docid: fhmhpobi

title: Virus infection-induced host mRNA degradation and potential application of live cell imaging

text: Abstract Viruses exist wherever there is life. They can cause allergy, immune response, inflammation, and even fatal diseases directly or indirectly. Accumulating evidence shows that host RNA undergoes rapid degradation during virus infection. Herein, we focus on several possible mechanisms of infection-induced host RNA turnover, which seems to be a common strategy for both prokaryotic and eukaryotic viruses during the very early stage of infection and a potential application of live cell imaging on its visualization.


title: Non-invasive ventilation in acute respiratory failure

text: Summary Non-invasive mechanical ventilation has been increasingly used to avoid or serve as an alternative to intubation. Compared with medical therapy, and in some instances with invasive mechanical ventilation, it improves survival and reduces complications in selected patients with acute respiratory failure. The main indications are exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, pulmonary infiltrates in immunocompromised patients, and weaning of previously intubated stable patients with chronic obstructive pulmonary disease. Furthermore, this technique can be used in postoperative patients or those with neurological diseases, to palliate symptoms in terminally ill patients, or to help with bronchoscopy; however further studies are needed in these situations before it can be regarded as first-line treatment. Non-invasive ventilation implemented as an alternative to intubation should be provided in an intensive care or high-dependency unit. When used to prevent intubation in otherwise stable patients it can be safely administered in an adequately staffed and monitored ward.


title: Heterotypic Infection and Spread of Rhinovirus A, B, and C among Childcare Attendees

text: BACKGROUND: Despite the frequency of human rhinovirus (HRV), data describing the molecular epidemiology of HRV in the community are limited. Childcare centers are optimal settings to characterize heterotypic HRV cocirculation. METHODS: HRV specimens were prospectively obtained from a cohort of childcare attendees at enrollment and weekly during respiratory illness. The 5′ noncoding region sequences were used to determine HRV species (A, B, C) and genotypes. RESULTS: Among 225 children followed, sequence data were available for 92 HRV infections: HRV-A (n = 80; 59%) was most common, followed by HRV-C (n = 52, 39%), and HRV-B (n = 3, 2%). Forty-one genotypes were identified and cocirculation was common. Frequent spread between classrooms occurred with 2 HRV-A genotypes. Repeated detections within single illnesses were a combination of persistent (n = 7) and distinct (n = 7) genotypes. Prevalence of HRV among asymptomatic children was 41%. HRV-C was clinically similar to HRV-A and HRV-B. CONCLUSIONS: HRV epidemiology in childcare consists of heterotypic cocirculation of genotypes with periodic spread within and among classrooms. Based on our finding of multiple genotypes evident during the course of single illnesses, the use of sequence-based HRV type determination is critical in longitudinal studies of HRV epidemiology and transmission.


title: Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.


title: Hydatidiform mole in the era of COVID‐19 pandemic. Is there an association?

text: Coronavirus disease 2019 (COVID‐19) is considered a worldwide pandemic. COVID‐19 patients had profound immune dysregulation so they could be susceptible for adverse pregnancy outcomes as hydatidiform mole. In this article, we tried to explain the link between hydatidiform mole and COVID‐19.


title: Available Evidence of Association between Zika Virus and Microcephaly

text: OBJECTIVE: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. DATA SOURCES: We did a comprehensive literature review with the keywords “zika” and/or “microcephaly” from inception to May 27, 2016, with PubMed. STUDY SELECTION: Studies were included and analyzed if they met all of the following criteria: “probable or confirmed infant microcephaly” and “probable or confirmed ZIKV infection among mothers or infants”. RESULTS: We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious “diagnosed” microcephaly. CONCLUSIONS: There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions.


title: Practical Guidelines for Collection, Manipulation and Inactivation of SARS‐CoV‐2 and COVID‐19 Clinical Specimens

text: SARS‐CoV‐2 is a novel coronavirus that causes the acute respiratory disease—Coronavirus disease 2019 (COVID‐19)—which has led to a global health crisis. Currently, no prophylactics or therapies exist to control virus spread or mitigate the disease. Thus, the risk of infection for physicians and scientists is high, requiring work to be conducted in Biosafety Level‐3 (BSL‐3) facilities if virus will be isolated or propagated. However, inactivation of the virus can enable safe handling at a reduced biosafety level, making samples accessible to a diverse array of institutions and investigators. Institutions of all types have an immediate need for guidelines that outline safe collection, handling, and inactivation of samples suspected to contain active virus. Here we provide a practical guide for physicians and researchers wishing to work with materials from patients who are COVID‐19 positive or suspected positive. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Practical guidelines for the safe collection and handling of specimens collected from COVID‐19 and suspected COVID‐19 patients Basic Protocol 2: Inactivating SARS‐CoV‐2


title: Modern approaches to understanding stress and disease susceptibility: A review with special emphasis on respiratory disease

text: Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels.


title: Porcine epidemic diarrhea (PED) infection, diagnosis and vaccination: A mini review

text: Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Historically, PED is one of major causes of loss in swine and remains prevalent in some parts of the world. Even with increase in the available tests for PED diagnosis, which include histological diagnosis; virological diagnosis and serological diagnosis, there is no vaccine or specific treatment for this disease yet. In this mini review, the overview and current situation of PED is described with updated techniques, in an effort to comprehensively discuss and understand the disease characteristics.


docid: gdhubnby

title: The rationale for the use of colchicine in COVID-19: comments on the letter by Cumhur Cure M et al.


Double trouble: methanol outbreak in the wake of the COVID-19 pandemic in Iran—a cross-sectional assessment


title: Unhealthy Landscapes: Policy Recommendations on Land Use Change and Infectious Disease Emergence

text: Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers’ objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.


title: Stable long‐term cultures of self‐renewing B cells and their applications

text: Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen‐presenting cells for the discovery of tumor neoantigens.


title: Full genome analysis of a novel type II feline coronavirus NTU156

text: Infections by type II feline coronaviruses (FCoVs) have been shown to be significantly correlated with fatal feline infectious peritonitis (FIP). Despite nearly six decades having passed since its first emergence, different studies have shown that type II FCoV represents only a small portion of the total FCoV seropositivity in cats; hence, there is very limited knowledge of the evolution of type II FCoV. To elucidate the correlation between viral emergence and FIP, a local isolate (NTU156) that was derived from a FIP cat was analyzed along with other worldwide strains. Containing an in-frame deletion of 442 nucleotides in open reading frame 3c, the complete genome size of NTU156 (28,897 nucleotides) appears to be the smallest among the known type II feline coronaviruses. Bootscan analysis revealed that NTU156 evolved from two crossover events between type I FCoV and canine coronavirus, with recombination sites located in the RNA-dependent RNA polymerase and M genes. With an exchange of nearly one-third of the genome with other members of alphacoronaviruses, the new emerging virus could gain new antigenicity, posing a threat to cats that either have been infected with a type I virus before or never have been infected with FCoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-012-0864-0) contains supplementary material, which is available to authorized users.


title: MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection

text: Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk2−/− cells, but not Jnk1−/− cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk7−/−) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk2−/− mice, but not Jnk1−/− mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.


title: Complete genomic sequence of the coronavirus transmissible gastroenteritis virus SHXB isolated in China

text: A strain of transmissible gastroenteritis virus (TGEV), SHXB, was isolated in Shanghai, China. The complete genome of strain SHXB was sequenced, and its sequence was compared those of other TGEV strains in the GenBank database. The comparison showed that there were no insertions or deletions in the 5′ and 3′- non-translated regions, in the nonstructural genes ORF1, ORF3, and ORF7, or in the genes encoding the structural proteins envelope (E), membrane (M) and nucleoprotein (N). A phenomenon in common with other strains was that nucleotide (nt) 655 of the spike (S) gene was G, and a common change in nt 1753 of the S gene was a T-to-G mutation that caused a serine-to-alanine mutation at amino acid 585, which is in the region of the main major antigenic sites A and B of the TGEV S protein. A 6-nt deletion was also found at nt 1123-1128 in all Purdue strains except the strain Virulent Purdue. Phylogenetic analysis showed that TGEV SHXB was closely related to the Purdue strains and shared a common ancestor with the Miller strains as well as strain PRCV-ISU-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-014-2080-9) contains supplementary material, which is available to authorized users.


title: Diagnostic strategies for SARS-CoV-2 infection and interpretation of microbiological results

text: BACKGROUND: To face the current COVID-19 pandemic, diagnostic tools are essential. It is recommended to use real-time RT-PCR for RNA viruses in order (i) to perform a rapid and accurate diagnostic, (ii) to guide patient care and management and (iii) to guide epidemiological strategies. Further studies are warranted to define the role of serological diagnosis and a possible correlation between serological response and prognosis. OBJECTIVES: To guide clinical microbiologists in the use of these diagnostic tests and clinicians in the interpretation of their results. SOURCES: A research of literature was performed through PubMed and Google Scholar using the keywords SARS-CoV-2, SARS-CoV-2 molecular diagnosis, SARS-CoV-2 immune response, SARS-CoV-2 serology/antibody testing, coronavirus diagnosis. CONTENT: The present review discusses performances, limitations and use of current and future diagnostic tests for SARS-CoV-2. IMPLICATIONS: Real-time RT-PCR remains the reference method for diagnosis of SARS-CoV-2 infection. On the other hand, notwithstanding its varying sensitivity according to the time of infection, serology represents a valid asset (i) to try to solve possible discrepancies between a highly suggestive clinical and radiological presentation and negative RT-PCR, (ii) to solve discrepancies between different PCR assays, and (iii) for epidemiological purposes.


title: Considerations for Management of Acute Coronary Syndromes During the SARS-CoV-2 (COVID-19) Pandemic

text: Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction (AMI). Despite these unprecedented times providers should not overlook ACS guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with acute coronary syndromes (ACS) and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic.


title: SYBR Green real-time reverse transcription-polymerase chain reaction assay for the generic detection of coronaviruses

text: Coronaviruses are etiologic agents of respiratory and enteric diseases in humans and in animals. In this study, a one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on SYBR Green chemistry and degenerate primers was developed for the generic detection of coronaviruses. The primers, designed in the open reading frame 1b, enabled the detection of 32 animal coronaviruses including strains of canine coronavirus, feline coronavirus, transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). A specific amplification was also observed with the human coronaviruses (HCoV) HCoV-NL63, HCoV-OC43, HCoV-229E and severe acute respiratory syndrome coronavirus (SARS-CoV). The real-time RT-PCR detected down to 10 cRNA copies from TGEV, BCoV, SARS-CoV and IBV. In addition, the assay exhibited a high sensitivity and specificity on clinical samples from different animal species. The developed assay represents a potential tool for laboratory diagnostics and for detecting still uncharacterized coronaviruses.


docid: ybvfkupu

title: Abstract 44. Paramyxovi rus induced changes of β-adrenergic receptor response and its immunological modulation


title: Lack of viral transmission to preterm newborn from a COVID‐19 positive breastfeeding mother at 11 days postpartum

text: In December 2019, novel coronavirus 2019 has appeared in China. On 11 February 2020, the World Health Organization officially names the disease as COVID-19.1 The new coronavirus is highly contagious. The rapid spread of SARS-CoV-2 lead to declare the pandemic on the 11th March 2020. On 10 May 2020 the number of infected people is 4,132,373 worldwide.2 This article is protected by copyright. All rights reserved.


title: Métodos de diagnóstico rápido de las infecciones respiratorias

text: Acute respiratory infections are the second cause of morbidity and mortality in children and adults worldwide, being viruses, bacteria and fungi involved in their etiology. The rapid diagnosis allows for a better clinical management of the patient, for adopting public health measures and for controlling possible outbreaks. The main etiologic agents can be diagnosed within the first hours after the onset of symptoms with antigen detection techniques, primarily immunochromatography. Results are obtained in 15–30 minutes, with 70–90% sensitivity and >95% specificity for the diagnosis of Streptococcus pneumoniae and Legionella pneumophila serogroup O1 infections from urine, Streptococcus pyogenes from throat swabs and respiratory syncytial virus from nasopharyngeal aspirates. Worse results are obtained for influenza viruses and Pneumocystis jirovecii with these techniques; however, other easy-to-perform molecular techniques are available for the rapid diagnosis of these microorganisms. In general, these techniques should not be used for monitoring the outcome or response to treatment.


title: Assessment of air purifier on efficient removal of airborne bacteria, Staphylococcus epidermidis, using single-chamber method

text: We evaluated the efficiency of an air purifier using the single-chamber method for the effective removal of airborne Staphylococcus epidermidis, a nosocomial infection–causing bacterium. In this experiment, the bacterial strain S. epidermidis was injected using a nebulizer into the test chamber, which was similar to a consumer living space (60 m(3)). The microbial sampling was conducted via the air sampler method, and the reduction in S. epidermidis growth was monitored by performing three consecutive tests. Initially, a blank test was conducted to determine the natural decay rate and calibrate the experimental setup. After injecting the bacterial strain from 1240 to 11180 CFU per unit volume (m(3)), the natural decay rate showed a maximum deviation of 3.1% with a sampling error of 1.1% p at a confidence level of 95%. In addition, the particle size distribution in the test chamber was found to range from 0.3 to 5.0 μm, and a subsequent decrease in large-sized particles was observed with the operation of the air purifier, which is the size similar to that of suspended airborne bacteria. This can be used to assess the performance of the air purifier by calibrating the natural reduction value to the reduced operation value. Thus, the single-chamber technique is a promising approach for analyzing the removal efficacy of airborne bacteria from indoor air.


title: Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review

text: In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β‐glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti‐inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well‐being.


title: Cutaneous involvement during COVID‐19 pandemic: an emerging sign of infection

text: Since December 2019, SARS‐CoV‐2 epidemic has spread all over the world.(1) To date, few reports regarding the cutaneous involvement in COVID‐19 have been published.(2,3) Herein, we report a four cases series describing skin lesions probably related with COVID‐19. The case 1 was a 66‐year‐old Caucasian female with a history of hypertension and dyslipidaemia. When hospitalized, she showed fever, nasal congestion and pneumonia symptoms. A chest‐TC displayed bilateral interstitial lungs’ involvement and a nasopharyngeal‐swab confirmed SARS‐CoV‐2 infection. At day 6 of hospitalization, an asymptomatic erythematous‐pomphoid skin rash occurred on the trunk (Figure 1A).


title: COVID-19 Pandemic and Cardiac Electrophysiology: Guidance Protocol From a UK Tertiary Cardiac Center

text: Since December 2019, the COVID-19 pandemic has resulted in more than 2,160,000 positive cases and more than 145,000 deaths until April 18, 2020. The pressure to the health services worldwide has been unprecedented. The redeployment of staff and resources to treat more efficiently COVID-19 cases along with the need to reduce disease transmission has affected the field of electrophysiology among many others. Amendments to clinical pathways are obligatory in this perspective to continue to provide the necessary health services to the people who need them, although at the same time, infection control and prevention are not compromised by inadvertent disease transmission or unnecessary use of resources. We aim to provide a guide of the logistic aspects of electrophysiology procedures derived from our tertiary cardiac center during the current COVID-19 pandemic.


title: Follow-up for pregnant women during the COVID-19 pandemic: French national authority for health recommendations

text: INTRODUCTION: In the context of the stage 3 SARS-Cov-2 epidemic situation, it is necessary to put forward a method of rapid response for an HAS position statement in order to answer to the requests from the French Ministry of Solidarity and Health, healthcare professionals and/or health system users’ associations concerning follow-up of pregnant women during the COVID-19 outbreak. METHODS: A simplified 7-step process that favours HAS collaboration with experts (healthcare professionals, health system users’ associations, scientific societies etc.), the restrictive selection of available evidence and the use of digital means of communication. A short and specific dissemination format, which can be quickly updated in view of the changes in available data has been chosen.


Systemic isotretinoin therapy in the era of COVID‐19


title: Appealing for efficient, well organized clinical trials on COVID-19.

text: Background The rapid emergence of clinical trials on COVID-19 stimulated a wave of discussion in scientific community. It is important to understand the characteristics of the ongoing or pending interventional clinical trials on COVID-19. Methods We reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and ClinicalTrials.gov. A total of 171 COVID-19-related interventional trials were identified on Feb 22, 2020. These trials are classified into 4 categories based on treatment modalities, including chemical drugs (CDs), biological therapies (BTs), traditional Chinese medicine (TCM) treatments and other therapies. Results Our analysis focused on the issues of stage, design, randomization, blinding, primary endpoints (PEs) definition and sample size of these trials. Although most trials use parallel-arm design (88.3%) and randomization (77.2%), blinding is applied in only 25 trials (14.6%). More than half of the trials planned to recruit ≤100 patients, indicating a possibility of insufficient statistical power. About one third of trials will recruit severe and critically ill patients. More trials on traditional Chinese medical treatment use 2 or more PEs than those on CDs or biological treatments (57.6%, 39.4% and 40.5%, respectively). Conclusions We found some studies with potential defects including unreasonable design, inappropriate PE and small sample size. Clinical trials on COVID-19 should be designed based on scientific rules, ethics and benefits for patients.


title: Atypical presentation of SARS-CoV-2 infection: A case report.

text: BACKGROUND The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.


docid: vwthwjlm

title: Synthesis, antitubercular and anticancer activity of new Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives

text: Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H(37)Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity.


title: SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway

text: Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.


Safeguarding Dermatologist Attendings and Residents Amid the COVID‐19 Pandemic: Focus on Special Populations


title: Evolution of a Search: The Use of Dynamic Twitter Searches During Superstorm Sandy

text: Background: Twitter has emerged as a critical source of free and openly available information during emergency response operations, providing an unmatched level of on-the-ground situational awareness in real-time. Responders and survivors turn to Twitter to share information and resources within communities, conduct rumor control, and provide a “boots on the ground” understanding of the disaster. However, the ability to tune out background “noise” is essential to effectively utilizing Twitter to identify important and useful information during an emergency response. Methods: This article highlights a two-prong strategy in which the use of a Twitter list paired with subject specific Boolean searches provided increased situational awareness and early event detection during the United States Department of Health and Human Services (HHS), Office of the Assistant Secretary for Preparedness and Response (ASPR) response to Superstorm Sandy in 2012. To maximize the amount of relevant information that was retrieved, the Twitter list and Boolean searches were dynamic and responsive to real-time developments, evolving health threats, and the informational needs of decision-makers. Conclusion: The use of a Twitter list combined with Boolean searches led to enhanced situational awareness throughout the HHS response. The incorporation of a dynamic search strategy over the course of the HHS Sandy response, allowed for the ability to account for over-tweeted information, changes in event related conversation, and decreases in the return of relevant information.


title: Measuring inequalities in the public health workforce at county-level Centers for Disease Control and Prevention in China

text: BACKGROUND: The public health workforce (PHW) is a key component of a country’s public health system. Since the outbreak of SARS (severe acute respiratory syndrome) in 2003, the scale of PHW in China has been continuously expanding, but policymakers and researchers still focus on the distribution of public health personnel, especially the regional inequality in such distribution. We aimed to identify the root cause of PHW inequality by decomposing different geographical units in China. METHODS: This study was based on data from a nationwide survey, which included 2712 county-level data. The distribution of the PHW in geographical units was evaluated by the Gini coefficient and Theil T index, and inequalities at regional, provincial, and municipal levels were decomposed to identify the root causes of inequalities in the PHW. Additionally, the contextual factors affecting the distribution of the PHW were determined through regression analysis. RESULTS: The overall inequality results show that health professional and field epidemiological investigators faced worse inequality than the staff. In particular, field epidemiological investigators had a Gini coefficient close to 0.4. Step decomposition showed that within-region inequalities accounted for 98.5% or more of overall inter-county inequality in the distribution of all PHW categories; provincial decomposition showed that at least 74% of inequality is still distributed within provinces; the overall contribution of within-municipal inequality and between-municipal inequality was basically the same. Further, the contextual factor that influenced between-municipality and within-municipality inequality for all three categories of PHWs was the agency building area per employee. Per capita GDP had a similar effect, except for between-municipality inequality of professionals and within-municipality inequality of field epidemiological investigators. CONCLUSIONS: The successive decomposition showed that inequality is mainly concentrated in counties at the within-province and within-municipal levels. This study clearly suggests that the government, especially the municipal government at the provincial level, should increase financial investment in Centers for Disease Control and Prevention (CDCs) with worse resource allocation in their jurisdiction through various ways of compensation and incentives, enhance their infrastructure, and improve the salary of personnel in these institutions, to attract more public health professionals to these institutions.


title: Covid-19 and lung cancer: A greater fatality rate?

text: BACKGROUND: Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes. PATIENTS AND METHODS: We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis. RESULTS: 17/1878 total diagnosis in our center had lung cancer (0.9%) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3%) versus 192/1878 Covid-19 patients in our center (p<0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018). CONCLUSIONS: Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.


title: Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China

text: Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3–16 days), 7 with anorexia (7–22 days), 6 with upper abdominal discomfort (1–7 days), and 4 with nausea (1–7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.


title: Increased Flavonoid Compounds from Fermented Houttuynia cordata using Isolated Six of Bacillus from Traditionally Fermented Houttuynia cordata

text: Flavonoids, which form a major component in Houttuynia cordata Thunb., display a wide range of pharmacological activities. The expression of plant flavonoids is partly regulated by fermentation. Therefore, we studied the effects of fermentation on H. cordata in order to identify the strains present during the fermentation process, and to determine whether fermented H. cordata could be used as a probiotic. Our results showed that all 6 of the bacterial strains isolated from fermented H. cordata (FHC) belonged to the genus Bacillus. As expected, fermenting H cordata also increased the flavonoid content as increases were observed in the levels of rutin, quercitrin, and quercetin. To test the effects of fermentation, we treated LPS-stimulated RAW264.7 cells with non-fermented H. cordata extracts (HCE) or FHC extracts (FHCE). Compared to the HCE-treated cells, the FHCE-treated cells showed increased viability. No cytotoxic effects were detected in the FHCE-treated groups in the 2 cell lines used in the study, namely, RAW264.7 and RBL-2H3. FHCE-treated HepG2 cells showed decreased growth, compared to HCE-treated HepG2 cells. These results indicate that the fermented H. cordata predominantly contained Bacillus strains. Furthermore, FHCE are able to prevent LPS-induced inflammatory effects and inhibit the growth of HepG2 cells.


title: The Story behind COVID-19: Animal Diseases at the Crossroads of Wildlife, Livestock and Human Health

text: A number of virological, epidemiological and ethnographic arguments suggest that COVID-19 has a zoonotic origin. The pangolin, a species threatened with extinction due to poaching for both culinary purposes and traditional Chinese pharmacopoeia, is now suspected of being the “missing link” in the transmission to humans of a virus that probably originated in a species of bat. Our predation of wild fauna and the reduction in their habitats have thus ended up creating new interfaces that favour the transmission of pathogens (mainly viruses) to humans. Domesticated animals and wild fauna thus constitute a reservoir for almost 80% of emerging human diseases (SARS-CoV, MERS-CoV, Ebola). These diseases are all zoonotic in origin. As if out of a Chinese fairy tale, the bat and the pangolin have taught us a lesson: within an increasingly interdependent world, environmental crises will become ever more intertwined with health crises. Questions relating to public health will no longer be confined to the secrecy of the physician’s consulting room or the sanitised environment of the hospital. They are now being played out in the arena of international trade, ports and airports and distribution networks. Simply put, all human activity creates new interfaces that facilitate the transmission of pathogens from an animal reservoir to humans. This pluri-disciplinary article highlights that environmental changes, such as the reduction in habitats for wild fauna and the intemperate trade in fauna, are the biggest causes of the emergence of new diseases. Against this background, it reviews the different measures taken to control, eradicate and prevent the emergence of animal diseases in a globalised world.


title: COVID-19 causes unprecedented educational disruption: Is there a road towards a new normal?

text: COVID-19 confronts the education system with a new and massive crisis. What should a “new normal” look like for future generations? How can countries use the innovativeness of the recovery period to “build back better”? This Viewpoint highlights the UNESCO-led Global Coalition for Education initiative, which is seeking solutions to support learners and teachers, as well as governments throughout the recovery process, with a principal focus on inclusion, equity, and gender equality. The Viewpoint also argues that the current crisis is an opportunity for stronger international collaboration, which might provide a better focus and deliver solutions, including digital tools. Resilience and adaptability will be crucial for the next generations to navigate through the present—and any future—pandemic.


title: Comparison of genomic and amino acid sequences of eight Japanese encephalitis virus isolates from bats

text: We compared nucleotide and deduced amino acid sequences of eight Japanese encephalitis virus (JEV) isolates derived from bats in China. We also compared the bat JEV isolates with other JEV isolates available from GenBank to determine their genetic similarity. We found a high genetic homogeneity among the bat JEVs isolated in different geographical areas from various bat species at different time periods. All eight bat JEV isolates belonged to genotype III. The mean evolutionary rate of bat JEV isolates was lower than those of isolates of other origin, but this difference was not statistically significant. Based on these results, we presume that the bat JEV isolates might be evolutionarily conserved. The eight bat JEV isolates were phylogenetically similar to mosquito BN19 and human Liyujie isolates of JEV. These results indicate that bats might be involved in natural cycle of JEV.


docid: snsqpizu

title: The cell receptor level is reduced during persistent infection with influenza C virus

text: Persistent influenza C virus infection of MDCK cells perpetuates the viral genome in a cell-associated form. Typically, virus production remains at a low level over extended periods, in the absence of lytic effects of replication. In this study, we demonstrate that persistently infected cells are very restricted in permissiveness for superinfection. By reconstitution experiments, using bovine brain gangliosides as artificial receptors, the degree of super-infection was markedly increased. Analysis of cellular receptor expression revealed reduced concentrations of sialoglycoproteins in general and a limited presentation of the major receptor gp40. Cocultures of persistently infected and uninfected cells (the latter carrying normal receptor levels) initiated a transient rise in virus titers. This kind of induction of virus synthesis appeared to be mainly receptor-linked, since a receptor-deprived subline, MDCK II, did not give rise to a similar effect. Susceptibility of MDCK II cocultures could be partly restored by ganglioside treatment. In accordance to related virus systems, these findings on influenza C virus suggest a role of cell receptor concentrations in the regulation of long-term persistence.


Entry of enveloped viruses into host cells is mediated by their surface envelope glycoproteins (Env). On the surface of the virus, Env is in a metastable, prefusion state, primed to catalyze the fusion of the viral and host membranes. An external trigger is needed to promote the drastic conformational changes necessary for the fusion subunit to fold into the low‐energy, 6‐helix bundle. These triggers typically facilitate pH‐independent entry at the plasma membrane or pH‐dependent entry in a low‐pH endosomal compartment. The α‐retrovirus avian sarcoma leukosis virus (ASLV) has a rare, 2‐step entry mechanism with both pH‐dependent and pH‐independent features. Here, we present the 2.0‐Å‐resolution crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural and biophysical studies indicated that unlike other pH‐dependent or pH‐independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two histidine residues (His490 and His492) in the chain reversal region confer stability at low pH. A structural comparison of class I viral fusion proteins suggests that the presence of a positive charge, either a histidine or arginine amino acid, stabilizes a helical dipole moment and is a signature of fusion proteins active at low pH. The structure now reveals key residues and features that explain its 2‐step mechanism, and we discuss the implications of the ASLV TM structure in the context of general mechanisms required for membrane fusion.—Aydin, H., Smrke, B.M., Lee, J. E. Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2‐step entry mechanism. FASEB J. 27, 5059–5071 (2013). http://www.fasebj.org


title: Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon‐ω therapy

text: OBJECTIVES: Recombinant feline interferon‐ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon‐ω therapy are lacking. This study aimed to determine whether interferon‐ω therapy influences acute phase protein concentrations namely serum amyloid‐A, α‐1‐glycoprotein and C‐reactive protein. METHODS: A single‐arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon‐ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid‐A and C‐reactive protein were measured by specific enzyme‐linked immunosorbent assay kits and α‐1‐glycoprotein by single radial immunodiffusion. RESULTS: All the acute phase proteins significantly increased in cats undergoing interferon‐ω therapy (D0/D65: P<0·05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be reasonable predictors of innate‐immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon‐ω therapy.


title: Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps

text: [Image: see text] Recent crystal structure data for protein–protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.


docid: qstpasvb

title: Open season

text: SARS caught China unawares. But the ensuing struggle to characterize and contain the virus has put the country's work on infectious diseases back on target. Apoorva Mandavilli reports.


Décision kinésithérapique: Mohamed S. 25 ans: Effets délétères et utiles du confinement COVID-19 dans un contexte de sclérose en plaques en Tunisie


COVID-19 and Mental Health: An Iranian Perspective


title: Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

text: Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.


title: A case of acute acquired obstructive hydrocephalus in a cat with suspected ischaemic cerebellar infarct

text: CASE SUMMARY: A case of acquired acute obstructive hydrocephalus that developed as a complication of an ischaemic infarct in the vascular territory of the rostral cerebellar artery is described in an adult domestic shorthair cat. The clinical findings, diagnostic investigations, treatment and prognosis are reported. MRI findings are described in detail. RELEVANCE AND NOVEL INFORMATION: This is the first report of obstructive hydrocephalus as a complication of an ischaemic infarct in the region of the rostral cerebellar artery in a cat. MRI findings are described in detail with regard to the recognition of the early signs of obstructive hydrocephalus. A brief review of the literature is included, as this complication has been frequently reported in humans.


title: A survey of recommended practices made by veterinary practitioners to cow-calf operations in the United States and Canada

text: ABSTRACT Practicing veterinarians (n = 148) who service commercial beef cow-calf herds responded to a survey describing general recommendations made to their clients in terms of vaccine protocol, health, and production practices. Responding veterinarians represented 35 states in the United States and 3 provinces in Canada. More than 50% of responding veterinarians devote over 50% of their practice to service commercial cow-calf producers. The largest group (33%) of veterinarians have been in practice for over 30 yr. Thirty-nine percent of responding veterinarians serviced more than 10,000 cows. Genetic advice is provided by 54% of practicing veterinarians. When vaccinating at branding, the most common recommended vaccines are clostridial (96%), infectious bovine rhinotracheitis (IBR; 94%), bovine respiratory syncytial virus (BRSV; 91%), parainfluenza-3 (PI-3; 90%), and bovine viral diarrhea (BVD) Types 1 and 2 (78 and 77%, respectively). When vaccinating before weaning, the most common recommended vaccines are IBR (99%), BRSV (98%), BVD Types 1 and 2 (96%), PI-3 (93%), clostridial (77%), and Mannheimia haemolytica (77%). When vaccinating after weaning, the most common recommended vaccines are BVD Type 2 (97%), IBR (97%), BVD Type 1 (96%), BRSV (96%), and PI-3 (91%). Over 60% of responding veterinarians recommended that the last preventative vaccine should be administered to cattle 7 to 21 d before shipping. The largest number of respondents (38%) recommended that the earliest age their clients should wean their calves is 90 to 120 d. Castrating bull calves at an age of 0 to 7 d was recommended by 34% of respondents. Calf nutrition is considered as extremely important during a preconditioning program by 82% of responding veterinarians.


title: A Practical Protocol for Carbohydrate Microarrays

text: We have established a high-throughput biochip platform for constructing carbohydrate microarrays. Using this technology, carbohydrate-containing macromolecules of diverse structures, including polysaccharides, natural glycoconjugates, and mono- and oligosaccharides coupled to carrier molecules, can be stably immobilized on a glass chip without chemical modification. Here, we describe a practical protocol for this technology. We hope that anyone who has access to a standard cDNA microarray facility will be able to explore this technology for his or her own research interest. We also provide an example to illustrate that the carbohydrate microarray is also a discovery tool; this is particularly useful for identifying immunologic sugar moieties, including complex carbohydrates of cancer cells and sugar signatures of previously unrecognized microbial pathogens.


title: Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds

text: Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.


title: China's Belt and Road Initiative: Incorporating public health measures toward global economic growth and shared prosperity

text: Abstract The unprecedented globalization of trade, travel, climate change, protectionism, and geopolitical populism, as well as pandemic health threats are no longer issues for a single nation. In the field of public health, China's Belt and Road Initiative (BRI) offers immense opportunities for partnership and collective actions involving multiple countries to combat globalization-linked infectious and/or chronic diseases, emerging pandemics, and outbreaks of potential threats to both laboratory information management systems and health information management. The national and global health challenges have increasingly proved that economic prosperity cannot be achieved when huge knowledge and capacity gaps exist in health systems. There is thus a need for public health initiatives aimed at strengthening the health systems beyond sovereign borders to influence global geo-economics. We highlight situational insights that offer approaches and strategies for increasing public health investment and capacity development in the countries along the Belt and Road, enhancing public and global health cooperation alongside participation in disease control and elimination, promoting public health governance and data sharing for pandemic threats, and building shared values and benefits in public health through Sino-African cooperation and the BRI. Our approach also examines the values of the China's BRI in relation to public health, projections and initiatives for increasing new investment and development capacity in public health systems, and enhanced public and global health cooperation and participation toward the BRI's framework and scope.


title: Membrane binding proteins of coronaviruses

text: Coronaviruses (CoVs) infect many species causing a variety of diseases with a range of severities. Their members include zoonotic viruses with pandemic potential where therapeutic options are currently limited. Despite this diversity CoVs share some common features including the production, in infected cells, of elaborate membrane structures. Membranes represent both an obstacle and aid to CoV replication – and in consequence – virus-encoded structural and nonstructural proteins have membrane-binding properties. The structural proteins encounter cellular membranes at both entry and exit of the virus while the nonstructural proteins reorganize cellular membranes to benefit virus replication. Here, the role of each protein in membrane binding is described to provide a comprehensive picture of their role in the CoV replication cycle.


title: Bats host major mammalian paramyxoviruses

text: The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses. Here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). Major discoveries include evidence of an origin of Hendra- and Nipah virus in Africa, identification of a bat virus conspecific with the human mumps virus, detection of close relatives of respiratory syncytial virus, mouse pneumonia- and canine distemper virus in bats, as well as direct evidence of Sendai virus in rodents. Phylogenetic reconstruction of host associations suggests a predominance of host switches from bats to other mammals and birds. Hypothesis tests in a maximum likelihood framework permit the phylogenetic placement of bats as tentative hosts at ancestral nodes to both the major Paramyxoviridae subfamilies (Paramyxovirinae and Pneumovirinae). Future attempts to predict the emergence of novel paramyxoviruses in humans and livestock will have to rely fundamentally on these data.


title: COVID‐19 and telemedicine in hemophilia in a patient with severe hemophilia A and orthopedic surgery

text: We describe the case of a patient with severe hemophilia A who underwent major orthopedic surgery managed postoperatively by telemedicine (TM). The case is a splendid example of the implementation of TM and good collaboration between a Comprehensive Hemophilia Treatment Center (CHTC) and a local hospital.


title: Viral detection by electron microscopy: past, present and future

text: Viruses are very small and most of them can be seen only by TEM (transmission electron microscopy). TEM has therefore made a major contribution to virology, including the discovery of many viruses, the diagnosis of various viral infections and fundamental investigations of virus—host cell interactions. However, TEM has gradually been replaced by more sensitive methods, such as the PCR. In research, new imaging techniques for fluorescence light microscopy have supplanted TEM, making it possible to study live cells and dynamic interactions between viruses and the cellular machinery. Nevertheless, TEM remains essential for certain aspects of virology. It is very useful for the initial identification of unknown viral agents in particular outbreaks, and is recommended by regulatory agencies for investigation of the viral safety of biological products and/or the cells used to produce them. In research, only TEM has a resolution sufficiently high for discrimination between aggregated viral proteins and structured viral particles. Recent examples of different viral assembly models illustrate the value of TEM for improving our understanding of virus—cell interactions.


title: Recommandations du Comité Lithiase de l’Association Française d’Urologie pour la prise en charge des calculs urinaires durant la crise sanitaire liée à la pandémie à COVID-19

text: Abstract For the first time, faced with a crisis with an exceptional magnitude due to the COVID-19 pandemic responsible for saturation of emergency services and intensive care units, the urolithiasis committee of the French Urology Association designed the recommendations for care and treatment of stone-forming patients and their treatment during crisis.


title: They're back! Post-financialization diversification benefits of commodities

text: Abstract Do alternative assets such as commodities improve portfolio diversification? The empirical evidence is generally positive but mixed, and almost exclusively focuses on U.S. data. Using several distinct commodity indexes over the period 1993–2019, we investigate the case of an investor in Canada, a commodity-currency country where equities are already exposed to commodity beta. We use spanning tests and several out-of-sample performance measures for both risk-averse and disappointment-averse investors. Overall, we find that while the diversification potential of commodities was limited in Canada before and during financialization, the post-financialization period offers new opportunities. The evidence suggests that portfolio performance is significantly improved using some, but not all, commodity indexes. Thus, the choice of a relevant commodity index matters as a vehicle for diversification. Finally, compounding an international component to the sectorial diversification of the portfolio can significantly improve its performance.


docid: kwjumabw

title: SARS in Hospital Emergency Room

text: Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.


title: Coronaviruses: Molecular Biology☆

text: Abstract Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona – Latin for ‘crown’), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido – Latin for ‘nest’) of 3′ co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002–03 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate before it was controlled by public health measures of isolation of infected individuals and contacts. Middle East Respiratory Syndrome CoV (MERS-CoV), first reported in 2012, is likely transmitted from camels to humans with potentially fatal consequences. To date, there are no approved vaccines or direct acting antiviral drugs to combat coronavirus infections in humans. The emergence or re-emergence of CoVs from animal reservoirs is a potential concern for public health.


title: Microbial Forensics☆

text: Abstract Biothreats are a high priority concern for public safety and national security. The field of microbial forensics was developed to analyze evidence associated with biological crimes in which microbes or their toxins are used as weapons. Microbial forensics is the scientific discipline dedicated to analyzing evidence from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release for attribution purposes. Microbial forensics combines the practices of epidemiology with the characterization of microbial and microbial-related evidence to assist in determining the specific source of the sample, as individualizing as possible, and/or the methods, means, processes and locations involved to determine the identity of the perpetrator(s) of an attack.


title: Preparation and Response to COVID-19 outbreak in Singapore: A Case Report

text: Abstract The COVID-19 pandemic has an overwhelming impact on the nursing profession. Nurses play a vital role before and during pandemics, with nurse leaders taking the lead in preparation for outbreaks. In response to an outbreak, early recognition and preparation for the increasing threat, managing staffing challenges together with the well-being of nurses are of utmost importance. Strategies to promote physical distancing while not compromising continuing nursing education and patient care are also essential. With prompt actions and coordinated efforts, risk of spreading the virus within the healthcare sector can be kept at the minimum. As nurses are in the frontline of healthcare, their confidence in being well-supported by the hospital should be maintained. This case report describes the preparation and response of the nurses in Singapore General Hospital to the COVID-19 outbreak in Singapore.


title: Dysphagia in COVID‐19 –multilevel damage to the swallowing network?

text: We read with great interest the article “COVID‐19: what if the brain had a role in causing the deaths?” by Tassorelli and co‐workers, in which the authors generate and summarize hypotheses how SARS‐CoV‐2 may enter the peripheral and central nervous system and cause life‐threatening complications [1]. With this letter we would like to contribute to this discussion by highlighting how different complications of COVID‐19 may result in damage to central and peripheral parts of the swallowing network leading to dysphagia in critically ill COVID‐survivors.


Oxigenoterapia de alto flujo y posición de prono con respiración espontanea en neumonía por SARS-CoV-2


title: Multiplex Platforms for the Identification of Respiratory Pathogens: Are They Useful in Pediatric Clinical Practice?

text: Respiratory tract infections (RTIs) are extremely common especially in the first year of life. Knowledge of the etiology of a RTI is essential to facilitate the appropriate management and the implementation of the most effective control measures. This perspective explains why laboratory methods that can identify pathogens in respiratory secretions have been developed over the course of many years. High-complexity multiplex panel assays that can simultaneously detect up to 20 viruses and up to four bacteria within a few hours have been marketed. However, are these platforms actually useful in pediatric clinical practice? In this manuscript, we showed that these platforms appear to be particularly important for epidemiological studies and clinical research. On the contrary, their routine use in pediatric clinical practice remains debatable. They can be used only in the hospital as they require specific equipment and laboratory technicians with considerable knowledge, training, and experience. Moreover, despite more sensitive and specific than other tests routinely used for respiratory pathogen identification, they do not offer significantly advantage for detection of the true etiology of a respiratory disease. Furthermore, knowledge of which virus is the cause of a respiratory disease is not useful from a therapeutic point of view unless influenza virus or respiratory syncytial virus are the infecting agents as effective drugs are available only for these pathogens. On the other hand, multiplex platforms can be justified in the presence of severe clinical manifestations, and in immunocompromised patients for whom specific treatment option can be available, particularly when they can be used simultaneously with platforms that allow identification of antimicrobial resistance to commonly used drugs. It is highly likely that these platforms, particularly those with high sensitivity and specificity and with low turnaround time, will become essential when new drugs effective and safe against most of the respiratory viruses will be available. Further studies on how to differentiate carriers from patients with true disease, as well as studies on the implications of coinfections and identification of antimicrobial resistance, are warranted.


Assessment of infectious risk in clinical xenotransplantation: The lessons for clinical allotransplantation


title: Global Burden of Infectious Diseases

text: Systematic efforts to quantify and monitor the burden of specific health conditions in populations, at the national level, started in the mid-1950s for malaria, poliomyelitis, and influenza in the United States. Comprehensive surveillance of morbidity and mortality for dozens of conditions has since been well established in the United States and in other industrialized countries. However, despite the clear need for epidemiological data to inform health policies, reliable and comprehensive health statistics are not available in many developing countries. International efforts to assess and monitor the burden of certain diseases have been limited in the past to a small number of infectious diseases in the context of global eradication programs – smallpox, poliomyelitis, guinea worm, and, more recently, HIV/AIDS, severe acute respiratory syndrome (SARS), and avian flu influenza A (H5N1). The Global Burden of Disease Study (GBD), published in 1996, filled an important gap in our knowledge of population health status. It created a common metric, the disability-adjusted life year (DALY), to estimate morbidity and mortality for eight regions that collectively span the world’s population, generating comparable information on incidence and prevalence in global health. However, patterns of disease, disability, and risk factors have since changed significantly and new data on their distribution are available. Furthermore, the unprecedented money and attention now pouring into international health has made an accurate assessment of global health patterns a matter of utmost urgency. The new Global Burden of Diseases, Injuries, and Risk Factors (GBD 2005) project, which began in 2007, represents the first major effort at a systematic revision of estimates in health for every region in the world comprehensively, and will ensure that that the global health community bases its research and policies on complete, valid, and reliable information. Burden of disease estimates provided in this article are for 2001 – the year for which the most recent estimates of the global burden of disease and risk factors are currently available. Causes of deaths were categorized into three main groups: group I (infectious diseases and maternal, perinatal, and nutritional conditions), group II (noncommunicable diseases), and group III (injuries). Accordingly, estimates of the global burden of infectious diseases are provided in the context of the overall burden from other conditions, diseases, and injuries. The relative importance of the burden of infectious diseases was forecasted to change by 2020. As the epidemiological transition progresses worldwide, a decline in the burden of infectious diseases is expected as the burden of noncommunicable diseases and injuries gradually increases. The pace of the epidemiological transition, however, varies greatly among regions so that the projected decreases in the burden of infectious diseases are expected to vary between regions. Trends in the global burden due to specific infectious diseases projected to 2020 also vary among specific conditions. The global burden of HIV/AIDS, for instance, is expected to greatly increase, whereas the global burden due to respiratory infections and diarrheal diseases is expected to decrease. Contrary to expectations, the global burden of malaria has increased in recent years.


title: Chapter 10 Cold-Chain Systems in China and Value-Chain Analysis

text: Abstract Cold supply chains or cold-chain systems are emerging rapidly in China. This chapter presents an overview of cold-chain systems in China, including those in fresh agricultural products, frozen processed products, and biopharmaceutical products. The rapid growth of the cold-chain supply systems emphasizes the need to establish integrated systems. We attempt to explain the integration of cold supply chains in China. This chapter is based on case studies of cold-chain companies in China within the framework of value-chain analysis. Recent integrations of cold-chain suppliers in China are reviewed along with the rationales behind the integration in terms of value creation. The findings will be of use for cold-chain practitioners and policy-makers to understand the observed behaviors of cold-chain systems. Practitioners will also be able to use the findings to guide supply chain integration decisions. This study will guide policy-makers and other stakeholders to manage the sustainable development of cold-chain systems.


title: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

text: The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics. Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies. We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development. The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics. Future applications of the model are also explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.


title: Theophylline-induced mesenteric periarteritis in F344/N rats

text: The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall.


title: Procedure 36 Genosensor on gold thin-films with enzymatic electrochemical detection of a SARS virus sequence

text: Publisher Summary This chapter presents a procedure for the construction of a hybridization-based genosensor for a SARS (severe acute respiratory syndrome) virus sequence on a 100nm sputtered gold film, which works as immobilization and transduction surface. The chapter tests the sensitivity and the selectivity of the SARS genosensor using complementary strands of SARS virus and three-base mismatch strands. Genosensor construction include following steps: a drop of 5 mL of 1.02 mM thiolated probe deposited on the gold film and maintain at 37°C for 20 min or at 41°C for 12 h; it is cleaned with 0.1M Tris-HCl buffer; further a15 mL drop of a 2% 1-hexanethiol solution is deposited on the gold film and maintained for 10 min and again cleaned with a 2×SSC buffer solution pH 7. From the results of hybridization assay and recording of the analytical signal no significant difference found between the analytical signal obtained for a 3.03nM solution of the complementary target strand and three-base mismatch strand. The limit of detection, calculated as the concentration corresponding to a signal which is three times the standard deviation of the intercept, results to be 5 pM. This means an improvement of various orders of magnitude when compared with limits of detection reported in the bibliography for DNA assays.


title: Comparative Genomic Analysis of Classical and Variant Virulent Parental/Attenuated Strains of Porcine Epidemic Diarrhea Virus

text: Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9−26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation.


Patients get viral infections: so, do vines


title: Teicoplanin potently blocks the cell entry of 2019-nCoV

text: Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.


title: Diagnostic Testing in Central Nervous System Infection

text: Patients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broad-range diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.


Human Adenovirus 14a: A New Epidemic Threat


title: Testing for SARS‐CoV‐2: the day the world turned its attention to the clinical laboratory

text: In the last few months, an unprecedented number of laboratory tests for COVID‐19 have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID‐19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the U.S. and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID‐19. We will first address the detection of Sars‐Cov‐2 directly by either nucleic acid amplification tests (NAAT) or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.


title: Reverse Genetics for Type I Feline Coronavirus Field Isolate To Study the Molecular Pathogenesis of Feline Infectious Peritonitis

text: Feline infectious peritonitis (FIP), one of the most important lethal infections of cats, is caused by feline infectious peritonitis virus (FIPV), the high-virulence biotype of feline coronaviruses (FCoVs). FIPVs are suggested to emerge from feline enteric coronaviruses (FECVs) by acquiring mutations in specific genes in the course of persistent infections. Although numerous studies identified mutations predicted to be responsible for the FECV-FIPV biotype switch, the presumed roles of specific genetic changes in FIP pathogenesis have not been confirmed experimentally. Reverse genetics systems established previously for serotype I and the less common serotype II FCoVs were based on cell culture-adapted FIPV strains which, however, were shown to be unsuitable for FIP pathogenesis studies in vivo. To date, systems to produce and manipulate recombinant serotype I field viruses have not been developed, mainly because these viruses cannot be grown in vitro. Here, we report the first reverse genetics system based on a serotype I FECV field isolate that is suitable to produce high-titer stocks of recombinant FECVs. We demonstrate that these recombinant viruses cause productive persistent infections in cats that are similar to what is observed in natural infections. The system provides an excellent tool for studying FCoVs that do not grow in standard cell culture systems and will greatly facilitate studies into the molecular pathogenesis of FIP. Importantly, the system could also be adapted for studies of other RNA viruses with large genomes whose production and characterization in vivo are currently hampered by the lack of in vitro propagation systems.


title: SARS-CoV-2 in Pregnancy: A Comprehensive Summary of Current Guidelines

text: Since the declaration of the global pandemic of COVID-19 by the World Health Organization on 11 March 2020, we have continued to see a steady rise in the number of patients infected by SARS-CoV-2. However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG, and CatSalut have released guidelines for the care of these patients. We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers, and healthcare institutions. We included 15 papers from 10 societies through a literature search of direct review of society’s websites and their journal publications up till 20 April 2020. Recommendations specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into Tables. The summary of guidelines for the management of COVID-19 in pregnancy across different perinatal societies is fairly consistent, with some variation in the strength of recommendations. It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy.


title: Experimental Evaluation of Musca domestica (Diptera: Muscidae) as a Vector of Newcastle Disease Virus

text: House flies, Musca domestica L. (Diptera: Muscidae), were examined for their ability to harbor and transmit Newcastle disease virus (family Paramyxoviridae, genus Avulavirus, NDV) by using a mesogenic NDV strain. Laboratory-reared flies were experimentally exposed to NDV (Roakin strain) by allowing flies to imbibe an inoculum consisting of chicken embryo-propagated virus. NDV was detected in dissected crops and intestinal tissues from exposed flies for up to 96 and 24 h postexposure, respectively; no virus was detected in crops and intestines of sham-exposed flies. The potential of the house fly to directly transmit NDV to live chickens was examined by placing 14-d-old chickens in contact with NDV-exposed house flies 2 h after flies consumed NDV inoculum. NDV-exposed house flies contained ≈10(4) 50% infectious doses (ID(50)) per fly, but no transmission of NDV was observed in chickens placed in contact with exposed flies at densities as high as 25 flies per bird. Subsequent dose–response studies demonstrated that oral exposure, the most likely route for fly-to-chicken transmission, required an NDV (Roakin) dose ≥10(6) ID(50). These results indicate that house flies are capable of harboring NDV (Roakin) but that they are poor vectors of the virus because they carry an insufficient virus titer to cause infection.


title: VIGOR, an annotation program for small viral genomes

text: BACKGROUND: The decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. It is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. Among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. However, accurate gene prediction is a challenge that persists for decoding a newly sequenced genome. Therefore, accurate and efficient gene prediction programs are highly desired for rapid and cost effective surveillance of RNA viruses through full genome sequencing. RESULTS: We have developed VIGOR (Viral Genome ORF Reader), a web application tool for gene prediction in influenza virus, rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding regions based on sequence similarity searches and can accurately detect genome specific features such as frame shifts, overlapping genes, embedded genes, and can predict mature peptides within the context of a single polypeptide open reading frame. Genotyping capability for influenza and rotavirus is built into the program. We compared VIGOR to previously described gene prediction programs, ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user friendly web-based genome annotation program for five different viral agents, influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the first gene prediction program for rotavirus and rhinovirus for public access. VIGOR is able to accurately predict protein coding genes for the above five viral types and has the capability to assign function to the predicted open reading frames and genotype influenza virus. The prediction software was designed for performing high throughput annotation and closure validation in a post-sequencing production pipeline.


Commentary: “Murder on the Orient Express of Pandemic: COVID was found guilty, but was it the murder?”


title: Will the Higher-Income Country Blueprint for COVID-19 Work in Low- and Lower Middle-Income Countries?

text: Strategies to radically suppress incidence of COVID-19, as used in higher-income countries, may be unrealistic and counterproductive in most low- and lower middle-income countries. Instead, strategies should be tailored to the setting, balancing expected benefits, potential harms, and feasibility.