title: Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

text: Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.


Remdesivir bei Patienten mit schwerer COVID-19


docid: sntawlnf

title: COVID‐19 and diabetes: Is there enough evidence?

text: The pandemic of COVID‐19, a disease caused by a novel coronavirus SARS‐CoV‐2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID‐19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID‐19 patients. There is only limited amount of data regarding follow‐up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID‐19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID‐19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID‐19 and its role in outcome in these patients.


Screening of respiratory virus PCR panel in adults with CNS infection


title: Clinical Characteristics of Hospitalized Covid-19 Patients in New York City

text: ABSTRACT Background: The coronavirus 2019 (Covid-19) pandemic is a global public health crisis, with over 1.6 million cases and 95,000 deaths worldwide. Data are needed regarding the clinical course of hospitalized patients, particularly in the United States. Methods Demographic, clinical, and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed Covid-19 between February 27 and April 2, 2020 were identified through institutional electronic health records. We conducted a descriptive study of patients who had in-hospital mortality or were discharged alive. Results A total of 2,199 patients with Covid-19 were hospitalized during the study period. As of April 2nd, 1,121 (51%) patients remained hospitalized, and 1,078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 ug/ml, C-reactive protein was 162 mg/L, and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 ug/ml, C-reactive protein was 79 mg/L, and procalcitonin was 0.09 ng/mL. Conclusions This is the largest and most diverse case series of hospitalized patients with Covid-19 in the United States to date. Requirement of intensive care and mortality were high. Patients who died typically had pre-existing conditions and severe perturbations in inflammatory markers.


docid: vatfdilt

title: Encephalomalacic Lesions in Pigs Dually Infected with Porcine Reproductive and Respiratory Syndrome Virus and Pseudorabies Virus

text: Abstract Four pigs (group 1) were infected with an aerosol containing porcine reproductive and respiratory syndrome virus (PRRSV) followed 7 days later by pseudorabies virus (PRV). Three further pigs (group 2) received PRRSV alone, two (group 3) received PRV alone, and two (group 4) remained as uninfected controls. Despite the admittedly small numbers of animals, the experiment appeared to throw light on aspects of synergy. Thus, the group 1 pigs showed severe neurological signs characterized by ataxia and muscular tremors. Total cell numbers in the bronchoalveolar lavage fluid were increased in all PRRSV-infected pigs, and PRRSV antigen was detected in the alveolar macrophages. Total cell numbers in the cerebrospinal fluid of group 1 pigs were considerably greater than those demonstrated in group 3, but no PRV antigen was found. Pigs of groups 1 and 2 showed pulmonary lesions, characterized by interstitial pneumonia and PRRSV antigen immunolabelling. Non-suppurative encephalitis was found in five of the six pigs of groups 1 and 3. In particular, one group 1 animal had severe necrotizing encephalitis with intranuclear inclusion bodies and associated immunolabelling of PRV antigen. The other three group 1 pigs had prominent malacic lesions, with macrophages. These neuropathological findings strongly suggested that PRRSV infection in pigs enhances the severity of brain lesions caused PRV.


docid: tkbliabh

title: The detection of influenza A and B viruses in clinical specimens using a quartz crystal microbalance

text: Abstract Current methods for the accurate diagnosis of influenza based on culture of the virus or PCR are highly sensitive and specific but require specialised laboratory facilities and highly trained personnel and, in the case of viral culture, can take up to 14 days to obtain a definitive result. In this study, a quartz crystal microbalance-based immunosensor (QCM) has been developed and its potential evaluated for the rapid and sensitive detection of both influenza A and B viruses in laboratory-cultured preparations and clinical samples. The effective limit for detection by QCM for stock preparations of both A/PR/8/34 and B/Lee/40 viruses was 1×104 pfu/mL, associated with observed frequency shifts of 30 (±5) and 37 (±6.5)Hz, respectively. Conjugation of 13nm gold nanoparticles to the detecting antibody improved the mass sensitivity of the immunosensor, resulting in a 10-fold increase in sensitivity and a detection limit of 1×103 pfu/mL for both preparations, with resulting frequency shifts of 102 (±11) and 115 (±5)Hz, respectively. Detection of virus in nasal washes with this technique was achieved by overnight passage in MDCK cultures prior to analysis. A comparison of results obtained from 67 clinical samples using existing RT-PCR, shell vial, cell culture and ELISA methods showed that QCM techniques were comparable in sensitivity and specificity to cell culture methods.


title: Protecting Labor and Delivery Personnel from COVID-19 during the Second Stage of Labor

text: The novel coronavirus disease 2019 (COVID-19) is spreading fast and is affecting the clinical workers at much higher risk than the general population. Little is known about COVID-19 effect on pregnant women; however, the emerging evidence suggests they may be at high risk of asymptomatic disease. In light of projected shortage of personal protective equipment (PPE), there is an aggressive attempt at conservation. In obstetrics, the guidelines on PPE use are controversial and differ among hospitals, globally, as well as nationally. The centers for disease control and prevention (CDC) recommend using N95 respirators, which are respirators that offer a higher level of protection instead of a facemask for when performing or present for an aerosol-generating procedures (AGP). However, the second stage of labor is not considered an AGP. The second stage of labor can last up to 4 hours. During that time, labor and delivery personnel is in close contact to patients, who are exerting extreme effort during and frequently blow out their breath, cough, shout, and vomit, all of which put the health care team at risk, considering that COVID-19 transmission occurs through aerosol generated by coughing and sneezing. The CDC and the American College of Obstetricians and Gynecologists (ACOG) do not provide clarification on the use of N95 during the second stage. We recommend that labor and delivery personnel have the utmost caution and be granted the protection they need to protect themselves and other patients. This includes providing labor and delivery personnel full PPE including N95 for the second stage of labor. This is critical to ensure the adequate protection for health care workers and to prevent spread to other health care workers and patients. Key Points: Second stage of labor exposes providers to aerosol. COVID-19 risk during second stage of labor is high. N95 should be used during second stage of labor.


title: Infectious disease and red wolf conservation: assessment of disease occurrence and associated risks

text: Infectious diseases pose a significant threat to global biodiversity and may contribute to extinction. As such, establishing baseline disease prevalence in vulnerable species where disease could affect persistence is important to conservation. We assessed potential disease threats to endangered red wolves (Canis rufus) by evaluating regional (southeastern United States) disease occurrences in mammals and parasite prevalence in red wolves and sympatric coyotes (Canis latrans) in North Carolina. Common viral pathogens in the southeast region, such as canine distemper and canine parvovirus, and numerous widespread endoparasites could pose a threat to the red wolf population. The most prevalent parasites in red wolves and sympatric coyotes were heartworm (Dirofilaria immitis), hookworm (Ancylostoma caninum), and Ehrlichia spp.; several red wolves and coyotes were also positive for bacteria causing Lyme disease (Borrelia burgdorferi). Coyotes had a more species-rich parasite community than red wolves, suggesting they could harbor more parasites and act as a disease reservoir. Species identity and sex did not significantly affect parasite loads, but young canids were less likely to have heartworm and more likely to have high levels of endoparasites. Continued disease monitoring is important for red wolf recovery because low levels of genetic variability may compromise the wolves’ abilities to combat novel pathogens from closely related species, such as domestic dogs and coyotes.


title: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)?

text: Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript. Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded. Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented. Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes. Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.


title: Multiprotein Complex Production in Insect Cells by Using Polyproteins

text: A powerful approach utilizing polyproteins for balancing stoichiometry of recombinant multiprotein complexes overproduced in baculovirus expression vector systems (BEVS) is described. This procedure has been implemented here in the MultiBac system but can also be directly adapted to all commonly used BEVS. The protocol details the design principles of polyprotein-expressing DNA constructs, the generation of composite baculovirus for polyprotein production, and the expression and in vivo processing of polyproteins in baculovirus infected insect cells.


title: Avian influenza, migratory birds and emerging zoonoses: Unusual viral RNA, enteropathogens and Cryptosporidium in poultry litter

text: Abstract The last decade has witnessed the emergence of several new viral infectious agents, most notably avian influenza H5N1, SARS and West Nile Virus. The emergence of these agents is heavily associated with zonotic animal hosts, as well as migratory pathways of infected bird vectors. The environmental survival and persistence of nucleic acid associated with these viral agents may be important for both the detection as well as the occurrence of related diseases. Our hypothesis suggests that nucleic acid from such emerging viruses may enter into a virus-parasite surrogate relationship to aid in viral persistence. We suggest that Cryptosporidium and other gastrointestinal parasites, including Giardia, could be a) a reservoir of genetic material and a environment where assortment between that genetic variation can occur and, b) a source of zoonoses through infection of the ‘target’ animal (including humans). One example which illustrates this may be the uptake dsRNA from rotavirus into cryptosporidial oocysts, as this parasite has previously been shown to contain dsRNA viral-like particles. The importance of such a surrogate relationship is discussed and its implications for human and animal health highlighted.


title: 10 Infectious Disease Genomics

text: During the past 20 years, the history and development of infectious disease genomics are tightly associated with the Human Genome Project (HGP). It has been emphasized since the beginning of the HGP that such effort must not be restricted to the human genome and should include other organisms including mouse, bacteria, yeast, fruit fly, and worm for comparative sequence analyses. A brief history is reviewed in this chapter. Currently, nearly 6000 genome sequencing projects have been reported. The majority of the more than 1000 completed genomes are bacterial sequences (>80%). An important motivation for these efforts is to develop preventative, diagnostic, and therapeutic strategies through the analysis of sequenced microorganisms, parasites, and vectors related to human health. A few examples are discussed in this chapter.


title: Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles

text: BACKGROUND: The hierarchical clustering tree (HCT) with a dendrogram [1] and the singular value decomposition (SVD) with a dimension-reduced representative map [2] are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures. RESULTS: This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose) seriation by Chen [3] as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends. CONCLUSION: We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at .


title: Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy

text: Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug–drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART.


title: Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells

text: BACKGROUND: Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. METHODS: Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. RESULTS: Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. CONCLUSIONS: At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells.


title: Gene-centric metagenomics analysis of feline intestinal microbiome using 454 junior pyrosequencing

text: Abstract The feline gastrointestinal microbiota have direct influence on feline health and also human health as a reservoir for potential zoonotic pathogens and antibiotic resistant bacterial strains. In order to describe the feline gastrointestinal microbial diversity, fecal samples from cats have been characterized using both culture-dependent and culture-independent methods. However, data correlating total microbial composition and their functions are lacking. Present descriptive study evaluated both phylogenetic and metabolic diversity of the feline intestinal microbiota using GS Junior titanium shotgun pyrosequencing. A total of 152,494 pyrosequencing reads (5405 assembled contigs) were generated and classified into both phylogenetic and metabolic profiles of the feline intestinal microbiota. The Bacteroides/Chlorobi group was the most predominant bacterial phylum comprising ~68% of total classified diversity, followed by Firmicutes (~13%) and Proteobacteria (~6%) respectively. Archaea, fungi and viruses made up the minor communities in the overall microbial diversity. Interestingly, this study also identified a range of potential enteric zoonotic pathogens (0.02–1.25%) and genes involved in antimicrobial resistance (0.02–0.7%) in feline fecal materials. Based on clustering among nine gastrointestinal metagenomes from five different monogastric hosts (dog, human, mice, cat and chicken), the cat metagenome clustered closely together with chicken in both phylogenetic and metabolic level (>80%). Future studies are required to provide deeper understandings on both intrinsic and extrinsic effects such as impact of age, genetics and dietary interventions on the composition of the feline gastrointestinal microbiome.


title: Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases

text: Exosomes are 40–100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may impact the fields of nephrology and renal physiology in the next few years.


title: Joint External Evaluation—Development and Scale-Up of Global Multisectoral Health Capacity Evaluation Process

text: The Joint External Evaluation (JEE), a consolidation of the World Health Organization (WHO) International Health Regulations 2005 (IHR 2005) Monitoring and Evaluation Framework and the Global Health Security Agenda country assessment tool, is an objective, voluntary, independent peer-to-peer multisectoral assessment of a country’s health security preparedness and response capacity across 19 IHR technical areas. WHO approved the standardized JEE tool in February 2016. The JEE process is wholly transparent; countries request a JEE and are encouraged to make its findings public. Donors (e.g., member states, public and private partners, and other public health institutions) can support countries in addressing identified JEE gaps, and implementing country-led national action plans for health security. Through July 2017, 52 JEEs were completed, and 25 more countries were scheduled across WHO’s 6 regions. JEEs facilitate progress toward IHR 2005 implementation, thereby building trust and mutual accountability among countries to detect and respond to public health threats.


title: Ophthalmologische Betreuung von stationären, intensivpflichtigen SARS-CoV-2-positiven Patienten

text: Early ophthalmological care of patients in intensive care with SARS-CoV‑2 (Severe-Acute-Respiratory-Syndrom-Corona-Virus-2) infections is very time-consuming; however, this approach might prevent other ophthalmological diseases, such as lagophthalmos. There is no difference in ophthalmological treatment between SARS-CoV‑2 positive and other intensive care patients. Due to the small number of cases in our observational study, a specific ophthalmological clinical pattern related to SARS-CoV‑2 infections cannot currently be identified; however, the increased occurrence of subconjunctival hemorrhage in intensive care SARS-CoV‑2 patients is remarkable. It remains unclear how ocular symptoms in SARS-CoV‑2 infections are related or how they occur in different stages of the disease. Therefore, further studies are necessary for representative statements.


title: Keeping up with the information explosion: a surge in consumption of data on pediatric SARS-CoV-2 infection by pediatric emergency physicians

text: PEM-Database.org is an unaffiliated, not-for-profit website, dedicated to the field’s advancement of pediatric emergency medicine. PEM-Database published the first early access pediatric-related SARS-CoV-2 articles on March 13th, two days following the World Health Organization’s declaration of a global pandemic. Over the following 2 weeks, the number of PEM-Database entries increased dramatically. This surge expresses interest by pediatric emergency medicine physicians in data on pediatric SARS-CoV-2 infection.


title: Viral Reproductive Pathogens of Dogs and Cats

text: This article reviews the current literature on the viral agents that cause reproductive failures in domestic carnivores (dogs and cats). A meaningful update is provided on the etiologic, clinical, pathologic, diagnostic, and prophylactic aspects of the viral infections impacting canine and feline reproduction as a consequence of either direct virus replication or severe debilitation of pregnant animals.


title: Treatment of SARS with human interferons

text: Effective antiviral agents are needed to treat severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. We assessed the antiviral potential of recombinant interferons against two clinical isolates of SARS-CoV—FFM-1, from Frankfurt patients, and Hong Kong—replicated in Vero and Caco2 cells. Interferon β was five to ten times more effective in Caco2 cells. Interferon α effectively inhibited SARS-CoV replication, but with a selectivity index 50–90 times lower than that for interferon β. Interferon γ was slightly better than interferon α in Vero cell cultures, but was completely ineffective in Caco2 cell cultures. Interferon β could be useful alone or in combination with other antiviral drugs for the treatment of SARS.


title: Point-of-care lung ultrasound in three neonates with COVID-19

text: Since March 2020, the world is involved in the COVID-19 pandemic, a disease caused by a novel virus called SARS-CoV-2. Some authors have described the ultrasonographic findings of COVID-19 pneumonia in adults and children, but data on neonates are lacking. Our objective was to describe the ultrasonographic lung pattern on newborns with SARS-CoV-2 infection during the COVID-19 pandemic. Newborns who tested positive for SARS-CoV-2 PCR in respiratory samples and were evaluated with point-of-care lung ultrasound (LU) from March to April 2020 were included. LU was performed bedside by a single investigator at the time of diagnosis and every 48 h during the first week following diagnosis. Six areas were studied. Three neonates were included. Infants’ comorbidities included meconium aspiration syndrome, bronchopulmonary dysplasia, and Hirschsprung’s disease. One required mechanical ventilation. No deaths occurred. LU showed B-lines, consolidation, and spared areas. No pneumothorax or pleural effusion was observed Conclusions: LU could be of value when managing COVID-19 neonates. We describe the findings of lung ultrasound monitoring during the first week following diagnosis in three neonates with SARS-CoV-2 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03706-4) contains supplementary material, which is available to authorized users.


title: ARIMA and NAR based Prediction Model for Time Series Analysis of COVID-19 cases in India

text: Abstract In this paper, we have applied the univariate time series model to predict the number of COVID-19 infected cases that can be expected in upcoming days in India. We adopted an Auto-Regressive Integrated Moving Average (ARIMA) model on the data collected from 31st January 2020 to 25th March 2020 and verified it using the data collected from 26th March 2020 to 04th April 2020. A nonlinear autoregressive (NAR) neural network is developed to compare the accuracy of predicted models. The model has been used for daily prediction of COVID-19 cases for next 50 days without any additional intervention. Statistics from various sources, including the Ministry of Health and Family Welfare (MoHFW) and http://covid19india.org/ are used for the study. The results showed an increasing trend in the actual and forecasted numbers of COVID-19 cases with approximately 1500 cases per day, based on available data as on 04th April 2020. The appropriate ARIMA (1,1,0) model was selected based on the Bayesian Information Criteria (BIC) values and the overall highest R2 values of 0.95. The NAR model architecture constitutes ten neurons, which is optimized using the Levenberg-Marquardt optimization training algorithm (LM) with the overall highest R2 values of 0.97.


docid: ujaqutrg

title: “Impact of the COVID-19 pandemic on Gastroenterology Divisions in Italy: a national survey”

text: BACKGROUND: In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. AIMS: to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. CONCLUSION: This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.


Meeting Report VLPNPV: Session 10: Rapid total particle quantification


title: Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO

text: BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,…) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed – the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(−4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 ± 0.34 vs. 6.44 ± 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1787-5) contains supplementary material, which is available to authorized users.


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

text: The article cited does not differentiate between Type I and Type II diabetes. More information is needed to properly assess risk.


title: An independent endocytic pathway stimulates different monocyte subsets by the a2 N-terminus domain of vacuolar-ATPase

text: The vacuolar ATPase (V-ATPase) plays an important role in tumor progression and metastases. A novel peptide from the a2 isoform of V-ATPase called a2NTD has been shown to exert an immunoregulatory role in the tumor microenvironment by controlling the maturation of monocytes toward a tumor-associated macrophage phenotype. Our data indicate that a2NTD binds to the surface of monocytes. a2NTD was preferentially endocytosed by pro-inflammatory monocytes bearing a CD14(++)CD16(+) phenotype, which is associated with the monocyte-to-macrophage maturation process. Both a2NTD binding and internalization led to production of the pro-inflammatory cytokines interleukin (IL)-1α and IL-1β by CD14(++)CD16(-) (classical) and CD14(++)CD16(+ )(intermediate) monocytes. a2NTD was internalized via a macropinocytosis mechanism utilizing scavenger receptors. However, the inhibition of a2NTD endocytosis did not reduce cytokine production by monocytes. This points to the existence of two receptors that respond to a2NTD: scavengers receptors that mediate cellular uptake and an hitherto unidentified receptor stimulating the production of inflammatory cytokines. Both of these monocyte receptors may be important in generating the localized inflammation that is often required to promote tumor growth and hence may constitute novel targets for the development of anticancer drugs.


Cardio-Oncology in Brazil: The Dimensions of a New Era in the Care of Patients


title: Predictions for Europe for the Covid-19 pandemic from a SIR model

text: We develop and apply a simplified SIR model to current data for the 2019–2020 SARS-Cov-2/Covid-19 pandemic for the United Kingdom (UK) and eight European countries: Norway, Sweden, Denmark, the Netherlands, France, Germany, Italy and Spain. The most important result of the model was the identification and segregation of pandemic characteristics into two distinct groups: those that are invariant across countries, and those that are highly variable. Amongst the former is the infective period T(L), which was very similar for all countries, with an average value of [Formula: see text] days. The other invariants were T(R), the average time between contacts and R = N(C), the average number of contacts while infective. We find [Formula: see text] days and [Formula: see text]. In contrast to these invariants, there was a highly variable time lag T(D) between the peak in the daily number of infected individuals and the peak in the daily number of deaths, ranging from a low of T(D) = 4 days for Italy and Denmark, to a high of T(D) = 17 for Norway. The mortality probability among identified cases was also highly variable, ranging from low values 3.5%, 5% and 5% for Norway, Denmark and Germany respectively to high values of 18%, 18% and 20% for France, Sweden and the UK respectively. Our analysis predicts that the number of deaths per million population until the pandemic ends (defined as when the daily number of deaths is less than 5) will be lowest for Norway (45 deaths/million) and highest for the United Kingdom (628 deaths/million). Finally, we observe a small but detectable effect of average temperature on the probability α of infection in each contact, with higher temperatures associated with lower infectivity.


title: Risk factors for disease progression in COVID-19 patients

text: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10–20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 °C, findings of pneumonia in chest X-ray, or diabetes.


title: Yellow head‐like viruses affecting the penaeid aquaculture industry: a review

text: This review focuses on relevant scientific information regarding the current knowledge of the yellow head complex viruses, yellow head virus and gill‐associated virus. The yellow head complex viruses have been problematic within the aquaculture industry for over 10 years and still retain their research topicality. Presently, there are numerous research papers from different journals covering the identification, disease expression and spread, pathogenesis, detection, morphology, genomic sequence and protein profiles of the yellow head complex viruses. Indeed, there has been no extensive review to compare these studies, and as a corollary, to assess flaws in contemporary research and knowledge. Additionally, the yellow head complex viruses rank within the top four prawn viruses with respect to disease impact and economic loss. This review collectively reports on all the findings and current methods of research and aims to identify weak areas of research where conclusions have been unjustifiably drawn and furthermore to elucidate areas that have a gap of knowledge.


title: Predicting stock returns in the presence of COVID-19 pandemic: The role of health news

text: Abstract This study derives its motivation from the current global pandemic, COVID-19, to evaluate the relevance of health-news trends in the predictability of stock returns. We demonstrate this using data for of top-20 affected countries, separately in terms of most cases and most deaths reporting countries. The results reveal that the model that incorporates health-news index outperforms the benchmark historical average model, indicating the significance of health news searches as a good predictor of stock returns since the emergence of the pandemic. We also find that accounting for “asymmetry” effect, adjusting for macroeconomic factors and incorporating financial news improves the forecast performance. These results are consistently robust to data sample, both in the in-sample and out-of-sample forecast periods, outliers and heterogeneity.


title: The Institutionalisation of Digital Public Health: Lessons Learned from the COVID-19 App

text: Amid the outbreak of the SARS-CoV-2 pandemic, there has been a call to use innovative digital tools for the purpose of protecting public health. There are a number of proposals to embed digital solutions into the regulatory strategies adopted by public authorities to control the spread of the coronavirus more effectively. They range from algorithms to detect population movements by using telecommunications data to the use of artificial intelligence and high-performance computing power to detect patterns in the spread of the virus. However, the use of a mobile phone application for contact tracing is certainly the most popular.


title: Why Are Children With Bronchiolitis At Risk Of Urinary Tract Infections?

text: Viral respiratory infections are frequently eliminated from human bodies without any sequelae. Secondary serious bacterial infection (SBI) in children with acute bronchiolitis has been an apprehension expressed by health care providers. Several published studies have shown an association between acute bronchiolitis and secondary bacterial infection, including urinary tract infections (UTI). However, the proposed mechanism by which a virus can induce UTIs is not yet known. The aim of this commentary is to update the current evidence of risk of UTI in children with bronchiolitis. We present several clinical studies related to the topic as well as a brief review of the potential pathophysiology of secondary infections that could present with viral respiratory illness.


The value of public agricultural and food knowledge during pandemics


Obesity and risk of COVID-19: analysis of UK Biobank


Chapter 86 Ocular Mucosal Immunity


Covid-19: UK ramps up testing by 500% as health minister tests positive for virus.


MERS Vaccine Candidate Offers Promise, but Questions Remain


title: Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea

text: Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.


title: Recent advances in the discovery and delivery of vaccine adjuvants

text: Adjuvant design has historically had a touch of alchemy at its heart due to its reliance on the complex biology of innate immune activation. However, a new mechanistic understanding of innate immunity, combined with new adjuvant and delivery platforms for exploiting this knowledge, has led to significant advances recently. Although many challenges remain, the field is moving rapidly and the proper tools and methodologies are in place for the use of traditional drug discovery engines in guiding the development of vaccine adjuvants. In this review, we outline the current trends in immune potentiator, delivery system and adjuvant design that will shape the vaccines of the future.


title: The mixed trunsored model with applications to SARS

text: Abstract The trunsored model, which is a new incomplete data model regarded as a unified model of the censored and truncated models in lifetime analysis, can not only estimate the ratio of the fragile population to the mixed fragile and durable populations or the cured and fatal mixed populations, but also test a hypothesis that the ratio is equal to a prescribed value with ease. Since SARS showed a severe case fatality ratio, our concern is to know such a case fatality ratio as soon as possible after a similar outbreak begins. The epidemiological determinants of spread of SARS can be dealt with as the probabilistic growth curve models, and the parameter estimation procedure for the probabilistic growth curve models may similarly be treated as the lifetime analysis. Thus, we try to do the parameter estimation to the SARS cases for the infected cases, fatal cases, and cured cases here, as we usually do it in the lifetime analysis. Using the truncated data models to the infected and fatal cases with some censoring time, we may estimate the total (or final) numbers of the patients and deaths, and the case fatality ratio may be estimated by these two numbers. We may also estimate the case fatality ratio using the numbers of the patients and recoveries, but this estimate differs from that using the numbers of the patients and deaths, especially when the censoring time is located at early stages. To circumvent this inconsistency, we propose a mixed trunsored model, an extension of the trunsored model, which can use the data of the patients, deaths, and recoveries simultaneously. The estimate of the case fatality ratio and its confidence interval are easily obtained in a numerical sense. This paper mainly treats the case in Hong Kong. The estimated epidemiological determinants of spread of SARS, fitted to the infected, fatal, and cured cases in Hong Kong, could be the logistic distribution function among the logistic, log-normal, gamma, and Weibull models. Using the proposed method, it would be appropriate that the SARS case fatality ratio is roughly estimated to be 17% in Hong Kong. Worldwide, it is roughly estimated to be about 12–18%, if we consider the safety side without the Chinese case. Unlike the questionably small confidence intervals for the case fatality ratio using the truncated models, the case fatality ratio in the proposed model provides a reasonable confidence interval.


A Canadian Response to the COVID-19 Pandemic: Is there a Silver Lining for Radiation Oncology Patients?


title: Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses

text: BACKGROUND: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. RESULTS: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. CONCLUSION: This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses.


title: Characterization of the frameshift signal of Edr, a mammalian example of programmed −1 ribosomal frameshifting

text: The ribosomal frameshifting signal of the mouse embryonal carcinoma differentiation regulated (Edr) gene represents the sole documented example of programmed −1 frameshifting in mammalian cellular genes [Shigemoto,K., Brennan,J., Walls,E,. Watson,C.J., Stott,D., Rigby,P.W. and Reith,A.D. (2001), Nucleic Acids Res., 29, 4079–4088]. Here, we have employed site-directed mutagenesis and RNA structure probing to characterize the Edr signal. We began by confirming the functionality and magnitude of the signal and the role of a GGGAAAC motif as the slippery sequence. Subsequently, we derived a model of the Edr stimulatory RNA and assessed its similarity to those stimulatory RNAs found at viral frameshift sites. We found that the structure is an RNA pseudoknot possessing features typical of retroviral frameshifter pseudoknots. From these experiments, we conclude that the Edr signal and by inference, the human orthologue PEG10, do not represent a novel ‘cellular class’ of programmed −1 ribosomal frameshift signal, but rather are similar to viral examples, albeit with some interesting features. The similarity to viral frameshift signals may complicate the design of antiviral therapies that target the frameshift process.


title: Estimating Survival of Hospitalized COVID-19 Patients from Admission Information

text: Background While clinical characteristics and a range of mortality risk factors of COVID-19 patients have been reported, a practical early clinical survival calculator specialized for the unique cohort of patients has not yet been introduced. Such a tool would provide timely and valuable guidance in clinical care decision-making during this global pandemic. Methods Demographic, laboratory, clinical, and treatment data (from 13 acute care facilities at Northwell Health) were extracted from electronic medical records and used to build and test the predictive accuracy of a survival probability calculator-the Northwell COVID-19 Survival (NOCOS) calculator-for hospitalized COVID-19 patients. The NOCOS calculator was constructed using multivariate regression with L1 regularization (LASSO). Model predictive performance was measured using Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) of the calculators tested. Results A total of 5,233 inpatients were included in the study. Patient age, serum blood urea nitrogen (BUN), Emergency Severity Index (ESI), red cell distribution width (RCDW), absolute neutrophil count, serum bicarbonate, and glucose were identified as the optimal early predictors of survival by multivariate LASSO regression. The predictive performance of the Northwell COVID-19 Survival (NOCOS) calculator was assessed for 14 consecutive days. Conclusions We present a rapidly developed and deployed estimate of survival probability that outperforms other general risk models. The 7 early predictors of in-hospital survival can help clinicians identify patients with increased probabilities of survival and provide critical decision support.


title: Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes

text: Host species-specific fitness landscapes largely determine the outcome of host switching during pathogen emergence. Using chikungunya virus (CHIKV) to study adaptation to a mosquito vector, we evaluated mutations associated with recently evolved sub-lineages. Multiple Aedes albopictus-adaptive fitness peaks became available after CHIKV acquired an initial adaptive (E1-A226V) substitution, permitting rapid lineage diversification observed in nature. All second-step mutations involved replacements by glutamine or glutamic acid of E2 glycoprotein amino acids in the acid-sensitive region, providing a framework to anticipate additional A. albopictus-adaptive mutations. The combination of second-step adaptive mutations into a single, ‘super-adaptive’ fitness peak also predicted the future emergence of CHIKV strains with even greater transmission efficiency in some current regions of endemic circulation, followed by their likely global spread. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms5084) contains supplementary material, which is available to authorized users.


title: Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

text: BACKGROUND: Although sexual reproduction of the parasite Toxoplasma gondii exclusively occurs in the cat intestine, knowledge about the alteration of gene expression in the intestine of cats infected with T. gondii is still limited. Here, we investigated the temporal transcriptional changes that occur in the cat intestine during T. gondii infection. METHODS: Cats were infected with 100 T. gondii cysts and their intestines were collected at 6, 12, 18, 24, 72 and 96 hours post-infection (hpi). RNA sequencing (RNA-Seq) Illumina technology was used to gain insight into the spectrum of genes that are differentially expressed due to infection. Quantitative RT-PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing. RESULTS: Our transcriptome analysis revealed 2363 DEGs that were clustered into six unique patterns of gene expression across all the time points after infection. Our analysis revealed 56, 184, 404, 508, 400 and 811 DEGs in infected intestines compared to uninfected controls at 6, 12, 18, 24, 72 and 96 hpi, respectively. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in catalytic activity and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the intestine of infected cats evolve over the course of infection, and the largest difference in the enriched pathways was observed at 96 hpi. The anti-T. gondii defense response of the feline host was mediated by Major Histocompatibility Complex class I, proteasomes, heat-shock proteins and fatty acid binding proteins. CONCLUSIONS: This study revealed novel host factors, which may be critical for the successful establishment of an intracellular niche during T. gondii infection in the definitive feline host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-3179-8) contains supplementary material, which is available to authorized users.


title: Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2

text: Summary The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 μg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.


title: Coordinated Implementation of Chikungunya Virus Reverse Transcription–PCR

text: A preformulated chikungunya virus real-time reverse transcription–PCR, quality-confirmed oligonucleotides, and noninfectious virus controls were distributed by the European Network for the Diagnosis of Imported Viral Diseases. An international proficiency study with 31 participants demonstrated that ad hoc implementation of molecular diagnostics was feasible and successful.


title: Spread of COVID-19 from Wuhan to rural villages in the Hubei Province

text: This study aimed to describe the spread of coronavirus disease 2019 (COVID-19) from Wuhan to rural villages in the Hubei Province. The analysis revealed the following: 1) COVID-19 spread from Wuhan to other cities and rural areas in Hubei, but the disease did not become widespread in rural villages because of strict prevention measures and urbanization; 2) According to the fluctuation in the number of confirmed cases reported in Hubei after January 23, 2020, we inferred that the infected patients on the same day will become ill during the next 20 days; 3) the advanced traffic system facilitates the direct spread of COVID-19 from Wuhan to counties, towns, and villages in the Hubei Province. There is a low possibility of COVID-19 spread from prefecture-level cities to rural areas. The findings imply that the government should limit the travelers from the cities to the rural areas, pay more attention to the prevention and control of SARS-CoV-2 in cities, and appropriately prolong the isolated observation period of travelers.


title: Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic

text: BACKGROUND: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. METHODS: We estimated the CFR of medically attended influenza (CFR(MA)) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009–2011) and post-pandemic (2012–2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFR(AR)). RESULTS: During the pandemic period, 5.0% (3.1%–6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%–12.6%) died. CFR(MA) for pH1N1 was 0.4% (0.2%–0.6%) in the pandemic period 2009–2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012–2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFR(AR) to be 0.025%, 16-fold lower than CFR(MA). CONCLUSIONS: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. CLINICAL TRIALS REGISTRATION: NCT01056354 and NCT010561.


title: Social Media can have an impact on how we manage and investigate the COVID-19 pandemic

text: • In situations of emergencies and urgencies, such as the COVID-19 pandemic, many are disseminating information through social media channels; this have an impact on billions of persons worldwide. • Misinformation about the current pandemic occurs frequently in these platforms and can have serious consequences. • When properly used, social media can be a useful tool that provides opportunities to disseminate and receive relevant information for patients, clinicians and scientists. • Better research methods and proper use of these platforms by health scientists and the public are warranted to address social media’s role in health policy and individual decisions. A multi-disciplinary approach with better outreach and dissemination is optimal.


title: Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

text: Abstract An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function.


title: Measles-derived vaccines to prevent emerging viral diseases

text: Abstract Infectious disease epidemics match wars and natural disasters in their capacity to threaten lives and damage economies. Like SARS previously and Zika recently, the Ebola crisis in 2015 showed how vulnerable the world is to these epidemics, with over 11,000 people dying in the outbreak. In addition to causing immense human suffering, these epidemics particularly affect low- and middle-income countries. Many of these deadly infectious diseases that have epidemic potential can become global health emergencies in the absence of effective vaccines. But very few vaccines against these threats have been developed to create proven medical products. The measles vaccine is an efficient, live attenuated, replicating virus that has been safely administered to 2 billion children over the last 40 years, affording life-long protection after a single dose. Taking advantage of these characteristics, this attenuated virus was transformed into a versatile chimeric or recombinant vaccine vector with demonstrated proof-of-principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Clinical trials have shown the safety and immunogenicity of this vaccine platform in individuals with preexisting immunity to measles. This review describes the potential of this platform to develop new vaccines against emerging viral diseases.


title: Impact of air‐handling system exhaust failure on dissemination pattern of simulant pathogen particles in a clinical biocontainment unit

text: Biocontainment units (BCUs) are facilities used to care for patients with highly infectious diseases. However, there is limited guidance on BCU protocols and design. This study presents the first investigation of how HVAC (heating, ventilation, air‐conditioning) operating conditions influence the dissemination of fluorescent tracer particles released in a BCU. Test conditions included normal HVAC operation and exhaust failure resulting in loss of negative pressure. A suspension of optical brightener powder and water was nebulized to produce fluorescent particles simulating droplet nuclei (0.5‐5 μm). Airborne particle number concentrations were monitored by Instantaneous Biological Analyzers and Collectors (FLIR Systems). During normal HVAC operation, fluorescent tracer particles were contained in the isolation room (average concentration = 1 × 10(4) ± 3 × 10(3)/L(air)). Under exhaust failure, the automated HVAC system maximizes airflow into areas adjacent to isolation rooms to attempt to maintain negative pressure differential. However, 6% of the fluorescent particles were transported through cracks around doors/door handles out of the isolation room via airflow alone and not by movement of personnel or doors. Overall, this study provides a systematic method for evaluating capabilities to contain aerosolized particles during various HVAC scenarios. Recommendations are provided to improve situation‐specific BCU safety.


title: The COVID‐19 information pandemic: how have we managed the surge?

text: The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) or Coronavirus 2019 (COVID-19) pandemic has permanently impacted our everyday normality. Since the outbreak of this pandemic, our e-mail inboxes, social media feeds and even general news outlets have become saturated with new guidelines, revisions of guidelines, new protocols and updated protocols, all subject to constant amendments. This constant stream of information has added uncertainty and cognitive fatigue to a workforce that is under pressure. While we adapt our practice and learn how to best manage our COVID-19 patients, a second pandemic - information overload - has become our Achilles' heel.


title: The Preparation of Chicken Kidney Cell Cultures for Virus Propagation

text: Chicken kidney (CK) cell cultures have historically proved useful for the assay of a number of viruses including coronaviruses. A technique for the preparation of such cell cultures, using a combination of manual and trypsin disaggregation of kidneys dissected from 2- to 3-week-old birds is described. This technique routinely gives high cell yield together with high viability and the resultant adherent primary cultures can be used for virus growth and plaque formation.


title: Belatacept, kidney transplantation and COVID‐19: successful management of the first reported case within the United Kingdom

text: Kidney transplant recipients may be at particular risk of acquiring SARS‐CoV‐2 infection with poor outcomes.(1) In a recent case report (2) it was hypothesised that kidney transplant recipients on maintenance belatacept, a cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) fusion protein, have a milder disease course due to belatacept mitigating the cytokine storm and resultant acute respiratory distress syndrome which have been linked to severity of COVID‐19. (3) Here we present the first reported case in the United Kingdom of a kidney transplant patient on belatacept who on the contrary developed a severe COVID‐19 pneumonia requiring intensive care admission and intubation.


title: Epidemiology of human respiratory viruses in children with acute respiratory tract infection in a 3-year hospital-based survey in Northern Italy

text: Abstract Acute respiratory tract infections (ARTIs) are among the leading causes of morbidity and mortality in children. The viral etiology of ARTIs was investigated over 3 years (October 2012–September 2015) in 2575 children in Parma, Italy, using indirect immunofluorescent staining of respiratory samples for viral antigens, cell culture, and molecular assays. Respiratory viruses were detected in 1299 cases (50.44%); 1037 (79.83%) were single infections and 262 (20.17%) mixed infections. The highest infection incidence was in children aged >6 months to ≤3 years (57.36%). Human respiratory syncytial virus (27.12%) and human adenovirus (23.58%) were the most common viruses identified. The virus detection rate decreased significantly between the first and third epidemic season (53.9% vs. 43.05%, P < 0.0001). The simultaneous use of different diagnostic tools allowed us to identify a putative viral etiology in half the children examined and to provide an estimate of the epidemiology and seasonality of respiratory viruses associated with ARTIs.


Please cite this paper as: Janjua et al. (2012) Transmission dynamics and risk factors for pandemic H1N1‐related illness: outbreak investigation in a rural community of British Columbia, Canada. Influenza and Other Respiratory Viruses 6(3), e54–e62. Objective To characterize the first‐wave epidemiologic features of influenza‐like illness (ILI) associated with the novel pandemic A/H1N1 [A(H1N1)pdm09] virus. Methods We used generalized linear mixed models (GLMM) to assess risk factors and non‐parametric and/or parametric distributions to estimate attack rates, secondary attack rates (SAR), duration of illness, and serial interval during a laboratory‐confirmed community outbreak of A(H1N1)pdm09 clustered around on‐reserve residents and households of an elementary school in rural British Columbia, Canada, in late April/early May 2009. ILI details were collected as part of outbreak investigation by community telephone survey in early June 2009. Results Overall, 92/408 (23%) of participants developed ILI and 36/408 (9%) experienced medically attended ILI (MAILI). The overall SAR in households was 22%: highest among participants 1–4 years of age (yoa) (50%) followed by <1 yoa (38%), 5–8 yoa (20%), 10–19 yoa (13%), 20–49 yoa (20%), and 50–64 yoa (0%). The median serial interval was estimated at 3·5 days (95% CI: 2·1–5·1). In multivariable GLMM analysis, having a chronic condition (OR: 2·58; 95% CI: 1·1–6·04), younger age [1–8 yoa: OR: 4·63; 95% CI: 2·25–9·52; 9–19 yoa: OR: 1·95; 95% CI: 0·97–3·9 (referent: ≥20 yoa)] and receipt of 2008–2009 influenza vaccine (OR: 2·68; 95% CI: 1·37–5·25) were associated with increased risk of ILI. Median duration of illness was 9 days, longer among those with chronic conditions (21 days). Median time to seeking care after developing illness was 4·5 days. On‐reserve participants had higher chronic conditions, household density, ILI, MAILI, and SAR. Conclusions During a community outbreak of A(H1N1)pdm09‐related illness, we identified substantial clinical ILI attack rates exceeding 20% with secondary household attack rates as high as 50% in young children. The serial interval was short suggesting a narrow period to prevent transmission.


title: COVID‐19 in kidney transplant recipients

text: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly and has already taken on pandemic proportions. After China, Italy is the country with the highest number of cases so far (41,035 confirmed cases according to Dipartimento della Protezione Civile as of March 19, and 3,405 deaths). In Northern Italy, where the current prevalence of confirmed cases has surpassed in some areas 2 per 1,000 people, kidney transplant patients are getting infected and starting to develop coronavirus disease 2019 (COVID-19).


First case diagnosed with both COVID-19 and dengue virus infections in Bangladesh: Possible dengue prevention strategies amid COVID-19 outbreak


NEUMONÍA VÍRICA BILATERAL POR COVID-19 COMO HALLAZGO CAUSAL EN 18F-FDG-PET-TC DE ESTADIFICACIÓN DE PACIENTE CON MELANOMA GEMELAR DERECHO


Everyday Ethics: When a Coronavirus Patient requests to Leave AMA


title: Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

text: CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.


title: Human Coronavirus Infection among Children with Acute Lower Respiratory Tract Infection in Thailand

text: OBJECTIVE: This study was performed to further identify the previously uncharacterized human coronavirus 229E (hCoV-229E) and human coronavirus OC43 (hCoV-OC43) in Thailand by using the RT-PCR technique. In addition, we performed this study in order to delineate the prevalence, the potential clinical impacts and evaluation of the genetic characterization of this pathogen in young children who presented with acute lower respiratory tract infections (ALRI). METHODS: We obtained nasopharyngeal secretions (NPs) from 226 children <5 years of age who were either attending the outpatient department or hospitalized with ALRI from March 2002 to July 2003. All clinical, laboratory, RT-PCR, direct sequencing and phylogenetic analysis data were collected and analyzed. RESULTS: Of the 226 NPs samples from infants and young children presented with ALRI, 8 (3.54%) were positive for hCoV-229E, 2 (0.88%) were positive for hCoV-OC43, and 1 (0.44%) had co-infection. The following clinical presentations were noted: fever (100%), rhinitis (44%), acute bronchiolitis (44%), viral pneumonia (33%), viral pneumonia triggering asthma exacerbation (11%) as well as viral pneumonia causing BPD exacerbation (11%). All positive samples were subjected to direct sequencing. The amino acid sequences had 82-99% similarity to previous sequences stored in the GenBank database. CONCLUSION: The molecular technique we applied to detect human coronavirus appears justified as a valuable diagnostic approach to elucidate the prevalence, cause and clinical implications of ALRI among infants and young children.


title: CHAPTER 14 Microbial Forensics Host Factors

text: Publisher Summary This chapter presents the elements of the host response in a simplified fashion. Microbial forensics aims at identifying: the biological agent, its source, and the individuals responsible for a biothreat event. Analytic approaches differ when the suspected biothreat agent is encountered in a container or the environment, as opposed to a human or an animal. However, once the microbe or its toxin is in the living host, all the preceding items except the microbial nucleic acid cannot be analyzed. Nevertheless, the host response to the biological agent is available for analysis. The host response to a foreign substance is often a well orchestrated series of events designed to protect the individual from any harm. Modern techniques help to elucidate the pathways and components of the host response. Similar to a live microbe, vaccines can also provoke an antibody response. A vaccine can compose of: a live or attenuated microbe, a whole nonproliferating microbe, or an antigenic part of the microbe. Regardless, the intent of the vaccine is to produce protection, often by protective antibodies. It is likely that the future understanding of the immune system and evolving technologies; such as microarrays will enhance analytic power.


Breast Cancer Care During COVID-19 Pandemic


title: Viral infections in outpatients with medically attended acute respiratory illness during the 2012–2013 influenza season

text: BACKGROUND: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013. METHODS: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses. RESULTS: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18–49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary. CONCLUSIONS: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.


title: Events postponed or cancelled because of the coronavirus outbreak

text: A number of events that cover developments in membrane technology and related products have been postponed, or even cancelled, in response to the rapidly changing circumstances associated with the coronavirus (COVID-19) outbreak.


title: Utilization of an Orthopedic Hood as Personal Protective Equipment for Intubation of Coronavirus Patients: a Brief Technical Report

text: BACKGROUND: The novel coronavirus disease (COVID-19) has afflicted millions of people worldwide since its first case was reported in December 2019. Personal protective equipment (PPE) has been tailored accordingly, but as of April 2020, close to 10 000 health care workers in the United States have contracted COVID-19 despite wearing recommended PPE. As such, standard guidelines for PPE may be inadequate for the health care worker performing high-risk aerosolizing procedures such as endotracheal intubation. In this brief technical report, we describe the integration of an orthopedic hood cover as an item for full barrier protection against COVID-19 transmission. TECHNICAL DESCRIPTION: The Coronavirus Airway Task Force at Virginia Commonwealth University Medical Center approved this initiative and went live with the full barrier suit during the last week of March 2020. The PPE described in this report includes a Stryker T4 Hood, normally used in conjunction with the Stryker Steri-Shield T4 Helmet. Instead of the helmet, the hood is secured to the head via a baseball cap and binder clip. This head covering apparatus is to be used as an accessory to other PPE items that include an N95 mask, waterproof gown, and disposable gloves. The motor ventilation system is not used in order to prevent airborne viral entry into the hood. DISCUSSION: An advantage of the full barrier suit is an additional layer of droplet protection during intubation. The most notable disadvantage is the absence of a ventilation system within the hood covering. CONCLUSION: Modification of existing PPE may provide protection for health care workers during high-risk aerosolizing procedures such as endotracheal intubation. Although the integration of this medical equipment meets the immediate needs of an escalating crisis, further innovation is on the horizon. More research is needed to confirm the safety of modified PPE.


title: Intervals Before Tuberculosis Diagnosis and Isolation at a Regional Hospital in Taiwan

text: Background/Purpose Nosocomial tuberculosis (TB) infection is still a problem in many Taiwanese hospitals. The objectives of this study were to explore the intervals before TB diagnosis and isolation at a regional hospital in Taiwan, and to provide useful knowledge to hospitals for the purpose of TB infection control. Methods From 2002 to 2005, we included a total of 343 patients with culture-positive pulmonary TB in a regional hospital in Southern Taiwan for this study. Their medical records were reviewed, and the time intervals between patient-hospital contact points and isolation were recorded. Results Of 343 culture-positive pulmonary TB patients, the majority were male, over 40 years old, and unemployed. The mean interval between the first admission and isolation was 20.5 days (median, 2.0 days). The mean intervals between the first admission from outpatient clinics, emergency department and hospitalization and suspected TB were < 1 day, 6.07 days and 25.53 days, respectively. The mean accumulated exposure time was 0.35 days, 0.61 days and 10.09 days in outpatient clinics, the emergency department and hospitalization, respectively; 75.5% of patients had their diagnosis confirmed at the chest department of the department of internal medicine. Conclusion Delayed diagnosis was most likely in the case of hospitalized patients and least likely in outpatient clinics. Delayed diagnosis in hospitalized patients also contributed more severely to TB exposure time than others. Enhancing the quality, speed and ability of specialists and physicians to diagnose TB, especially in emergency departments and in hospitalized patients, is essential.


title: Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19. METHODS: Three medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects. RESULTS: A total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1–43.3]), anorexia (30.0% [23.2–36.9]), dyspnea/shortness of breath (26.9% [19.2–34.6]), and malaise (26.7% [13.3–40.1]). The common specific neurological symptoms included olfactory (35.7–85.6%) and gustatory (33.3–88.8%) disorders, especially in mild cases. Guillain–Barré syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19. CONCLUSIONS: Neurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09974-2) contains supplementary material, which is available to authorized users.


title: Non-Human Primate Models of Enteric Viral Infections

text: There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections including its applicability to human disease.


title: Effects of CuO addition on the sinterability and electric properties in PbNb(2)O(6)-based ceramics

text: PbNb(2)O(6) (PN)-based ceramics with tungsten bronze structure are promising piezoelectric materials in high-temperature devices such as piezoelectric vibration transducers. However, the PN-based ceramics usually exhibit a low bulk density, which greatly limits their practical applications. In this work, CuO was used as the sintering aid to form a liquid-phase bridge, leading to an obvious increase of the bulk density of PN-based ceramics by 11% (from 5.25 to 5.85 g cm(−3)) and the improvement of the piezoelectric constant (d(33)) (from 168 to 190 pC/N) and the Curie temperature (T(C)) from 367 to 395 °C. The positive influence of CuO on densification has been proved by SEM and fracture toughness. The XRD patterns confirmed that there was no secondary phase introduced by CuO addition. The Raman spectra revealed that part of Cu(2+) ions has probably diffused into host lattice of the PN and preferred to occupy on A-sites. These results not only demonstrate the high potential of the CuO added PN-based ceramics for high-temperature piezoelectric applications, but also reveal the corresponding structure-properties relationship as well as provide a way to improve the sinterability, d(33), and T(C) simultaneously.


title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination

text: RIG-I-like receptors (RLRs) play important roles in response to virus infection by regulating host innate immune signaling pathways. Meanwhile, the RLR signaling pathway is also tightly regulated by host and virus to achieve the immune homeostasis between antiviral responses and virus survival. Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. Post-RGNNV infection, zbTRIM25 expression was obviously inhibited and ectopic expression of zbTRIM25 led to enhanced expression of RLR signaling pathway-related genes. Overexpression and knockdown analysis revealed that zbTRIM25 promoted zebrafish RIG-I (zbRIG-I)-mediated IFN signaling and inhibited RGNNV replication. Mechanistically, zbTRIM25 bound to zbRIG-I; in particular, the SPRY domain of zbTRIM25 interacted with the tandem caspase activation and recruitment domains (2CARD) and repressor domain (RD) regions of zbRIG-I. zbTRIM25 promoted the K63 polyubiquitination of 2CARD and RD regions of zbRIG-I. Furthermore, zbTRIM25-mediated zbRIG-I activation of IFN production was enhanced by K63-linked ubiquitin, indicating that zbTRIM25-mediated zbRIG-I polyubiquitination was essential for RIG-I-triggered IFN induction. In conclusion, these findings reveal a novel mechanism that zbTRIM25 positively regulates the innate immune response by targeting and promoting the K63-linked polyubiquitination of zbRIG-I.


title: Proteomic analysis reveals platelet factor 4 and beta‐thromboglobulin as prognostic markers in severe acute respiratory syndrome

text: Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS‐associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS‐associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression. Proteomic features of m/z 6634, m/z 7769, m/z 8635, and m/z 8865 were identified as independent prognostic markers. After purification by cation‐exchange chromatography and gel electrophoresis, proteomic features of m/z 7769 and m/z 8865 were found to be platelet factor 4 (PF4) and beta‐thromboglobulin (beta‐TG) by tandem mass spectrometry, respectively. The associations of decreased serum PF4 and increased serum beta‐TG levels with poor prognosis were confirmed by Western blot. Previous studies suggest that PF4 and beta‐TG are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) in a negative and positive way, respectively. Our results suggest that PF4 and beta‐TG may also play similar roles in the development of ARDS in SARS patients.


title: Why N95 Should Be the Standard for All COVID-19 Inpatient Care

text: Guidelines differ in their guidance on the use of N95 respirators versus medical masks for frontline health care workers working with patients with COVID-19, particularly when aerosolized procedures are not involved. This article makes the case that the existing data are inconclusive regarding the comparative effectiveness of N95 versus medical masks and could be misinterpreted. The authors suggest a reevaluation of this evidence or acknowledgement of these deficiencies in the setting of guidelines.


title: Challenges and opportunities for enhanced cognitive behaviour therapy (CBT-E) in light of COVID-19

text: In the past few weeks, coronavirus disease 2019 (COVID-19) has dramatically expanded across the world. To limit the spread of COVID-19 and its negative consequences, many countries have applied strict social distancing rules. In this dramatic situation, people with eating disorders are at risk of their disorder becoming more severe or relapsing. The risk comes from multiple sources including fears of infection and the effects of social isolation, as well as the limited availability of adequate psychological and psychiatric treatments. A potential practical solution to address some of these problems is to deliver enhanced cognitive behaviour therapy (CBT-E), an evidence-based treatment for all eating disorders, remotely. In this guidance we address three main topics. First, we suggest that CBT-E is suitable for remote delivery and we consider the challenges and advantages of delivering it in this way. Second, we discuss new problems that patients with eating disorders may face in this period. We also highlight potential opportunities for adapting some aspects of CBT-E to address them. Finally, we provide guidelines about how to adapt the various stages, strategies and procedures of CBT-E for teletherapy use in the particular circumstances of COVID-19. KEY LEARNING AIMS: (1).. To appreciate that CBT-E is suitable for remote delivery, and to consider the main challenges and potential advantages of this way of working. (2).. To identify and discuss the additional eating disorder-related problems that may arise as a result of COVID-19, as well as potential opportunities for adapting some aspects of CBT-E to address them. (3).. To learn how to adapt CBT-E for remote delivery to address the consequences of COVID-19. Specifically, to consider adaptations to the assessment and preparation phase, the four stages of treatment and its use with underweight patients and adolescents.


title: Tumour travel tours – Why circulating cancer cells value company

text: Welcome to the New Year and a new issue of the Biomedical Journal, where we learn that travelling with company boosts the metastatic potential of circulating tumour cells, as well as that a worm could be an excellent model to study antidiabetic drugs. In addition, we discover another pair of molecular scissors for genetic engineering, how exactly Leptospira wreaks havoc on its run through the host organism, and that hyperparathyroidism brings its own risks, but does not worsen the outcome of papillary thyroid carcinoma. Furthermore, the importance of taking into account differing beauty ideals for aesthetic surgery surveys is discussed, alongside the question how bad isolated local recurrence is in the case of HR + breast cancer. Finally, we find out that virtual colonoscopy deserves more credit, that the first medical experiment in space was all about the H-reflex, and that it is possible to survive advanced necrotising fasciitis of the face and neck.


title: An antigen to remember: regulation of B cell memory in health and disease

text: Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM+ MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown. Similarly, the T-bet-driven transcriptional program drives formation of MBCs phenotypically similar to atypical MBCs. Identifying protective or detrimental roles of MBC subsets, and their regulators, will be important for clinical intervention.


title: The role of peripheral blood eosinophil counts in COVID‐19 patients

text: BACKGROUND: Coronavirus disease 2019 (COVID‐19) emerged in Wuhan city and rapidly spread globally outside China. We aimed to investigate the role of peripheral blood eosinophil (EOS) as a marker in the course of the virus infection to improve the efficiency of diagnosis and evaluation of COVID‐19 patients. METHODS: 227 pneumonia patients who visited the fever clinics in Shanghai General Hospital and 97 hospitalized COVID‐19 patients admitted to Shanghai Public Health Clinical Center were involved in a retrospective research study. Clinical, laboratory, and radiologic data were collected. The trend of EOS level in COVID‐19 patients and comparison among patients with different severity were summarized. RESULTS: The majority of COVID‐19 patients (71.7%) had a decrease in circulating EOS counts, which was significantly more frequent than other types of pneumonia patients. EOS counts had good value for COVID‐19 prediction, even higher when combined with NLR. Patients with low EOS counts at admission were more likely to have fever, fatigue and shortness of breath, with more lesions in chest CT and radiographic aggravation, longer length of hospital stay and course of disease than those with normal EOS counts. Circulating EOS level gradually increased over the time, and was synchronous with the improvement of chest CT(12days vs 13days, P=0.07), later than that of body temperature(12days vs 10days, P=0.014), but was earlier than the negative conversion of nucleic acid assays(12days vs 17days, P=0.001). CONCLUSION: Peripheral blood EOS counts may be an effective and efficient indicator in diagnosis, evaluation and prognosis monitoring of COVID‐19 patients.