was produced by an RNA about 880 nucleotides long, whereas longer RNAs from 1400 to 2500 nucleotides were efficient mRNAs for polypeptides from Mr 30,000 up to the largest translation products consistent with the size of the RNA.


RASH MACULOPAPULOSO COMO MANIFESTACIÓN INICIAL DE INFECCIÓN POR SARS-CORONAVIRUS-2


title: Rapid Identification of Emerging Pathogens: Coronavirus

text: We describe a new approach for infectious disease surveillance that facilitates rapid identification of known and emerging pathogens. The process uses broad-range polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry for accurate mass measurements of PCR products, and base composition signature analysis to identify organisms in a sample. We demonstrate this principle by using 14 isolates of 9 diverse Coronavirus spp., including the severe acute respiratory syndrome–associated coronavirus (SARS-CoV). We show that this method could identify and distinguish between SARS and other known CoV, including the human CoV 229E and OC43, individually and in a mixture of all 3 human viruses. The sensitivity of detection, measured by using titered SARS-CoV spiked into human serum, was ≈1 PFU/mL. This approach, applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens, is capable of automated analysis of >900 PCR reactions per day.


title: Interpretable detection of novel human viruses from genome sequencing data

text: Viruses evolve extremely quickly, so reliable methods for viral host prediction are necessary to safeguard biosecurity and biosafety alike. Novel human-infecting viruses are difficult to detect with standard bioinformatics workflows. Here, we predict whether a virus can infect humans directly from next-generation sequencing reads. We show that deep neural architectures significantly outperform both shallow machine learning and standard, homology-based algorithms, cutting the error rates in half and generalizing to taxonomic units distant from those presented during training. We propose a new approach for convolutional filter visualization to disentangle the information content of each nucleotide from its contribution to the final classification decision. Nucleotide-resolution maps of the learned associations between pathogen genomes and the infectious phenotype can be used to detect virulence-related genes in novel agents, as we show here for the SARS-CoV-2 coronavirus, unknown before it caused a COVID-19 pandemic in 2020.


title: Association energetics of membrane spanning α-helices

text: Since Popot and Engelman proposed the ‘two-stage’ thermodynamic framework for dissecting the energetics of helical membrane protein folding, scientists have endeavored to measure the free energies of helix–helix associations to better understand how interactions between helices stabilize and specify native membrane protein folds. Chief among the biophysical tools used to probe these energies are sedimentation equilibrium analytical ultracentrifugation, fluorescence resonance energy transfer, and thiol disulfide interchange experiments. Direct and indirect comparisons of thermodynamic results suggest that differences in helix–helix stabilities between micelles and bilayers may not be as large as previously anticipated. Genetic approaches continue to become more quantitative, and the propensities for helices to interact in bacterial membranes generally correlate well with in vitro measurements.


title: Nipah shell disorder, modes of infection, and virulence

text: Abstract The Nipah Virus (NiV) was first isolated during a 1998–9 outbreak in Malaysia. The outbreak initially infected farm pigs and then moved to humans from pigs with a case-fatality rate (CFR) of about 40%. After 2001, regular outbreaks occurred with higher CFRs (~71%, 2001–5, ~93%, 2008–12). The spread arose from drinking virus-laden palm date sap and human-to-human transmission. Intrinsic disorder analysis revealed strong correlation between the percentage of disorder in the N protein and CFR (Regression: r2 = 0.93, p < 0.01, ANOVA: p < 0.01). Distinct disorder and, therefore, genetic differences can be found in all three group of strains. The fact that the transmission modes of the Malaysia strain are different from those of the Bangladesh strains suggests that the correlations may also be linked to the modes of viral transmission. Analysis of the NiV and related viruses suggests links between modes of transmission and disorder of not just the N protein but, also, of M shell protein. The links among shell disorder, transmission modes, and virulence suggest mechanisms by which viruses are attenuated as they passed through different cell hosts from different animal species. These have implications for development of vaccines and epidemiological molecular analytical tools to contain outbreaks.


title: Development of a New Resequencing Pathogen Microarray Based Assay for Detection of Broad-Spectrum Respiratory Tract Viruses in Patients with Community-Acquired Pneumonia

text: A Resequencing Pathogen Microarray (RPM) is a single, highly multiplexed assay for detecting and differentiating similarly related pathogens by using closely overlapping probe sets to determine a target organism’s nucleotide sequence. In this study, a new RPM (RPM-IVDC1) that consisted of 224-bp detector tiles corresponding to 9 influenza A subtypes, 11 rhinoviruses, 28 enteroviruses and 38 other respiratory viruses was developed and optimized to provide individual and simultaneous detection sensitivities ranging from 15 to 750 genomic copies for 16 common respiratory pathogens. A total of 110 consecutive patients with community-acquired pneumonia (CAP) admitted to 5 district general hospitals in Beijing during a 1-year period were assessed using the new assay. Among the children (under age 5) and adult patients (above age 18), respiratory syncytial virus (RSV) and rhinovirus (RV) were the most common etiological agents, respectively, which is consistent with reference assays. Atypical pathogens that may cause CAP-like illness, including rubella virus, measles virus, influenza type C virus, human herpesvirus (HHV) were also detected. The results show the capability of RPM-IVDC1 for the accurate detection and identification of multiple virus types, which may be of significant use in epidemic surveillance and outbreak investigations of atypical pathogens.


title: Diagnosis and Management of Pneumonia in the Emergency Department

text: Pneumonia is a condition that is often treated by emergency physicians. This article reviews the diagnosis and management of pneumonia in the emergency department and highlights dilemmas in diagnostic testing, use of blood and sputum cultures, hospital admission decisions, infection control, quality measures for pneumonia care, and empiric antimicrobial therapy.


title: A Web Resource for Designing Subunit Vaccine Against Major Pathogenic Species of Bacteria

text: Evolution has led to the expansion of survival strategies in pathogens including bacteria and emergence of drug resistant strains proved to be a major global threat. Vaccination is a promising strategy to protect human population. Reverse vaccinology is a more robust vaccine development approach especially with the availability of large-scale sequencing data and rapidly dropping cost of the techniques for acquiring such data from various organisms. The present study implements an immunoinformatic approach for screening the possible antigenic proteins among various pathogenic bacteria to systemically arrive at epitope-based vaccine candidates against 14 pathogenic bacteria. Thousand four hundred and fifty nine virulence factors and Five hundred and forty six products of essential genes were appraised as target proteins to predict potential epitopes with potential to stimulate different arms of the immune system. To address the self-tolerance, self-epitopes were identified by mapping on 1000 human proteome and were removed. Our analysis revealed that 21proteins from 5 bacterial species were found as virulent as well as essential to their survival, proved to be most suitable vaccine target against these species. In addition to the prediction of MHC-II binders, B cell and T cell epitopes as well as adjuvants individually from proteins of all 14 bacterial species, a stringent criteria lead us to identify 252 unique epitopes, which are predicted to be T-cell epitopes, B-cell epitopes, MHC II binders and Vaccine Adjuvants. In order to provide service to scientific community, we developed a web server VacTarBac for designing of vaccines against above species of bacteria. This platform integrates a number of tools that includes visualization tools to present antigenicity/epitopes density on an antigenic sequence. These tools will help users to identify most promiscuous vaccine candidates in a pathogenic antigen. This server VacTarBac is available from URL (http://webs.iiitd.edu.in/raghava/vactarbac/).


title: The global effects of Covid-19-induced uncertainty()

text: We estimate a VAR with world-level variables to simulate the effects of the Covid-19 outbreak-related uncertainty shock. We find a peak (cumulative over one year) negative response of world output of 1.6% (14%).


Infectious diarrhoea in foals


title: THE COMMON COLD

text: The common cold has intrigued physicians and the general public for centuries. It has been defined as an acute epidemic respiratory disease characterized by mild coryzal symptoms of rhinorrhea, nasal obstruction, and sneezing. The nasal discharge is usually copious and thin during the first 2 days of illness, then it generally becomes more viscous and purulent. 22 The disease is self-limited. Symptoms may persist for 2 days to more than 14 days; however, the cold may abort after only 1 day. Fever, cough, sore throat, or lacrimation may or may not be present. The common cold is of itself harmless, but bacterial invasion frequently follows the initial infection. It is these secondary invaders that may produce disorders of serious consequence. The common cold is the most frequent acute illness in the United States and throughout the industrialized world. About half the population gets at least one cold every year. 5 Colds account for 40% of all time lost from jobs among employed people (23 million days of work per year) and about 30% of absenteeism from schools (26 million school days per year). Estimates vary, but the average preschool child has somewhere between 4 and 10 colds per year, and the average adult has about two to four colds per year. The actual cost of caring for patients with colds in US physicians' offices is estimated to be $1.5 billion annually. 64 Seasonal patterns of infection can be identified for some of the various types of viruses that are responsible for outbreaks of the common cold. For example, available epidemiologic data suggest early fall and late spring are the most common times to find more outbreaks of rhinovirus. Respiratory syncytial virus (RSV) tends to follow winter and spring incidence, with a peak number of cases found mainly in January. Parainfluenza types 1 and 2 seem to peak during the autumn, whereas parainfluenza type 3 has an increased incidence during the late spring. Adenoviruses and coronaviruses tend to produce epidemics during the winter and spring (Fig. 1) This article presents data concerning the cause, pathogenesis, and treatment of the common cold, as well as discussion of the available diagnostic tests and their use in formulating differential diagnoses.


docid: nkxojtvb

title: A Novel Pathogenic Mammalian Orthoreovirus from Diarrheic Pigs and Swine Blood Meal in the United States

text: Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S. swine industry, causing immense economic losses. Two different swine enteric coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been isolated from the affected swine population. The disease has been reported from at least 32 states of the United States and other countries, including Mexico, Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated outbreaks in previously infected herds. Here we report the isolation and characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces of piglets from these outbreaks in three states and ring-dried swine blood meal from multiple sources. MRV3 could not be isolated from healthy or pigs that had recovered from epidemic diarrhea from four states. Several MRV3 isolates were obtained from chloroform-extracted pig feces or blood meal in cell cultures or developing chicken embryos. Biological characterization of two representative isolates revealed trypsin resistance and thermostability at 90°C. NextGen sequencing of ultrapurified viruses indicated a strong homology of the S1 segment to mammalian and bat MRV3. Neonatal piglets experimentally infected with these viruses or a chloroform extract of swine blood meal developed severe diarrhea and acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore, the novel porcine MRV3 may contribute to enteric disease along with other swine enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic diarrhea in the United States remains to be determined, but the pathogenic nature of the virus warrants further investigations on its epidemiology and prevalence.


Abstract for the 8th International congress, Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases


title: A novel real-time RT-PCR assay for influenza C tested in Peruvian children

text: Abstract Background Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases. Objectives To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting. Study design Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences. Primers and probes were designed based on conserved regions. Multiple primer-probe sets were tested against multiple ICV strains. Results The ICV M and NP genes offered the most conserved sequence regions. Primers and probes based on newer sequence data offered enhanced detection of ICV, especially for low titer specimens. An NP-targeted assay yielded the best performance and was capable of detecting 10–100 RNA copies per reaction. The NP assay detected multiple clinical isolates of ICV collected in a field epidemiology study conducted in Peru. Conclusions We report a new real-time RT-PCR assay for ICV with high sensitivity and specificity.


title: ACE2: The Key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel?

text: Recently, the SARS-CoV-2 induced disease COVID-19 has spread all over the world. Nearly 20% of the patients have severe or critical conditions. SARS-CoV-2 exploits ACE2 for host cell entry. ACE2 plays an essential role in the renin–angiotensin–aldosterone system (RAAS), which regulates blood pressure and fluid balance. ACE2 also protects organs from inflammatory injuries and regulates intestinal functions. ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs. SARS-CoV-2 infection-caused ACE2 dysfunction worsens COVID-19 and could initiate multi-organ failure. Here, we will explain the role of ACE2 in the pathogenesis of severe and critical conditions of COVID-19 and discuss auspicious strategies for controlling the disease.


title: Opening the discussion on a closed intubation box

text: Abstract Background Airway management for patients with COVID-19 poses a significant infection risk to clinicians. As such, some providers have adopted the "COVID intubation box", a cuboid barrier which which separates the clinician from the airway. While this device has limitations, there is promising evidence on its effectiveness. Aim To summarize the history, evidence, and limitations of the popular intubation box design. Furthermore, we share our modified design and experiences from airway simulations. Methods Using our prototyping and validation facilities, our team designed and iteratively improved our device to arrive at a final design. The expert panel, consisting of anesthesiologists, infection control staff, and emergency clinicians, trialed the device using airway simulation mannequins and provided feedback. Results Our final device features a dome shape, increased height, wider arm port diameter, additional side port for assistants, and drapes to reduce viral escape. Feedback from simulations was overall positive, especially noting that the height and arm port diameter facilitated arm motion within the box. The infection control team preferred the unique dome shape for safe disinfection. Conclusion Our intubation box overcomes several challenges and criticisms of the popular intubation box. This device is an important harm reduction tool for clinicians during this COVID-19 pandemic.


title: Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut

text: Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined. Here, we used mini-gut organoids to define the functions of types I and III IFNs to protect the human gut against viral infection. We show that primary non-transformed human IECs, upon viral challenge, upregulate the expression of both type I and type III IFNs at the transcriptional level but only secrete type III IFN in the supernatant. However, human IECs respond to both type I and type III IFNs by producing IFN-stimulated genes that in turn induce an antiviral state. Using genetic ablation of either type I or type III IFN receptors, we show that either IFN can independently restrict virus infection in human IECs. Importantly, we report, for the first time, differences in the mechanisms by which each IFN establishes the antiviral state. Contrary to type I IFN, the antiviral activity induced by type III IFN is strongly dependent on the mitogen-activated protein kinases signaling pathway, suggesting a pathway used by type III IFNs that non-redundantly contributes to the antiviral state. In conclusion, we demonstrate that human intestinal epithelial cells specifically regulate their innate immune response favoring type III IFN-mediated signaling, which allows for efficient protection against pathogens without producing excessive inflammation. Our results strongly suggest that type III IFN constitutes the frontline of antiviral response in the human gut. We propose that mucosal surfaces, particularly the gastrointestinal tract, have evolved to favor type III IFN-mediated response to pathogen infections as it allows for spatial segregation of signaling and moderate production of inflammatory signals which we propose are key to maintain gut homeostasis.


title: COVID-19 infection and rheumatoid arthritis: Faraway, so close!

text: Abstract The outbreak of the new coronavirus infections COVID-19 in December 2019 in China has quickly become a global health emergency. Given the lack of specific anti-viral therapies, the current management of severe acute respiratory syndrome coronaviruses (SARS-CoV-2) is mainly supportive, even though several compounds are now under investigation for the treatment of this life-threatening disease. COVID-19 pandemic is certainly conditioning the treatment strategy of a complex disorder as rheumatoid arthritis (RA), whose infectious risk is increased compared to the general population because of an overall impairment of immune system typical of autoimmune diseases combined with the iatrogenic effect generated by corticosteroids and immunosuppressive drugs. However, the increasing knowledge about the pathophysiology of SARS-CoV-2 infection is leading to consider some anti-rheumatic drugs as potential treatment options for the management of COVID-19. In this review we will critically analyse the evidences on either positive or negative effect of drugs commonly used to treat RA in this particular scenario, in order to optimize the current approach to RA patients.