title: Structural basis of quinolone derivatives, inhibition of type I and II topoisomerases and inquiry into the relevance of bioactivity in odd or even branches with molecular docking study

text: The structural modification of quinolone derivatives has been a hot spot in recent years, especially the modification of the N-1 position, which is the part that this article focuses on. In this paper, series of synthesized quinoline quaternary ammonium salts with odd and even carbon number alkyl groups in N-1 position were used to explain the influence of the alkyl side chain on activity. With respect to all the recently synthesized twenty products, the biological activity results exhibited significant antitumor and antibacterial activity with obvious differences in the target alkyliodine substituted compounds and the antibacterial activities apparently had the prominent odd-carbon number predominance. Compound 8-((4-(benzyloxy)phenyl)amino)-7-(ethoxycarbonyl)-5-propyl-[1,3]dioxolo[4,5-g]quinolin-5-ium (4d) was found to be the most potent derivative with IC(50) values of 4±0.88, 4±0.42, 14±1.96, and 32±3.66 against A-549, Hela, SGC-7901, and L-02 cells, respectively, stronger than the positive control 5-FU and MTX. Furthermore, it had the most potent bacterial inhibitory activity of MIC value against Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739) at 3.125 nmol mL(−1). With respect to molecular simulations, in order to illustrate the possible mechanism of the difference between the series of compounds in the even or odd carbon chain alkyliodine substitution, this paper simulated the conceivable mode and explained the main interactions. Finally, we could find that the position and proportion of hydrogen bonds and other interactions in each series were regarded as the main reasons for this difference in activity.


title: Rapid Implementation of a SARS-CoV-2 Diagnostic qRT-PCR Test with Emergency Use Authorization at a Large Academic Safety-Net Hospital

text: Summary The COVID-19 pandemic is a global public health crisis. Significant delays in the rapid development and distribution of diagnostic testing for SARS-CoV-2 infection have prevented adequate public health management of the disease, impacting the timely mapping of viral spread and the conservation of personal protective equipment. Furthermore, vulnerable populations such as those served by Boston Medical Center (BMC), the largest safety net hospital in New England, represent a high-risk group across multiple dimensions, including a higher prevalence of pre-existing conditions and substance use disorders, lower health maintenance, unstable housing, and a propensity for rapid community spread, highlighting the urgent need for expedient and reliable in-house testing. Here, we report the implementation of a SARS-CoV-2 diagnostic RT-PCR assay with rapid turnaround time enabling more informed decisions with personal and public health ramifications. This work provides a blueprint for academic centers and community hospitals lacking capital-intensive automated laboratory machinery to implement in-house testing.


title: Perspective of Use of Antiviral Peptides against Influenza Virus

text: The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.


title: Marqueurs biologiques de gravité initiale des bronchiolites aiguës et d’évolution vers un asthme du nourrisson

text: Résumé La bronchiolite aiguë est une infection virale respiratoire épidémique du nourrisson. Le virus respiratoire syncytial est l’agent infectieux le plus fréquent au cours des bronchiolites. D’autres virus sont retrouvés, seuls ou en co-infections virales. Ce travail est une étude dont le but est de rechercher un ou des marqueurs biologiques prédictifs de la gravité d’un épisode de bronchiolite aiguë et de l’évolution vers un asthme du nourrisson, dans le cadre du protocole Bronchiolite (PHRC 2000 no 2000/020/HP), étude de cohorte, prospective, multicentrique, réalisée de novembre 2001 à janvier 2006. Sept centres ont participé : Rouen, Le Havre, Lille, Elbeuf, Evreux, Brest et Saint-Nazaire en association avec Nantes. Les données clinicobiologiques étaient recueillies au cours de l’hospitalisation initiale, puis lors des visites suivantes à un mois et à un an. Ainsi, 209 nourrissons âgés en moyenne de trois mois ont été suivis avec une évaluation de la gravité sur des critères cliniques. Les résultats de laboratoires ont été corrélés aux éléments de gravité pour les résultats suivants : identification virale, numération des leucocytes, lymphocytes et éosinophiles, étude en cytométrie en flux de populations lymphocytaires et allergologie incluant les IgE, l’eosinophilic cationic protein et test d’activation des basophiles. Les résultats de cette étude sont présentés et discutés. Summary Acute bronchiolitis is an acute respiratory infection which commonly occurs in infancy. Respiratory syncytial virus is the major cause of lower respiratory tract infection. Some other virus may be found during co-infections. The aim of this study was to search for biological markers correlated with gravity and risk factors for asthma and allergy. The follow-up was done during the multicenter and prospective study Bronchiolitis (PHRC 2000 No. 2000/020/HP), performed between November 2001 and January 2006, which included seven centers in France: Rouen, Le Havre, Lille, Elbeuf, Evreux, Brest and Saint-Nazaire associated with Nantes. Clinical and biological data were gathered during initial course, then at 1month and 1year. For the population of 209 infants, mean age was 3months, the gravity was evaluated by scoring. The laboratory results correlated with clinical scoring were the following: viral evaluation, absolute numbers of leucocytes, lymphocytes and eosinophils, flow cytometry for sub-populations of lymphocytes, allergology including IgE, eosinophilic cationic protein, and basophil activation test. The results of the study are presented and discussed.


title: A type-specific blocking ELISA for the detection of infectious bronchitis virus antibody

text: Abstract Infectious bronchitis virus (IBV) infection has been a major threat to the poultry industry worldwide. Current commercially available ELISA kits detect group-specific antibodies; however, to understand the status of field infection, a monoclonal antibody (mAb) blocking ELISA (b-ELISA) against local IBVs was developed. The selected mAb showed specificity to Taiwan IBV strains but had no cross-reactivity with the vaccine strain H120. Using the hemagglutination inhibition (HI) test as a standard, the cut-off value, sensitivity, and specificity of a b-ELISA using this mAb were evaluated in 390 field samples. The type-specificity of detection was validated using a panel of chicken hyperimmune sera. The results showed that the b-ELISA demonstrated high sensitivity (98.0%) and specificity (97.2%) of detection. The agreement between the results of the b-ELISA and the HI test was statistically significant (Kappa=0.95), and there was no significant difference between these two methods (McNemar p =0.72). The b-ELISA specifically detected Taiwan IBV serotypes but not three non-Taiwan IBV serotypes nor sera against other avian pathogens. This b-ELISA provides type-specific antibody detection of local IBV strains. It has the potential to serve as a rapid and reliable diagnostic method for IBV clinical infections in the field in Taiwan.


title: Identification of host cell proteins that interact with the M protein of porcine epidemic diarrhea virus

text: Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes severe diarrhea in pigs of all ages and a high fatality rate in neonates. The PEDV membrane protein (M) plays crucial roles in viral assembly, viral budding and host immune regulation, most likely by interacting with host cell proteins that have yet to be identified. In this study, co-immunoprecipitation (Co-IP) using an M-specific monoclonal antibody, coupled with LC-MS/MS, was employed to identify M protein-interacting proteins in PEDV-infected cells. Three viral proteins (S, E and ORF3) and 218 host cell proteins were identified as putative M-interacting partners. Bioinformatic analysis showed that the identified host cell proteins were related to 131 signal pathways and 10 biological processes. In addition, interaction between translation initiation factor 3(eIF3L) and M protein was validated by Co-IP. Down-regulation of eIF3L expression significantly increased viral production, which suggests that eIF3L could be a negative regulator in PEDV replication. This interactome study of the PEDV M protein will serve to clarify its function during viral replication.


An Evolving Problem - Mental Health Symptoms Among Health Care Workers During COVID-19 Pandemic


title: Transcriptome changes in the phenylpropanoid pathway in senescing leaves of Toona sinensis

text: Toona sinensis is a deciduous tree native to eastern and southeastern Asia that has important culinary and cultural values. To expand current knowledge of the transcriptome and functional genomics in this species, a de novo transcriptome sequence analysis of young and mature leaf tissues of T. sinensis was performed using the Illumina platform. Over 8.1 Gb of data were generated, assembled into 64,541 unigenes, and annotated with known biological functions. Proteins involved in primary metabolite biosynthesis were identified based on similarities to known proteins, including some related to biosynthesis of carbohydrates, amino acids, lipids, and energy. Analysis of unigenes differentially expressed between young and mature leaves (transcriptomic libraries ‘YL’ and ‘ML’, respectively) showed that the KEGG pathways of phenylpropanoid, naringenin, lignin, cutin, suberin, and wax biosynthesis were significantly enriched in mature leaves. These results not only expand knowledge of transcriptome characteristics for this valuable species, but also provide a useful transcriptomic dataset to accelerate the researches on its metabolic mechanisms and functional genomics. This study can also further the understanding of unique aromatic metabolism and Chinese medicinal properties of T. sinensis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11738-019-2915-9) contains supplementary material, which is available to authorized users.


title: Detection of murine norovirus by reverse transcription loop-mediated isothermal amplification

text: Abstract Murine norovirus (MNV) has considerable genetical and biological diversity and is recognized worldwide as the most common contaminant in laboratory mouse colonies. This study developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method with the potential to detect a broad range of MNV. RT-LAMP, using a set of five primers containing mixed bases, obtained results under isothermal conditions at 62°C for 90min. Sensitivity of RT-LAMP was 50-fold less than that of two-step TaqMan real-time reverse transcription-polymerase chain reaction (TaqMan RT-PCR). Diagnostic performance of RT-LAMP on RNA extracted from mouse fecal specimens was compared with TaqMan RT-PCR and nested RT-PCR. MNV was detected in 54 of 120 mouse fecal specimens by RT-LAMP, and RT-LAMP had an estimated sensitivity and specificity of 96.4% and 100% compared with TaqMan RT-PCR, and 94.7% and 100% compared with nested RT-PCR. RT-LAMP, which does not require expensive instruments, might be useful for the screening of mice actively or persistently infected with MNV.


title: Severe Acute Respiratory Syndrome Complicated by Spontaneous Pneumothorax

text: Severe acute respiratory syndrome (SARS) presents an unprecedented diagnostic and therapeutic challenge to clinicians. Despite recent progress in identifying and analyzing the coronavirus that is responsible for it, few reports have addressed the clinical complications of SARS. The present study was a two-center retrospective cohort study. All patients in the study had SARS, were managed in the two major Hong Kong hospitals (ie, Prince of Wales Hospital and United Christian Hospital), and had developed spontaneous pneumothorax during their hospitalization between March 10, 2003, and April 28, 2003. Spontaneous pneumothorax was reported in 6 of 356 SARS patients who were treated at the two hospitals during the period. This represents an incidence of 1.7%. None of the six patients had a history of smoking or pulmonary disease. The rate of admission to the ICU was 66.7% and the crude mortality rate was 33.3% in this group of patients. There was a trend for the mean neutrophil count in these patients to be higher than in previously reported cohorts of comparable SARS patients (14.5 × 10 9 vs 4.6 × 10 9 neutrophils per liter, respectively). Conservative measures like tube thoracostomy or observation alone offered satisfactory initial symptomatic management in five of six patients. Spontaneous pneumothorax is a specific and potentially life-threatening complication in SARS patients. Patients with extensive lung injury, as indicated by severe clinical courses, and in particular high neutrophil counts, appear to be most at risk. The benefits of surgical management must be balanced against the potential risks to health-care workers.


title: Coronavirus-19 Disease (COVID-19): A case series of early suspects reported and the implications towards the response to the pandemic in Zimbabwe

text: Abstract Zimbabwe is among the countries that have been identified to be at risk of the COVID-19 pandemic. As of the 15th of March 2020, there has been no confirmed case of the virus. Official reports of suspect cases were used to appraise the general screening, case management, and preparedness of the country towards the COVID-19 pandemic. In terms of the surveillance and capacity to screen at ports of entry, the country seems to be faring well. The country might not be screening optimally, considering the number of COVID-19 tests conducted to date and suspected cases who missed testing. Three of the suspected cases faced mental, social, and psychological consequences due to them being suspects of COVID-19. There is a need to enhance the screening process and infrastructure at all ports of entry. More COVID-19 diagnostic tests should be procured to increase the testing capacity. Training and awareness of mental, social, and psychological consequences of COVID-19 should be offered to health care workers and the public. More financial resources should be sourced to enable the country to control the pandemic.


Effectiveness for the Response to COVID-19: The MERS Outbreak Containment Procedures


Une infection par le SARS-CoV-2 peut en cacher une autre


title: Outbreaks in Health Care Settings

text: Outbreaks and pseudo-outbreaks in health care settings can be complex and should be evaluated systematically using epidemiologic tools. Laboratory testing is an important part of an outbreak evaluation. Health care personnel, equipment, supplies, water, ventilation systems, and the hospital environment have been associated with health care outbreaks. Settings including the neonatal intensive care unit, endoscopy, oncology, and transplant units are areas that have specific issues which impact the approach to outbreak investigation and control. Certain organisms have a predilection for health care settings because of the illnesses of patients, the procedures performed, and the care provided.


title: Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein suggest Malayan pangolin as intermediary host

text: An emergence of a novel coronavirus, causative agent of COVID19, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred due to cross-species transmission. Coronaviruses are a large family of viruses able to infect a great number of hosts. Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. Molecular analysis supported bats as natural hosts for SARS-CoV and involved them in MERS-CoV origin. The genomic similarity between bat RaTG13 CoV strain and SARS-CoV-2 implicates bats in the origin of the new outbreak. Additionally, there is a hypothesis for the zoonotic transmission based on contact with Malayan pangolins by humans in Huanan seafood market in Wuhan, China. To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. Phylogeny showed SARS-like-CoV-2 strains that infected pangolin and bats are close to SARS-CoV-2. In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet—the main intermediary host of SARS-CoV. Thus, pangolin has become an opportune host to intermediates bat-to-human SARS-CoV-2 jump and entry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-020-00321-1) contains supplementary material, which is available to authorized users.


title: Clinical evaluation of a SARS-CoV-2 RT-PCR assay on a fully automated system for rapid on-demand testing in the hospital setting

text: Abstract Background The ongoing SARS-CoV-2 pandemic presents a unique challenge for diagnostic laboratories around the world. Automation of workflows in molecular diagnostics is instrumental for coping with the large number of tests ordered by clinicians, as well as providing fast-tracked rapid testing for highly urgent cases. In this study we evaluated a SARS-CoV-2 LDT for the NeuMoDx 96 system, a fully automated device performing extraction and real-time PCR. Methods A publicly available SARS-CoV-2 RT-PCR assay was adapted for the automated system. Analytical performance was evaluated using in-vitro transcribed RNA and clinical performance was compared to the cobas 6800-based reference assay within the lab. Results The Envelope (E) Gene-LDT displayed good analytical performance with an LoD of 95.55 cp/ml and no false positives during evaluation of cross-reactivity. A total of 176 patient samples were tested with both the E-Gene-LDT and the reference assay. Positive and negative agreement were 100% and 99.2% respectively. Invalid-rate was 6.3%. Conclusion The E-Gene-LDT showed analytical and clinical performance comparable to the cobas6800-based reference assay. Due to its random-access workflow concept and rapid time-to-result of about 80 minutes, the system is very well suited for providing fast-tracked SARS-CoV-2 diagnostics for urgent clinical samples in the hospital setting.


title: Productive and economic parameters of pigs supplemented from weaning to finishing with prebiotic and probiotic feed additives

text: Practical evidence suggests possible beneficial effects with the combined use of prebiotics and probiotics which can improve production parameters. The objective of the study was to investigate the addition of Saccharomyces cerevisiae (SC) as prebiotic and the combination of Lactobacillus spp. (L), Bacillus spp. (B) as probiotics on productive parameters and economic feasibility. Four hundred male pigs, hybrids of commercial genetic lines (Pietrain), were used: T1 = control group, T2 = 4 kg/tonne SC, T3 = 0.8 kg/tonne feed L and B, T4 = 4 kg/tonne SC + 0.8 kg/tonne L and B. Productive parameters were recorded in the treatment groups for four periods. Then, the viscera of five pigs per treatment were collected after slaughter to evaluate the histological changes and cytokine concentrations in the ileum. The weight gains of groups at 70–100, 100–125 and 125–150 days in the T4 group showed statistically increases (p < .05). Feed intake had a significant difference (p < .05) in T3 versus T1. The feed‐conversion ratio improved for all periods in the T4 group (p < .05). The eosinophil, mononuclear infiltration and cytokines (tumor necrosis factor‐α and interleukin‐6) in the mucosa were lower for treatments with probiotics. In conclusion, there was an economic benefit when using both prebiotics and probiotics in the diet of pigs from weaning to finishing.


title: Nipah virus fusion protein: Influence of cleavage site mutations on the cleavability by cathepsin L, trypsin and furin

text: Abstract Nipah virus (NiV), a highly pathogenic member of the Paramyxoviridae which originated from bats, encodes for a fusion (F) protein which is proteolytically processed within endosomes by cathepsin L. We show here that sequence requirements for NiV F activation differ markedly from other para- or orthomyxoviral fusion proteins. In contrast to other viral fusion proteins with monobasic cleavage sites, processing of NiV F proteins with one single basic amino acid in the cleavage peptide by exogenous trypsin is very inefficient, and introduction of a consensus sequence for furin does not result in cleavage by this ubiquitous protease. In contrast, a multibasic cleavage peptide in the NiV F protein completely impairs proteolytic processing and the generation of biological activity.


title: Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

text: The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities.


title: Functions of the 5′ and 3′ ends of calicivirus genomes

text: The Caliciviridae family of small positive sense RNA viruses contains a diverse range of pathogens of both man and animals. The molecular mechanisms of calicivirus genome replication and translation have not been as widely studied as many other RNA viruses. With the relatively recent development of robust cell culture and reverse genetics systems for several members of the Caliciviridae family, a more in-depth analysis of the finer detail of the viral life cycle has now been obtained. As a result, the identification and characterization of the role of RNA structures in the calicivirus life cycle has also been possible. This review aims to summarize the current state of knowledge with respect to the role of RNA structures at the termini of calicivirus genomes.


title: Associations of Clinical Characteristics and Treatment Regimens with Viral RNA Shedding Duration in Patients with COVID-19

text: Abstract Objective The novel coronavirus disease 2019 (COVID-19) has become a global pandemic, but the factors influencing viral RNA shedding remain unclear to inform optimal control strategies. Methods The clinical course and viral RNA shedding pattern of 267 consecutive symptomatic COVID-19 patients admitted to the hospital from January 20, 2020 to March 15, 2020 were retrospectively evaluated. Results The median viral RNA shedding duration was 12 days (interquartile range, 8–16 d) after the onset of illness. Of the 267 patients included in this study, 65.2% had viral RNA cleared within 14 days, 88.8% within 21 days, and 94.4% within 28 days. Older age (hazard ratio [HR], 0.99; 95% confidence interval [CI]: 0.98–1.00; P = 0.04), time lag from illness onset to hospital admission (HR, 0.91; 95% CI: 0.88–0.94; P < 0.001), diarrhea (HR, 0.59; 95% CI: 0.36–0.96; P = 0.036), corticosteroid treatment (HR, 0.60; 95% CI: 0.39–0.94; P = 0.024), and lopinavir/ritonavir use (HR, 0.70; 95% CI: 0.52–0.94; P = 0.014) were significantly independently associated with prolonged viral RNA shedding. Conclusions Early detection and timely hospital admission may be warranted for symptomatic COVID-19 patients, especially for older patients and patients with diarrhea. Corticosteroid treatment is associated with prolonged viral RNA shedding and should be used with caution. Lopinavir/ritonavir use may be associated with prolonged viral RNA shedding in non-severe patients; further randomized controlled trials are needed to confirm this finding.


title: Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam

text: Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.


Social distancing: implications for the operating room in the face of COVID-19


title: COVID‐19 in patients with myasthenia gravis

text: INTRODUCTION: Coronavirus disease 2019 (COVID‐19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG). METHODS: We studied the clinical course of COVID‐19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle‐specific tyrosine kinase antibodies) between April 1, 2020‐April 30‐2020. RESULTS: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID‐19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications. DISCUSSION: Our findings suggest that the clinical course and outcomes in patients with MG and COVID‐19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.


Chapter 18 The Role of Mucosal Microbiota in the Development, Maintenance, and Pathologies of the Mucosal Immune System


title: Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data

text: SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5–74.0), and specificity of 98.0% (95%CI 95.8–99.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.


title: Early COVID‐19 infection after lung transplantation

text: COVID‐19, the clinical syndrome caused by the novel coronavirus, SARS‐CoV‐2, continues to rapidly spread, leading to significant stressors on global healthcare infrastructure. The manifestations of COVID‐19 in solid organ transplant recipients are only beginning to be understood with cases reported to date in transplant recipients on chronic immunosuppression. Herein, we report the first case of COVID‐19 in a lung transplant recipient in the immediate posttransplant period, and we describe the epidemiologic challenges in identifying the source of infection in this unique situation.


title: The first detection of influenza in the Finnish pig population: a retrospective study

text: BACKGROUND: Swine influenza is an infectious acute respiratory disease of pigs caused by influenza A virus. We investigated the time of entry of swine influenza into the Finnish pig population. We also describe the molecular detection of two types of influenza A (H1N1) viruses in porcine samples submitted in 2009 and 2010. This retrospective study was based on three categories of samples: blood samples collected for disease monitoring from pigs at major slaughterhouses from 2007 to 2009; blood samples from pigs in farms with a special health status taken in 2008 and 2009; and diagnostic blood samples from pigs in farms with clinical signs of respiratory disease in 2008 and 2009. The blood samples were tested for influenza A antibodies with an antibody ELISA. Positive samples were further analyzed for H1N1, H3N2, and H1N2 antibodies with a hemagglutination inhibition test. Diagnostic samples for virus detection were subjected to influenza A M-gene-specific real-time RT-PCR and to pandemic influenza A H1N1-specific real-time RT-PCR. Positive samples were further analyzed with RT-PCRs designed for this purpose, and the PCR products were sequenced and sequences analyzed phylogenetically. RESULTS: In the blood samples from pigs in special health class farms producing replacement animals and in diagnostic blood samples, the first serologically positive samples originated from the period July–August 2008. In samples collected for disease monitoring, < 0.1%, 0% and 16% were positive for antibodies against influenza A H1N1 in the HI test in 2007, 2008, and 2009, respectively. Swine influenza A virus of avian-like H1N1 was first detected in diagnostic samples in February 2009. In 2009 and 2010, the avian-like H1N1 virus was detected on 12 and two farms, respectively. The pandemic H1N1 virus (A(H1N1)pdm09) was detected on one pig farm in 2009 and on two farms in 2010. CONCLUSIONS: Based on our study, swine influenza of avian-like H1N1 virus was introduced into the Finnish pig population in 2008 and A(H1N1)pdm09 virus in 2009. The source of avian-like H1N1 infection could not be determined. Cases of pandemic H1N1 in pigs coincided with the period when the A(H1N1)pdm09 virus was spread in humans in Finland.


New evidence in infective and cardiovascular medicine


title: Hepatitis C virus entry into the hepatocyte

text: Hepatitis C virus (HCV) is a small enveloped virus with a positive stranded RNA genome belonging to the Flaviviridae family. The virion has the unique ability of forming a complex with lipoproteins, which is known as the lipoviroparticle. Lipoprotein components as well as the envelope proteins, E1 and E2, play a key role in virus entry into the hepatocyte. HCV entry is a complex multistep process involving sequential interactions with several cell surface proteins. The virus relies on glycosaminoglycans and possibly the low-density lipoprotein receptors to attach to cells. Furthermore, four specific entry factors are involved in the following steps which lead to virus internalization and fusion in early endosomes. These molecules are the scavenger receptor SRB1, tetraspanin CD81 and two tight junction proteins, Claudin-1 and Occludin. Although they are essential to HCV entry, the precise role of these molecules is not completely understood. Finally, hepatocytes are highly polarized cells and which likely affects the entry process. Our current knowledge on HCV entry is summarized in this review.


Can breathing exercises help protect you from covid-19?


In Silico Investigations of Possible Routes of Assembly of 3a from SARS-Co Virus


title: Bioinformatics and functional analyses of coronavirus nonstructural proteins involved in the formation of replicative organelles

text: Abstract Replication of eukaryotic positive-stranded RNA viruses is usually linked to the presence of membrane-associated replicative organelles. The purpose of this review is to discuss the function of proteins responsible for formation of the coronavirus replicative organelle. This will be done by identifying domains that are conserved across the order Nidovirales, and by summarizing what is known about function and structure at the level of protein domains.


Disposable customized aerosol containment chamber for oral cancer biopsy: A novel technique during COVID‐19 pandemic


title: Using imaging to combat a pandemic: rationale for developing the UK National COVID-19 Chest Imaging Database

text: The National COVID-19 Chest Imaging Database (NCCID) is a repository of chest X-Ray, CT and MRI images and clinical data from COVID-19 patients across the UK, to support research and development of AI technology that may proffer insights into the disease.


title: New-onset atrial fibrillation: incidence, characteristics, and related events following a national COVID-19 lockdown of 5.6 million people

text: AIM: To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. METHODS AND RESULTS: Using nationwide Danish registries, we included all patients, aged 18–90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12–1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56–0.78), 0.53 (0.45–0.64), and 0.41 (0.34–0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA(2)DS(2)-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93–2.12). CONCLUSIONS: Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.


title: Immune response biomarkers in human and veterinary research

text: Abstract Biomarkers are increasingly utilised in biological research and clinical practice for diagnosis of disease, monitoring of therapeutic prognosis, or as end points in clinical studies. Cytokines are small molecules that orchestrate immune responses and as such have great potential as biomarkers for both human and veterinary fields. Given the ease of sampling in the blood, and their high prevalence in clinical applications we will focus on protein detection as an area for biomarker discovery. This is facilitated by new technological developments such as digital ELISA that have led to significant increases in sensitivity. Two highly relevant examples include type I interferons, namely IFNα, that is now directly quantifiable by digital ELISA from biological samples. The application of this approach to the study of the unique bat interferon response may reveal novel findings with applications in both human and veterinary research. As a second example we will describe the use of CXCL10 as a disease biomarker in Tuberculosis, highlighting findings from human and mouse studies that should be considered in veterinary research. In summary, we describe how cytokines may be applied as novel biomarkers and illustrate two key examples where human and veterinary research may complement each other in line with the One Health objectives.


title: Innate and Adaptive Immunity through Autophagy

text: The two main proteolytic machineries of eukaryotic cells, lysosomes and proteasomes, receive substrates by different routes. Polyubiquitination targets proteins for proteasomal degradation, whereas autophagy delivers intracellular material for lysosomal hydrolysis. The importance of autophagy for cell survival has long been appreciated, but more recently, its essential role in both innate and adaptive immunity has been characterized. Autophagy is now recognized to restrict viral infections and replication of intracellular bacteria and parasites. Additionally, this pathway delivers cytoplasmic antigens for MHC class II presentation to the adaptive immune system, which then in turn is able to regulate autophagy. At the same time, autophagy plays a role in the survival and the cell death of T cells. Thus, the immune system utilizes autophagic degradation of cytoplasmic material, to both restrict intracellular pathogens and regulate adaptive immunity.


Bréve : Chloroquine OTC : danger !


title: Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

text: BACKGROUND: Although the detection of SARS-CoV-2 viral load in respiratory specimens has been widely used to diagnose coronavirus disease-19 (COVID-19), it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of COVID-19 patients. However, it is not clear whether testing for RNAaemia is correlated with the occurrence of cytokine storms or with the specific class of patients. METHODS: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the “Diagnosis and Treatment of New Coronavirus Pneumonia (6(th) edition)” issued by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load and IL-6 levels were determined. . RESULTS: Clinical characteristics analysis of 48 cases of COVID-19 showed that RNAaemia was diagnosed only in the critically ill group and seemed to reflect the severity of the disease. Furthermore, the level of inflammatory cytokine IL-6 in critically ill patients increased significantly, almost 10 times that in other patients. More importantly, the extremely high IL-6 level was closely correlated with the detection of RNAaemia (R = 0.902). CONCLUSIONS: Detectable serum SARS-Cov-2 RNA(RNAaemia) in COVID-19 patients was associated with elevated IL-6 concentration and poor prognosis. Because the elevated IL-6 may be part of a larger cytokine storm which could worsen outcome, IL-6 could be a potential therapeutic target for critically ill patients with an excessive inflammatory response.


title: Discovering novel quercetin-3-O-amino acid-esters as a new class of Src tyrosine kinase inhibitors

text: Quercetin-3-O-amino acid-esters, a new type of quercetin derivatives, were successfully prepared for the first time. Different from quercetin, the novel compounds show higher selectivity as inhibitors against Src tyrosine kinase (IC(50) values ranging from 3.2 μM to 9.9 μM) than against EGFR tyrosine kinase. Molecular docking reveals that both hydrophobic and hydrogen bonding interactions are important to the selectivity. Therefore, this study provides a new promising scaffold for further development of new anticancer drugs targeting Src tyrosine kinase.


title: Intravenous Vitamin C for reduction of cytokines storm in Acute Respiratory Distress Syndrome

text: Abstract The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specifically address the cytokines' storm characteristic of the Acute Respiratory Distress Syndrome (ARDS) that occur in the later cycle of the Covid19 infectious disease.


title: Detection of parvovirus B19 in the lower respiratory tract

text: Abstract Background Human parvovirus B19 infection generally displays a self-limiting course followed by viral clearance; although, in some cases, persistent infection may occur. Few cases of severe pulmonary disease following primary infection in both immunocompetent and immunocompromised patients were reported. Objectives To investigate the prevalence and clinical impact of parvovirus B19 in the lower respiratory tract. Study design The prevalence of parvovirus B19-DNA was evaluated by Real-Time PCR in 264 bronchoalveolar lavages (BAL) from 189 adult patients over a full-year period and related to demographic characteristics, underlying pathologies, immune status, admission to intensive care unit, mortality within 28 days, and discharge diagnosis. Results Parvovirus B19-DNA was detected in 7/189 (3.7%) patients, without significant association to demographic characteristics, immune status, transplant versus non-transplant status, admission to intensive care unit, presence of haematological conditions. In two lung transplant recipients surveillance specimens were positive to B19. Four of the remaining five patients presented respiratory insufficiency. A significant association to mortality was found, as 3/7 (42.9%) positive patients died within 28 days. No patient presented serological evidence of recent or acute infection and viremia. Conclusions Parvovirus B19 may be detected at low frequency in BAL specimens from patients with different pathological backgrounds. This finding could be due to chronic infection with virus persistence in the lower respiratory tract, also in the absence of symptoms unequivocally attributable to B19. The high rate of mortality warrants the need for further studies to evaluate the opportunity to consider parvovirus B19 in the diagnostic work-up of lower respiratory tract infections.


title: Expression Profiles of mRNA and lncRNA in HCT-8 Cells Infected With Cryptosporidium parvum IId Subtype

text: Cryptosporidium parvum is one of the most important enteric protozoan pathogens, responsible for severe diarrhea in immunocompromised human and livestock. However, few effective agents were available for controlling this parasite. Accumulating evidences suggest that long non-coding RNA (lncRNA) played key roles in many diseases through regulating the gene expression. Here, the expression profiles of lncRNAs and mRNAs were analyzed in HCT-8 cells infected with C. parvum IId subtype using microarray assay. A total of 821 lncRNAs and 1,349 mRNAs were differentially expressed in infected cells at 24 h post infection (pi). Of them, all five types of lncRNAs were identified, including 22 sense, 280 antisense, 312 intergenic, 44 divergent, 33 intronic lncRNAs, and 130 lncRNAs that were not found the relationship with mRNAs’ location. Additionally, real-time polymerase chain reactions of 10 lncRNAs and 10 mRNAs randomly selected were successfully confirmed the microarray results. The co-expression and target prediction analysis indicated that 27 mRNAs were cis-regulated by 29 lncRNAs and 109 were trans-regulated by 114 lncRNAs. These predicted targets were enriched in several pathways involved in the interaction between host and C. parvum, e.g., hedgehog signaling pathway, Wnt signaling pathway, and tight junction, suggesting that these differentially expressed lncRNAs would play important regulating roles during the infection of C. parvum IId subtype.


Living in a Covid‐19 World


title: Building an Intelligent Hospital to Fight Contagion

text: The idea of building hospitals to fight contagion was born with the lazarettos. At the time when the microorganisms were not yet known, the mechanisms of transmission of contagion were already well apprehended. Based on the same knowledge but thanks to new technologies, such hospitals have now been built downtown, next to the most highly performing technological plateau. Regrouping patient care, diagnostics, research, and development, the University Hospital Institute Méditerranée Infection building offers a wonderful tool to contain and understand contagion, in a well-designed setting, creating excellent working conditions that are attractive for interested scientists.


title: Development of the Electronic Surveillance Monitoring System on Web Applications

text: Abstract This paper presents the electronic surveillance monitoring system (ESMS) via the web based application used especially for the health sector. The system is created for three purposes, the alert function for the surveillance and rapid response team (SRRT), the monitoring for inspection and evaluation, and the back-office report. With the import and export functions that are capable to retrieve electronic health record and edit the R506 and R507 data, the SRRT and local team can easily set up and manage their resources. The GPS function helps care takers to identify the geographical data for any countermeasure and action. The program is designed to submit reports automatically to the Ministry of Public Health (MOPH). The SRRT module can operate in both on-line and off-line conditions.


docid: qauaqwhl

title: COVID-19 Impact on Well-Being and Education in Radiology Residencies: a survey of the Association of Program Directors in Radiology

text: RATIONALE AND OBJECTIVES: The COVID-19 pandemic has forced rapid evolution of the healthcare environment. Efforts to mitigate the spread of the virus through social distancing and shelter-at-home edicts have unintended consequences upon clinical and educational missions and mental well-being of radiology departments. We sought to understand the impact of the COVID-19 pandemic on radiology residencies with respect to the educational mission and perceptions of impact on well-being. MATERIALS AND METHODS: This study was IRB exempt. An anonymous 22 question survey regarding the impact of COVID-19 pandemic on educational and clinical missions of residencies, its perceived impact upon morale of radiologists and trainees and a query of innovative solutions devised in response, was emailed to the APDR membership. Survey data were collected using SurveyMonkey® (San Mateo, California). RESULTS: Respondents felt the COVID-19 pandemic has negatively impacted their residency programs. Regarding the educational mission impact, 70.1% (75/107) report moderate/marked negative impact and 2.8% (3/107) that educational activities have ceased. Regarding the pandemic's impact on resident morale, 44.8% (48/107) perceive moderate/marked negative effect; perceived resident morale in programs with redeployment is significantly worse with 57.1% (12/21) reporting moderate/marked decrease. Respondents overwhelmingly report adequate resident access to mental health resources during the acute phase of the pandemic (88.8%, 95/107). Regarding morale of program directors, 61% (65/106) report either mild or marked decreased morale. Program innovations reported by program directors were catalogued and shared. CONCLUSION: The COVID-19 pandemic has markedly impacted the perceived well-being and educational missions of radiology residency programs across the United States.


Afectación clínica y sintomatológica en pacientes mayores de 65 años por COVID-19


title: miRNA repertoire and host immune factor regulation upon avian coronavirus infection in eggs

text: Avian infectious bronchitis virus (IBV) is a coronavirus with great economic impact on the poultry industry, causing an acute and highly contagious disease in chickens that primarily affects the respiratory and reproductive systems. The cellular regulation of IBV pathogenesis and the host immune responses involved remain to be fully elucidated. MicroRNAs (miRNAs) have emerged as a class of crucial regulators of numerous cellular processes, including responses to viral infections. Here, we employed a high-throughput sequencing approach to analyze the miRNA composition of the spleen and the lungs of chicken embryos upon IBV infection. Compared to healthy chicken embryos, 13 and six miRNAs were upregulated in the spleen and the lungs, respectively, all predicted to influence viral transcription, cytokine production, and lymphocyte functioning. Subsequent downregulation of NFATC3, NFAT5, SPPL3, and TGFB2 genes in particular was observed only in the spleen, demonstrating the biological functionality of the miRNAs in this lymphoid organ. This is the first study that describes the modulation of miRNAs and the related host immune factors by IBV in chicken embryos. Our data provide novel insight into complex virus-host interactions and specifically highlight components that could affect the host’s immune response to IBV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04527-4) contains supplementary material, which is available to authorized users.


Psychosocial Support for Healthcare Frontliners during COVID-19 Pandemic in Malaysia


Covid-19 quarantine has increased the incidence of ethyl alcohol burns


title: Effects of non-facilitated meaningful activities for people with dementia in long-term care facilities: A systematic review

text: This systematic review sought to evaluate the effectiveness of non-facilitated meaningful activities for older people with dementia in long-term care facilities. Searches were conducted in PubMed; CINAHL; EMBASE; Web of science; PsycINFO; Cochrane; ProQuest; and ClinicalTrials.gov to identify articles published between January 2004 and October 2019. A total of six studies were included. Results implied that current randomised controlled trials or controlled trials about non-facilitated meaningful activities for people with living dementia in long-term care facilitates are limited, but those included in this review were of adequate methodological quality. Meaningful non-facilitated activities, such as music, stimulated family presence, animal-like social robot PARO/plush toy and lifelike dolls, may have beneficial effects on agitation, emotional well-being, feelings of pleasure, engagement, and sleep quality. However, there remains a lack of conclusive and robust evidence to support these psychological and physiological effects of non-facilitated meaningful activities for older people with dementia living in long-term care facilities by care staff.


title: Self-Collected Nasal Swabs for Respiratory Virus Surveillance

text: We tested whether 135 patients reporting acute respiratory illness (ARI) could self-collect nasal swab specimens and ship them for laboratory testing. Most subjects (78.2%) collected and shipped their specimens without errors; 10.5% excluded ≥1 packing components; 12.9% made ≥1 packing errors. Self-swabbing at home is feasible for confirming ARI etiology.


docid: froywddm

title: Preventing intra-hospital infection and transmission of COVID-19 in healthcare workers

text: Abstract Coronavirus disease 2019 (COVID-19) poses an occupational health risk to healthcare workers. Several thousand healthcare workers have already been infected, mainly in China. Preventing intra-hospital transmission of the communicable disease is therefore a priority. Based on the Systems Engineering Initiative for Patient Safety model, the strategies and measures to protect healthcare workers in an acute tertiary hospital are described along the domains of work task, technologies and tools, work environmental factors, and organizational conditions. The principle of zero occupational infection remains an achievable goal that all healthcare systems need to strive for in the face of a potential pandemic.


title: Risk management of viral infectious diseases in wastewater reclamation and reuse: Review

text: Abstract Inappropriate usage of reclaimed wastewater has caused outbreaks of viral infectious diseases worldwide. International and domestic guidelines for wastewater reuse stipulate that virus infection risks are to be regulated by the multiple-barrier system, in which a wastewater treatment process composed of sequential treatment units is designed based on the pre-determined virus removal efficiency of each unit. The objectives of this review were to calculate representative values of virus removal efficiency in wastewater treatment units based on published datasets, and to identify research topics that should be further addressed for improving implementation of the multiple-barrier system. The removal efficiencies of human noroviruses, rotaviruses and enteroviruses in membrane bioreactor (MBR) and conventional activated sludge (CAS) processes were obtained by a systematic review protocol and a meta-analysis approach. The log10 reduction (LR) of norovirus GII and enterovirus in MBR were 3.35 (95% confidence interval: 2.39, 4.30) and 2.71 (1.52, 3.89), respectively. The LR values of rotavirus, norovirus GI and GII in CAS processes were 0.87 (0.20, 1.53), 1.48 (0.96, 2.00) and 1.35 (0.52, 2.18), respectively. The systematic review process eliminated a substantial number of articles about virus removal in wastewater treatment because of the lack of information required for the meta-analysis. It is recommended that future publications should explicitly describe their treatment of left-censored datasets. Indicators, surrogates and methodologies appropriate for validating virus removal performance during daily operation of wastewater reclamation systems also need to be identified.


Assessing the Impact of the COVID-19 Pandemic and Accompanying Mitigation Efforts on Older Adults


title: Effects of virulent and attenuated transmissible gastroenteritis virus on the ability of porcine dendritic cells to sample and present antigen

text: Abstract Virulent transmissible gastroenteritis virus (TGEV) results in an acute, severe pathology and high mortality in piglets, while attenuated TGEV only causes moderate clinical reactions. Dendritic cells (DCs), through uptake and presentation of antigens to T cells, initiate distinct immune responses to different infections. In this study, an attenuated TGEV (STC3) and a virulent TGEV (SHXB) were used to determine whether porcine DCs play an important role in pathogenetic differences between these two TGEVs. Our results showed that immature and mature monocyte-derived dendritic cells (Mo-DCs) were susceptible to infection with SHXB and STC3. However, only SHXB inhibited Mo-DCs to activate T-cell proliferation by down-regulating the expression of cell–surface markers and the secretion of cytokines in vitro. In addition, after 48h of SHXB infection, there was the impairment in the ability of porcine intestinal DCs to sample the antigen, to migrate from the villi to the lamina propria and to activate T-cell proliferation in vivo. In contrast, these abilities of intestinal DCs were enhanced in STC3-infected piglets. In conclusion, our results show that SHXB significantly impaired the functions of Mo-DCs and intestinal DCs in vitro and in vivo, while STC3 had the opposite effect. These differences may underlie the pathogenesis of virulent and attenuated TGEV in piglets, and could help us to develop a better strategy to prevent virulent TGEV infection.


title: Clinical aspects of feline immunodeficiency and feline leukemia virus infection

text: Abstract Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries.


title: An Evidence-Based Approach to the Diagnosis and Management of Acute Respiratory Infections

text: Abstract Acute respiratory infections (ARIs) are commonly experienced in primary care. Although most ARIs are viral in nature and resolve without treatment, nurse practitioners and other clinicians prescribe antibiotics for them 40% to 50% of the time. Thus, the purpose of this article is to review current evidence-based recommendations about the diagnosis and management of ARIs in adults.


title: Chronic, eventually fatal, Kawasaki-like disease in an adult with spondylarthropathy responding to IVIG therapy

text: Abstract We report on an unusual case of a 40-year-old Caucasian male displaying severe Kawasaki-like symptoms. The disease lasted for seven years before diffuse coronary aneurysms occurred, leading to the patient's death, despite ongoing treatment by intravenous immunoglobulins (IVIGs). The patient had also been suffering from a disabling inflammation of the spine, which was reported to have started at the onset of the disorder. Whereas neither NSAIDS, nor high doses corticosteroids, or anti-TNF drugs had a clear effect, the clinical features of spinal inflammation were highly sensitive to IVIGs, and were attributed definitively to HLA-B27-negative axial spondylarthropathy after bone scan and magnetic resonance imaging disclosed typical enthesitis of both heels and bilateral sacroiliitis.


title: Response to “Comments on "Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross‐species transmission from snake to human” and “Codon bias analysis alone is uninformative for identifying host(s) of new virus”

text: We have recently reported for the first time that SARS‐CoV‐2 maybe a bat‐originated coronavirus with a recombination occurred within the spike (S) protein gene based on phylogenetic and simplot analyses(1). These two conclusions are supported by findings recently reported by others and are well accepted in the field of SARS‐CoV‐2 research(2‐4). This article is protected by copyright. All rights reserved.


title: Strategies for intranasal delivery of vaccines

text: The vast majority of human pathogens colonize and invade at the mucosal surfaces. Preventing infection at these sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, it is only recently that the stimulation of local immunity at the mucosal surfaces has become a primary objective in addition to inducing systemic immunity. This review describes vaccine formulations designed for mucosal delivery to the nasal-associated lymphoid tissue, via intranasal administration. The association of antigens with mucosal adjuvants and delivery systems is emphasised.


title: Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

text: BACKGROUND: Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. METHODS: Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. RESULTS: EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl(4)) induced mouse liver fibrosis model. CONCLUSION: EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.


title: Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

text: Griffithsin (GRFT), an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV) infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.


title: Novel approaches and challenges to treatment of CNS viral infections

text: Existing and emerging viral CNS infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus. Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antivirals and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists, and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T-lymphocytes have been used in humans and may provide an effective therapies for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies.


Rethinking states of emergency


The spreading of infectious diseases in modern socio-technical systems Comment on “Pattern transitions in spatial epidemics: Mechanisms and emergent properties” by Gui-Quan Sun et al.


title: Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics

text: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.


title: SARS: epidemiology

text: Severe acute respiratory syndrome (SARS) originated in Southern China in November 2002, and was brought to Hong Kong in February 2003. From Hong Kong, the disease spread rapidly worldwide but mostly to Asian countries. At the end of the epidemic in June, the global cumulative total was 8422 cases with 916 deaths (case fatality rate of 11%). People of all ages were affected, but predominantly females. Health care workers were at high risk and accounted for one‐fifth of all cases. Risk factors for death included old age and comorbid illnesses, especially diabetes. The disease is caused by a novel coronavirus and is transmitted by droplets or direct inoculation from contact with infected surfaces. Contaminated sewage was found to be responsible for the outbreak in a housing estate in Hong Kong affecting over 300 residents. The mean incubation period was 6.4 days (range 2–10). The duration between onset of symptoms and hospitalisation was from 3 to 5 days. The relatively prolonged incubation period allowed asymptomatic air travellers to spread the disease globally. The number of individuals infected by each case has been estimated to be 2.7. Effective control of nosocomial transmission included early detection of disease, strict isolation of patients, practice of droplet and contact precautions and compliance with the use of personal protective equipment. Effective control of disease spread in the community included tracing and quarantine of contacts. Development of a validated diagnostic test and an effective vaccine as well as elimination of possible animal reservoirs are measures needed to prevent another epidemic.


title: A Subset of Protective γ(9)δ(2) T Cells Is Activated by Novel Mycobacterial Glycolipid Components

text: γ(9)δ(2) T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ(9)δ(2) T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ(9)δ(2) T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ(9)δ(2) T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ(9)δ(2) T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ(9)δ(2) T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.


title: Psychological correlates of COVID-19 conspiracy beliefs and preventive measures: Evidence from Turkey

text: COVID-19 pandemic has led to popular conspiracy theories regarding its origins and widespread concern over the level of compliance with preventive measures. In the current preregistered research, we recruited 1088 Turkish participants and investigated (a) individual differences associated with COVID-19 conspiracy beliefs; (2) whether such conspiracy beliefs are related to the level of preventive measures; and (3) other individual differences that might be related to the preventive measures. Higher faith in intuition, uncertainty avoidance, impulsivity, generic conspiracy beliefs, religiosity, and right-wing ideology, and a lower level of cognitive reflection were associated with a higher level of belief in COVID-19 conspiracy theories. There was no association between COVID-19 conspiracy beliefs and preventive measures while perceived risk was positively and impulsivity negatively correlated with preventive measures. We discuss the implications and directions for future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12144-020-00903-0) contains supplementary material, which is available to authorized users.


title: Drugs with new lease of life as quorum sensing inhibitors: for combating MDR Acinetobacter baumannii infections

text: The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is an urgent need for novel strategies to combat bacterial infections caused by MDR strains like Pseudomonas aeruginosa and Acinetobacter baumannii. Quorum sensing (QS) is a critical communication system in bacterial community controlling survival and virulence. The awareness of the importance of QS in bacterial infections has stimulated research to identify QS inhibitors (QSIs) to defeat microbes. In this study, four FDA-approved drugs (besides azithromycin as positive QSI) were tested for potential QS inhibition against clinical A. baumannii isolates and P. aeruginosa (PAO1) standard strain. The inhibitory effect of these drugs on virulence factors of both microbes has been investigated. The studied virulence factors include biofilm formation, twitching and swarming motilities, proteolytic enzyme production, and resistance to oxidative stress. The four tested drugs (erythromycin, levamisole, chloroquine, and propranolol) inhibited QS in Chromobacterium violaceum by 84, 72, 55.1, and 37.3%, respectively. They also significantly inhibited virulence factors in both PAO1 and A. baumannii at sub-inhibitory concentrations. These findings were confirmed by qRT-PCR and mice mortality test, where tested drugs highly repressed the expression of abaI gene and showed significantly improved mice survival rates. In addition, molecular docking studies against AbaI and AbaR proteins of QS system in A. baumannii revealed the potential inhibition of QS by tested drugs. Beside their known activities, the tested drugs could be given new life as QSIs to combat A. baumannii nosocomial infections (alone or in combination with antimicrobials). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-03882-z) contains supplementary material, which is available to authorized users.


docid: mjnbqbrz

title: The digital clinic: Implementing technology and augmenting care for mental health

text: Increasing both access to and quality of mental healthcare is a global priority. One solution is to integrate technologies such as smartphone apps and sensors directly into care. Acknowledging many prior attempts and barriers, we introduce the Digital Clinic which is an already functioning clinic using smartphone apps to augment and extend care today at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts. In this piece, we outline the theoretical foundation of the Digital Clinic and its emphasis on the therapeutic alliance, measurement-based care, and shared decision making. We explore both workflow and engagement challenges as well as solutions including a new care team member, the Digital Navigator, and the customization of technology. Acknowledging that the Digital Clinic is an evolving program, we offer details on our implementation in order to allow others to replicate, expand on, and improve these initial efforts.


title: Hepatitis E: A disease of reemerging importance

text: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. Originally considered to be restricted to humans, it is now clear that HEV and HEV-like viruses have several animal reservoirs with complex ecology and genetic diversity, as exemplified by the recent discovery of HEV in dromedaries, a previously underestimated reservoir of zoonotic viruses prior to the emergence of Middle East Respiratory Syndrome coronavirus. Zoonotic foodborne transmission from pigs and feral animals such as wild boar is of increasing importance in the rapidly industrializing countries of the Asia Pacific region. Such zoonotic hepatitis E infection has particular relevance to the increasing population living with immunosuppression, due to the risk of chronic hepatitis E in these patients. Fortunately, major strides have been made recently in the management of chronic hepatitis E patients. Furthermore, an effective vaccine is also available that promises better control of hepatitis E burden in the near future. This review highlights these major recent developments in the epidemiology, treatment, and prevention of hepatitis E.


Abstract Identification of diagnostic antigens for South American Babesia caballi infections. International Journal for Parasitology 24: 255–258. Sera from 60 horses held in breeding herd in Brazil were examined monthly by ELISA, immunofluorescence antibody test (IFAT) and Western blot. All foals had maternal antibodies detectable by ELISA and IFAT, and seroconversion took place between the 2nd and 5th month of age. The 48 and 50 kDa antigens were recognized first in the course of infection. Of 79 sera taken after sero-conversion 78 reacted with the 48 kDa antigen, 76 with the 50 kDa, 50 with the 70 kDa, 54 with the 112 kDa, 72 with the 141 kDa antigen. In general, sera from horses older than 1 year reacted with all 5 diagnostic antigen bands, but sera from horses older than 3 years only weakly. The antigens of 48 and 50 kDa appear to be conserved among all strains of B. caballi examined so far and are consistently recognized by all infected horses. They are the target antigens for a serological test based on anitigens produced by recombinant DNA techniques.


title: Progress and outlook in structural biology of large viral RNAs

text: The field of viral molecular biology has reached a precipice for which pioneering studies on the structure of viral RNAs are beginning to bridge the gap. It has become clear that viral genomic RNAs are not simply carriers of hereditary information, but rather are active players in many critical stages during replication. Indeed, functions such as cap-independent translation initiation mechanisms are, in some cases, primarily driven by RNA structural determinants. Other stages including reverse transcription initiation in retroviruses, nuclear export and viral packaging are specifically dependent on the proper 3-dimensional folding of multiple RNA domains to recruit necessary viral and host factors required for activity. Furthermore, a large-scale conformational change within the 5′-untranslated region of HIV-1 has been proposed to regulate the temporal switch between viral protein synthesis and packaging. These RNA-dependent functions are necessary for replication of many human disease-causing viruses such as severe acute respiratory syndrome (SARS)-associated coronavirus, West Nile virus, and HIV-1. The potential for antiviral development is currently hindered by a poor understanding of RNA-driven molecular mechanisms, resulting from a lack of structural information on large RNAs and ribonucleoprotein complexes. Herein, we describe the recent progress that has been made on characterizing these large RNAs and provide brief descriptions of the techniques that will be at the forefront of future advances. Ongoing and future work will contribute to a more complete understanding of the lifecycles of retroviruses and RNA viruses and potentially lead to novel antiviral strategies.


Noninvasive Versus Invasive Ventilation in COVID-19 One Size Does Not Fit All!


title: Sequence analysis of the 3' termini of RNA1 and RNA2 of blueberry leaf mottle virus

text: Abstract The 3' termini of RNA1 and RNA2 of blueberry leaf mottle virus (BBLMV) were cloned and the cDNA sequence of a portion of the putative polymerase gene, the complete coat protein (CP) gene, and the 3' non-coding regions was determined. The N terminus of the coat protein gene was precisely located by comparison with the amino acid sequence determined by the Edman degradation sequencing of the purified coat protein. The coat protein gene encoded a polypeptide of 521 amino acids with a predicted Mr of 57,542. Homology to BBLMV coat protein was highest with tomato ringspot virus (TomRSV) and cherry leaf roll virus (CLRV); two other nepoviruses also belonging to a sub-group defined by the presence of large RNA2 components. The 3' terminal 1390 nt of RNA1 and RNA2 were nearly identical and apparently non-coding. No statistically significant sequence homology was found between the 3' non-coding regions of BBLMV and other nepoviruses. A highly conserved 3' non-coding region of this length is unusual, but has been reported for two other related viruses, TomRSV and CLRV. The biological function of the long 3' non-coding region and how the high level of sequence homology is maintained between RNA1 and RNA2, is unknown. Possible mechanisms for conservation of the 3' terminus are discussed.


title: SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation

text: Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3(−/−) mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.


436. Developing a Synthetic DNA Vaccine for an Emerging Pathogen - Middle East Respiratory Syndrome


title: A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis

text: Abstract Background There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the Coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. Objectives To describe the characteristics of the currently registered clinical trials related to COVID-19. Methods We searched the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) on May 15, 2020. We included any entry that is related to COVID-19. We abstracted then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. Results We identified 1,308 eligible registered trials. The majority of trials were initially registered with ClinicalTrials.gov (n= 703; 53.7%) and the Chinese Clinical Trial Registry (ChiCTR) (n= 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most-commonly studied intervention category was pharmacologic (n=763; 58.3%), with antiparasitic medications being the most common subcategory. While over half of trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. Conclusion There is a relatively large number of registered trials but very few results published so far. While our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.


title: Straight talk with...Ian Lipkin

text: How do you sequence a virus that no one has identified before? With the right technology, it's not as difficult a task as it might seem, says Ian Lipkin, director of the Center for Infection and Immunity at Columbia University's Mailman School of Public Health. Lipkin has been working on the technology involved with viral discovery since the late 1980s, when he became the first researcher to identify a microbe using only molecular tools. He and the Center's team of about 50 researchers have identified close to 200 new viruses so far. Most recently, Lipkin and his colleague Thomas Briese identified a new hemorrhagic fever virus that killed several patients in southern Africa last year. Now, in addition to processing samples from around the world, Lipkin has been working to export his sequencing technology—and the expertise needed to use it—to the developing world. Erica Westly spoke with Lipkin about how the viral discovery techniques he uses could help prevent future viral disease outbreaks, from swine flu to the unknown.


title: The Magnetic Resonance Imaging Appearance of Monophasic Acute Disseminated Encephalomyelitis An Update Post Application of the 2007 Consensus Criteria

text: Acute disseminated encephalomyelitis (ADEM) is an immunologically mediated inflammatory disease of the central nervous system that typically occurs after a viral infection or recent vaccination, and is most commonly seen in the pediatric population. In 2007 the International Pediatric Multiple Sclerosis Study Group proposed a consensus definition for ADEM for application in research and clinical settings. This article gives an overview of ADEM in children, focusing on differences that have emerged since the consensus definition was established. Although the focus is on neuroimaging in these patients, a synopsis of the clinical features, immunopathogenesis, treatment, and prognosis of ADEM is provided.


title: Editorial: increasing IBD prevalence and its complications in the context of the COVID‐19 pandemic. Authors' reply

text: LINKED CONTENT This article is linked to King et al and Benson‐Pope and Greary papers. To view these articles, visit https://doi.org/10.1111/apt.15701 and https://doi.org/10.1111/apt.15759.


title: “Running the Gauntlet”: Formidable challenges in advancing neglected tropical diseases vaccines from development through licensure, and a “Call to Action”

text: Translational science for new biotechnologies (e.g. drugs, vaccines, devices, or diagnostics) depend on the development of a robust ‘business case’. This is driven by complex scientific, technical, logistical, financial and operational elements to determine the feasibility and probability of traversing the “valleys of death” leading to licensure. The potential results in terms of profitability and financial realization, called ‘product value proposition’ play a crucial role in establishing incentives for investment during and after development. With this review, our goal is to summarize the challenges in taking vaccines against neglected tropical diseases (NTDs) from development through licensure and provide a perspective that these vaccines can have measurable public health and economic profitability and market success. Understanding these processes and its challenges would open the opportunity to accelerate and advance these essential NTD vaccines through the last mile towards licensure and for the delivery to afflicted populations in low- and middle-income countries.


title: EndoU is a novel regulator of AICD during peripheral B cell selection

text: Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(−/−[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag–specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.


title: Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: Implication in neuropathogenesis

text: Abstract Japanese encephalitis (JE) is one of the leading causes of acute encephalopathy affecting children and adolescents in the tropics. JE virus (JEV) infection causes prominent neurological sequelae in approximately one-third of the survivors. In humans, the inflammatory response of CNS consequent to JEV induced viral encephalitis is mediated through chemokines released by various cells of CNS. In the present study, the chemokine profiles of mouse neuroblastoma cells (N2A) following JEV infection was analyzed by cDNA microarray followed by real-time RT-PCR. Eighty mRNA transcripts belonging to various functional classes exhibited significant alterations in gene expression. There was considerable induction of genes involved in apoptosis and anti-viral response. Modified levels of several transcripts involved in proinflammatory and anti-inflammatory processes exemplified the balance between opposing forces during JEV pathogenesis. Other genes displaying altered transcription included those associated with host translation, cellular metabolism, cell cycle, signal transduction, transcriptional regulation, protein trafficking, neurotransmitters, neuron maturation, protein modulators, ER stress and cytoskeletal proteins. The infection of neurons results in the synthesis of proinflammatory chemokines, which are early important mediators of leukocyte recruitment to sites of viral infection. Our results clearly suggest the implication of chemokines in neuropathogenesis of JEV infection leading to neurological sequelae. Pro- and anti-inflammatory agents targeted against chemokines such as CXCL10 may provide possible therapeutic modalities that can mitigate the morbidity associated with JEV infection of the CNS.


title: The COVID-19 AAGP Online Trainee Curriculum: Development and Method of Initial Evaluation

text: OBJECTIVES: : One effect of the COVID-19 pandemic is the disruption of in-person clinical experiences within geriatric psychiatry residency education. Online resources for trainees are needed to fill resultant gaps. METHODS: : The AAGP Teaching & Training Committee leadership collaborated with geriatric psychiatry experts to develop a web-based geriatric psychiatry curriculum for psychiatry residents and other learners. In addition, we planned to obtain initial self-report outcomes of the curricular modules. RESULTS: : The COVID-19 AAGP Online Trainee Curriculum (aagponline.org/covidcurriculum) consists of approximately 30 video-recorded lectures provided by AAGP member experts. A demographic survey and pre-post survey attached to each module allow us to obtain learner characteristics and feedback on each module. CONCLUSIONS: : The Curriculum has the potential to supplement psychiatry residency education during the pandemic and potentially raise the profile of AAGP, with the goal of inspiring interest within geriatric psychiatry. Results of the initial self-report evaluation should be available in 1 year.


title: Growth pattern of various JHM coronavirus isolates in primary rat glial cell cultures correlates with differing neurotropism in vivo

text: Abstract The JHM strain of murine hepatitis coronavirus is neurotropic in rats, causing either fatal acute encephalomyelitis or subacute demyelinating encephalomyelitis. We have examined the growth properties of three JHM virus isolates in primary rat glial cultures and found a correlation with their ability to cause disease. Wild type JHM virus has the propensity to cause lytic infections in glial cultures, and a temperature-sensitive mutant designated JHM-ts43 invariably produces persistent infections with reduced cytopathic effects (CPE) as compared to the wild type. Moreover, a non-neurotropic isolate, designated JHM-Pi virus, produces either non-productive persistent infections at low multiplicity of infection (m.o.i.) or productive persistent infections at high m.o.i., with, however, no CPE. The phenotypic expression of persistence is glial cell-dependent, since all three viruses produce similarly lytic infections when grown on various susceptible cell lines. The genetic basis of JHM virus persistence can be explained at the level of direct virus-glial cell interactions.


title: High diversity of picornaviruses in rats from different continents revealed by deep sequencing

text: Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.


title: Hazard control for communicable disease transport at Ornge

text: Transporting patients with communicable diseases is common in critical care transport operations. At Ornge, Ontario's critical care transport provider, 13.7% of patients required contact, droplet, or airborne precautions during transport in 2019–2020. Ensuring that staff are protected while transporting patients with communicable diseases must remain a prime directive for medical transport administrators and operators. Success in safety requires a robust system of hazard identification and adherence to generally accepted methods of hazard control. This commentary will discuss some of the administrative and engineering controls, as well as the personal protective equipment (PPE) strategies deployed at Ornge.


title: Spillover effects of Great Recession on Hong-Kong’s Real Estate Market: An analysis based on Causality Plane and Tsallis Curves of Complexity–Entropy

text: Abstract This paper investigates the impact of the sub-prime loan crisis on the Real Estate Market of Hong-Kong. Based on permutation entropy, complexity–entropy causality plane and Tsallis complexity–entropy curve, we characterize the complexity of the housing indices-both in terms of size and region-and distinguish the level of informational efficiency. By calculating the quantifiers we report that most indices exhibit a behavior equivalent to a persistent stochastic dynamics with Hurst exponents between 0.5 and 0.7. The outbreak of the crisis had changed the dynamical structure of the indices decreasing the level of randomness and increasing considerably their regularity and predictability. Only the index of the Kowloon area seems not impacted by the crisis, exhibiting higher levels of informational efficiency. The results are robust based on the utilization of two different entropy definitions: The Shannon and Tsallis-q entropy. Lastly, with the temporal evolution of the indices, we identify periods where the underlying dynamical structure of the market was impacted by certain events like the SARS epidemic and the imposition of Special Stamp Duty on housing.