title: Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16

text: Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of malignant gliomas, are assumed to be selective for tumor cells because their replication is strongly attenuated in quiescent cells, but not in cycling cells. Oncolytic selectivity is thought to occur because mutations in viral ICP6 (encoding a viral ribonucleotide reductase function) and/or γ34.5 function are respectively complemented by mammalian ribonucleotide reductase and GADD34, whose genes are expressed in cycling cells. However, it is estimated that only 5–15% of malignant glioma cells are in mitosis at any one time. Therefore, effective replication of HSV oncolytic viruses might be limited to a subpopulation of tumor cells, since at any one time the majority of tumor cells would not be cycling. However, we report that an HSV with defective ICP6 function replicates in quiescent cultured murine embryonic fibroblasts obtained from mice with homozygous p16 deletions. Furthermore, intracranial inoculation of this virus into the brains of p16−/− mice provides evidence of viral replication that does not occur when the virus is injected into the brains of wild-type mice. These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs are ‘molecularly targeted,’ because they replicate in quiescent tumor cells carrying specific oncogene deletions, independent of cell cycle status.


title: Evaluation of factors associated with immunoglobulin G, fat, protein, and lactose concentrations in bovine colostrum and colostrum management practices in grassland-based dairy systems in Northern Ireland

text: ABSTRACT The objectives of this study were to investigate colostrum feeding practices and colostrum quality on commercial grassland-based dairy farms, and to identify factors associated with colostrum quality that could help inform the development of colostrum management protocols. Over 1 yr, background information associated with dairy calvings and colostrum management practices were recorded on 21 commercial dairy farms. Colostrum samples (n = 1,239) were analyzed for fat, protein, lactose, and IgG concentration. A subset was analyzed for somatic cell count and total viable bacteria count. Factors associated with nutritional and IgG concentrations were determined using both univariate and multivariate models. This study found that 51% of calves were administered their first feed of colostrum via esophageal tube, and the majority of calves (80%) were fed >2 L of colostrum at their first feed (mean = 2.9 L, SD = 0.79), at a mean time of 3.2 h (SD 4.36) after birth, but this ranged across farms. The mean colostral fat, protein, and lactose percentages and IgG concentrations were 6.4%, 14%, 2.7%, and 55 mg/mL, respectively. The mean somatic cell count and total viable count were 6.3 log10 and 6.1 log10, respectively. Overall, 44% of colostrum samples contained <50 mg/mL IgG, and almost 81% were in excess of industry guidelines (<100,000 cfu/mL) for bacterial contamination. In the multivariate model, IgG concentration was associated with parity and time from parturition to colostrum collection. The nutritional properties of colostrum were associated with parity, prepartum vaccination, season of calving, and dry cow nutrition. The large variation in colostrum quality found in the current study highlights the importance of routine colostrum testing, and now that factors associated with lower-quality colostrum on grassland-based dairy farms have been identified, producers and advisers are better informed and able to develop risk-based colostrum management protocols.


title: Clinical description of human bocavirus viremia in children with LRTI, Eastern Province, Saudi Arabia

text: Human bocavirus (HBoV) is a major etiology of lower respiratory tract infection (LRTI) in young children. We tested 149 patients admitted to King Fahd Hospital of the University with diagnosis of LRTI. Viremia caused by the different studied viruses was detected in 31.5% of the total cases by Real-time Polymerase chain reaction. We report five patients who were positive for HBoV in serum samples. Clinical presentation ranged from mild to severe disease as one of them required admission to intensive care unit. Wheezing was a striking feature in most of our patients, but fever was not a consistent finding.


title: Chapter 97 Emerging Viral Infections

text: Emerging and re-emerging viral diseases pose a continuous health threat and disease burden to humans. Research efforts to mitigate the effects of infectious threats, focusing on improved surveillance and diagnostic capabilities, but also on the development of intervention strategies like the use of vaccines and antiviral agents, are crucial. We describe how genomic approaches may aid in mitigating viral threats, by highlighting potential roles and limitations of genomics approaches in virus surveillance and diagnostics, and development of vaccines and antivirals. Keywords antiviral, diagnostics, (emerging) infectious disease, evolution and diversity, gene expression profiling, genome-wide association studies, genome-wide functional screens, host genomics, prevention, surveillance, treatment, viral genomics, virus discovery, vaccine


title: Comprehensive Insights into the Catalytic Mechanism of Middle East Respiratory Syndrome 3C-Like Protease and Severe Acute Respiratory Syndrome 3C-Like Protease

text: [Image: see text] Coronavirus 3C-like protease (3CL(Pro)) is a highly conserved cysteine protease employing a catalytic dyad for its functions. 3CL(Pro) is essential to the viral life cycle and, therefore, is an attractive target for developing antiviral agents. However, the detailed catalytic mechanism of coronavirus 3CL(Pro) remains largely unknown. We took an integrated approach of employing X-ray crystallography, mutational studies, enzyme kinetics study, and inhibitors to gain insights into the mechanism. Such experimental work is supplemented by computational studies, including the prereaction state analysis, the ab initio calculation of the critical catalytic step, and the molecular dynamic simulation of the wild-type and mutant enzymes. Taken together, such studies allowed us to identify a residue pair (Glu-His) and a conserved His as critical for binding; a conserved GSCGS motif as important for the start of catalysis, a partial negative charge cluster (PNCC) formed by Arg-Tyr-Asp as essential for catalysis, and a conserved water molecule mediating the remote interaction between PNCC and catalytic dyad. The data collected and our insights into the detailed mechanism have allowed us to achieve a good understanding of the difference in catalytic efficiency between 3CL(Pro) from SARS and MERS, conduct mutational studies to improve the catalytic activity by 8-fold, optimize existing inhibitors to improve the potency by 4-fold, and identify a potential allosteric site for inhibitor design. All such results reinforce each other to support the overall catalytic mechanism proposed herein.


title: OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids

text: Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP–AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2′–5′-linked second messenger molecules, which — through distinct mechanisms — have crucial antiviral functions. 2′–5′-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2′–5′-linked cGAMP activates downstream signalling pathways to induce de novo antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri3719) contains supplementary material, which is available to authorized users.


title: Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies

text: Many viruses, including coronaviruses, induce host translational shutoff, while maintaining synthesis of their own gene products. In this study we performed genome‐wide microarray analyses of the expression patterns of mouse hepatitis coronavirus (MHV)‐infected cells. At the time of MHV‐induced host translational shutoff, downregulation of numerous mRNAs, many of which encode protein translation‐related factors, was observed. This downregulation, which is reminiscent of a cellular stress response, was dependent on viral replication and caused by mRNA decay. Concomitantly, phosphorylation of the eukaryotic translation initiation factor 2α was increased in MHV‐infected cells. In addition, stress granules and processing bodies appeared, which are sites for mRNA stalling and degradation respectively. We propose that MHV replication induces host translational shutoff by triggering an integrated stress response. However, MHV replication per se does not appear to benefit from the inhibition of host protein synthesis, at least in vitro, since viral replication was not negatively affected but rather enhanced in cells with impaired translational shutoff.


title: Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1

text: Abstract Crystals of the two ammo-terminal domains of intercellular adhesion molecule-1, the receptor for the major group of human rhinovirus serotypes, diffract to 3.0 Å resolution. The crystals are trigonal in space group P3121 or P3221 with cell dimensions of a = b = 55.7 A ̊ , c = 166.3 A ̊ , with probably six molecules per unit cell.


title: Realigning Pakistan's Bioethics Center during Covid‐19

text: The arrival of the Covid‐19 pandemic in Pakistan necessitated that the Centre of Biomedical Ethics and Culture in Karachi realign its activities to changing realities in the country. As Pakistan's only bioethics center, and with no guidelines available for allocation of scarce medical resources, CBEC developed “Guidelines for Ethical Healthcare Decision‐Making in Pakistan” with input from medical and civil society stakeholders. The CBEC blog connected to the center's bioethics programs for students from Pakistan and Kenya shifted to Covid‐related issues specific to the context of existing social and political realities within these countries. As part of its outreach activities, CBEC initiated a popular Facebook series, #HumansofCovid, as an experience‐sharing platform for health care professionals and members of the public. Narratives received vary from those by frustrated physicians under quarantine to those concerning street vendors left jobless and a transsexual person in whose opinion “social distancing” is not a new phenomenon for their communities.


Anestesiología y los anestesiólogos en la COVID-19


¿Cómo podemos ayudar a nuestras pacientes con cáncer ginecológico durante la pandemia COVID-19?


title: RNAi Therapy for HIV Infection: Principles and Practicalities

text: Inside eukaryotic cells, small RNA duplexes, called small interfering RNAs (siRNAs), activate a conserved RNA interference (RNAi) pathway which leads to specific degradation of complementary target mRNAs through base-pairing recognition. As with other viruses, studies have shown that replication of the HIV-1 in cultured cells can be targeted and inhibited by synthetic siRNAs. The relative ease of siRNA design and the versatility of RNAi to target a broad spectrum of mRNAs have led to the promise that drug discovery in the RNAi pathway could be effective against pathogens. This review discusses the current experimental principles that guide the application of RNAi against HIV and describes challenges and limitations that need to be surmounted in order for siRNAs to become practical antiviral drugs. The practical use of RNAi therapy for HIV infection will depend on overcoming several challenges, including the ability to establish long-term expression of siRNA without off-target effects and the capacity to counteract mutant escape viruses.


SARS‐Coronavirus‐2 and acute urticaria


title: Spine Surgical Procedures during Coronavirus Disease 2019 Pandemic: Is It Still Possible to Take Care of Patients? Results of an Observational Study in the First Month of Confinement

text: STUDY DESIGN: Observational study. PURPOSE: The actual sanitary crisis led to a massive mobilization of the sanitary system toward intensive care units and management of coronavirus disease 2019 (COVID-19) patients. However, some patients still require spinal interventions. The present study aimed to assess the impact of the COVID-19 pandemic on spine surgical in a moderate COVID-19 cluster region. OVERVIEW OF LITERATURE: Previous studies have reported screening and management of patients with spinal conditions during the COVID-19 pandemic. However, to date, knowledge, no observational study on spine surgeries during the pandemic has not been reported. METHODS: Between March 17, 2020 and April 17, 2020, information on spine surgical activity was prospectively collected at our institution. This surgical activity related to the first month of confinement in France was compared to the activity during the same period in 2019 to evaluate the impact of the COVID-19 pandemic on surgical activities. RESULTS: In order to reduce the contamination rate of patients and medical staff during hospitalization, the spine department was completely reorganized. Non-urgent elective spine surgeries were cancelled. When considering the global amount of surgeries procedures during the first month of confinement, a decrease of almost 50% was observed in the number of surgical procedures. During the study period, 62 patients were eligible for spine surgery. The numbers of patients managed for tumor and infectious cases were stable, while a considerable reduction was observed in the number of trauma and degenerative cases. During the follow-up period, two patients were tested as COVID+ during the postoperative course, and no cases of medical or paramedical staff contamination were reported using polymerase chain reaction-testing. CONCLUSIONS: During the COVID-19 pandemic, it is possible to maintain spine surgical activity. Each surgical procedure must be discussed and organized with all the caregivers involved. Indications for surgery must be in line with the scientific guidelines and adapted to each healthcare facility.


title: The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus

text: Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which require residues in the HD. Mutation of the HD of IBV E in a recombinant virus background results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV spike (S) protein on the plasma membrane compared to wild-type (WT) IBV-infected cells, and aberrant cleavage of IBV S on virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with an increased Golgi luminal pH. Infection with IBV or expression of IBV E induces neutralization of Golgi pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cell factors, protecting IBV S from premature cleavage and leading to the efficient release of infectious virus from the cells. This is the first demonstration of a coronavirus-induced alteration in the microenvironment of the secretory pathway. IMPORTANCE Coronaviruses are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including the use of attenuated viruses that lack the CoV E protein or express E mutants. However, no approved vaccines or antiviral therapeutics exist. Understanding the role of the CoV E protein in virus assembly and release is thus an important prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.


title: Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)

text: BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics. METHODS/DESIGN: The cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses. DISCUSSION: In the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment. With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.


title: Virological and clinical characterization of respiratory infections in children attending an emergency department during the first autumn-winter circulation of pandemic A (HINI) 2009 influenza virus

text: To characterize respiratory virus infections during the first autumn-winter season of pandemic A (HINI) 2009 influenza virus (A/HINI/2009) circulation, a prospective study in children attending a paediatric emergency department at the Sapienza University hospital, Rome, was conducted from November 2009 to March 2010. By means of both nasal washings and pharyngeal swabs, enrolled children were checked for 14 respiratory viruses. The majority of acute respiratory infections resulted from viral pathogens (135/231, 58%). Overall, the most common was respiratory syncytial virus (RSV), in 64% of positive samples; A/HINI/2009 was the only influenza virus found in 16% and rhinovirus (RV) in 15%. Virus-positive children did not differ significantly from virus-negative children in signs and symptoms at presentation; of the virus groups, RSV-infected children were younger and more frequently admitted to intensive-care units than those infected with A/HINI/2009 and RV. Of the hospitalized children, stratified by age, both infants and children aged >1 year with RSV were most severely affected, whereas A/HINI/2009 infections were the mildest overall, although with related pulmonary involvement in older children. Children with RV infections, detected in two flares partially overlapping with the A/HINI/2009 and RSV peaks, presented with bronchiolitis, wheezing and pneumonia. Leukocytosis occurred more frequently in RV-infected and A/HINI/2009-infected children, and numbers of blood eosinophils were significantly elevated in RV-infected infants. Given the fact that clinical and epidemiological criteria are not sufficient to identify viral respiratory infections, a timely virological diagnosis could allow different infections to be managed separately.


title: Adenovirus types associated with severe respiratory diseases: A retrospective 4‐year study in Kuwait

text: Human adenovirus (HAdV) infection can result in a severe respiratory disease. The aim of this study was to identify HAdV types detected in patients hospitalized for severe respiratory illness. The study population consisted of 743 patients with severe respiratory disease admitted to four major hospitals in Kuwait between January 2013 and December 2016. Respiratory specimens were retrospectively screened for 20 respiratory viruses by real‐time PCR. The HAdV hexon gene was amplified and directly sequenced, and HAdV types were identified by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%) patients, with peaks in November and March. Most patients were infants and young children suffering from pneumonia or acute bronchiolitis. The detected HAdV types were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with high posterior probability. All patients infected with HAdV C5 and 50% of patients infected with HAdV C2 or B7 were admitted to the intensive care unit (ICU). Co‐infection with other viruses was detected in 44.4% of patients. The most common co‐infecting virus was rhinovirus (HRV). HAdV/HRV co‐infection was detected in two children who presumably developed disseminated HAdV infection and died. This is the first report describing the circulation of HAdV types associated with severe outcomes in Kuwait. These findings highlight the need for a national surveillance system to monitor changes in predominant HAdV types and increased numbers of severe respiratory infections.


Estudio de contactos en el siglo XXI: se precisan innovaciones


title: Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it?

text: The insidious VTE seems mainly a problem in the ICU ventilated patients, while patients in the general ward, treated with thromboprophylaxis (0.5 mg/kg), had a low incidence of insidious VTE.


title: A line immunoassay utilizing recombinant nucleocapsid proteins for detection of antibodies to human coronaviruses

text: Abstract Most coronaviruses infecting humans cause mild diseases, whereas severe acute respiratory syndrome (SARS)-associated coronavirus is an extremely dangerous pathogen. Here, we report the development of a serologic assay for detection of antibodies to human coronaviruses (HCoVs) based on recombinant nucleocapsid (N) proteins of all known pathogenic strains (229E, NL63, OC43, HKU1, SARS). The novel immunoassay is highly useful for epidemiologic surveys, where use of nucleic acid diagnostics often is limited. Purified recombinant antigens were immobilized on nitrocellulose membranes and applied in a line immunoassay, which allows rapid detection of antibodies to 5 different HCoVs in a single experiment. For assay evaluation, serum samples from persons infected with 229E or OC43 (acute/convalescent), recovered SARS patients and healthy donors were analyzed. Screening for nucleocapsid (N)-specific immunoglobulin G (IgG) in convalescent sera reached 100% sensitivity. With this new technique, we found that recently identified NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infections. Possibly, cross-reactive antibody responses were observed using 229E and OC43 serum pairs. However, the potential of this assay could clearly be demonstrated employing SARS-positive serum samples, where nonspecific binding to nucleocapsids of other HCoVs was not observed. This coronavirus strain-specific line immunoassay represents a powerful tool for serologic diagnostics.


title: Antimicrobial activity of flavonoids

text: Abstract Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (−)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2′-trihydroxy-5′-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.


title: Post-translational Control of Intracellular Pathogen Sensing Pathways

text: Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP–AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes. Recent studies have demonstrated that the signal transduction initiated by these sensors is sophisticatedly regulated by post-translational modifications (PTMs) resulting in a robust yet ‘tunable’ cytokine response to maintain immune homeostasis. Here we summarize recent advances in our understanding of how PTMs and regulatory enzymes control the signaling activity of RLRs, cGAS, and IFI16 as well as their proximal adaptor proteins.


Evidence informing the UK's COVID-19 public health response must be transparent


title: Using routine testing data to understand circulation patterns of influenza A, respiratory syncytial virus and other respiratory viruses in Victoria, Australia

text: Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002–2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.


The changes of sub-group of T-lymphocyte in the peripheral blood of the SARS patients


Response to correspondence received on our paper:Interpret with caution: an evaluation of the commercial AusDiagnostics versus in-house developed assays for the detection of SARS-CoV-2 virus


Bilateral paresthesia associated with cardiovascular disease and COVID‐19


docid: muwwyktk

title: Distinct conformational states of SARS-CoV-2 spike protein

text: The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes - the first key step of viral infection. Here we report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1Å resolution) and postfusion (3.3Å resolution) conformations, respectively. The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance our understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.


title: Diagnóstico y tratamiento empírico de la neumonía adquirida en la comunidad en situaciones especiales: pacientes inmunocomprometidos sin infección por el VIH y ancianos

text: Resumen La neumonía en el anciano tiene con frecuencia una presentación clínica menos florida que en el adulto de menor edad y que a menudo se complica por la descompensación de patologías concomitantes. En el anciano existen particularidades relativas a los gérmenes implicados en la neumonía, entre otros motivos por el mayor riesgo de infecciones por gérmenes multirresistentes al tratarse de enfermos con un contacto frecuente con los servicios de asistencia sanitaria. Las infecciones pulmonares en el individuo inmunodeprimido presentan causas diferentes en función del déficit inmune del que se trate. Tras una estratificación del riesgo, se decidirá el ingreso hospitalario o el tratamiento ambulatorio; tratamiento este determinado por las particularidades del momento de aparición de la neumonía, la situación epidemiológica local referida al porcentaje de resistencias a antibióticos en el área y las particularidades clínicas. Abstract In the elderly, pneumonia often has a less florid clinical presentation and is frequently complicated by decompensation of concomitant diseases. Elderly patients have special characteristics in terms of the pathogens involved in pneumonia; they are at greater risk of multiresistant bacterial infections because of their frequent contact with the health services. Lung infections in immunosuppressed individuals have different causes depending on the immune deficiency in question. Admission to hospital or ambulatory treatment will be decided after stratifying the risk; this treatment will be determined by the characteristics at the time of onset of the pneumonia, the local epidemiological situation in terms of the percentage of antibiotic resistance in the area, and the clinical particularities.


title: Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies

text: Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector.


Decisiones en UCI basadas en la estrategia Living Systematic Review durante la pandemia de SARS-COV-2. Resultados de una serie prospectiva de casos


Fokussiert: Lernen in Extremsituationen


title: Genetic Characterisation of African Swine Fever Virus in Outbreaks in Ha Nam Province, Red River Delta Region of Vietnam, and Activity of Antimicrobial Products Against Virus Infection in Contaminated Feed

text: INTRODUCTION: African swine fever (ASF) was officially reported in Vietnam in February 2019 and spread across the whole country, affecting all 63 provinces and cities. MATERIAL AND METHODS: In this study, ASF virus (ASFV) VN/Pig/HaNam/2019 (VN/Pig/HN/19) strain was isolated in primary porcine alveolar macrophage (PAM) cells from a sample originating from an outbreak farm in Vietnam’s Red River Delta region. The isolate was characterised using the haemadsorption (HAD) test, real-time PCR, and sequencing. The activity of antimicrobial feed products was evaluated via a contaminated ASFV feed assay. RESULTS: Phylogenetic analysis of the viral p72 and EP402R genes placed VN/Pig/HN/19 in genotype II and serogroup 8 and related it closely to Eastern European and Chinese strains. Infectious titres of the virus propagated in primary PAMs were 10(6) HAD(50)/ml. Our study reports the activity against ASFV VN/Pig/HN/19 strain of antimicrobial Sal CURB RM E Liquid, F2 Dry and K2 Liquid. Our feed assay findings suggest that the antimicrobial RM E Liquid has a strong effect against ASFV replication. These results suggest that among the Sal CURB products, the antimicrobial RM E Liquid may have the most potential as a mitigant feed additive for ASFV infection. Therefore, further studies on the use of antimicrobial Sal CURB RM E Liquid in vivo are required. CONCLUSIONS: Our study demonstrates the threat of ASFV and emphasises the need to control and eradicate it in Vietnam by multiple measures.


title: Dual Infection of Infants by Human Metapneumovirus and Human Respiratory Syncytial Virus Is Strongly Associated with Severe Bronchiolitis

text: The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) was investigated in !2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001–2002 winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage by enzyme immunoassay, tissue culture, and RT-PCR. Dual infection with hMPV and hRSV confers a 10-fold increase in relative risk (RR) of admission to a pediatric intensive-care unit for mechanical ventilation (RR, 10.99 [95% confidence interval, 5.0–24.12]; P < .001, by Fisher exact test). Dual infection by hMPV and hRSV is associated with severe bronchiolitis.


Letter to the Editor on “Bonafè M, Prattichizzo F, Giuliani A, Storci G, Sabbatinelli J, Olivieri F. Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes. Cytokine Growth Factor Rev”


title: Communication of bed allocation decisions in a critical care unit and accountability for reasonableness

text: BACKGROUND: Communication may affect perceptions of fair process for intensive care unit bed allocation decisions through its impact on the publicity condition of accountability for reasonableness. METHODS: We performed a qualitative case study to describe participant perceptions of the communication of bed allocation decisions in an 18-bed university affiliated, medical-surgical critical care unit at Sunnybrook and Women's College Health Sciences Centre. Interviewed participants were 3 critical care physicians, 4 clinical fellows in critical care, 4 resource nurses, 4 "end-users" (physicians who commonly referred patients to the unit), and 3 members of the administrative staff. Median bed occupancy during the study period (Jan-April 2003) was 18/18; daily admissions and discharges (median) were 3. We evaluated our description using the ethical framework "accountability for reasonableness" (A4R) to identify opportunities for improvement. RESULTS: The critical care physician, resource nurse, critical care fellow and end-users (trauma team leader, surgeons, neurosurgeons, anesthesiologists) functioned independently in unofficial "parallel tracks" of bed allocation decision-making; this conflicted with the official designation of the critical care physician as the sole authority. Communication between key decision-makers was indirect and could exclude those affected by the decisions; notably, family members. Participants perceived a lack of publicity for bed allocation rationales. CONCLUSION: The publicity condition should be improved for critical care bed allocation decisions. Decision-making in the "parallel tracks" we describe might be unavoidable within usual constraints of time, urgency and demand. Formal guidelines for direct communication between key participants in such circumstances would help to improve the fairness of these decisions.


title: Influenza, respiratory syncytial virus and SARS

text: Abstract Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood, and are ranked first among the conditions contributing to the global burden of disease. About 30–50% of acute LRTIs are viral in origin; of these, influenza and respiratory syncytial virus (RSV) are associated with the greatest disease burden in humans. Vaccination against circulating human influenza strains and the use of neuraminidase inhibitor drugs have improved the options for control of influenza, but as yet there are no successful vaccines or antiviral drugs for use against RSV infection. The recent emergence of the SARS coronavirus in the human population in 2003, with an ensuing global epidemic affecting more than 8000 individuals with a case fatality of about 10%, underlines the fact that respiratory viral infections of humans may originate in animals, and that many different influenza A viruses also occur naturally in animal reservoirs, representing a constant threat of zoonotic infections of humans and ensuing global pandemics. Avian influenza viruses have transmitted directly to humans from domestic poultry on several occasions in the last decade, and the current extensive burden of disease from avian influenza in South East Asia provides a real possibility for the emergence of a novel influenza virus pathogenic in humans.


title: L565M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure

text: Abstract N-terminal and C-terminal heptad repeats (NHR and CHR) of HIV type 1 (HIV-1) glycoprotein 41 are known to be regions directly related to cell fusion during virus attack, and their complex core constructs a coiled-coil structure in the fusion process. In our recent studies, MT-4/17-3-6, a strain of HIV-1, showed the strong resistance to peptide fusion inhibitors compared with other strains such as MT-4/LAI, L-2 and CU98-26, and had a distinctive L565M mutation in the central region of NHR. To investigate the relationship between the mutation and resistance, we performed a molecular modeling of the coiled-coil of MT-4/17-3-6 by using energy minimization and molecular dynamics simulation based on the MT-4/LAI X-ray structure. As a result, we found that H564 in the NHR was pushed to the outer side by this mutation, and three hydrogen bond bridges of Y638-H564-E560-Q650 could be formed, enclosing the coiled-coil. The binding of peptide inhibitors would be disturbed by the structural stabilization of these bridges in MT-4/17-3-6.


title: A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak

text: Abstract Objective Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. Methods Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. Results Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. Conclusions Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.


title: SHIP deficiency causes Crohn's disease-like ileitis

text: BACKGROUND: Inflammatory bowel disease (IBD) can arise from genetic mutations that compromise intestinal epithelial cell integrity or immune regulation. SHIP has previously been shown to play a pivotal role in limiting the number of immunoregulatory cells and their function. AIM: To determine whether SHIP plays a pivotal role in control of immune tolerance in the gut mucosa. METHODS: Gastrointestinal pathology was assessed in three separate strains of SHIP-deficient mice and their respective wild-type (WT) littermates. Gastrointestinal pathology was analysed in SHIP-deficient hosts reconstituted with WT haematopoietic cell grafts, and WT hosts reconstituted with SHIP-deficient haematopoietic cell grafts including whole splenocytes, purified T cells or natural killer (NK) cells. Major immune cell populations were also analysed in the small intestine of SHIP-deficient mice and WT controls. RESULTS: SHIP-deficient mice developed segmental, transmural pyo-granulomatous ilietis that recapitulated classical features of Crohn's disease enteric pathology. Analysis of haematopoietic chimeras showed that WT bone marrow reconstitution of SHIP(−/−) hosts corrects ileitis. Reconstitution with SHIP(−/−) splenocytes transferred ileitis to WT hosts. Adoptive transfer of purified SHIP(−/−) T cells or NK cells to WT hosts did not transfer ileitis. There was a paucity of both CD4 and CD8 T cells in the small intestines of SHIP-deficient mice; however, neutrophil numbers were significantly increased. CONCLUSIONS: SHIP plays a pivotal role in immune function in the intestine; further scrutiny of this pathway in IBD patients is warranted. It is proposed that SHIP-deficient ileitis results from a local deficit in mucosal T cell immunity that promotes a damaging granulocyte–monocyte inflammation of the distal ileum.


title: Evaluating ultraviolet sensitivity of adventitious agents in biopharmaceutical manufacturing

text: Incidents of contamination in biopharmaceutical production have highlighted the need to apply alternative or supplementary disinfection techniques. Ultraviolet (UV) irradiation is a well-established method for inactivating a broad range of microorganisms, and is therefore a good candidate as an orthogonal technique for disinfection. To apply UV as a safeguard against adventitious agents, the UV sensitivity of these target agents must be known so that the appropriate dose of UV may be applied to achieve the desired level of inactivation. This document compiles and reviews experimentally derived 254 nm sensitivities of organisms relevant to biopharmaceutical production. In general, different researchers have found similar sensitivity values despite a lack of uniformity in experimental design or standardized quantification techniques. Still, the lack of consistent methodologies has led to suspicious UV susceptibilities in certain instances, justifying the need to create a robust collection of sensitivity values that can be used in the design and sizing of UV systems for the inactivation of adventitious agents.


title: Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

text: The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3C(pro)s) of picornaviruses share similar spatial structures and it is becoming apparent that 3C(pro) plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3C(pro) are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3C(pro) can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3C(pro) and these essential factors, 3C(pro) is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3C(pro) are ongoing and a better understanding of the roles played by 3C(pro) may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3C(pro) is summarized.


title: Unmet Needs in Respiratory Diseases: “You Can’t Know Where You Are Going Until You Know Where You Have Been”—Anonymous

text: The care of patients with respiratory diseases has improved vastly in the past 50 years. In spite of that, there are still massive challenges that have not been resolved. Although the incidence of tuberculosis has decreased in the developed world, it is still a significant public health problem in the rest of the world. There are still over 2 million deaths annually from tuberculosis, with most of these occurring in the developing world. Even with the development of new pharmaceuticals to treat tuberculosis, there is no indication that the disease will be eradicated. Respiratory syncytial virus, severe acute respiratory syndrome, and pertussis are other respiratory infectious diseases with special problems of their own, from vaccine development to vaccine coverage. Asthma, one of the most common chronic diseases in children, still accounts for significant mortality and morbidity, as well as high health care costs worldwide. Even in developed countries such as the USA, there are over 4,000 deaths per year. Severe asthma presents a special problem, but the question is whether there can be one treatment pathway for all patients with severe asthma. Severe asthma is a heterogeneous disease with many phenotypes and endotypes. The gene for cystic fibrosis was discovered over 24 years ago. The promise of gene therapy as a cure for the disease has fizzled out, and while new antimicrobials and other pharmaceuticals promise improved longevity and better quality of life, the average life span of a patient with cystic fibrosis is still at about 35 years. What are the prospects for gene therapy in the twenty-first century? Autoimmune diseases of the lung pose a different set of challenges, including the development of biomarkers to diagnose and monitor the disease and biological modulators to treat the disease.


title: How Much May COVID‐19 School Closures Increase Childhood Obesity?

text: In a recent paper entitled, “COVID‐19 Related School Closings and Risk of Weight Gain Among Children” Rundle et al. (2020) proposed the COVID‐19 pandemic may increase obesity among American children because the pandemic, “will likely double out‐of‐school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess” (pg. 1). I add support to Rundle et al.’s argument by demonstrating that doubling of out‐of‐school time alone may lead to a sizable increase in childhood obesity.


title: Impact of COVID‐19 on Mohs micrographic surgery: UK‐wide survey and recommendations for practice

text: Coronavirus Disease 2019 (COVID‐19) pandemic has overwhelmed and disrupted healthcare systems including dermatology services. National directives were issued to reduce patient footfall within hospitals in anticipation of a deluge of COVID‐19 admissions. We conducted a survey focusing on the impact of the pandemic upon Mohs micrographic surgery (MMS) practices and invited all British Society for Dermatological Surgery (BSDS) members undertaking MMS to complete over three weeks commencing 27(th) April 2020.


title: Chapter 1 Cycloaddition reactions for antiviral compounds

text: Abstract Prominent in the current stage of drug development, antiviral compounds can be efficiently prepared through cycloaddition reactions. The chapter reports the use of classical Diels–Alder and their hetero version for the design and synthesis of compounds that were tested for their antiviral activities against a variety of viruses. Furthermore, 1,3-dipolar cycloaddition reactions of selected 1,3-dipoles, such as azides, nitrones, and nitrile oxides, are reviewed in the light of their application in the preparation of key intermediates for antiviral synthesis. A few examples of [2+2] cycloaddition reactions are also presented. The products obtained from these pericyclic reaction approaches were all tested for their activities in terms of blocking the virus replication, and the relevant biological data are highlighted.


title: Role of Molecular Diagnostics in the Management of Infectious Disease Emergencies

text: Clinical laboratories have traditionally relied on time-consuming phenotypic methods such as culture, serology, and biochemical tests for detection, identification, and characterization of microbial pathogens. Real-time polymerase chain reaction technology can now identify many pathogenic organisms that constitute infectious disease emergencies in normal and immune-compromised hosts. Use of this molecular technology for the accurate diagnosis of infectious disease agents by clinical laboratories reduces the time to diagnosis for many pathogens. This article is designed such that the clinician evaluating a patient with severe acute illness can reference the most relevant molecular diagnostics available pertinent to the predominant organ system involved.


Screening of Donor and Recipient in Solid Organ Transplantation


The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK


title: Fatal Varicella Myocarditis in a Child with Down Syndrome—A Case Report

text: A 12-year-old male child with Down syndrome, who had recovered from congenital heart disease, succumbed to severe varicella myocarditis. His clinical presentation at admission mimicked acute coronary syndrome. Analysis of this case throws insight into several aspects of varicella myocarditis.


title: Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID‐19 adult patient group

text: INTRODUCTION: This statement was planned on 11 March 2020 to provide clinical guidance and aid staff preparation for the coronavirus disease 2019 (COVID‐19) pandemic in Australia and New Zealand. It has been widely endorsed by relevant specialty colleges and societies. MAIN RECOMMENDATIONS: Generic guidelines exist for the intubation of different patient groups, as do resources to facilitate airway rescue and transition to the “can't intubate, can't oxygenate” scenario. They should be followed where they do not contradict our specific recommendations for the COVID‐19 patient group. Consideration should be given to using a checklist that has been specifically modified for the COVID‐19 patient group. Early intubation should be considered to prevent the additional risk to staff of emergency intubation and to avoid prolonged use of high flow nasal oxygen or non‐invasive ventilation. Significant institutional preparation is required to optimise staff and patient safety in preparing for the airway management of the COVID‐19 patient group. The principles for airway management should be the same for all patients with COVID‐19 (asymptomatic, mild or critically unwell). Safe, simple, familiar, reliable and robust practices should be adopted for all episodes of airway management for patients with COVID‐19. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Airway clinicians in Australia and New Zealand should now already be involved in regular intensive training for the airway management of the COVID‐19 patient group. This training should focus on the principles of early intervention, meticulous planning, vigilant infection control, efficient processes, clear communication and standardised practice.


title: Stress, anxiety, and depression levels in the initial stage of the COVID-19 outbreak in a population sample in the northern Spain.

text: The SARS-CoV-2 virus reached Spain in March 2020, and a nationwide state of alert was declared on March 14th, leading to the confinement of the entire population. The current study was conducted in the Basque Autonomous Community in northern Spain. The authors analyzed stress, anxiety, and depression with the arrival of the virus and the levels of symptoms according to age, comorbidity, and confinement. Levels of anxiety, stress, and depression were measured in a sample of 976 adults, using the DASS scale (Depression Anxiety, and Stress Scale). Although levels of symptoms were generally low at the start of the alert, younger individuals with chronic diseases reported more symptoms than the rest of the population. The study also detected higher levels of symptoms after the stay-at-home order was issued. Such symptoms are predicted to increase as the confinement continues. The authors propose psychological interventions for prevention and treatment in order to mitigate the pandemic's psychological impacts.


title: Coalescent inference for infectious disease: meta-analysis of hepatitis C

text: Genetic analysis of pathogen genomes is a powerful approach to investigating the population dynamics and epidemic history of infectious diseases. However, the theoretical underpinnings of the most widely used, coalescent methods have been questioned, casting doubt on their interpretation. The aim of this study is to develop robust population genetic inference for compartmental models in epidemiology. Using a general approach based on the theory of metapopulations, we derive coalescent models under susceptible–infectious (SI), susceptible–infectious–susceptible (SIS) and susceptible–infectious–recovered (SIR) dynamics. We show that exponential and logistic growth models are equivalent to SI and SIS models, respectively, when co-infection is negligible. Implementing SI, SIS and SIR models in BEAST, we conduct a meta-analysis of hepatitis C epidemics, and show that we can directly estimate the basic reproductive number (R(0)) and prevalence under SIR dynamics. We find that differences in genetic diversity between epidemics can be explained by differences in underlying epidemiology (age of the epidemic and local population density) and viral subtype. Model comparison reveals SIR dynamics in three globally restricted epidemics, but most are better fit by the simpler SI dynamics. In summary, metapopulation models provide a general and practical framework for integrating epidemiology and population genetics for the purposes of joint inference.


title: Methods Using Social Media and Search Queries to Predict Infectious Disease Outbreaks

text: OBJECTIVES: For earlier detection of infectious disease outbreaks, a digital syndromic surveillance system based on search queries or social media should be utilized. By using real-time data sources, a digital syndromic surveillance system can overcome the limitation of time-delay in traditional surveillance systems. Here, we introduce an approach to develop such a digital surveillance system. METHODS: We first explain how the statistics data of infectious diseases, such as influenza and Middle East Respiratory Syndrome (MERS) in Korea, can be collected for reference data. Then we also explain how search engine queries can be retrieved from Google Trends. Finally, we describe the implementation of the prediction model using lagged correlation, which can be calculated by the statistical packages, i.e., SPSS (Statistical Package for the Social Sciences). RESULTS: Lag correlation analyses demonstrated that search engine data/Twitter have a significant temporal relationship with influenza and MERS data. Therefore, the proposed digital surveillance system can be used to predict infectious disease outbreaks earlier. CONCLUSIONS: This prediction method could be the core engine for implementing a (near-) real-time digital surveillance system. A digital surveillance system that uses Internet resources has enormous potential to monitor disease outbreaks in the early phase.


title: Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis

text: BACKGROUND: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI. RESULTS: Healthy children (n = 47) aged 49–84 months from a prospective cohort study based in Wisconsin, USA, were examined. Demographic and clinical data and NP swab samples were obtained from participants upon entry to the study. All NP samples were profiled for bacterial microbiota using a phylogenetic microarray, and these data were related to demographic characteristics and upper respiratory health outcomes. The composition of the NP bacterial community of children was significantly related prior to the history of acute sinusitis (R(2) = 0.070, P < 0.009). History of acute sinusitis was associated with significant depletion in relative abundance of taxa including Faecalibacterium prausnitzii and Akkermansia spp. and enrichment of Moraxella nonliquefaciens. Enrichment of M. nonliquefaciens was also a characteristic of baseline NP samples of children who subsequently developed acute sinusitis over the 1-year study period. Time to develop URI was significantly positively correlated with NP diversity, and children who experienced more frequent URIs exhibited significantly diminished NP microbiota diversity (P ≤ 0.05). CONCLUSIONS: These preliminary data suggest that previous history of acute sinusitis influences the composition of the NP microbiota, characterized by a depletion in relative abundance of specific taxa. Diminished diversity was associated with more frequent URIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0179-9) contains supplementary material, which is available to authorized users.


title: Population response to the risk of vector-borne diseases: lessons learned from socio-behavioural research during large-scale outbreaks

text: Vector-borne infectious diseases, such as malaria, dengue, chikungunya, and West Nile fevers are increasingly identified as major global human health threats in developing and developed countries. The success or failure of vector control rests mainly on the nature and scale of the behavioural response of exposed populations. Large-scale adoption of recommended protective behaviour represents a critical challenge that cannot be addressed without a better understanding of how individuals perceive and react to the risk of infection. Recently, French overseas territories faced large-scale outbreaks: an epidemic of chikungunya fever in La Re′ union and Mayotte (2005–2006) and four successive outbreaks of dengue fever in one Caribbean island, Martinique (1995–2007). To assess how these populations perceived and responded to the risk, and how the nature and scale of protection affected their clinical status, socio-epidemiological surveys were conducted on each island during the outbreaks. These surveys address three crucial and interconnected questions relevant to the period after persons infected by the virus were identified: which factors shape the risk of acquiring disease? Which socio- demographic characteristics and living conditions induce a higher likelihood of infection? What is the impact of risk perception on protective behaviours adopted against mosquito bites? Grounded on the results of these surveys, a general framework is proposed to help draw out the knowledge needed to reveal the factors associated with higher probability of infection as an outbreak emerges. The lessons learnt can inform health authorities’ efforts to improve risk communication programmes, both in terms of the target and content of messages, so as to explore new strategies for ensuring sustainable protective behaviour. The authors compare three epidemics of vector-borne diseases to elucidate psychosocial factors that determine how populations perceive and respond to the risk of infectious disease.


title: Issues Related to the Use of Animals in Biocontainment Research Facilities

text: The expansion and improvement of high-containment animal facilities has been driven by terrorism, economics, the emergence of new pathogens, and the re-emergence of other pathogens in new areas. Working with highly infectious viral agents requires a team of trained scientists, laboratory technicians, veterinarians, animal care staff, biological safety officers, engineers, and physical plant staff to ensure safety, biocontainment, and the animals' well being, while providing essential scientific data. The challenges of working with infectious disease agents in high levels of containment, and some solutions to these challenges, are described from an animal care point of view.


title: Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

text: BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.


title: Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?

text: The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.


Inpatient Use of Ambulatory Telemetry Monitors for COVID-19 Patients Treated with Hydroxychloroquine and/or Azithromycin


title: Structure-based virtual screening for novel inhibitors of Japanese encephalitis virus NS3 helicase/nucleoside triphosphatase

text: Japanese encephalitis (JE) is a significant cause of human morbidity and mortality throughout Asia and Africa. Vaccines have reduced the incidence of JE in some countries, but no specific antiviral therapy is currently available. The NS3 protein of Japanese encephalitis virus (JEV) is a multifunctional protein combining protease, helicase and nucleoside 5′-triphosphatase (NTPase) activities. The crystal structure of the catalytic domain of this protein has recently been solved using a roentgenographic method. This enabled structure-based virtual screening for novel inhibitors of JEV NS3 helicase/NTPase. The aim of the present research was to identify novel potent medicinal substances for the treatment of JE. In the first step of studies, the natural ligand ATP and two known JEV NS3 helicase/NTPase inhibitors were docked to their molecular target. The refined structure of the enzyme was used to construct a pharmacophore model for JEV NS3 helicase/NTPase inhibitors. The freely available ZINC database of lead-like compounds was then screened for novel inhibitors. About 1 161 000 compounds have been screened and 15 derivatives of the highest scores have been selected. These compounds were docked to the JEV NS3 helicase/NTPase to examine their binding mode and verify screening results by consensus scoring procedure.


title: Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface

text: PURPOSE: The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear. METHODS: Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface. RESULTS: The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2(+)TMPRSS2(+) cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. CONCLUSIONS: Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.


title: Arbidol as a broad-spectrum antiviral: An update

text: Abstract Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. In this review, we will explore the possibility and pertinence of ARB as a broad-spectrum antiviral, after a careful examination of its physico-chemical properties, pharmacokinetics, toxicity, and molecular mechanisms of action. Recent studies suggest that ARB’s dual interactions with membranes and aromatic amino acids in proteins may be central to its broad-spectrum antiviral activity. This could impact on the virus itself, and/or on cellular functions or critical steps in virus-cell interactions, thereby positioning ARB as both a direct-acting antiviral (DAA) and a host-targeting agent (HTA). In the context of recent studies in animals and humans, we will discuss the prospective clinical use of ARB in various viral infections.


docid: qjowxcdl

title: The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases

text: It can be argued that the arrival of the “genomics era” has significantly shifted the paradigm of vaccine and therapeutics development from microbiological to sequence-based approaches. Genome sequences provide a previously unattainable route to investigate the mechanisms that underpin pathogenesis. Genomics, transcriptomics, metabolomics, structural genomics, proteomics, and immunomics are being exploited to perfect the identification of targets, to design new vaccines and drugs, and to predict their effects in patients. Furthermore, human genomics and related studies are providing insights into aspects of host biology that are important in infectious disease. This ever-growing body of genomic data and new genome-based approaches will play a critical role in the future to enable timely development of vaccines and therapeutics to control emerging infectious diseases.


title: SARS‐CoV2 (COVID‐19) infection: is fetal surgery in times of national disasters reasonable?

text: Even though the global COVID‐19 pandemic may affect how medical care is delivered in general, most countries try to maintain steady access for women to routine pregnancy care, including fetal anomaly screening. This means that, also during this pandemic, fetal anomalies will be detected, and that discussions regarding invasive genetic testing and possibly fetal therapy will need to take place. For patients, concerns about Severe Acute Respiratory Syndrome‐Corona Virus 2 will add to the anxiety caused by the diagnosis of a serious fetal anomaly. Yet, also for fetal medicine teams the situation gets more complex as they must weigh up the risks and benefits to the fetus as well as the mother, while managing a changing evidence base and logistic challenges in their healthcare system.


title: Increased vulnerability of clinical research units during the COVID‐19 crisis and their protection

text: Currently, the complexity of clinical trial development in oncology is being further complicated by the coronavirus disease 2019 (COVID‐19) pandemic, which is reducing the resources needed to comply with protocol‐specific procedures while putting patients in units, who are already vulnerable, at increased general risk not only for COVID‐19 infection but also with respect to their baseline disease. Individualizing the management of patients while ensuring their safety and adherence to the study protocol, establishing specific staff contingency plans, and maintaining sponsor and contract research organization (CRO) alignment are some of the key issues for maintaining the continuity of cancer patients’ investigational treatment and minimizing their infection risk as well as the risk to staff members of the unit, sponsors, and CROs while maintaining the integrity of data quality and compliance with good clinical practice.


title: Emergence of a novel human coronavirus threatening human health

text: In late December 2019, a cluster of patients with ‘atypical pneumonia’ of unknown etiology was reported in Wuhan, China. A novel human coronavirus, now provisionally called ‘SARS-CoV-2’, was identified as the cause of this disease, now named ‘COVID-19’.


From the Editor’s Desk: JGIM and COVID-19


title: A balanced approach to decision-making in supporting people with IDD in extraordinarily challenging times

text: A balanced approach to decision-making during challenging times is necessary in order to avoid risks that jeopardize the lives and wellbeing of people with intellectual and developmental disabilities (IDD). The COVID-19 pandemic is the recent example of a crisis that places people with IDD at risk for lopsided societal reactions and threats to them or their wellbeing. Attention to decision-making is required to safeguard hard-earned achievements, including public policies and organization practices that emphasize human and legal rights, self-advocacy, individualized supports, inclusive environments, choices, and community inclusion. We suggest maintaining a holistic approach to understanding the lives and human functioning of people with IDD, a balanced approach to accountability and performance management, an understanding of the multidimensional properties of context, and a heightened vigilance in professional responsibility. A balanced approach will strengthen the likelihood of a return to high quality services and supports to people after the crisis, reduce loss of critical progress, and enhance stability across future social, political, and financial changes and challenges.


title: Influence of Colostrum and Vitamins A, D(3), and E on Early Intestinal Colonization of Neonatal Holstein Calves Infected with Mycobacterium avium subsp. paratuberculosis

text: Exposure of neonates to Mycobacterium avium subsp. paratuberculosis (MAP) via infected dams is the primary mode of transmission of Johne’s disease. Little is known about the impacts of feeding colostrum and supplemental vitamins on the gut microbiome in calves exposed to MAP. In the present study, calves were assigned at birth to one of six treatment groups: (1) Colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D(3); (5) CR, vitamin E; (6) CR, vitamins A, D(3), E, with five calves per treatment in a 14-day study. All calves were orally inoculated with MAP on days 1 and 3 of the study. Differences due to vitamin supplementation were not significant but treatment groups CR-A, CR-E, and CR-ADE had higher numbers of MAP-positive tissues overall. Shannon diversity indices demonstrated regional differences in microbial communities, primarily Proteobacteria, Bacteroidetes, and Firmicutes, between the ileum, cecum, and spiral colon of all calves. CD calves exhibited increased richness compared with CR calves in the cecum and spiral colon and harbored increased Proteobacteria and decreased Bacteroidetes in the mucosa compared with the lumen for all three tissues. Overall, supplementation with vitamins did not appear to influence gut microbiome or impact MAP infection. Feeding of colostrum influenced gut microbiome and resulted in fewer incidences of dysbiosis.


Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment


title: Two Cases of Primary Human Parainfluenza Virus 1 Pneumonia in Which Bronchoalveolar Lavage Fluid Yielded Human Parainfluenza Virus 1

text: Two patients, a 76-year-old woman and 66-year-old woman, presented to our hospital with symptoms of lower respiratory tract infection. Both patients showed chest imaging findings of bilateral ground-glass opacities and consolidations. We initially suspected these patients of having influenza-associated pneumonia and cryptogenic organizing pneumonia, respectively, and performed bronchoalveolar lavage, but only human parainfluenza virus-1 infection was detected by multiplex polymerase chain reaction testing. These findings suggest that pneumonia due to human parainfluenza virus-1 should be included in the differential diagnosis of such cases.


title: Patient Burden and Real-World Management of Chemotherapy-Induced Myelosuppression: Results from an Online Survey of Patients with Solid Tumors

text: INTRODUCTION: Chemotherapy-induced myelosuppression (CIM) is one of the most common dose-limiting complications of cancer treatment, and is associated with a range of debilitating symptoms that can significantly impact patients’ quality of life. The purpose of this study was to understand patients’ perspectives on how the side effects of CIM are managed in routine clinical practice. METHODS: An online survey was conducted of participants with breast, lung, or colorectal cancer who had received chemotherapy treatment within the past 12 months, and had experienced at least one episode of myelosuppression in the past year. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. RESULTS: Of 301 participants who completed the online survey, 153 (51%) had breast cancer, 100 (33%) had lung cancer, and 48 (16%) had colorectal cancer. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Most participants (79%) reported having received treatment for CIM, and 64% of participants recalled chemotherapy dose modifications as a result of CIM. Although most participants believed their oncologist was aware of the side effects of CIM, and treated them quickly, 30% of participants felt their oncologists did not understand how uncomfortable they were due to the side effects of CIM. Overall, 88% of participants considered CIM to have a moderate or major impact on their lives. CONCLUSION: The data highlight that despite the various methods used to address CIM, and the patient-focused approach of oncologists, the real-world impact of CIM on patients is substantial. Improving communication between patients and health care providers may help improve patients’ understanding of CIM, and foster shared decision-making in terms of treatment. Additional insights from patients should be obtained to further elucidate the totality of life burden associated with CIM.


title: Neurosurgery Residents Perspective on the COVID-19: Knowledge, Readiness, and Impact of this Pandemic.

text: Abstract Background The novel Coronavirus disease (COVID-19) is a life-threatening illness, which represents a challenge to all the health-care workers. Neurosurgeons around the world are being affected in different ways. Objectives This is the first study regarding the readiness of neurosurgery residents towards the COVID-19 pandemic and its impact. The aim is to identify the level of knowledge, readiness, and the impact of this virus among neurosurgery residents in different programs. Methods A cross-sectional analysis in which 52 neurosurgery residents from different centers were selected to complete a questionnaire-based survey. The questionnaire comprised of three sections and 27 questions that ranged from knowledge to impact of the current pandemic on various features. Results The median knowledge score was 4 out of 5. The proportion of participants with satisfactory knowledge level was 60%. There was a statistically significant difference between the knowledge score and location of the program. Around 48% of the neurosurgery residents dealt directly with COVID-19 patients. Receiving a session about personal protective equipment (PPE) was reported by 57.7%. The neurosurgery training at the hospital was affected. About 90% believed that this pandemic influenced their mental health. Conclusion Neurosurgery residents have a relatively good knowledge about COVID-19. The location of the program was associated with knowledge level. Most of the participants did not receive a sufficient training about PPE. Almost all responders agree that their training at the hospital was affected. Further studies are needed to study the impact of this pandemic on neurosurgery residents.


title: Roadblocks to Infection Prevention Efforts in Health Care: SARS-CoV-2/COVID-19 Response

text: The outbreak of a novel coronavirus, SARS-CoV-2, is challenging international public health and health care efforts. As hospitals work to acquire enough personal protective equipment and brace for potential cases, the role of infection prevention efforts and programs has become increasingly important. Lessons from the 2003 SARS-CoV outbreak in Toronto and 2015 MERS-CoV outbreak in South Korea have unveiled the critical role that hospitals play in outbreaks, especially of novel coronaviruses. Their ability to amplify the spread of disease can rapidly fuel transmission of the disease, and often those failures in infection prevention and general hospital practices contribute to such events. While efforts to enhance infection prevention measures and hospital readiness are underway in the United States, it is important to understand why these programs were not able to maintain continued, sustainable levels of readiness. History has shown that infection prevention programs are primarily responsible for preparing hospitals and responding to biological events but face understaffing and focused efforts defined by administrators. The current US health care system, though, is built upon a series of priorities that often view biopreparedness as a costly endeavor. Awareness of these competing priorities and the challenges that infection prevention programs face when working to maintain biopreparedness is critical in adequately addressing this critical infrastructure in the face of an international outbreak.


title: Bacterial expression of antigenic sites A and D in the spike protein of transmissible gastroenteritis virus and evaluation of their inhibitory effects on viral infection

text: The spike (S) protein is a key structural protein of coronaviruses including, the porcine transmissible gastroenteritis virus (TGEV). The S protein is a type I membrane glycoprotein located in the viral envelope and is responsible for mediating the binding of viral particles to specific cell receptors and therefore specific cell types. It is also an important immune target for the host in neutralizing the virus. Four antigenic sites A, B, C, and D that reside near the N-terminal domain have been defined in the S protein. Of these, the region encoding antigenic sites A and to a lesser extent D, herein defined as S-AD, are most critical in eliciting host neutralizing antibodies. Herein, we enzymatically amplified, cloned, and expressed the S-AD fragment from TGEV in the prokaryotic expression vector, pET-30a. Maximum protein expression was achieved at 30°C over a 5-h period post-induction. Rabbit polyclonal antiserum was generated using recombinant S-AD (rS-AD) protein. In contrast to prior studies showing no activity with bacterially produced S protein, results indicated that polyclonal serum recognized TGEV-infected cells and reduced infection by 100%. Furthermore, the truncated rS-AD peptide was able to bind to the surface of cells from swine testes in a competitive manner and completely inhibit viral infection.


title: Achieving a Popliteal Venous Access for RRT in Critically Ill COVID-19 Patient in Prone position

text: Abstract This patient is a 67-year-old male who initially presented to our facility with acute respiratory failure secondary to COVID-19. Soon after arrival at our facility, the patient decompensated, developing severe ARDS requiring intubation and prone positioning to maintain adequate oxygenation. Over the next few days, the patient developed acute kidney injury with oliguria and severe volume overload. The vascular surgery service was consulted to obtain central venous access for emergent CRRT. Upon our exam, the patient was sedated and paralyzed in a rotating prone-positioning bed. He could not be positioned supine without immediately becoming hypoxic and decompensating. A 50-cm Permcath was inserted via left popliteal vein. This case report outlines a possible challenging scenario that may encounter vascular interventionist when dealing with COVID-19 patients with respiratory compromise in prone position.


Protecting frontline healthcare workers should be the top priority in low-resource health systems: Bangladesh and COVID-19


title: Qualitative and Quantitative Analysis of 24 Components in Jinlianhua Decoction by UPLC–MS/MS

text: Jinlianhua Decoction (JD), composed of Flos Trollii, Herba Taraxaci, Folium Isatidis, Radix Puerariae Lobatae, and Folium Perillae in a ratio of 6:15:10:10:6, is a prescription for Fengwen which is a group of febrile diseases due to wind in Chinese medicine. It was originally used for the prevention and treatment of severe acute respiratory syndrome (SARS), and could also be used to treat influenza due to their common pathomechanism. To elucidate the unclear pharmacodynamic basis of JD, the LC-QExactive-MS system was used to qualitatively analyze its main components in this study. As a result, 89 compounds were identified and 24 important ones were selected thereby to further perform the simultaneous quantification in 8 batches of JD samples using LC-QTrap-MS with multiple reaction monitoring (MRM). Based on the qualitative and quantitative results in combination with the bioactivities reported, 16 compounds including orientin, 2″-O-β-l-galactopyranosylorientin, puerarin, trollisin I, rosmarinic acid, 2″-O-(2′″-methylbutanoyl) isoswertisin, daidzin, scutellarin, 3′-methoxy puerarin, vitexin, 3′-hydroxy puerarin, 2″-O-(2′″-methylbutanoyl) vitexin, kaempferol, caffeic acid, 3,4-dimethoxybenzoic acid, and cynaroside were determined as the major components of JD. This study provides a useful combinational method for analyzing the major pharmacodynamic substances of JD and lays a foundation for the quality control research of the decoction.


title: Effect of state regulatory environments on advanced psychiatric nursing practice()

text: The first key message in the landmark Future of Nursing report is that “Nurses should practice to the full extent of their education and training” (Institute of Medicine, 2011). Although there has been significant progress across states to remove or diminish barriers to the exercise of full scope of practice by advanced practice registered nurses (APRN), state regulations continue to unnecessarily restrict APRN practice in most of the United States. This article integrates data from studies that examine how state and local regulation affects psychiatric mental health APRN practice with the literature on how state scope of practice regulation affects the size and distribution of the broader APRN workforce, access to care, health care costs and prices, and innovation in health care service delivery. Common themes include confusion about regulatory requirements and mixed experiences of mandated physician supervision.


title: Genetic analysis of calicivirus genomes detected in intestinal contents of piglets in Japan

text: Enteric caliciviruses, noroviruses, and sapoviruses are emerging path- ogens responsible for diarrhea or gastroenteritis in their respective hosts. In this study, swine enteric caliciviruses were detected in ten samples of intestinal contents from 24 piglets in Japan by reverse transcription-polymerase chain reaction using a broadly reactive primer pair (P290/289) that targeted the highly conserved RNA polymerase regions of the enteric caliciviruses. From the positive samples, the entire viral genome of strain K7/JP and 3′-end parts of the genomes of strains K5/JP and K10/JP were cloned and sequenced. K7/JP had an RNA genome of 7144 bases, excluding its 3′ poly (A) tail. The K7/JP genome possessed two open reading frames and characteristics common to sapoviruses. In phylogenetic analysis using amino acid sequences of VP1, K5/JP was demonstrated to be close to the noroviruses previously detected in pigs, and K7/JP and K10/JP were considered to be classified as a new genogroup of sapoviruses.


title: Molecular characterization of a novel Muscovy duck parvovirus isolate: evidence of recombination between classical MDPV and goose parvovirus strains

text: BACKGROUND: Muscovy duck parvovirus (MDPV) and Goose parvovirus (GPV) are important etiological agents for Muscovy duck parvoviral disease and Derzsy’s disease, respectively; both of which can cause substantial economic losses in waterfowl industry. In contrast to GPV, the complete genomic sequence data of MDPV isolates are still limited and their phylogenetic relationships largely remain unknown. In this study, the entire genome of a pathogenic MDPV strain ZW, which was isolated from a deceased Muscovy duckling in 2006 in China, was cloned, sequenced, and compared with that of other classical MDPV and GPV strains. RESULTS: The genome of strain ZW comprises of 5071 nucleotides; this genome was shorter than that of the pathogenic MDPV strain YY (5075 nt). All the four deleted nucleotides produced in strain ZW are located at the base-pairing positions in the palindromic stem of inverted terminal repeats (ITR) without influencing the formation of a hairpin structure. Recombination analysis revealed that strain ZW originated from genetic recombination between the classical MDPV and GPV strain. The YY strain of MDPV acts as the major parent, whereas the virulent strains YZ99–6 and B and the vaccine strain SYG61v of GPV act as the minor parents in varying degrees. Two recombination sites were detected in strain ZW, with the small recombination site surrounding the P9 promoter, and the large recombination site situated in the middle of the VP3 gene. The SYG61V strain is a vaccine strain used for preventing goose parvoviral disease. This strain was found to be solely involved in the recombination event detected in the P9 promoter region. Phylogenetic analyses between strain ZW and other classical strains of MDPV and GPV were performed. The results supported the in silico recombination analysis conclusion. CONCLUSIONS: MDPV Strain ZW is a novel recombinant parvovirus, and the bulk of its genome originates from the classical MDPV strain. Two virulent strains and a vaccine strain of GPV were involved in the recombination process in varying degrees.


title: Macrolide-Resistant Mycoplasma pneumoniae, United States

text: Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae–positive specimens from 6 US locations.


title: Chapter 12 Synthesis

text: Abstract The preceding chapters have described in detail specific examples of viruses that have emerged or re-emerged from animal sources. Most, although not all, are zoonotic and have caused significant human morbidity and mortality. This final chapter will attempt to bring together a number of the common themes raised by these examples. These include the role of historical events in shaping the emergence of viruses in the present, the ability to retrospectively test samples to trace the emergence of disease and the technologies used to detect viruses. Technologies such as the polymerase chain reaction and mass sequencing have revolutionized virus detection and enabled the rapid identification and characterization of viruses. The application of these methods has led to the identification of new groups of viruses in samples obtained from a range of animal species without the need for invasive sampling or the recovery of live virus. However, with the detection of such a large range of viruses that exist asymptomatically with other species, the challenge now becomes the identification of those with the potential to become pathogenic for humans.


(90)Y Radioembolization: Telemedicine During COVID-19 Outbreak, Opportunity for Prime Time


title: Side effects of ruxolitinib in patients with SARS-CoV-2 infection: two case reports

text: • Innovative drugs are not always available in emergency settings; • Use of ruxolitinib in patients with COVID-19 has given unsatisfactory results; • Janus kinase (JAK) inhibitors may be associated with a major incidence of side effects in COVID-19 patients.


title: Public image and governance of epidemics: Comparing HIV/AIDS and SARS

text: Abstract A comparative analysis of the 2002–2003 infectious disease outbreak, severe acute respiratory syndrome (SARS), and the HIV/AIDS epidemic that has affected the world over the past two decades reveals the significant role of socio-cultural beliefs and attitudes in the shaping of people's lifestyles and approaches to the control and prevention of epidemics. The main research question is: what can we learn from the SARS experience about effective prevention of HIV/AIDS? The sources of data include population figures on the development of these epidemics and findings from two sociological studies of representative samples of Singapore's multi-ethnic population. The comparative study illustrates the impact of cultural beliefs and attitudes in shaping the public image of these two different infectious diseases; the relevance of public image of the disease for effective prevention and control of epidemics.