title: Structure of the equine arteritis virus nucleocapsid protein reveals a dimer–dimer arrangement

text: Equine arteritis virus (EAV) is an enveloped positive‐sense RNA virus belonging to the Arteriviridae family, which also includes the porcine pathogen PRRSV and is genetically and structurally related to the coronaviruses. EAV is an important equine pathogen that has caused significant economic losses to the horse‐breeding industry and has been difficult to control. The EAV virion consists of a genome‐containing nucleocapsid core made of nucleocapsid (N) protein surrounded by a lipid envelope containing several membrane proteins. Here, the crystal structure of the capsid‐forming domain of the EAV N protein is presented at 2.0 Å resolution. The dimeric N‐protein structure is similar to the previously determined structure of the N protein from PRRSV, with most differences localized to the terminal helices and flexible loops. The N protein is organized as dimers of dimers in the crystal, which may reflect the arrangement of the protein in the viral nucleocapsid.


title: Coronavirus Disease 2019 (COVID‐19) in autoimmune hepatitis: a lesson from immunosuppressed patients

text: BACKGROUND & AIMS: Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Our aim was to describe the clinical course of immunosuppressed autoimmune hepatitis (AIH) patients during coronavirus disease 2019 (COVID‐19) infection in Italy. METHODS: Our study is a case series of AIH patients treated with immunosuppression, who tested positive for SARS‐CoV‐2 in March 2020 during outbreak of COVID‐19. RESULTS: Ten patients from six different hospitals in Italy were diagnosed with COVID‐19 during the outbreak of SARS‐CoV‐2 in March 2020. Seven subjects were female (70%) and age ranged from 27 to 73 years. Before the onset of SARS‐CoV‐2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and were consequently started high‐dose steroids, as per induction protocol. All patients had a respiratory syndrome and had a positive nasal swab for SARS‐CoV‐2. Five patients developed a CT‐confirmed COVID‐19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS‐CoV‐2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high‐dose steroids. The clinical outcome was comparable to the reported cases occurring in non‐immunosuppressed subjects. CONCLUSION: Patients under immunosuppressive therapy for AIH developing COVID‐19 show a disease course presumptively similar to that reported in non‐immunosuppressed population. These data might help medical decision when dealing with SARS‐CoV‐2 infection in immunocompromised patients.


title: Informed Consent for Emergency Obstetric Care During COVID-19 Pandemic

text: Informed consent process has become a challenging issue before surgery for any emergency obstetric care during this COVID pandemic. There is an increased risk of morbidity if there is a need of intensive care unit postoperatively and a risk of high mortality if patient has symptoms of COVID-19. Admission to intensive care unit adds on to the financial burden to the patient. Also, there is an increased risk of perinatal anxiety and depression during the COVID pandemic. When an asymptomatic carrier develops symptoms of COVID after delivery or caesarean section, the morbidity increases. So we have designed an informed consent form for patients undergoing emergency obstetric surgeries incorporating some points specific for COVID-19.


title: Feed batch sequencing to decrease the risk of porcine epidemic diarrhea virus (PEDV) cross-contamination during feed manufacturing

text: Feed has been identified as a vector of transmission for porcine epidemic diarrhea virus (PEDV). The objective of this study was to determine if feed batch sequencing methods could minimize PEDV cross-contamination. Porcine epidemic diarrhea virus-free swine feed was manufactured to represent the negative control. A 50 kg feed batch was mixed in a pilot scale feed mill for 5 min, sampled, then discharged for 10 min into a bucket elevator and sampled again upon exit. Next, a pathogenic PEDV isolate was used to inoculate 49.5 kg of PEDV-free feed to form the positive control. The positive control was mixed, conveyed and sampled similar to the negative control. Subsequently, 4 sequence batches (sequence 1 to 4) were formed by adding a 50 kg batch of PEDV-negative feed to the mixer after the prior batch was mixed and conveyed; all sequences were mixed, conveyed, and sampled similar to the negative and positive control batches. None of the equipment was cleaned between batches within a replicate. This entire process was replicated 3 times with cleaning the feed mill between replicates. Feed was then analyzed for PEDV RNA by real-time reverse transcriptase semiquantitative polymerase chain reaction (rRT-PCR) as measured by cycle threshold (Ct) and for infectivity by bioassay. Sequence 1 feed had higher (P ˂ 0.05) rRT-PCR Ct values than the positive batch and sequence 2 feed had higher (P ˂ 0.05) Ct values than sequence 1, regardless of sampled location. Feed sampled from the mixer from sequence 2, 3, and 4 was rRT-PCR negative whereas feed sampled from the bucket elevator was rRT-PCR negative from sequence 3 and 4. Bioassay was conducted using 66 mixed sex 10-d-old pigs confirmed negative for PEDV allocated to 22 different rooms. Pigs were initially 10-d old. Control pigs remained PEDV negative for the study. All pigs from the mixer positive batch (9/9) and bucket elevator positive batch (3/3) were rRT-PCR positive on fecal swabs by the end of the study. One replicate of pigs from mixer sequence 1 was rRT-PCR positive (3/3) by 7 dpi. One replicate of mixer pigs from sequence 2 was rRT-PCR positive (3/3) by 7 dpi although no detectable PEDV RNA was found in the feed. The results demonstrate sequenced batches had reduced quantities of PEDV RNA although sequenced feed without detectible PEDV RNA by rRT-PCR can be infectious. Therefore, a sequencing protocol can reduce but not eliminate the risk of producing infectious PEDV carryover from the first sequenced batch of feed.


title: Clinical Issues—January 2012

text: This Month Venous thromboembolism prophylaxis in pediatric patients Key words: pediatric patients, venous thromboembolism, prophylaxis. The Centers for Disease Control and Prevention surgical wound classification system Key words: surgical wound, wound classification, clean wound, clean-contaminated wound, contaminated wound, dirty infected wound. Using the Surgical Wound Classification Decision Tree tool Key words: surgical wound, wound classification, clean-contaminated wound, contaminated wound. Using cotton surgical masks Key words: allergy, cotton surgical masks, fabric surgical masks, disposable surgical masks. Using povidone-iodine solution for surgical skin antisepsis before thyroid procedures Key words: povidone iodine, thyroid, surgical skin antisepsis.


title: The rubella virus E1 glycoprotein is arrested in a novel post-ER, pre- Golgi compartment

text: Evidence is accumulating that a distinct compartment(s) exists in the secretory pathway interposed between the rough ER (RER) and the Golgi stack. In this study we have defined a novel post-RER, pre-Golgi compartment where unassembled subunits of rubella virus (RV) E1 glycoprotein accumulate. When RV E1 is expressed in CHO cells in the absence of E2 glycoprotein, transport of E1 to the Golgi complex is arrested. The compartment in which E1 accumulates consists of a tubular network of smooth membranes which is in continuity with the RER but has distinctive properties from either the RER, Golgi, or previously characterized intermediate compartments. It lacks RER and Golgi membrane proteins and is not disrupted by agents which disrupt either the RER (thapsigargin, ionomycin) or Golgi (nocodazole and brefeldin A). However, luminal ER proteins bearing the KDEL signal have access to this compartment. Kinetically the site of E1 arrest lies distal to or at the site where palmitylation occurs and proximal to the low temperature 15 degrees C block. Taken together the findings suggest that the site of E1 arrest corresponds to, or is located close to the exit site from the ER. This compartment could be identified morphologically because it is highly amplified in cells overexpressing unassembled E1 subunits, but it may have its counterpart among the transitional elements of non-transfected cells. We conclude that the site of E1 arrest may represent a new compartment or a differentiated proximal moiety of the intermediate compartment.


title: New Antimicrobial Potential and Structural Properties of PAFB: A Cationic, Cysteine-Rich Protein from Penicillium chrysogenum Q176

text: Small, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact β-folded structure, comprising five β-strands connected by four solvent exposed and flexible loops and an “abcabc” disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.


docid: afpbaqgx

title: Potential for elimination of SAR‐CoV‐2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination

text: The ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by the novel virus SARS‐CoV‐2 has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, the future vaccination against COVID‐19 may fall into long‐term costly guerrilla warfare between SARS‐CoV‐2 and humans. Elimination of SARS‐CoV‐2 through vaccination to avoid the potential long‐term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to elimination of three human influenza viruses which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggested that rapid establishment of global herd immunity through mass vaccination using a proper vaccine could eliminate SARS‐CoV‐2. The coming two years is the golden time for the elimination through vaccination which requires tremendous national and international collaboration. This review also prioritized the efficacy of vaccines for COVID‐19 and elucidated the importance for development of more live vaccines for COVID‐19. This article is protected by copyright. All rights reserved.


title: De novo transcriptome assembly and characterization of nine tissues of Lonicera japonica to identify potential candidate genes involved in chlorogenic acid, luteolosides, and secoiridoid biosynthesis pathways

text: Lonicera japonica is one of the most important medicinal plants with applications in traditional Chinese and Japanese medicine for thousands of years. Extensive studies on the constituents of L. japonica extracts have revealed an accumulation of pharmaceutically active metabolite classes, such as chlorogenic acid, luteolin and other flavonoids, and secoiridoids, which impart characteristic medicinal properties. Despite being a rich source of pharmaceutically active metabolites, little is known about the biosynthetic enzymes involved, and their expression profile across different tissues of L. japonica. In this study, we performed de novo transcriptome assembly for L. japonica, representing transcripts from nine different tissues. A total of 22 Gbps clean RNA-seq reads from nine tissues of L. japonica were used, resulting in 243,185 unigenes, with 99,938 unigenes annotated based on a homology search using blastx against the NCBI-nr protein database. Unsupervised principal component analysis and correlation studies using transcript expression data from all nine tissues of L. japonica showed relationships between tissues, explaining their association at different developmental stages. Homologs for all genes associated with chlorogenic acid, luteolin, and secoiridoid biosynthesis pathways were identified in the L. japonica transcriptome assembly. Expression of unigenes associated with chlorogenic acid was enriched in stems and leaf-2, unigenes from luteolin were enriched in stems and flowers, while unigenes from secoiridoid metabolic pathways were enriched in leaf-1 and shoot apex. Our results showed that different tissues of L. japonica are enriched with sets of unigenes associated with specific pharmaceutically important metabolic pathways and, therefore, possess unique medicinal properties. The present study will serve as a resource for future attempts for functional characterization of enzyme coding genes within key metabolic processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11418-016-1041-x) contains supplementary material, which is available to authorized users.


title: Abordaje del duelo y de la muerte en familiares de pacientes con covid-19: revisión narrativa

text: Resumen Objetivo: Realizar una síntesis de la evidencia disponible para establecer recomendaciones sobre el abordaje del duelo y la muerte en familiares de pacientes Covid19 así como ofrecer recursos sustitutivos de los rituales y procedimientos necesarios con el fin de favorecer duelos funcionales y prevenir duelos complicados. Método: Se realizó búsqueda bibliográfica en bases de datos MEDLINE, EMBASE, SCIENCEDIRECT, WOS, CINAHL y CUIDEN, utilizando términos MeSH, (family, patient, isolation hospitals, grief, death, ceremonial behavior, self care, affects y social networking) con su ecuación boleana correspondiente. Los artículos seleccionados se sometieron a una lectura crítica a través del Critical Apraisal Skill Programme en español (CASPe). Resultados: Se encontraron 560 artículos atingentes, tras aplicar los criterios de selección, 13 estudios se incluyeron en el análisis, de los cuales 8 eran revisiones sistemáticas, 3 estudios cualitativos,1 estudio piloto prospectivo transversal y 1 guía clínica, que permitieron identificar estrategias para el abordaje del duelo y la muerte atendiendo a este momento de excepcionalidad covid19, incidiendo en el manejo competencial de los profesionales sanitarios en apoyo emocional y el acompañamiento así como el seguimiento durante todo el proceso, así como en la comunicación con la familia. Conclusión: En el proceso final de la vida en tiempos de COVID19, los profesionales sanitarios deben trabajar despedidas, los ritos fúnebres alternativos, la atención espiritual y el afrontamiento precoz que permitirán a su vez la prevención del duelo complicado. Abstract The objective of this review was to synthesize the possible evidence to establish recommendations on the approach of mourning and death in relatives of Covid19 patients, as well as offering substitute resources for the necessary rituals and procedures in order to build up functional griefs and prevent complicated bereavements. Method: A bibliographic research was conducted in MEDLINE, EMBASE, SCIENCEDIRECT, WOS, CINAHL and CUIDEN databases, using MeSH terms, (family, patient, isolation hospitals, grief, death, ceremonial behavior, self-care, affects and social networks) with its corresponding boolean equation. The selected articles have been published in a critical reading through the Critical Assessment Skills Program in Spanish (CASPe). Result: A total of 560 articles were initially found, after applying the selection criteria, 13 studies were included in the analysis, of which 8 were systematic reviews, 3 qualitative studies, 1 cross-sectional prospective pilot study and 1 clinical guide, which allowed identifying strategies for the approach grief and death attending to this moment of exceptionality covid19, influencing the competence management of health professionals in emotional support and accompaniment as well as the monitoring throughout the process, as well as in the communication with the family. Conclusion: In the final process of life in COVID19´s time, health professionals must work farewells, alternative funeral rites, spiritual care and early coping that will allow the prevention of complicated grief.


title: Local cross-border disease surveillance and control: experiences from the Mekong Basin

text: BACKGROUND: The Mekong Basin Disease Surveillance cooperation (MBDS) is one of several sub-regional disease surveillance networks that have emerged in recent years as an approach to transnational cooperation for infectious disease prevention and control. Since 2003 MBDS has pioneered a unique model for local cross-border cooperation. This study examines stakeholders’ perspectives of these MBDS experiences, based on a survey of local managers and semi-structured interviews with MBDS leaders and the central coordinator. RESULTS: Fifteen managers from 12 of 20 paired cross-border sites completed a written survey. They all monitor most or all of the 17 diseases agreed upon for MBDS surveillance information sharing. Fourteen agreed or strongly agreed with statements about the core MBDS values of cooperation, mutual trust, and transparency, and their own contributions to national and regional disease control (average score of 4.4 of 5.0). Respondents felt they implemented well to very well activities related to surveillance reporting (average scores 3.4 to 3.9 of 4.0), using computers for their work (3.9/4.0), and using surveillance data for action (3.8/4.0). Respondents reported that they did worst in implementing research (2.1/4.0) and somewhat poorly for local laboratory testing (2.9/4.0) and local coordination with cross-border counterparts (2.9/4.0), although all 15 maintain a list with contact information for these counterparts and many know their counterparts. Implementation of specified activities within their collective regional action plan was uneven across the cross-border sites. Most respondents reported positive lessons learned about local cooperation, information sharing and joint problem solving, based on trusting relationships with their cross-border counterparts. They recommend expansion of cross-border sites within MBDS and consideration of the cross-border cooperation model by other sub-regional networks. CONCLUSIONS: MBDS has over a decade of experience with its model of local cross-border cooperation in disease surveillance and control. Frontline managers have documented success with this model, strongly support it and recommend its expansion within and beyond the MBDS network. The MBDS cross-border cooperation model is standing the test of time as a solid approach to building and sustaining the public health capabilities needed for disease surveillance and control from the local to national and global levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1047-6) contains supplementary material, which is available to authorized users.


title: Solid organ transplantation programs facing lack of empiric evidence in the COVID‐19 pandemic: A By‐proxy Society Recommendation Consensus approach

text: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow‐up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID‐19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus‐based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction‐based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available.


title: Heat sensitivity of a SARS‐associated coronavirus introduced into plasma products

text: Background and Objectives Various measures to inactivate/remove viruses have been implemented for manufacturing plasma‐derived products. Here, we examined the heat inactivation ability of an agent of the severe acute respiratory syndrome (SARS), SARS coronavirus (CoV). Materials and Methods The Frankfurt‐1 strain of SARS‐CoV was incorporated in manufacturing processes of several products by using samples collected immediately before liquid heat treatment at 60 °C. Results SARS‐CoV was easily inactivated by this treatment for 60 min in all in‐process samples. However, the different composition of the tested samples affected the heat sensitivity of the virus strain: the infectivity of the virus in Antithrombin III preparation still remained after heating for 30 min at 60 °C. Conclusion If by rare chance SARS‐CoV contaminates source plasma, there should be no or only minor risk of this virus infection, due to sufficient inactivation by the 60 °C 10 h liquid heating step, although we must pay attention to the composition used for blood product preparation.


docid: aktfbriw

title: Recommendations for Management of Acute Pharyngitis in Adults

text: Abstract Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners’ consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%–30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.


title: Fluorescent linear polyurea based on toluene diisocyanate: easy preparation, broad emission and potential applications

text: In contrast to conventional fluorescent polymers featured by large conjugation structures, a new class of fluorescent polymers without above conjugations are gaining constant interest owing to their significant academic importance and promising applications in diverse fields. These unconventional fluorescent polymers are in general composed of heteroatoms (e.g. N, O, P, and S) under different forms. Here we report our recent study on polyurea, prepared by a very simple one step precipitation polymerization of toluene diisocyanate in a binary solvent of water-acetone. This polyurea, basically consisting of phenyl ring and urea group, shows fluorescent emission in a broad concentration range, from very low (10(-5) mg/mL) to its solubility limit (50 mg/mL), and in a wide range of emission wavelength from UV to visible regions of up to 500 nm under varied excitation wavelength. The emission behaviors were fully studied under different concentrations and excitations. It was concluded that the emission in UV region was intrinsic due to the conjugation between the phenyl and the adjacent urea unit; while the emission in visible region, strongly excitation dependent, was caused by the cluster formation of the molecular chains, in accordance with the cluster-triggered-emission (CTE) mechanism. The formation of the cluster was tested through dynamic light scattering, FTIR and UV absorbance. Tested in presence of different metal ions, Fe(3+) demonstrated a quenching effect with high selectivity. Based on this study, different paper-based sensors were designed to detect Fe(3+), H(2)O(2) in bioanalysis and for data encryption. This work provides a simple way to prepare a polyurea, a novel type of unconventional fluorescent polymer, with high emission performance distinct from its known analogues.


title: X-Ray Structure and Inhibition of 3C-like Protease from Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL(pro)) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 Å X-ray structure of 3CL(pro) from PEDV. Analysis of the PEDV 3CL(pro) structure and comparison to other coronaviral 3CL(pro)’s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL(pro)’s are conserved, with the exception of a loop that comprises the protease S(2) pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL(pro), (R)-16, to have inhibitor activity against PEDV 3CL(pro), despite that SARS-3CL(pro) and PEDV 3CL(pro) share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL(pro) are conserved in PEDV-3CL(pro); however, the sequence variation and positional difference in the loop forming the S(2) pocket may account for large observed difference in IC(50) values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL(pro) architecture and contributes to the broader structural knowledge of coronaviral 3CL(pro)’s.


title: Regulating epidemic space: the nomos of global circulation

text: After the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002, legal theorist David Fidler diagnosed the arrival of the ‘first post-Westphalian pathogen’. The coinage indicates that the spread of infectious disease transforms the spatial coordinates of the modern political environment. This article analyses this transformation by asking how the legal regime, designed to prepare for the pandemic, envisions the globe as an object of government. It demonstrates that the WHO’s International Health Regulations (IHR) articulate a space of global circulation that exhibits two features. First, the infrastructures of microbial traffic become the primary matters of concern. The IHR do not focus on human life so much as they aim at securing transnational mobilities. Second, the IHR circumscribe a space that is fragmented by zones of intensified governmental control at transportational nodal points, such as airports and harbours. In these zones, technologies of screening and quarantine are applied to modulate the connectivity of people, organic matter and things. As a whole, the article investigates how processes of de- and re-territorialisation interact in the context of global health security. In analysing forms of legal worldmaking, it unearths a nomos of global circulation which applies its regulatory force to the post-human materialities of microbial traffic.


title: Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages

text: Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8(+) T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.


title: New concepts in antimalarial use and mode of action in dermatology

text: ABSTRACT: Although chloroquine, hydroxychloroquine and quinacrine were originally developed for the treatment of malaria, these medications have been used to treat skin disease for over 50 years. Recent clinical data have confirmed the usefulness of these medications for the treatment of lupus erythematosus. Current research has further enhanced our understanding of the pharmacologic mechanisms of action of these drugs involving inhibition of endosomal toll‐like receptor (TLR) signaling limiting B cell and dendritic cell activation. With this understanding, the use of these medications in dermatology is broadening. This article highlights the different antimalarials used within dermatology through their pharmacologic properties and mechanism of action, as well as indicating their clinical uses. In addition, contraindications, adverse effects, and possible drug interactions of antimalarials are reviewed.


title: Public Health in Big Cities: Looking Back, Looking Forward

text: This commentary provides reflections of a public health official on the important role public health departments play in advancing the goals of the larger public health enterprise in big cities, counties, and large metropolitan areas.


title: An analysis of the ethics of lockdown in India

text: Over the past 6 months, coronavirus-induced disease (COVID-19) has spread across 212 countries, affecting millions of people. As it has no known cure, social distancing is highly recommended for prevention of spread of the disease. Here, we have described the impact of the social distancing measures implemented by the Government of India on various sections of the society, especially the vulnerable sections. Furthermore, we have presented an analysis of these measures, according to the World Health Organization´s Guidance for Managing Ethical Issues in Infectious Disease Outbreaks (2016); we have also applied principles, as applicable, from the Indian Council of Medical Research’s National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017). Finally, we have presented several measures that should have been adopted before and in addition to implementing the lockdown to improve its effectiveness.


title: The remarkable adaptability of syndromic surveillance to meet public health needs

text: Abstract The goal of syndromic surveillance is the earlier detection of epidemics, allowing a timelier public health response than is possible using traditional surveillance methods. Syndromic surveillance application for public health purposes has changed over time and reflects a dynamic evolution from the collection, interpretation of data with dissemination of data to those who need to act, to a more holistic approach that incorporates response as a core component of the surveillance system. Recent infectious disease threats, such as severe acute respiratory syndrome (SARS), avian influenza (H5N1) and pandemic influenza (H1N1), have all highlighted the need for countries to be rapidly aware of the spread of infectious diseases within a region and across the globe. The International Health Regulations (IHR) obligation to report public health emergencies of international concern has raised the importance of early outbreak detection and response. The emphasis in syndromic surveillance is changing from automated, early alert and detection, to situational awareness and response. Published literature on syndromic surveillance reflects the changing nature of public health threats and responses. Syndromic surveillance has demonstrated a remarkable ability to adapt to rapidly shifting public health needs. This adaptability makes it a highly relevant public health tool.


title: Virtual Management of Patients With Cancer During the COVID-19 Pandemic: Web-Based Questionnaire Study

text: BACKGROUND: During the coronavirus disease (COVID-19) pandemic, patients with cancer in rural settings and distant geographical areas will be affected the most by curfews. Virtual management (telemedicine) has been shown to reduce health costs and improve access to care. OBJECTIVE: The aim of this survey is to understand oncologists’ awareness of and views on virtual management, challenges, and preferences, as well as their priorities regarding the prescribing of anticancer treatments during the COVID-19 pandemic. METHODS: We created a self-administrated electronic survey about the virtual management of patients with cancer during the COVID-19 pandemic. We evaluated its clinical sensibility and pilot tested the instrument. We surveyed practicing oncologists in Gulf and Arab countries using snowball sampling via emails and social media networks. Reminders were sent 1 and 2 weeks later using SurveyMonkey. RESULTS: We received 222 responses from validated oncologists from April 2-22, 2020. An awareness of virtual clinics, virtual multidisciplinary teams, and virtual prescriptions was reported by 182 (82%), 175 (79%), and 166 (75%) respondents, respectively. Reported challenges associated with virtual management were the lack of physical exam (n=134, 60%), patients’ awareness and access (n=131, 59%), the lack of physical attendance of patients (n=93, 42%), information technology (IT) support (n=82, 37%), and the safety of virtual management (n=78, 35%). Overall, 111 (50%) and 107 (48%) oncologists did not prefer the virtual prescription of chemotherapy and novel immunotherapy, respectively. However, 188 (85%), 165 (74%), and 127 (57%) oncologists preferred the virtual prescription of hormonal therapy, bone modifying agents, and targeted therapy, respectively. In total, 184 (83%), 183 (83%), and 176 (80%) oncologists preferred to continue neoadjuvant, adjuvant, and perioperative treatments, respectively. Overall, 118 (53%) respondents preferred to continue first-line palliative treatment, in contrast to 68 (30%) and 47 (21%) respondents indicating a preference to interrupt second- and third-line palliative treatment, respectively. For administration of virtual prescriptions, all respondents preferred the oral route and 118 (53%) preferred the subcutaneous route. In contrast, 193 (87%) did not prefer the intravenous route for virtual prescriptions. Overall, 102 (46%) oncologists responded that they would “definitely” prefer to manage patients with cancer virtually. CONCLUSIONS: Oncologists have a high level of awareness of virtual management. Although their survey responses indicated that second- and third-line palliative treatments should be interrupted, they stated that neoadjuvant, adjuvant, perioperative, and first-line palliative treatments should continue. Our results confirm that oncologists’ views on the priority of anticancer treatments are consistent with the evolving literature during the COVID-19 pandemic. Challenges to virtual management should be addressed to improve the care of patients with cancer.


Is varicella zoster virus really involved in the pathogenesis of multiple sclerosis?


title: A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy

text: Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCas(E) murine retrovirus on day 8 after birth die of leukemia within 4–5 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through FcγR-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies.


title: Anesthesiologists’ and Intensive Care Providers’ Exposure to Coronavirus Disease 2019 Infection in a New York City Academic Center: A Prospective Cohort Study Assessing Symptoms and Coronavirus Disease 2019 Antibody Testing

text: Protecting first-line health care providers against work-related Coronavirus Disease 2019 (COVID-19) infection at the onset of the pandemic has been a crucial challenge in the United States. Anesthesiologists in particular are considered at risk, since aerosol-generating procedures, such as intubation and extubation, have been shown to significantly increase the odds for respiratory infections during severe acute respiratory syndrome (SARS) outbreaks. This study assessed the incidence of COVID-19–like symptoms and thepresence of COVID-19 antibodies after work-related COVID-19 exposures, among physicians working in a large academic hospital in New York City (NYC). METHODS: An e-mail survey was addressed to anesthesiologists and affiliated intensive care providers at Columbia University Irving Medical Center on April 15, 2020. The survey assessed 4 domains: (1) demographics and medical history, (2) community exposure to COVID-19 (eg, use of NYC subway), (3) work-related exposure to COVID-19, and (4) development of COVID-19–like symptoms after work exposure. The first 100 survey responders were invited to undergo a blood test to assess antibody status (presence of immunoglobulin M [IgM]/immunoglobulin G [IgG] specific to COVID-19). Work-related exposure was defined as any episode where the provider was not wearing adequate personal protective equipment (airborne or droplet/contact protection depending on the exposure type). Based on the clinical scenario, work exposure was categorized as highrisk (eg, exposure during intubation) or lowrisk (eg, exposure during doffing). RESULTS: Two hundred and five health care providers were contacted and 105 completed the survey (51%); 91 completed the serological test. Sixty-one of the respondents (58%) reported at least 1 work-related exposure and 54% of the exposures were highrisk. Among respondents reporting a work-related exposure, 16 (26.2%) reported postexposure COVID-19–like symptoms. The most frequent symptoms were myalgia (9 cases), diarrhea (8 cases), fever (7 cases), and sore throat (7 cases). COVID-19 antibodies were detected in 11 of the 91 tested respondents (12.1%), with no difference between respondents with (11.8%) or without (12.5%) a work-related exposure, including high-risk exposure. Compared with antibody-negative respondents, antibody-positive respondents were more likely to use NYC subway to commute to work and report COVID-19–like symptoms in the past90 days. CONCLUSIONS: In the epicenter of the United States’ pandemic and within 6–8 weeks of the COVID-19 outbreak, a small proportion of anesthesiologists and affiliated intensive care providers reported COVID-19–like symptoms after a work-related exposure and even fewer had detectable COVID-19 antibodies. Thepresenceof COVID-19 antibodies appeared to be associated with community/environmental transmission rather than secondary to work-related exposures involving high-risk procedures.


title: Acute Respiratory Decompensation Requiring Intubation in Pregnant Women with SARS-CoV-2 (COVID-19)

text: There is a current paucity of information about the obstetric and perinatal outcomes of pregnant novel coronavirus disease 2019 (COVID-19) patients in North America. Data from China suggest that pregnant women with COVID-19 have favorable maternal and neonatal outcomes, with rare cases of critical illness or respiratory compromise. However, we report two cases of pregnant women diagnosed with COVID-19 in the late preterm period admitted to tertiary care hospitals in New York City for respiratory indications. After presenting with mild symptoms, both quickly developed worsening respiratory distress requiring intubation, and both delivered preterm via caesarean delivery. These cases highlight the potential for rapid respiratory decompensation in pregnant COVID-19 patients and the maternal-fetal considerations in managing these cases.


title: COVID-19 Pneumonia Mimicking Immunotherapy-Induced Pneumonitis on (18)F-FDG PET/CT in a Patient Under Treatment With Nivolumab

text: Within a few months, coronavirus disease 2019 (COVID-19) has become a pandemic with more than 2 million patients infected and a high mortality rate. Early detection of COVID-19 in oncologic patients is crucial in order to rapidly apply isolation measures and avoid nosocomial spread. However, early diagnosis may be challenging, especially in cancer patients under treatment with immunotherapy as drug-induced pneumonitis can present similar clinical and radiological features. We describe the findings of a SARS-CoV-2 infection on PET/CT with (18)F-FDG in a 51-year-old man with metastatic renal cell carcinoma under treatment with nivolumab.


title: Risk, uncertainty, and leverage()

text: Using mostly theoretical models and traditional risk/uncertainty measures (VIX index, panic, precaution, scary bad news, etc.), the current literature tries to clarify the risk/uncertainty-deleveraging pattern. The findings are not sufficient to explain the dynamic empirical relationship between modern risk/uncertainty indicators and leverage. We fill this gap in the literature by using US quarterly data, from 1985:1 to 2018:4, Granger causality tests, and a structural vector autoregression model. We find that commercial bank leverage rises when geopolitical risk and macroeconomic, policy, and equity uncertainty increase. Client-based business relationships of banks and high government borrowing from banks during crises periods are responsible for this relationship. We find that the leverage of broker-dealers and shadow banks declines when Chicago risk and macroeconomic, policy, financial, and equity uncertainty increase. We argue that the vulnerability of broker-dealers and shadow banks to the risk/uncertainty of the entire market system is responsible for this relationship.


title: What is the Role of Respiratory Viruses in Community Acquired Pneumonia; What is the Best Therapy for Influenza and Other Viral Causes of CAP?

text: Respiratory viruses including influenza have long been appreciated as a cause of community acquired pneumonia (CAP), particularly among children, people with serious medical co-morbidities and military recruits. They are increasingly recognized as a cause of CAP among adults, particularly older adults. Polymerase chain reaction-based testing has allowed detection of newer agents (e.g. human metapneumovirus, coronavirus HKU1 and NL63) as well as improved the ability to detect “old” viral infections such as influenza virus and rhinovirus. When PCR is used, viruses have been detected in 45–75% of children and 15–54% of adults with CAP. Co-infection with viruses and bacteria is common and it remains challenging to determine which patients have only viral infection as the cause of CAP. Treatment for influenza with neuraminidase inhibitors should be started promptly for patients with CAP when influenza is suspected or documented, regardless of evidence of bacterial co-infection. Better ways to diagnose viral CAP and to integrate detection into management are urgently needed, as well as better treatment options for non-influenza respiratory viral infections.


title: Respiratory Virus Infections in Adults with Hematologic Malignancies: A Prospective Study

text: During a 2-year period, 157 consecutive episodes of respiratory virus infections that occurred in 130 patients with upper or lower respiratory tract infection were analyzed for respiratory viruses. A respiratory virus was identified in 75 episodes (48%), and several viruses were found in 13 episodes: there were a total of 56 influenza A virus infections, 14 respiratory syncytial virus infections, 8 adenovirus infections, 8 infections with parainfluenza virus types 1 or 3, and 7 enterovirus infections. On multivariate analysis, the only variable that predicted progression to pneumonia in patients with an upper respiratory tract infection was the presence of respiratory syncytial virus, whereas lymphocytopenia had a nonsignificant trend. Also, among the 38 patients who had pneumonia at any time during the episode, both respiratory syncytial virus and lymphocytopenia were commonly found. For both epidemiological and therapeutic considerations, frequent screening for respiratory viruses should be incorporated into the routine diagnostic study of patients with hematologic malignancies.


title: The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells

text: Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process.


title: Stopping Clinical Trials in Inflammatory Bowel Disease During the COVID-19 Pandemic is not a Responsible Act

text: The intense competition for resources to combat COVID-19 has greatly reduced access to health care for patients with other diseases. After the disastrous overrun of hospitals through COVID-19 patients in some jurisdictions, availability of resources for “elective” medical procedures including care for the chronically ill have been greatly reduced in many places as a pre-emptive measure before or during the blooming of infection clusters. Pharmaceutical companies have either stopped recruitment or even cancelled ongoing clinical trials in chronic diseases. Pre-emptive triage and its impact on medical ethics is discussed in the framework of care for inflammatory bowel disease.


title: Catastrophe In Radiology: Considerations Beyond Common Emergencies

text: Abstract Disasters often occur without warning and have the potential to affect large numbers of people. Those in the radiology environment experience unique effects on them, their equipment, and their ability to provide quality patient care. Lessons can be learned by reviewing events and their impact on imaging departments around the world. Radiology departments need to be actively involved in the disaster planning and the management of disasters when they occur. Common themes emerge regardless of the type of disaster and these themes should be included in all planning.


title: Corrigendum to “Coronavirus Disease-19: The First 7,755 Cases in the Republic of Korea” [Osong Public Health Res Perspect 2020;11(2):85–90]

text: [This corrects the article on p. 85 in vol. 11, PMID: 32257774.].


title: Managing head and neck cancer patients with tracheostomy or laryngectomy during the COVID‐19 pandemic

text: Head and neck cancer patients with tracheostomies and laryngectomies, as well as their healthcare providers, face unique challenges in the context of the current COVID‐19 pandemic. This document consolidates best available evidence to date and presents recommendations to minimize the risks of aerosolization and SARS‐CoV‐2 exposures in both the inpatient and outpatient settings. The cornerstones of these recommendations include the use of closed‐circuit ventilation whenever possible, cuffed tracheostomy tubes, judicious use of heat moisture exchange units, appropriate personal protective equipment for providers and patients, meticulous hand hygiene, and minimal manipulation of tracheostomy tubes.


title: Human B cell memory

text: Following an immune response two types of differentiated B cells persist in the memory pool: plasma cells, which confer immediate protection by the secretion of specific antibodies; and memory B cells, which confer rapid and enhanced response to secondary challenge. We will review recent advances in understanding the heterogeneity, dynamics, and persistence of human memory B cells and plasma cells as well as new methods to isolate human monoclonal antibodies. These findings offer new insights into the human B cell response, which are relevant for vaccination and therapeutic intervention.


title: Real-Time Reverse Transcription–Polymerase Chain Reaction Assay for SARS-associated Coronavirus

text: A real-time reverse transcription–polymerase chain reaction (RT-PCR) assay was developed to rapidly detect the severe acute respiratory syndrome–associated coronavirus (SARS-CoV). The assay, based on multiple primer and probe sets located in different regions of the SARS-CoV genome, could discriminate SARS-CoV from other human and animal coronaviruses with a potential detection limit of <10 genomic copies per reaction. The real-time RT-PCR assay was more sensitive than a conventional RT-PCR assay or culture isolation and proved suitable to detect SARS-CoV in clinical specimens. Application of this assay will aid in diagnosing SARS-CoV infection.


title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A Narrative Review

text: Abstract Aims Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to glycemic control and role of anti-diabetic agents in patients with diabetes. Methods A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. Results There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe variety of COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. Conclusions Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.


title: Community-associated methicillin-resistant Staphylococcus aureus necrotizing pneumonia without evidence of antecedent viral upper respiratory infection

text: BACKGROUND: USA300 community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains causing necrotizing pneumonia have been reported in association with antecedent viral upper respiratory tract infections (URI). METHODS: A case series of necrotizing pneumonia presenting as a primary or coprimary infection, secondary to CA-MRSA without evidence of antecedent viral URI, is presented. Cases were identified through the infectious diseases consultation service records. Clinical and radiographic data were collected by chart review and electronic records. MRSA strains were isolated from sputum, bronchoalveolar lavage, pleural fluid or blood cultures and confirmed using standard laboratory procedures. MRSA strains were characterized by susceptibility testing, pulsed-field gel electrophoresis, spa typing, agr typing and multilocus sequence typing. Testing for respiratory viruses was performed by appropriate serological testing of banked sera, or nucleic acid testing of nasopharyngeal or bronchoalveloar lavage specimens. RESULTS: Ten patients who presented or copresented with CA necrotizing pneumonia secondary to CA-MRSA from April 2004 to October 2011 were identified. The median length of stay was 22.5 days. Mortality was 20.0%. Classical risk factors for CA-MRSA were identified in seven of 10 (70.0%) cases. Chest tube placement occurred in seven of 10 patients with empyema. None of the patients had historical evidence of antecedent URI. In eight of 10 patients, serological or nucleic acid testing testing revealed no evidence of acute viral coinfection. Eight strains were CMRSA-10 (USA300). The remaining two strains were a USA300 genetically related strain and a USA1100 strain. CONCLUSION: Pneumonia secondary to CA-MRSA can occur in the absence of an antecedent URI. Infections due to CA-MRSA are associated with significant morbidity and mortality. Clinicians need to have an awareness of this clinical entity, particularly in patients who are in risk groups that predispose to exposure to this bacterium.


title: Epidemiological control measures and predicted number of infections for SARS-CoV-2 Pandemic: Case Study Serbia March-April 2020

text: BACKGROUND: In this paper, we are studying the response of the Serbian government and health authorities to the SARS-CoV-2 pandemic in the early stage of the local outbreak between Mar. 15(th) and Apr. 15(th), 2020 by predictive numerical models. Such a study should be helpful to access the effectiveness of measures conducted to suppress the pandemic at a local scale. METHODS: We have performed extrapolation of the number of SARS-CoV-2 infections with the first stable set of data exploiting exponential growth (linear in logarithmic scale). Based on obtained coefficients it is performed prediction of a number of cases until the end of March. After initial exponential growth, we have changed predictive model to the generalized gamma function. Obtained results are compared with the number of infections and the prediction for the remainder of the outbreak is given. FINDINGS: We have found that the daily growth rate was above 21.5% at the beginning of the period, increased slightly after the introduction of the State of Emergency and the first set of strict epidemical control measures. It took about 13 days after the first set of strict measures to smooth daily growth. It seems that early government measures had an only moderate impact to reduce growth due to the social behavior of citizens and influx of diaspora returning to Serbia from highly affected areas, i.e., the exponential growth of infected persons is kept but with a reduced slope of about 14-15%. Anyway, it is demonstrated that period required that any measure has effect is up to 15 days after introduction, firstly to exponential growth with a smaller rate and after to smooth function representing the number of infected persons below exponential growth rate. CONCLUSIONS: Obtained results are consistent with findings from other countries, i.e., initial exponential growth slows down within the presumed incubation period of 2 weeks after adopting lockdown and other non-pharmaceutical epidemiological measures. However, it is also shown that the exponential growth can continue after this period with a smaller slope. Therefore, quarantine and other social distancing measures should be adopted as soon as possible in a case of any similar outbreak since alternatives mean prolonged epidemical situation and growing costs in human life, pressure on the health system, economy, etc. For modeling the remainder of the outbreak generalized gamma function is used showing accurate results but requiring more samples and pre-processing (data filtering) concerning exponential part of the outbreak. We have estimated the number of infected persons for the remaining part of the outbreak until the end of June.


title: Supporting Clinicians During the COVID-19 Pandemic

text: The COVID-19 pandemic has upended clinicians' sense of order and control, creating the potential for stress in the short term and burnout over the long term. This commentary offers suggestions to encourage a culture that will sustain the clinician workforce during the pandemic.


title: Potential of regulatory T cell-based therapies in the management of severe COVID-19

text: In view of dysregulated immune response, cytokine storm and inflammation-induced severe lung damage in severely ill COVID-19 patients, we propose that CD4+CD25+FoxP3+ regulatory T cell-based therapies could be considered for the patient management.


title: Knowledge and awareness of Middle East respiratory syndrome coronavirus among Saudi and Non-Saudi Arabian pilgrims

text: OBJECTIVE: The current study was intended to evaluate the knowledge and awareness toward Middle East respiratory syndrome coronavirus (MERS-CoV) of pilgrims from Saudi Arabia and from different Arabian countries. METHODS: A prospective study was conducted among pilgrims from Saudi Arabia and those from other Arab nations. A total number of 2120 participants including 736 Saudi pilgrims (436 males and 300 females) and 1384 non-Saudi Arabian pilgrims (1384; 909 males and 475 females) were included in the study. The responses of the participants were descriptively analyzed. Pearson correlation coefficient was used to screen the possible correlations among different variables. The differences in the responses between the two groups were evaluated using Mann–Whitney analysis. RESULTS: The responses of the Saudi pilgrims showed statistically significant results in comparison to non-Saudi pilgrims in answering all questions except those related to the presence of efficient vaccination or treatment and the source of information. It was clear that the Saudi pilgrims were more oriented about different aspects of MERS-CoV including the nature of the causative agent, the signs, the severity of the disease, the animals that can transmit the infection to humans, the risk groups, and when one need to be screened for infection. In both Saudi and non-Saudi pilgrims, the official websites of health organizations constitute the main source of their information. CONCLUSION: It was concluded that Saudi pilgrims possess good knowledge about the MERS-CoV although more orientation is still required.


title: Brain Meta-Transcriptomics from Harbor Seals to Infer the Role of the Microbiome and Virome in a Stranding Event

text: Marine diseases are becoming more frequent, and tools for identifying pathogens and disease reservoirs are needed to help prevent and mitigate epizootics. Meta-transcriptomics provides insights into disease etiology by cataloguing and comparing sequences from suspected pathogens. This method is a powerful approach to simultaneously evaluate both the viral and bacterial communities, but few studies have applied this technique in marine systems. In 2009 seven harbor seals, Phoca vitulina, stranded along the California coast from a similar brain disease of unknown cause of death (UCD). We evaluated the differences between the virome and microbiome of UCDs and harbor seals with known causes of death. Here we determined that UCD stranded animals had no viruses in their brain tissue. However, in the bacterial community, we identified Burkholderia and Coxiella burnetii as important pathogens associated with this stranding event. Burkholderia were 100% prevalent and ~2.8 log2 fold more abundant in the UCD animals. Further, while C. burnetii was found in only 35.7% of all samples, it was highly abundant (~94% of the total microbial community) in a single individual. In this harbor seal, C. burnetii showed high transcription rates of invading and translation genes, implicating it in the pathogenesis of this animal. Based on these data we propose that Burkholderia taxa and C. burnetii are potentially important opportunistic neurotropic pathogens in UCD stranded harbor seals.


title: Nitric oxide and virus infection

text: Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. The mechanisms of many events induced by NO are now well defined, so that a fundamental understanding of NO biology is almost established. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Although antimicrobial activity of NO is appreciated for bacteria and protozoa, NO has opposing effects in virus infections such as influenza virus pneumonia and certain other neurotropic virus infections. iNOS produces an excessive amount of NO for long periods, which allows generation of a highly reactive nitrogen oxide species, peroxynitrite, via a radical coupling reaction of NO with superoxide. Thus, peroxynitrite causes oxidative tissue injury through potent oxidation and nitration reactions of various biomolecules. NO also appears to affect a host's immune response, with immunopathological consequences. For example, overproduction of NO in virus infections in mice is reported to suppress type 1 helper T-cell-dependent immune responses, leading to type 2 helper T-cell-biased immunological host responses. Thus, NO may be a host response modulator rather than a simple antiviral agent. The unique biological properties of NO are further illustrated by our recent data suggesting that viral mutation and evolution may be accelerated by NO-induced oxidative stress. Here, we discuss these multiple roles of NO in pathogenesis of virus infections as related to both non-specific inflammatory responses and immunological host reactions modulated by NO during infections in vivo.


title: Structural and biochemical characterization of SADS‐CoV papain‐like protease 2

text: Swine acute diarrhea syndrome coronavirus (SADS‐CoV) is a novel coronavirus that is involved in severe diarrhea disease in piglets, causing considerable agricultural and economic loss in China. The emergence of this new coronavirus increases the importance of understanding SADS‐CoV as well as antivirals. Coronaviral proteases, including main proteases and papain‐like proteases (PLP), are attractive antiviral targets because of their essential roles in polyprotein processing and thus viral maturation. Here, we describe the biochemical and structural identification of recombinant SADS papain‐like protease 2 (PLP2) domain of nsp3. The SADS‐CoV PLP2 was shown to cleave nsp1 proteins and also peptides mimicking the nsp2|nsp3 cleavage site and also had deubiquitinating and deISGynating activity by in vitro assays. The crystal structure adopts an architecture resembling that of PLPs from other coronaviruses. We characterize both conserved and unique structural features likely directing the interaction of PLP2 with the substrates, including the tentative mapping of active site and other essential residues. These results provide a foundation for understanding the molecular basis of coronaviral PLPs' catalytic mechanism and for the screening and design of therapeutics to combat infection by SADS coronavirus.


title: Saprolegnia australis R. F. Elliott 1968 infection in Prussian carp Carassius gibelio (Bloch, 1782) eggs and its control with herb extracts

text: In order to control saprolegniosis in Prussian carp (Carassius gibelio (Bloch, 1782) eggs, it is important to screen herb extracts as potential anti‐Saprolegnia drugs in Prussian carp hatcheries. For this purpose, an oomycete water mould (strain SC) isolated from Prussian carp [Carassius gibelio (Bloch, 1782)] eggs suffering from saprolegniosis was characterised morphologically as well as from ITS rDNA sequence data. Initially identified as a Saprolegnia sp. based on its morphological features, the constructed phylogenetic tree using the neighbour joining method further indicated that the SC strain was closely related to Saprolegnia australis R. F. Elliott 1968 strain VI05733 (GenBank accession no. HE798564), and which could form biofilm communities as virulence factors. In addition, aqueous extracts from forty Chinese herbs were screened as possible anti‐Saprolegnia agents. Among them, a 1 g ml(−1) extract from Radix sanguisorbae was the most efficacious anti‐Saprolegnia agent, indicated by the minimum inhibitory concentration that was as low as 256 mg L(−1). Relative survival of 73 and 88% was obtained against the SC strain in fish eggs at concentrations of 256 and 1280 mg L(−1), respectively. This is the first known report of Saprolegnia australis R. F. Elliott 1968 infection in C. gibelio (Bloch, 1782) eggs involving the screening of R. sanguisorbae extracts as potential anti‐Saprolegnia agents.


title: B Cells and Antibodies in Kawasaki Disease

text: The etiology of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology supports a relationship of KD to an infectious disease. Several pathological mechanisms are being considered, including a superantigen response, direct invasion by an infectious etiology or an autoimmune phenomenon. Treating affected patients with intravenous immunoglobulin is effective at reducing the rates of coronary aneurysms. However, the role of B cells and antibodies in KD pathogenesis remains unclear. Murine models are not clear on the role for B cells and antibodies in pathogenesis. Studies on rare aneurysm specimens reveal plasma cell infiltrates. Antibodies generated from these aneurysmal plasma cell infiltrates showed cross-reaction to intracellular inclusions in the bronchial epithelium of a number of pathologic specimens from children with KD. These antibodies have not defined an etiology. Notably, a number of autoantibody responses have been reported in children with KD. Recent studies show acute B cell responses are similar in children with KD compared to children with infections, lending further support of an infectious disease cause of KD. Here, we will review and discuss the inconsistencies in the literature in relation to B cell responses, specific antibodies, and a potential role for humoral immunity in KD pathogenesis or diagnosis.


title: H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis

text: BACKGROUND: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. METHODS: We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. RESULTS: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. CONCLUSIONS: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.


title: Low Transmission Risk of 9 Asymptomatic Carriers Tested Positive for both SARS-CoV-2 Nucleic Acid and Serum IgG

text: • Asymptomatic carriers (RT-PCR+ and serum IgG+) are unable to transmit virus. • Such a low transmission risk might be partly associated with high Ct values. • A new pattern in SARS-CoV-2 infected patients might have emerged.


title: Cytoplasmic Inclusion Bodies Are Detected by Synthetic Antibody in Ciliated Bronchial Epithelium during Acute Kawasaki Disease

text: BackgroundIn developed nations, Kawasaki disease (KD) is the most common cause of acquired heart disease in children. An infectious etiology is likely but has not yet been identified. We have previously reported that oligoclonal immunoglobulin A plasma cells infiltrate acute KD tissues and that synthetic KD antibodies detect a distinctive spheroidal antigen in acute KD ciliated bronchial epithelium MethodsTo further characterize the antigen in acute KD bronchi, we examined paraffin-embedded ciliated bronchial epithelium using light microscopy (LM) and transmission electron microscopy (TEM) ResultsThe spheroids observed by immunohistochemistry (IHC) are visualized as inclusion bodies with hematoxylin-eosin and nucleic acid stains and in methylene blue/azure II/basic fuchsin trichrome–stained plastic sections, suggesting the presence of both protein and nucleic acid. The structures visualized by LM correspond to homogeneous electron-dense perinuclear inclusion bodies (up to 1.4 microns in diameter) in ciliated bronchial epithelium from 4 patients with acute KD examined by TEM. Inclusion bodies were not present in control bronchial epithelium or in nonciliated cells ConclusionsThe antigen detected in acute KD ciliated bronchial epithelium by IHC with synthetic KD antibodies resides in cytoplasmic inclusion bodies that are consistent with aggregates of viral proteins and associated nucleic acid and may derive from the etiologic agent of KD


title: A Model of Support for Families of Children With Autism Living in the COVID-19 Lockdown: Lessons From Italy

text: Italy has been the European country most affected by the COVID-19 pandemic to date and has been in social lockdown for the longest period of time compared to other countries outside China. Almost overnight, Italian behavior analysts were faced with the challenge of setting up remotely whole-family systems aimed at maintaining adaptive skills and low levels of challenging behavior to be carried out solely by caregivers. Given these extraordinary circumstances, the protocols available from the applied behavior-analytic, parent training, and autism literature did not appear to fully meet the needs of parents having to be with their children under extreme levels of stress in a confined space with limited reinforcers for 24 hr a day, 7 days a week. To meet this unprecedented challenge, we developed a dynamic and holistic protocol that extended to the full day and that recognized the need for sustainable intervention delivered solely by parents, who were often looking after more than one child. These practices are presented in this article, together with a discussion of lessons we have learned thus far, which may be useful for behavior analysts working in other regions in which the effects of the pandemic are not yet fully realized. Although somewhat unorthodox, we include some parent comments at the end with the goal of sharing the parent perspective in real time as this pandemic unfolds across the world.


title: Feasibility and acceptability of an oral pathology asynchronous tele-mentoring intervention: A protocol

text: Introduction: Oral cancer remains prevalent, despite being largely preventable. The widespread use of technology at chairside, combined with advances in electronic health record (EHR) capabilities, present opportunities to improve oral cancer screening by dentists, especially for disadvantaged patients with severe health needs. Design and methods: Using a mixed-methods approach, we will evaluate the feasibility and acceptability of integrating a telementoring component into the identification of oral lesions using the following 3 methods: 1) administering provider surveys that consist of a checklist of 10 key components of the intervention based on process, and asking the dental provider subjects if each one was covered; 2) conducting semi-structured interviews informed by the Consolidated Framework for Implementation Research and the Implementation Outcomes Framework with dental resident subjects to assess specific barriers to sustaining the intervention and strategies for addressing these barriers to facilitate integration of the intervention into the routine workflow of the dental clinics; and 3) administering brief exit interviews with patient subjects regarding the acceptability of the intervention to assess satisfaction with the use of intra-oral cameras at chairside to screen for and refer patients with oral lesions and identification of these oral lesions via EHR and secure e-mail tele-mentoring with an oral pathology expert. Expected impact of the study for public health: If successful, then later clinical trials will maximize the external validity of the intervention and facilitate the widespread implementation and dissemination of the model for the teaching of dentists and residents, with the ultimate goal of improving patient care.


An Invited Commentary on “The Socio-Economic Implications of the Coronavirus and COVID-19 Pandemic: A Review”


docid: kqrbyrsp

title: Analytical detection of 9(4)-O-acetylated sialoglycoproteins and gangliosides using influenza C virus

text: Abstract The unique glycoprotein of influenza C virus, designated hemagglutinin (HEF), exhibits three functions: hemagglutination, esterase activity, and fusion factor. As the virus uses 9-O-acetylated sialic acid as a high-affinity receptor determinant for attachment to cells, its binding activity was used to reveal O-acetylated sialic acid residues after polyacrylamide gel electrophoresis and transfer onto nitrocellulose sheets of proteins and thin-layer chromatography of lipids. The specificity of the binding for O-acetylated sialoglycoconjugates was investigated. Our results showed that influenza C virus could detect the different forms of the two murine glycophorins which are known to be O-acetylated sialoglycoconjugates. The virus also bound to O-acetylated gangliosides isolated from embryonic chicken brain such as purified O-acetylated NeuAcα(2–8)NeuAcα(2–8)NeuAcα(2–3)Galβ(1–4)Glcβ(1-1)ceramide (GT3). The esterase activity of the HEF protein of influenza C virus was used to unmask the sialic acid. After its deacetylation by the virus enzyme, the O-acetylated GT3 was recognized by a monoclonal antibody which binds only to the nonacetylated derivative. The results presented here show that influenza C virus is a discriminating analytical probe for identifying O-acetylated sialoglycoconjugates directly after Western blotting of proteins and thin-layer chromatography of lipids, thus providing a new analytical tool.


title: Cross-sectional survey on public health informatics workforce in China: issues, developments and the future

text: Abstract Objective To explore the current situation and issues related to the development of the public health informatics (PHI) workforce in provincial and prefectural centers for disease control and prevention (CDCs) in China, and to describe the corresponding strategies to address these issues for the future. Study design National cross-sectional study. Methods One thousand two hundred and eighty-one respondents were selected at random from provincial and prefectural CDCs. The survey used a self-administered, structured questionnaire with an online data collection tool that integrated data quality control and user management. The questionnaire was divided into seven main categories. Score percentage of satisfaction and proportion in each part were calculated. Descriptive statistics were used to analyse the data, stratifying by country region, CDC level, job role and educational level. Results One hundred and sixty staff from provincial CDCs and 1121 staff from prefectural CDCs were selected. Only 7.4% (33/445) of prefectural CDCs were not involved in this survey, due to lack of PHI practitioners. CDC staff in the eastern region were predominantly aged 30–39 years (39.5%), which was much younger compared with the other regions (P = 0.0012). Only 34 respondents (2.7%) had academic majors in both health and information technology. More staff had Master's degrees and a higher level of education (18.7%) in the eastern region compared with the other regions (P < 0.0001). Staff in the eastern region in high-level positions and with a higher level of education were more knowledgeable about PHI strategy. Prefectural CDC staff were more satisfied with their work and training than provincial CDC staff. In the eastern region, 34.9% of staff were hired through competitive recruitment, and 57.8% of staff had received a job description with detailed information about their responsibilities, which was higher than in the other regions. Staff in the western region were more likely to leave if a better job became available (37.7%) compared with staff in the other regions (P = 0.0116). Conclusion This study found regional disparities in PHI workforce development, possibly related to disparities in overall regional development. Findings showed a severe shortage of staff with a background in PHI, and occupational development paths were clearly lacking. Based on this study of current workforce issues, a comprehensive strategy for PHI workforce development in China has been described.


title: The Landscape of Risk Communication Research: A Scientometric Analysis

text: Risk communication is a significant research domain with practical importance in supporting societal risk governance and informed private decision making. In this article, a high-level analysis of the risk communication research domain is performed using scientometrics methods and visualization tools. Output trends and geographical patterns are identified, and patterns in scientific categories determined. A journal distribution analysis provides insights into dominant journals and the domain’s intellectual base. Thematic clusters and temporal evolution of focus topics are obtained using a terms analysis, and a co-citation analysis provides insights into the evolution of research fronts and key documents. The results indicate that the research volume grows exponentially, with by far most contributions originating from Western countries. The domain is highly interdisciplinary, rooted in psychology and social sciences, and branching mainly into medicine and environmental sciences. Narrative themes focus on risk communication in medical and societal risk governance contexts. The domain originated from public health and environmental concerns, with subsequent research fronts addressing risk communication concepts and models. Applied research fronts are associated with environmental hazards, public health, medical risks, nuclear power, and emergency response to various natural hazards. Based on the results, various avenues for future research are described.


title: COVID-19 Serological Tests: How Well Do They Actually Perform?

text: In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests


title: CRISPR Editing in Biological and Biomedical Investigation

text: The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)‐CRISPR‐associated protein 9 (Cas9) system has sparked advancements in biological and biomedical research. The scientific breakthrough of the development of CRISPR‐Cas9 technology has allowed us to recapitulate human diseases by generating animal models of interest ranging from zebrafish to non‐human primates. The CRISPR‐Cas9 system can also be used to delineate the mechanisms underlying the development of human disorders and to precisely correct disease‐causing mutations. Repurposing this technology enables wider applications in transcriptome and epigenome manipulation and holds promise to reach the clinic. In this review, we highlight the latest advances of the CRISPR‐Cas9 system in different platforms and discuss the hurdles and challenges this technology is facing. J. Cell. Biochem. 118: 4152–4162, 2017. © 2017 Wiley Periodicals, Inc.


title: An assessment of the level of concern among hospital-based health-care workers regarding MERS outbreaks in Saudi Arabia

text: BACKGROUND: Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). More than 80% of reported cases have occurred in Saudi Arabia, with a mortality exceeding 50%. Health-care workers (HCWs) are at risk of acquiring and transmitting this virus, so the concerns of HCWs in Saudi Arabia regarding MERS were evaluated. METHODS: An anonymous, self-administered, previously validated questionnaire was given to 1031 HCWs at three tertiary hospitals in Saudi Arabia from October to December, 2014. Concerns regarding the disease, its severity and governmental efforts to contain it, as well as disease outcomes were assessed using 31 concern statements in five distinct domains. A total concern score was calculated for each HCW. Multiple regression analyses were used to identify predictors of high concern scores. RESULTS: The average age of participants was 37.1 ± 9.0 years, 65.8% were married and 59.1% were nurses. The majority of respondents (70.4%) felt at risk of contracting a MERS-CoV infection at work, 69.1% felt threatened if a colleague contracted MERS-CoV, 60.9% felt obliged to care for patients infected with MERS-CoV and 87.8% did not feel safe at work using standard precautions. In addition, 87.7% believed that the government should isolate patients with MERS in specialized hospitals, 73.7% agreed with travel restriction to and from areas affected by MERS and 65.3% agreed with avoiding inviting expatriates from such areas. After adjustment for covariates, high concern scores were significantly associated with being a Saudi national (p < 0.001), a non-physician (p < 0.001) and working in the central region (p < 0.001). CONCLUSIONS: The majority of respondents reported concern regarding MERS-CoV infection from exposure at work. The overall level of concern may be influenced by previous experience of MERS outbreaks and related cultural issues. The concerns of HCWs may affect their overall effectiveness in an outbreak and should be addressed by incorporating management strategies in outbreak planning.


title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data

text: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.


title: Purifying Selection Can Obscure the Ancient Age of Viral Lineages

text: Statistical methods for molecular dating of viral origins have been used extensively to infer the time of most common recent ancestor for many rapidly evolving pathogens. However, there are a number of cases, in which epidemiological, historical, or genomic evidence suggests much older viral origins than those obtained via molecular dating. We demonstrate how pervasive purifying selection can mask the ancient origins of recently sampled pathogens, in part due to the inability of nucleotide-based substitution models to properly account for complex patterns of spatial and temporal variability in selective pressures. We use codon-based substitution models to infer the length of branches in viral phylogenies; these models produce estimates that are often considerably longer than those obtained with traditional nucleotide-based substitution models. Correcting the apparent underestimation of branch lengths suggests substantially older origins for measles, Ebola, and avian influenza viruses. This work helps to reconcile some of the inconsistencies between molecular dating and other types of evidence concerning the age of viral lineages.


title: Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States

text: BACKGROUND: Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world – China being the standout case – have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues. METHODS: We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries – China, Kuwait and the United States – to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific "bug-drug" data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries' patterns of drug resistance. RESULTS: We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community- acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S. CONCLUSION: Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.


title: Induction of interferon by virus glycoprotein(s) in lymphoid cells through interaction with the cellular receptors via lectin-like action: An alternative interferon induction mechanism

text: When animals and cells are infected with a virus, interferon is produced. Viral-nucleic acid is considered to be one of actual components for interferon induction. In addition, viral glycoproteins trigger interferon induction in lymphoid cells by membrane-membrane interaction via a lectin-like activity. A biological significance of lectin-like activity of viral glycoproteins is discussed.


title: Comparison of lentiviruses pseudotyped with S proteins from coronaviruses and cell tropisms of porcine coronaviruses

text: The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins (S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected Vero- CCL-81 (monkey kidney), Huh-7 (human liver), and PK-15 (pig kidney) cells efficiently. CCL94 (cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening. [Image: see text]


title: Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019

text: The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1–specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema in lungs causing the acute respiratory distress syndrome (ARDS)4-6, the leading cause of death in SARS-CoV-1 and SARS-CoV-2 infection7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.