title: Phytocompounds for the control of human enteric viruses

text: Plant extracts and associated polyphenols are known for their varied health benefits that include antioxidant effects and antimicrobial properties. The increasing consumer demand for cost-effective and natural alternatives to chemically-synthesized antimicrobials and therapeutics that are also sustainable makes the field of phytochemical research rather intriguing and challenging. Human enteric viruses are increasingly recognized worldwide as significant causes of human disease in adults and children, alike. In the absence of available vaccines for the human noroviruses, plant extracts are gaining popularity for the prevention and treatment of viral diseases. Research on plant extracts (particularly polyphenols derived from fruits) for human enteric virus control will be briefly summarized in this article.


A mathematical model of the transmission of middle East respiratory syndrome coronavirus in dromedary camels (Camelus dromedarius)


docid: dgnbfzli

title: The renin–angiotensin system: An integrated view of lung disease and coagulopathy in COVID-19 and therapeutic implications

text: The renin–angiotensin system (RAS) has long been appreciated as a major regulator of blood pressure, but has more recently been recognized as a mechanism for modulating inflammation as well. While there has been concern in COVID-19 patients over the use of drugs that target this system, the RAS has not been explored fully as a druggable target. The abbreviated description of the RAS suggests that its dysregulation may be at the center of COVID-19.


title: Severe Acute Respiratory Syndrome in a Naval Diver

text: Severe acute respiratory syndrome (SARS) is a highly infectious, rapidly progressive, emerging disease. Early diagnosis and preventive measures are key for treatment and minimization of secondary spread. In the context of the armed forces, aggressive containment measures are essential to prevent an outbreak. In this study, we present the first reported case, to our knowledge, of SARS in a naval diver. The special physical requirements for divers and the potential complications associated with deep sea diving necessitate extensive investigation before certification of fitness for diving after SARS. In the early recovery period, potential problems during diving are caused by inadequate lung ventilation in relation to exercise level and increased breathing resistance attributable to weak respiratory muscles, with corresponding risk of hypoxia and hypercapnia, as well as decreased ability to respond to nonrespiratory problems during diving. Problems in the late recovery period include increased risk of diving complications (such as pulmonary barotrauma) resulting from fibrosis and scarring within the lung parenchyma, which are known complications of SARS. From our experience, we suggest that computed tomographic scans of the thorax, lung function tests, and careful follow-up monitoring should play a vital role in the assessment of patients during the convalescent period, before certification of fitness to dive.


title: Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations

text: [Image: see text] The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.


Handling the COVID-19 Pandemic: Proposing a Community Based Toolkit for Psycho-social Management and Preparedness


title: Turkey’s response to COVID-19 in terms of mental health

text: Coronavirus disease (also known as COVID-19) continues to spread throughout the world. In Turkey, which has a strong health system, most hospitals have been turned into pandemic hospitals, elective procedures have been postponed, and doctors have been reassigned to treat COVID-19. Efforts to limit spread of COVID-19 have been effective in reducing the spread of COVID-19. Behind this success was not only the intrinsic strength of the health system but also the strict changes in everyday life wrought by the crisis. It is an inescapable fact that these new measures, such as the imposition of curfew and lockdown, have had a significant effect on the mental health of the general population. Anxiety caused by COVID-19 has spread to the mental state of everyone. Although coronavirus-related diseases will end soon, it is predicted that serious psychiatric disorders will be a lasting consequence of the pandemic. Despite the many negatives brought by COVID-19, it has led to a positive unity between the public and healthcare professionals, and in spite of significant risks to their own health, healthcare workers have risen to the challenge of COVID-19.


title: Derivatives of activated H-ras lacking C-terminal lipid modifications retain transforming ability if targeted to the correct subcellular location

text: To examine the ability of ras to activate signal transduction pathways in the absence of lipid modifications, fusion proteins were constructed that target ras(WT) or activated ras(61L) to cellular membranes as integral membrane proteins, using the first transmembrane domain of the E1 protein of avian infectious bronchitis virus (IBV), which contains a cis-Golgi targeting signal. Golgi-targeted derivatives of activated ras were completely inactive in transformation assays. However, when examined in focus formation assays, transformation of NIH3T3 cells were seen with derivatives of ras(61L) containing a mutated E1 targeting sequence that results in plasma membrane localization. Removal of the lipid modification sites in and upstream of the CAAX motif did not abrogate the transforming activity of plasma membrane-localized ras(61L) derivatives, indicating that these lipid modifications are not essential for ras activity, as long as the protein is correctly localized to the plasma membrane. Interestingly, the activity of integral membrane versions of ras(61L) was strictly dependent on a minimum distance between the transmembrane domain anchor region and the coding sequence of ras. Derivatives with only a 3-amino acid linker were inactive, while linkers of either 11- or 22-amino acids were sufficient to restore transforming activity. These results demonstrate that: (1) activated ras targeted to Golgi membranes is unable to cause transformation; (2) lipid modifications at the C-terminus are not required for the transforming activity of plasma membrane-anchored ras(61L) derivatives, and serve primarily a targeting function; (3) a transmembrane domain can effectively substitute for C-terminal modifications that would normally target ras to the inner surface of the plasma membrane, indicating that ras(61L) does not need to reversibly dissociate from the membrane as might be allowed by the normal lipidation; and (4) in order to function properly, there exists a critical distance that the ras protein must reside from the plasma membrane.


title: Postscript: COVID-19 and the Legal Determinants of Health

text: This is a short postscript to the Public Health Ethics special issue on the legal determinants of health. We reflect briefly on emerging responses to COVID-19, and raise important questions of ethics and law that must be addressed; including through the lens of legal determinants, and with critical attention to what it means to protect health with justice.


title: Audiological profile of asymptomatic Covid-19 PCR-positive cases

text: OBJECTIVE: The current study compared the amplitude of transient evoked otoacoustic emissions (TEOAEs) and latencies of vestibular evoked myogenic potentials (VEMPs) between asymptomatic COVID-19 PCR-positive cases and normal non-infected subjects. METHODS: Twenty cases who were confirmed positive for COVID-19 and had none of the known symptoms for this viral infection formed the test group for 2 full weeks. Their age ranged between 20 and 50 years to avoid any age-related hearing affection. Patients who had definite symptoms of COVID-19 infection as well as those who had a history of hearing loss or a history of any known cause of hearing loss were excluded from the examined sample. TEOAEs amplitude was measured for all participants. RESULTS: The high frequency pure-tone thresholds as well as the TEOAE amplitudes were significantly worse in the test group. CONCLUSIONS: COVID-19 infection could have deleterious effects on cochlear hair cell functions despite being asymptomatic. The mechanism of these effects requires further research.


docid: dygxjnwi

title: Pathogenesis and clinical aspects of a respiratory porcine reproductive and respiratory syndrome virus infection

text: Abstract Some pathogenetic and clinical aspects of the respiratory tract infection with porcine reproductive and respiratory syndrome virus (PRRSV) are discussed. The acute and persistent stages of PRRSV infection are treated separately. Special attention is given to the author's work on experimental dual infections with PRRSV and other enzootic porcine respiratory viruses. It was concluded that: (1) Studies on the interactions of PRRSV and its target cell, the pulmonary alveolar macrophage, are very scarce. So far, the hypothesis of impaired macrophage function has not been proven. (2) The possibility that PRRSV causes disease in growing pigs in combination with other viral or bacterial infections has been demonstrated experimentally. Variation in disease resulting from such combined PRRSV infections will probably hamper future research into disease mechanisms. (3) There remains a need for more data on the clinicopathological significance of the persistent stage of PRRSV infections.


title: Misinformation sharing and social media fatigue during COVID-19: An affordance and cognitive load perspective

text: Social media plays a significant role during pandemics such as COVID-19, as it enables people to share news as well as personal experiences and viewpoints with one another in real-time, globally. Building off the affordance lens and cognitive load theory, we investigate how motivational factors and personal attributes influence social media fatigue and the sharing of unverified information during the COVID-19 pandemic. Accordingly, we develop a model which we analyse using the structural equation modelling and neural network techniques with data collected from young adults in Bangladesh (N = 433). The results show that people, who are driven by self-promotion and entertainment, and those suffering from deficient self-regulation, are more likely to share unverified information. Exploration and religiosity correlated negatively with the sharing of unverified information. However, exploration also increased social media fatigue. Our findings indicate that the different use purposes of social media introduce problematic consequences, in particular, increased misinformation sharing.


title: A qualitative descriptive study of the contextual factors influencing the practice of emergency nurses in managing emerging infectious diseases

text: Purpose: Emergency nurses are engaged in the management of epidemic events that unfold along with the evolution of diseases. The goal of this study was to explore the contextual factors that inhibited the ability of emergency nurses to perform their duties in response to an outbreak. Methods: A qualitative descriptive design was used to explore the experiences and perceptions of emergency nurses. Participants were purposively recruited from 12 emergency departments in Hong Kong. Semi-structured face-to-face individual interviews were conducted with 26 emergency nurses. The audio-recorded interviews were transcribed verbatim and interpreted with a thematic analysis approach. Results: Four intertwined themes emerged from the analysis: resource constraints, threats of infection, ubiquitous changes and lingering uncertainties. These themes portrayed the constraints and challenges surrounding the work environment of emergency nurses. Conclusion: This study described the instabilities and vulnerabilities of the circumstances in which the emergency nurses were situated in during epidemic events. The findings shed light on the importance of hospitals and emergency departments in addressing both the technical problems and adaptive challenges that face emergency nurses during epidemic events.


title: Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases

text: Abstract Used since ancient times especially for the local treatment of pulmonary diseases, lungs and airways are a versatile target route for the administration of both local and systemic drugs. Despite the existence of different platforms and devices for the pulmonary administration of drugs, only a few formulations are marketed, partly due to physiological and technological limitations. Respiratory infections represent a significant burden to health systems worldwide mainly due to intrahospital infections that more easily affect immune-compromised patients. Moreover, tuberculosis (TB) is an endemic infectious disease in many developing nations and it has resurged in the developed world associated with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. Currently, medicine faces the specter of antibiotic resistance. Besides the development of new anti-infectious drugs, the development of innovative and more efficient delivery systems for drugs that went off patent appears as a promising strategy pursued by the pharmaceutical industry to improve the therapeutic outcomes and to prolong the utilities of their intellectual property portfolio. In this context, nanotechnology-based drug delivery systems (nano-DDS) emerged as a promising approach to circumvent the limitations of conventional formulations and to treat drug resistance, opening the hypothesis for new developments in this area.


title: Pathology and treatment of Eimeria zuernii coccidiosis in calves: Investigations in an infection model

text: Abstract Two studies were conducted in the Eimeria zuernii infection model in order to investigate the pathology of E. zuernii coccidiosis and the efficacy of toltrazuril (Baycox 5% suspension) in this infection. For this purpose, a total of 30 calves were infected experimentally with E. zuernii oocysts and faecal samples taken regularly from the rectum and examined for faecal consistency and oocyst excretion. Six of the calves underwent pathological examination at various points in time after infection. Significant macroscopic and microscopic changes were demonstrated and parasitic stages were identified in the intestinal mucosa of infected calves during the late prepatent and patent period. Inflammatory reactions revealed by light microscopy were confirmed by electron microscopical investigations. Treatment of calves with toltrazuril during the late prepatent period resulted in significantly lower frequencies of diarrhoea and levels of oocyst excretion, and weight gain was significantly higher than in shamtreated animals.


title: Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

text: Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.


title: 3D organ models—Revolution in pharmacological research?

text: Abstract 3D organ models have gained increasing attention as novel preclinical test systems and alternatives to animal testing. Over the years, many excellent in vitro tissue models have been developed. In parallel, microfluidic organ-on-a-chip tissue cultures have gained increasing interest for their ability to house several organ models on a single device and interlink these within a human-like environment. In contrast to these advancements, the development of human disease models is still in its infancy. Although major advances have recently been made, efforts still need to be intensified. Human disease models have proven valuable for their ability to closely mimic disease patterns in vitro, permitting the study of pathophysiological features and new treatment options. Although animal studies remain the gold standard for preclinical testing, they have major drawbacks such as high cost and ongoing controversy over their predictive value for several human conditions. Moreover, there is growing political and social pressure to develop alternatives to animal models, clearly promoting the search for valid, cost-efficient and easy-to-handle systems lacking interspecies-related differences. In this review, we discuss the current state of the art regarding 3D organ as well as the opportunities, limitations and future implications of their use.


title: A decade after SARS: Strategies to control emerging coronaviruses

text: Two novel coronaviruses have emerged in humans in the 21(st) century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome human coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and have high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, a priority in the field is the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains. This review will: describe the emergence and identification of novel human coronaviruses over the last 10 years; review their key biological features, including tropism and receptor use; and summarize approaches to develop broadly effective vaccines.


title: Murine Coronavirus-Induced Apoptosis in 17Cl-1 Cells Involves a Mitochondria-Mediated Pathway and Its Downstream Caspase-8 Activation and Bid Cleavage

text: Abstract Mouse hepatitis virus (MHV) infection in murine 17Cl-1 cells results in apoptotic cell death. Inhibition of MHV-induced apoptosis by the pancaspase inhibitor Z-VAD-FMK promoted virus production late in infection, indicating that apoptosis could be a host response to limit the production of viral progeny. Activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and delay of apoptosis by Bcl-2 overexpression. Analyses of the subcellular distribution of cytochrome c, procaspase-9, and Apaf-1 suggested an aberrant apoptosome formation in the vicinity of the mitochondria, which could be a cell type-specific event. An increase in the amount of Fas (APO-1/CD95), caspase-8 activation, caspase-8-mediated Bid cleavage, and subsequent translocation of truncated Bid to mitochondria, all of which relate to the Fas-mediated pathway, also occurred in MHV-infected 17Cl-1 cells, whereas the formation of the death-inducing signaling complex, a direct indication of the activation of Fas-mediated pathway, was undetectable. Caspase-8 and Bid activation appeared to be downstream of mitochondria, because Bcl-2 overexpression suppressed both events, suggesting that infected 17Cl-1 cells might have activated a receptor-mediated “type II” signaling pathway, in which primary and low levels of receptor-mediated pathway activation lead to the activation of the mitochondria-mediated pathway. All our data indicate that a mitochondria-mediated pathway played a major regulatory role in apoptosis in MHV-infected 17Cl-1 cells.


title: Viral etiology of bronchiolitis among pediatric inpatients in northern Taiwan with emphasis on newly identified respiratory viruses

text: Purpose Viral etiology of bronchiolitis in children in Taiwan has been fragmentary. We conducted a prospective study to figure out the viral epidemiology of bronchiolitis in Taiwan. Materials and methods From January 2009 to March 2011, a total of 113 children with bronchiolitis, aged <2 years, hospitalized in Chang Gung Children’s Hospital were randomly selected for viral etiology investigation. Nasopharyngeal aspirates were obtained from each case and sent for viral detection by tissue culture, antigen test, and polymerase chain reaction. Results A total of 120 viruses were detected from 113 children. Positive viral etiology was identified in 86 (76%) children. Mixed viral pathogens were found in 28 cases (25%). Respiratory syncytial virus (RSV) was the most common pathogen and was identified in 43.4% of the cases. Human bocavirus (hBoV) was the second most common identified virus (in 19.5%), followed by human metapneumovirus (hMPV), rhinovirus, influenza viruses, and coronavirus OC43. In terms of clinical characteristics, no significant difference was found among the children with bronchiolitis either caused by different single or mixed viral infection. Conclusion RSV was the most common etiologic agent for children with bronchiolitis in Taiwan. Newly identified viruses, including hMPV and hBoV, were also among the common causative agents. Clinical characteristics were not significantly different among the children with bronchiolitis caused by different viruses.


title: Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease

text: Summary The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.


title: SPAAN: a software program for prediction of adhesins and adhesin-like proteins using neural networks

text: Motivation: The adhesion of microbial pathogens to host cells is mediated by adhesins. Experimental methods used for characterizing adhesins are time-consuming and demand large resources. The availability of specialized software can rapidly aid experimenters in simplifying this problem. We have employed 105 compositional properties and artificial neural networks to develop SPAAN, which predicts the probability of a protein being an adhesin (P(ad)). Results: SPAAN had optimal sensitivity of 89% and specificity of 100% on a defined test set and could identify 97.4% of known adhesins at high P(ad) value from a wide range of bacteria. Furthermore, SPAAN facilitated improved annotation of several proteins as adhesins. Novel adhesins were identified in 17 pathogenic organisms causing diseases in humans and plants. In the severe acute respiratory syndrome (SARS) associated human corona virus, the spike glycoprotein and nsps (nsp2, nsp5, nsp6 and nsp7) were identified as having adhesin-like characteristics. These results offer new lead for rapid experimental testing. Availability: SPAAN is freely available through ftp://203.195.151.45 Contact: ramu@igib.res.in


title: Chapter 10 Respiratory syncytial virus

text: Abstract Respiratory Syncytial Virus (RSV) is a leading cause of hospitalization and mortality associated with lower respiratory tract illness in infants and young children worldwide. The World Health Organization recognizes the need to develop and implement prevention strategies to reduce the impact of RSV in early life as a global health priority. RSV vaccination during pregnancy is a feasible strategy to achieve this goal. Vaccines for maternal immunization against RSV are in active development and could be implemented in the near future within existing maternal-child health platforms. In addition, infant protection may be achieved through either passive antibody administration or active immunization, depending on infant health status, given that options for these complementary interventions are being developed in parallel to vaccines for maternal immunization.


title: Prevalence and clinical characteristics of human CoV-HKU1 in children with acute respiratory tract infections in China

text: Abstract Background Human CoV-HKU1 (HCoV-HKU1) has been isolated from a 71-year-old man with pneumonia; however, the impact and role of emerging HCoV-HKU1 have not been defined in children with acute respiratory tract infection (ARTI). Objective To investigate the Prevalence and clinical characteristics of HCoV-HKU1 in children with ARTI in Lanzhou, China. Study design The reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen HCoV-HKU1 and other common respiratory viruses in 645 nasopharyngeal aspirate (NPA) specimens collected from children with ARTI from November 2006 to October 2008. All PCR positive products were sequenced. And the demographic and clinical data were collected for all patients. Results Nineteen of 645 (2.95%) specimens tested positive for HCoV-HKU1, and all HCoV-HKU1 positive specimens were distributed in the winter and spring season. The HCoV-HKU1 co-infection rate with other respiratory viruses was 47.37% (9/19). There was no statistically significant difference in the detection rate between groups by age or gender, except between patients with and without underlying diseases. The phylogenetic analysis indicated that HCoV-HKU1 genotype B was circulating in the years 2007 and 2008 in children with ARTI in Lanzhou, China. Conclusions HCoV-HKU1 is an uncommon virus existing among Chinese children with ARTI. Children with underlying diseases are more vulnerable to viral infection. Only HCoV-HKU1 genotype B circulated locally.


title: Biogenesis of secretory granules in the trans-Golgi network of neuroendocrine and endocrine cells

text: Abstract Secretory granule formation requires selection of soluble and membrane proteins into nascent secretory granules, and exclusion of proteins not required for the function of secretory granules. Both selection and exclusion presumably can occur in the compartment where assembly of the secretory granule begins, the trans most cisternae of the Golgi complex. Current research focused on the initial stages of secretory granule formation includes a search for the ‘signals’ which may mediate active sorting of components into secretory granules, and the role of aggregation of regulated secretory proteins in sorting. In addition, the temporal sequence of the sorting events in the Golgi, and post-Golgi compartments has gained much attention, as summarized by the alternative but not mutually exclusive ‘sorting for entry’ vs. ‘sorting by retention’ models. ‘Sorting for entry’ which encompasses the most popular models requires selection of cargo and membrane and exclusion of non-secretory granule proteins in the TGN prior to secretory granule formation. ‘Sorting by retention’ stipulates that protein selection or exclusion may occur after secretory granule formation: secretory granule specific components are retained during maturation of the granule while non-secretory granule molecules are removed in vesicles which bud from maturing secretory granules. Finally, some progress has been made in the identification of cytosolic components involved in the budding of nascent secretory granules from the TGN. This review will focus on the recent data concerning the events in secretory granule formation which occur, in the trans-Golgi network.


title: Effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen to treat adults with moderate to severe COVID-19: structured summary of a study protocol for a randomized controlled trial

text: OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9(th) to April 14(th) 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: ≥ 18 years of age AND (oxygen saturation (SPO2) ≤ 93% OR respiratory rate ≥ 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of ≥37.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days ≤ 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-β 1a, Interferon-β 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-β 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-β 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan–Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package ‘randomizeR’ in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9(th) April 2020 and the end date was on 14(th) April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study’s follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Current and future developments in the treatment of virus-induced hypercytokinemia

text: Emerging pathogenic viruses such as Ebola and Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) can cause acute infections through the evasion of the host's antiviral immune responses and by inducing the upregulation of inflammatory cytokines. This immune dysregulation, termed a cytokine storm or hypercytokinemia, is potentially fatal and is a significant underlying factor in increased mortality of infected patients. The prevalence of global outbreaks in recent years has offered opportunities to study the progression of various viral infections and have provided an improved understanding of hypercytokinemia associated with these diseases. However, despite this increased knowledge and the study of the infections caused by a range of emerging viruses, the therapeutic options still remain limited. This review aims to explore alternative experimental strategies for treating hypercytokinemia induced by the Ebola, avian influenza and Dengue viruses; outlining their modes of action, summarizing their preclinical assessments and potential clinical applications.


title: Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

text: Abstract The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide α,β-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 >100μM), the ketomethylene isosteres and tripeptide α,β-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 =11–39μM). The Phe-Phe dipeptide inhibitors 18a–e are designed on the basis of computer modeling of the enzyme–inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52μM is obtained by condensation of the Phe-Phe dipeptide α,β-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18μM.


title: Ten simple rules for researchers while in isolation from a pandemic

text: The scale and intensity of the coronavirus disease 2019 (COVID-19) worldwide pandemic is unprecedented in all our lifetimes This is written for all of us involved in scientific research - graduate student, postdoc, academic, staff scientist, in academia, government or industry Rule 3: Follow institutional guidance and provide feedback By institution, we mean everything from the government (federal, state, and local) to your workplace to your individual laboratory Rule 4: Embrace a new work habit and environment How science is conducted has changed, almost overnight [Extracted from the article] Copyright of PLoS Computational Biology is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )


title: Evaluation of Echinacea for Treatment of the Common Cold

text: Considered to have immunostimulating activity, echinacea is a widely used phytomedicinal for treatment of the common cold and upper respiratory tract infections (URTIs). We reviewed the literature from the MEDLINE database (January 1966–July 1999), International Pharmaceutical Abstracts (IPA) online database, Cambridge Scientific Abstracts Biological Sciences online database, Alt‐Health Watch online database, EMBase CD‐ROM database, and references from published articles, reviews, and letters to evaluate evidence from clinical trials of echinacea's purported efficacy for treating or preventing URTIs. Twelve clinical studies published from 1961–1997 concluded that echinacea was efficacious for treating the common cold, but the results are unclear due to inherent flaws in study design. Five trials were published since 1997; two showed that echinacea lacked efficacy for treating and preventing URTI symptoms, and three concluded that it was effective in reducing the frequency, duration, and severity of common cold symptoms. Again, these results are unclear because of methodologic uncertainties, such as small populations and use of noncommercially available, nonstandardized dosage forms. Although evidence for echinacea's efficacy is inconclusive, it appears to be safe. Patients without contraindications to it may not be dissuaded from using an appropriate preparation to treat the common cold.


title: More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?

text: Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses.


title: X-Ray structure and inhibition of the feline infectious peritonitis virus 3C-like protease: structural implications for drug design

text: Feline infectious peritonitis (FIP) is a deadly disease that effects both domestic and wild cats and is caused by a mutation in feline coronavirus (FCoV) that allows the virus to replicate in macrophages. Currently, there are no treatments or vaccines available for the treatment of FIP even though it kills approximately 5% of cats in multi-cat households per year. In an effort to develop small molecule drugs targeting FIP for the treatment of cats, we screened a small set of designed peptidomimetic inhibitors for inhibition of FIPV-3CL(pro), identifying two compounds with low to sub-micromolar inhibition, compound 6 (IC(50)= 0.59 ± 0.06 nM) and compound 7 (IC(50)= 1.3 ± 0.1 μM). We determined the first X-ray crystal structure of FIPV-3CL(pro) in complex with the best inhibitor identified, compound 6, to a resolution of 2.10 Å to better understand the structural basis for inhibitor specificity. Our study provides important insights into the structural requirements for the inhibition of FIPV-3CL(pro) by peptidomimetic inhibitors and expands the current structural knowledge of coronaviral 3CL(pro) architecture.


title: Chapter 1 Introduction

text: Abstract A biomarker may refer to a protein whose concentration refers to the severity or presence of some disease state. These biomarkers may be detectable and measurable by a variety of methods including physical examination, laboratory assays, and medical imaging. College Hill indicates that “Biomarkers are valued tools used across the biological spectrum from research to diagnostics, as indicators of normal or disease processes to assess pharmacological responses.” Biomarker (biological marker) is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to a therapeutic intervention. Biomarkers are proposed to measure the delivery of drugs to their intended targets, and to understand and predict pathophysiology, and how it is altered by therapy, through monitoring variables known to have chemical relevance. The intent is to use biomarkers for their predictive power to select compounds and design dosing regimens for meeting the pharmacokinetic criteria for a new drug.


title: DV-Curve Representation of Protein Sequences and Its Application

text: Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. This graphical representation not only avoids degeneracy, but also has good visualization no matter how long these sequences are, and can reflect the length of protein sequence. Then we transform the 2D-graphical representation into a numerical characterization that can facilitate quantitative comparison of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins.


title: Epidemiology of Parkinson’s Disease

text: The major source of error in epidemiologic studies of Parkinson’s disease is diagnostic uncertainty. Prevalence varies widely in community-based studies, ranging from 31 per 100,000 persons in Libya to 328 per 100,000 persons in the Par si community in Bombay, India, possibly reflecting the differences in risk factors among the populations studied, in addition to the methodologic differences. Parkinson’s disease is common with advancing age. Heredity may be a risk factor in some cases, and whites may be more susceptible. The many controlled studies examining the increased risk for this disease are discussed.


Collateral effects of Covid-19 pandemic emergency response on worldwide immunizations


title: Asthma and viral infections An intricate relationship

text: Abstract Objective To synthesize available data related to the complex associations among viral infections, atopy, and asthma. Data Sources Key historical articles, articles highlighted in our recent review of most significant recent asthma advancements, and findings from several birth cohorts related to asthma and viral infections were reviewed. In addition, PubMed was searched for review articles and original research related to the associations between viral infection and asthma, using the search words asthma, viral infections, atopy, development of asthma, rhinovirus (RV), and respiratory syncytial virus (RSV). Study Selections Articles were selected based on novelty and relevance to our topic of interest, the role of asthma and viral infections, and possible mechanisms to explain the association. Results There is a large body of evidence demonstrating a link between early viral infections (especially RV and RSV) and asthma inception and exacerbations. RV-induced wheezing is an important risk factor for asthma only when atopy is present, with much evidence supporting the idea that sensitization is a risk factor for early RV-induced wheezing, which in turn is a risk factor for asthma. RSV, on the other hand, is a more important risk factor for nonatopic asthma, with severe infections conferring greater risk. Conclusion There are important differences in the development of atopic and nonatopic asthma, with several proposed mechanisms explaining the association between viral infections and the development of asthma and asthma exacerbations. Understanding these complex associations is important for developing asthma prevention strategies and targeted asthma therapies.


title: Human parainfluenza virus type 4 infection in Chinese children with lower respiratory tract infections: A comparison study

text: Abstract Background Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Although HPIV-4 has been associated with mild ARTIs for years, recent investigations have also associated HPIV-4 infection with severe respiratory syndromes and with outbreaks of ARTIs in children. Objectives To characterize the role of HPIV-4 and its clinical features in children with acute lower respiratory tract infections (ALRTIs) in Beijing, China. Study design Nasopharyngeal aspirates were collected from 2009 hospitalized children with ALRTIs between March 2007 and April 2010. RT-PCR and PCR analyses were used to identify HPIV types and other known respiratory viruses. Results HPIVs were detected in 246 (12.2%) patients, of whom 25 (10.2%) were positive for HPIV-4, 11 (4.5%) for HPIV-2, 51 (20.7%) for HPIV-1, 151 (61.4%) for HPIV-3, and 8 (3.3%) were co-detected with different types of HPIVs. Like HPIV-3, HPIV-4 was detected in spring, summer, and late fall over the study period. Seasonal incidence varied for HPIV-1 and -2. The median patient age was 20 months for HPIV-4 infections and 7–11 months for HPIV-1, -2, and -3 infections, but the clinical manifestations did not differ significantly between HPIV-1, -2, -3, and -4 infections. Moreover, co-detection of HPIV-4 (44%) with other respiratory viruses was lower than that of HPIV-1 (62.7%), HPIV-2 (63.6%), and HPIV-3 (72.7%). Conclusions HPIV-4 plays an important role in Chinese paediatric ALRTIs. The epidemiological and clinical characteristics reported here improve our understanding of the pathogenesis associated with HPIV-4.


Hopeful genes and immunology


After careful consideration of the rapidly changing situation relating to the Coronavirus outbreak


title: Integrated Approaches and Empirical Models for Investigation of Parasitic Diseases in Northern Wildlife

text: The North is a frontier for exploration of emerging infectious diseases and the large-scale drivers influencing distribution, host associations, and evolution of pathogens among persons, domestic animals, and wildlife. Leading into the International Polar Year 2007–2008, we outline approaches, protocols, and empirical models derived from a decade of integrated research on northern host–parasite systems. Investigations of emerging infectious diseases associated with parasites in northern wildlife involved a network of multidisciplinary collaborators and incorporated geographic surveys, archival collections, historical foundations for diversity, and laboratory and field studies exploring the interface for hosts, parasites, and the environment. In this system, emergence of parasitic disease was linked to geographic expansion, host switching, resurgence due to climate change, and newly recognized parasite species. Such integrative approaches serve as cornerstones for detection, prediction, and potential mitigation of emerging infectious diseases in wildlife and persons in the North and elsewhere under a changing global climate.


title: Quantitative label-free proteomic analysis reveals differentially expressed proteins in the digestive juice of resistant versus susceptible silkworm strains and their predicted impacts on BmNPV infection

text: Abstract Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen causing severe economic loss. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity. In this study, antiviral activity examination of different resistant strains showed that the digestive juice of the resistant strain (A35) had higher inhibition to virus than the susceptible strain (P50). Subsequently, the label-free quantitative proteomics was used to study the midgut digestive juice response to BmNPV infection in P50 and A35 strains. A total of 98 proteins were identified, of which 80 were differentially expressed proteins (DEPs) with 54 enzymes and 26 nonenzymatic proteins by comparing the proteomes of infected and non-infected P50 and A35 silkworms. These DEPs are mainly involved in metabolism, proteolysis, neuroactive ligand receptor interaction, starch and sucrose metabolism and glutathione metabolism. After removing the genetic background and individual immune stress response proteins, 9 DEPs were identified potentially involved in resistance to BmNPV. Further studies showed that a serine protease, an alkaline phosphatase and serine protease inhibitor 2 isoform X1 were differentially expressed in A35 compared to P50 or post BmNPV infection. Taken together, these results provide insights into the potential mechanisms for silkworm digestive juice to provide resistance to BmNPV infection. Signifcance: Bombyx mori nucleopolyhedrovirus (BmNPV) is highly pathogenic, which has a great impact on the sericulture. BmNPV entered the midgut lumen and exposed to digestive juices after oral infection. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity, however, current information on the digestive juice proteome of high resistant silkworm strain after BmNPV challenge compared to susceptible strain is incomprehensive. Here, we combined label-free quantification method, bioinformatics, RT-qPCR and western blot analysis and found that BmNPV infection causes some protein changes in the silkworm midgut digestive juice. The DEPs were identified in the digestive juices of different resistant strains following BmNPV infection, and screened out some proteins potentially related to resistance to BmNPV. Three important differentially expression proteins were validated by independent approaches. These findings uncover the potential role of silkworm digestive juice in providing resistance to BmNPV and supplemented the profile of the proteome of the digestive juices in B. mori.


title: Pneumothorax nach COVID-19-Pneumonie

text: Ein 61-jähriger Patient kam mit quälendem Husten, Tachypnoe und Tachykardie in die Notaufnahme. 17 Tage zuvor war er wegen einer COVID-19-Pneumonie stationär behandelt worden. Nun zeigte sich im Röntgen ein rechtsseitiger Spannungspneumothorax. Weitere 20 Tage später wiederholte sich das Geschehen auf der linken Seite.


title: Febrile Rhinovirus Illness During Pregnancy Is Associated With Low Birth Weight in Nepal

text: BACKGROUND: Adverse birth outcomes, including low birth weight (LBW), defined as <2500 grams, small-for-gestational-age (SGA), and prematurity, contribute to 60%–80% of infant mortality worldwide and may be related to infections during pregnancy. The aim of this study was to assess whether febrile human rhinovirus (HRV) illness is associated with adverse birth outcomes. METHODS: Active household-based weekly surveillance was performed for respiratory illness episodes in pregnant women as part of a community-based, prospective, randomized trial of maternal influenza immunization in rural Nepal. Rhinovirus (HRV) febrile illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia with HRV detected on mid-nasal swab. Multivariate regression analysis evaluated the association between febrile HRV respiratory illness and adverse birth outcomes. RESULTS: Overall, 96 (3%) of 3693 pregnant women had HRV-positive febrile respiratory illnesses. Infants born to pregnant women with HRV febrile illness had a 1.6-fold increased risk of being LBW compared with those with non-HRV febrile illness (28 of 96 [38%] vs 109 of 458 [24%]; relative risk [RR], 1.6; 95% confidence interval [CI], 1.1–2.3). No difference in risk of LBW was observed between infants born to mothers with non-HRV febrile respiratory illness and those without respiratory illness during pregnancy (109 of 458 [24%] vs 552 of 2220 [25%], respectively; RR, 1.0; 95% CI, 0.8–1.2). CONCLUSIONS: Febrile illness due to rhinovirus during pregnancy was associated with increased risk of LBW in a rural South Asian population. Interventions to reduce the burden of febrile respiratory illness due to rhinovirus during pregnancy may have a significant impact on LBW and subsequent infant mortality.


title: Performance of a novel microarray multiplex PCR for the detection of 23 respiratory pathogens (SYMP-ARI study)

text: Symptoms of acute febrile respiratory tract infection are often unspecific, but the rapid identification of pathogens allows optimised patient management. The objective of this study was to evaluate a novel multiplex polymerase chain reaction (PCR) suspension microarray which detects 19 viral and four atypical bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays was used for each pathogen as the gold standard. A panel of archived as well as 300 prospectively collected clinical samples was analysed by both methods. At least one target was detected in 165/300 (55 %) samples by monoplex PCR and in 140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was significantly higher in paediatric patients compared to adults [126/154 (82 %) vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7 %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from 57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance between both methods was 77 % [95 % confidence interval (CI) 72–81 %]. False-negative results by multiplex PCR were mainly due to the low target concentration. Compared to monoplex PCR, the novel microarray assay proved its principle but displayed overall lower sensitivities, potentially restricting its use to paediatric patients. For some targets, only small numbers of positive samples were available, requiring larger studies to firmly assess the sensitivity and specificity.


title: Structural Basis for the dsRNA Specificity of the Lassa Virus NP Exonuclease

text: Lassa virus causes hemorrhagic fever characterized by immunosuppression. The nucleoprotein of Lassa virus, termed NP, binds the viral genome. It also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded RNA (dsRNA). dsRNA is a strong signal to the innate immune system of viral infection. Digestion of dsRNA by the NP exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. Although the fold of the NP enzyme is conserved and the active site completely conserved with other exonucleases in its DEDDh family, NP is atypical among exonucleases in its preference for dsRNA and its strict specificity for one substrate. Here, we present the crystal structure of Lassa virus NP in complex with dsRNA. We find that unlike the exonuclease in Klenow fragment, the double-stranded nucleic acid in complex with Lassa NP remains base-paired instead of splitting, and that binding of the paired complementary strand is achieved by “relocation” of a basic loop motif from its typical exonuclease position. Further, we find that just one single glycine that contacts the substrate strand and one single tyrosine that stacks with a base of the complementary, non-substrate strand are responsible for the unique substrate specificity. This work thus provides templates for development of antiviral drugs that would be specific for viral, rather than host exonucleases of similar fold and active site, and illustrates how a very few amino acid changes confer alternate specificity and biological phenotype to an enzyme.


title: Social Media and Internet-Based Data in Global Systems for Public Health Surveillance: A Systematic Review

text: Context: The exchange of health information on the Internet has been heralded as an opportunity to improve public health surveillance. In a field that has traditionally relied on an established system of mandatory and voluntary reporting of known infectious diseases by doctors and laboratories to governmental agencies, innovations in social media and so-called user-generated information could lead to faster recognition of cases of infectious disease. More direct access to such data could enable surveillance epidemiologists to detect potential public health threats such as rare, new diseases or early-level warnings for epidemics. But how useful are data from social media and the Internet, and what is the potential to enhance surveillance? The challenges of using these emerging surveillance systems for infectious disease epidemiology, including the specific resources needed, technical requirements, and acceptability to public health practitioners and policymakers, have wide-reaching implications for public health surveillance in the 21st century. Methods: This article divides public health surveillance into indicator-based surveillance and event-based surveillance and provides an overview of each. We did an exhaustive review of published articles indexed in the databases PubMed, Scopus, and Scirus between 1990 and 2011 covering contemporary event-based systems for infectious disease surveillance. Findings: Our literature review uncovered no event-based surveillance systems currently used in national surveillance programs. While much has been done to develop event-based surveillance, the existing systems have limitations. Accordingly, there is a need for further development of automated technologies that monitor health-related information on the Internet, especially to handle large amounts of data and to prevent information overload. The dissemination to health authorities of new information about health events is not always efficient and could be improved. No comprehensive evaluations show whether event-based surveillance systems have been integrated into actual epidemiological work during real-time health events. Conclusions: The acceptability of data from the Internet and social media as a regular part of public health surveillance programs varies and is related to a circular challenge: the willingness to integrate is rooted in a lack of effectiveness studies, yet such effectiveness can be proved only through a structured evaluation of integrated systems. Issues related to changing technical and social paradigms in both individual perceptions of and interactions with personal health data, as well as social media and other data from the Internet, must be further addressed before such information can be integrated into official surveillance systems.


docid: rxocrgfu

title: Clinical Evaluation of a Single-Tube Multiple RT-PCR Assay for the Detection of 13 Common Virus Types/Subtypes Associated with Acute Respiratory Infection

text: Respiratory viruses are among the most important causes of human morbidity and mortality worldwide, especially for infants and young children. In the past years, a few commercial multiplex RT-PCR assays have been used to detect respiratory viruses in spite of the high cost. In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. Of 310 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 226 (72.90%, 226/310) and 214 (69.03%, 214/310) positive for one or more viruses were identified by the single-tube and the two-tube assays, respectively, with combined test results showing good concordance (Kappa value = 0.874). Individually, the single-tube assay for adenovirus (Adv), human metapneumovirus (HMPV), human rhinovirus (HRV), parainfluenza virus type 1 (PIV1), parainfluenza virus type 3 (PIV3) and parainfluenza virus type 4 (PIV4) showed the significantly superior sensitivities to those of the two-tube assay. No false positives were found. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China.


title: Modelling testing frequencies required for early detection of a SARS-CoV-2 outbreak on a university campus

text: Background: Early detection and risk mitigation efforts are essential for averting large outbreaks of SARS-CoV-2. Active surveillance for SARS-CoV-2 can aid in early detection of outbreaks, but the testing frequency required to identify an outbreak at its earliest stage is unknown. We assess what testing frequency is required to detect an outbreak before there are 10 detectable infections. Methods: A dynamic compartmental transmission model of SARS-CoV-2 was developed to simulate spread among a university community. After introducing a single infection into a fully susceptible population, we calculate the probability of detecting at least one case on each succeeding day with various NAT testing frequencies (daily testing achieving 25%, 50%, 75%, and 100% of the population tested per month) assuming an 85% test sensitivity. A proportion of infected individuals (varied from 1-60%) are assumed to present to health services (HS) for symptomatic testing. We ascertain the expected number of detectable infections in the community when there is a >90% probability of detecting at least 1 case. Sensitivity analyses examine impact of transmission rates (Rt=0=2, 2.5,3), presentation to HS (1%/5%/30%/60%), and pre-existing immunity (0%/10%) Results: Assuming an 85% test sensitivity, identifying an outbreak with 90% probability when the expected number of detectable infections is 9 or fewer requires NAT testing of 100% of the population per month; this result holds for all transmission rates and all levels of presentation at health services we considered. . If 1% of infected people present at HS and Rt=0=3, testing 75%/50%/25% per month could identify an outbreak when the expected numbers of detectable infections are 12/17/30 respectively; these numbers decline to 9/11/12 if 30% of infected people present at HS . As proportion of infected individuals present at health services increases, the marginal impact of active surveillance is reduced. Higher transmission rates result in shorter time to detection but also rapidly escalating cases without intervention. Little differences were observed with 10% pre-existing immunity. Conclusions: Widespread testing of 100% of the campus population every month is required to detect an outbreak when there are fewer than 9 detectable infections for the scenarios examined, but high presentation of symptomatic people at HS can compensate in part for lower levels of testing. Early detection is necessary, but not sufficient, to curtail disease outbreaks; the proposed testing rates would need to be accompanied by case isolation, contact tracing, quarantine, and other risk mitigation and social distancing interventions.


docid: jbtrdvhe

title: Coronavirus disease 2019 (COVID-19): current status and future perspectives

text: ABSTRACT Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.


title: "Will they just pack up and leave?" – attitudes and intended behaviour of hospital health care workers during an influenza pandemic

text: BACKGROUND: There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs) are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza. METHODS: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation. RESULTS: Respondents were categorized into four main groups by occupation: Nursing (47.5%), Medical (26.0%), Allied (15.3%) and Ancillary (11.2%). Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873) but less than half were able to correctly define it (43.9%, n = 473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p < 0.001). Only 42.5% (n = 459) of respondents considered that neuraminidase inhibitor antiviral medications (oseltamivir/zanamivir) would protect them against pandemic influenza, whereas 77.5% (n = 836) believed that vaccination would be of benefit. CONCLUSION: We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All health care worker strategies should include non clinical and ancillary staff to ensure adequate business continuity for hospitals. HCW education, psychosocial support and staff communication could improve knowledge of appropriate pandemic interventions and confidence in antivirals.


Visualization of Putative Coronavirus in Kidney


title: Infection control measures in ophthalmology during the COVID-19 outbreak: A narrative review from an early experience in Italy

text: INTRODUCTION: The novel coronavirus (SARS-CoV-2) is infecting people and spreading easily from person-to-person. Cases have been detected in most countries worldwide. Italy is one of the most affected countries as of 30 March 2020. Public health response includes a rapid reorganization of the Italian National Healthcare System in order to reduce transmission of COVID-19 within hospitals and healthcare facilities, while optimizing the assistance to patients with severe COVID-19 complications. METHODS: We analysed the actions that were taken in three ophthalmology centres in northern Italy during the SARS-CoV-2 outbreak and how these measures affected patient’s attendance. In addition, due to the rapidly evolving scenario, we reviewed the evidence available during the course of this pandemic. RESULTS: A full reorganization of ophthalmology services is mandatory according to current existing infection containment measures in order to continue dispensing urgent procedures without endangering the community with amplification of the diffusion chain. Ophthalmologists are considered at elevated risk of exposure when caring patients and vice versa, due to their close proximity during eye examination. High volumes of procedures typically generated by ophthalmologists with concurrent implications on the risk of infection are considered when re-assessing healthcare facilities reorganization. CONCLUSION: Containment measures in the event of pandemic due to infective agents should be well known by healthcare professionals and promptly applied in order to mitigate the risk of nosocomial transmission and outbreak.


title: Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs

text: The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15–20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the “pattern recognition receptors” (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the “cytokine storm syndrome,” a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered.


title: Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients

text: BACKGROUND: Single-nucleotide polymorphisms (SNPs) that impact on the differential expression of interleukin 28B (IL28B) are implicated in the progression of viral-induced diseases. In this prospective longitudinal cohort study, we evaluated the association between IL28B SNPs rs12979860 and rs8099917 and the clinical outcome of bronchiolitis in pediatric patients. METHODS: A total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917. RESULTS: When infants were categorized exclusively based on the final clinical outcome, no association was established between IL28B SNPs and the severity of bronchiolitis. However, when stratified by sex, the homozygotes for the minor alleles of rs12979860 (T) and rs8099917 (G) were associated with a mild disease in girls but not in boys. CONCLUSION: SNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. These findings suggest that innate immunity and female sex links with the outcome of the diseases induced by respiratory viruses, such as RSV.


Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin


title: Loneliness and social isolation during the COVID-19 pandemic

text: Loneliness and social isolation are associated with adverse physical and psychological consequences which are particularly prevalent in older persons. During this unprecedented time of the COVID-19 pandemic, we must follow social distancing guidelines to protect ourselves and to reduce the spread of coronavirus. At the same time, it is crucial to maintain social connections with each other, especially with older persons, to help cope and reduce the negative consequences of loneliness and social isolation. It is important to develop new strategies (e.g. virtual health care and new government policy) to address loneliness and social isolation among older adults for the post-pandemic era.


title: Pedestrian level wind environment assessment around group of high-rise cross-shaped buildings: Effect of building shape, separation and orientation

text: Abstract Blockage of air circulation caused by the mutual sheltering effect of high-rise buildings in built-up areas in dense cities causes various health- and comfort-related problems. The combined effect of neighborhood geometry (e.g., re-entrant corners, wind incident angle, passage angle, and building separation) on wind flow at the pedestrian level is an active field of research. This study investigates the influence of the wind incident angle and passage width on the wind flow characteristics at the re-entrant corners of cross-shaped high-rise buildings. This study also examines the influence of stagnant zones and wake regions on ventilation potential and wind comfort around the case study arrangements at various wind incident directions. An investigation was performed from 16 wind directions using the standard k–ε turbulence model with revised closure coefficients. A wind tunnel experiment was conducted to validate the results, which revealed that wind circulation at re-entrant corners was substantially affected by the building orientations and separation. The wind catchment effect within the re-entrant corners and the sheltering effect of buildings at various wind incident directions and building separations are also discussed. Unstable vortices were formed in oblique wind directions; these vortices facilitate contaminant dispersion and wind comfort at re-entrant corners and near buildings.


title: Cloning and further sequence analysis of the ORF3 gene of wild- and attenuated-type porcine epidemic diarrhea viruses

text: The open reading frame (ORF3) genes of the parent DR13, attenuated DR13, KPED-9, P-5V, and 12 field samples were cloned and sequenced to further explore the functions of wild- and attenuated-type porcine epidemic diarrhea viruses (PEDVs). Sequencing revealed that wild-type PEDVs ORF3 genes had a single ORF of 675 nucleotides encoding a protein of 224 amino acids with a predicted M (r) of 25.1–25.3 kDa. Attenuated-type PEDVs ORF3 genes had a single ORF of 624 nucleotides encoding a protein of 207 amino acids with a predicted M (r) of 23.4 kDa. The coding region of the ORF3 gene of attenuated-type PEDVs including attenuated DR13, KPED-9, and P-5V had 51 nucleotide deletions that were not found in the ORF3 genes of wild-type PEDVs including CV777, Br1/87, LZC, parent DR13, and 12 field samples. In addition, attenuated-type PEDVs have previously been found to exhibit reduced pathogenicity in pigs. Therefore, 51 nucleotide deletions appear to be meaningful and may be significant for PEDV pathogenicity, because they lead to changes in the predicted amino acid sequences of attenuated-type PEDVs. Reverse transcriptase-polymerase chain reaction (RT-PCR) on the partial ORF3 gene including 51 nucleotide deletions revealed that all PEDVs fell into two types, wild- and attenuated-type PEDVs. Wild-type PEDVs containing parent DR13 and 12 field samples had RT-PCR products of 245 bp in size, while attenuated-type PEDVs containing PEDV vaccine strains (attenuated DR13, KPED-9, P-5V) had products of 194 bp. In addition, all PEDV vaccine strains were used as live virus vaccine, because they previously exhibited a reduced pathogenicity in pigs. Therefore, large deletion region, which is comprise 17 amino acid deletions caused by 51 nucleotide deletions and is seen in all PED live vaccine strains, may be important site for PEDV pathogenicity, and we can use it for differentiation of wild- and attenuated-type PEDVs.


The challenges of research nursing in an outbreak setting http://ow.ly/jOFu301NzRh


Peptidases: structure, function and modulation of peptide‐mediated effects in the human lung


Anestesia espinhal em pacientes com COVID-19, mais pesquisa é necessária


docid: snldtqsn

title: Comparison of SARS and NL63 Papain-Like Protease Binding Sites and Binding Site Dynamics: Inhibitor Design Implications

text: The human severe acute respiratory syndrome coronavirus (SARS-CoV) and the NL63 coronaviruses are human respiratory pathogens for which no effective antiviral treatment exists. The papain-like cysteine proteases encoded by the coronavirus (SARS-CoV: PLpro; NL63: PLP1 and PLP2) represent potential targets for antiviral drug development. Three recent inhibitor-bound PLpro structures highlight the role of an extremely flexible six-residue loop in inhibitor binding. The high binding site plasticity is a major challenge in computational drug discovery/design efforts. From conventional molecular dynamics and accelerated molecular dynamics (aMD) simulations, we find that with conventional molecular dynamics simulation, PLpro translationally samples the open and closed conformation of BL2 loop on a picosecond–nanosecond timescale but does not reproduce the peptide bond inversion between loop residues Tyr269 and Gln270 that is observed on inhibitor GRL0617 binding. Only aMD simulation, starting from the closed loop conformation, reproduced the 180° ϕ–Ψ dihedral rotation back to the open loop state. The Tyr–Gln peptide bond inversion appears to involve a progressive conformational change of the full loop, starting at one side, and progressing to the other. We used the SARS-CoV apo X-ray structure to develop a model of the NL63-PLP2 catalytic site. Superimposition of the PLP2 model on the PLpro X-ray structure identifies binding site residues in PLP2 that contribute to the distinct substrate cleavage site specificities between the two proteases. The topological and electrostatic differences between the two protease binding sites also help explain the selectivity of non-covalent PLpro inhibitors.


title: Protecting health care workers from SARS and other respiratory pathogens: A review of the infection control literature

text: BACKGROUND: Severe Acute Respiratory Syndrome (SARS) was responsible for outbreaks in Canada, China, Hong Kong, Vietnam, and Singapore. SARS focused attention on the adequacy of and compliance with infection control practices in preventing airborne and droplet-spread transmission of infectious agents. METHODS: This paper presents a review of the current scientific knowledge with respect to the efficacy of personal protective equipment in preventing the transmission of respiratory infections. The effectiveness of infection control polices and procedures used in clinical practice is examined. RESULTS: Literature searches were conducted in several databases for articles published in the last 15 years that related to infection control practices, occupational health and safety issues, environmental factors, and other issues of importance in protecting workers against respiratory infections in health care settings. CONCLUSION: Failure to implement appropriate barrier precautions is responsible for most nosocomial transmissions. However, the possibility of a gradation of infectious particles generated by aerosolizing procedures suggests that traditional droplet transmission prevention measures may be inadequate in some settings. Further research is needed in this area.


title: The Orchestra of Reovirus Cell Entry

text: PURPOSE OF REVIEW: the ability of viruses to infect host cells is dependent on several factors including the availability of cell-surface receptors, antiviral state of cells, and presence of host factors needed for viral replication. Here we review findings from in vitro and in vivo studies using mammalian orthoreovirus (reovirus) that have identified an intricate group of molecules and mechanisms used by the virus to attach and enter cells. RECENT FINDINGS: recent findings provide an improved mechanistic understanding of reovirus cell entry. Of special note is the identification of a cellular mediator of cell entry in neuronal and non-neuronal cells, the effect of cell entry on the outcome of infection and cytopathic effects on the host cell, and an improved understanding of the components that promote viral penetration of cellular membranes. SUMMARY: a mechanistic understanding of the interplay between host and viral factors has enhanced our view of how viruses usurp cellular processes during infection.


title: Establishment of method for dual simultaneous detection of PEDV and TGEV by combination of magnetic micro-particles and nanoparticles

text: Abstract Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are the main pathogens causing viral diarrhea in pig, mixed infections of these two viruses are very common in intensive pig rearing. However, there is a lack of a method to simultaneously detect and distinguish PEDV and TGEV in preclinical levels. In this study, we aimed to establish a dual ultrasensitive nanoparticle DNA probe-based PCR assay (dual UNDP-PCR) based on functionalized magnetic bead enrichment and specific nano-technology amplification for simultaneous detection and distinguish diagnosis of PEDV and TGEV. The detection limit of dual UNDP-PCR for single or multiple infections of PEDV and TGEV is 25 copies/g, which is 400 times more sensitive than the currently known duplex RT-PCR, showing better specificity and sensitivity without cross-reaction with other viruses. For pre-clinical fecal samples, the dual UNDP-PCR showed a markedly higher positive detection rate (52.08%) than conventional duplex RT-PCR (13.21%), can rapidly and accurately identify targeted pathogens whenever simple virus infection or co-infection. In summary, this study provides a technique for detecting and distinguishing PEDV and TGEV in preclinical levels, which is high sensitivity, specificity, repeatability, low cost and broad application prospect.


title: Relationship of viral infections to wheezing illnesses and asthma

text: Viral infections can influence both the development and the severity of asthma. In early life, viral infections can either increase or, remarkably, decrease the risk of subsequent asthma. In children and adults with existing asthma, viral respiratory infections frequently cause acute airway obstruction and wheezing. This article discusses the influence of viral infections on mechanisms of virus-induced airway inflammation in relationship to the development, persistence and severity of asthma.


title: Measuring the Severity of Respiratory Illness in the First 2 Years of Life in Preterm and Term Infants

text: Objective To develop a valid research tool to measure infant respiratory illness severity using parent-reported symptoms. Study design Nose and throat swabs were collected monthly for 1 year and during respiratory illnesses for 2 years in a prospective study of term and preterm infants in the Prematurity, Respiratory Outcomes, Immune System and Microbiome study. Viral pathogens were detected using Taqman Array Cards. Parents recorded symptoms during respiratory illnesses using a Childhood Origins of Asthma (COAST) scorecard. The COAST score was validated using linear mixed effects regression modeling to evaluate associations with hospitalization and specific infections. A data-driven method was also used to compute symptom weights and derive a new score, the Infant Research Respiratory Infection Severity Score (IRRISS). Linear mixed effects regression modeling was repeated with the IRRISS illness data. Results From April 2013 to April 2017, 50 term, 40 late preterm, and 28 extremely low gestational age (<29 weeks of gestation) infants had 303 respiratory illness visits with viral testing and parent-reported symptoms. A range of illness severity was described with 39% of illness scores suggestive of severe disease. Both the COAST score and IRRISS were associated with respiratory syncytial virus infection and hospitalization. Gestational age and human rhinovirus infection were inversely associated with both scoring systems. The IRRISS and COAST scores were highly correlated (r = 0.93; P < .0001). Conclusions Using parent-reported symptoms, we validated the COAST score as a measure of respiratory illness severity in infants. The new IRRISS score performed as well as the COAST score.


title: Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers

text: Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine “click”-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar “raft-like” nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity.


Letter: does vitamin D have a potential role against COVID‐19?


title: Retroviral DNA—the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats

text: BACKGROUND: The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. RESULTS: Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. CONCLUSIONS: Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0231-z) contains supplementary material, which is available to authorized users.


title: Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection

text: Motivation: Although the outbreak of the severe acute respiratory syndrome (SARS) is currently over, it is expected that it will return to attack human beings. A critical challenge to scientists from various disciplines worldwide is to study the specificity of cleavage activity of SARS-related coronavirus (SARS-CoV) and use the knowledge obtained from the study for effective inhibitor design to fight the disease. The most commonly used inductive programming methods for knowledge discovery from data assume that the elements of input patterns are orthogonal to each other. Suppose a sub-sequence is denoted as P(2)P(1)P(1′)P(2′), the conventional inductive programming method may result in a rule like ‘if P(1) = Q, then the sub-sequence is cleaved, otherwise non-cleaved’. If the site P(1) is not orthogonal to the others (for instance, P(2), P(1′) and P(2′)), the prediction power of these kind of rules may be limited. Therefore this study is aimed at developing a novel method for constructing non-orthogonal decision trees for mining protease data. Result: Eighteen sequences of coronavirus polyprotein were downloaded from NCBI (http://www.ncbi.nlm.nih.gov). Among these sequences, 252 cleavage sites were experimentally determined. These sequences were scanned using a sliding window with size k to generate about 50 000 k-mer sub-sequences (for short, k-mers). The value of k varies from 4 to 12 with a gap of two. The bio-basis function proposed by Thomson et al. is used to transform the k-mers to a high-dimensional numerical space on which an inductive programming method is applied for the purpose of deriving a decision tree for decision-making. The process of this transform is referred to as a bio-mapping. The constructed decision trees select about 10 out of 50 000 k-mers. This small set of selected k-mers is regarded as a set of decisive templates. By doing so, non-orthogonal decision trees are constructed using the selected templates and the prediction accuracy is significantly improved. Availability: The program for bio-mapping can be obtained by request to the author. Contact: z.r.yang@exeter.ac.uk


title: Large granular leukemia with concurrent central nervous system and articular infiltration in a cat

text: Summary A 2-year-old female domestic shorthair cat was referred with a 2month history of lethargy, weight loss, recurrent hyperthermia and polyarthropathy despite prednisolone. Upon physical examination, the cat showed apathy, hyperthermia, multiple appendicular joint pain and swelling. The CBC showed severe macrocytic normochromic non-regenerative anemia and thrombocytopenia. A population of immature large granular lymphocytes (LGL) was noted on blood smear. Abdominal ultrasonography revealed enlarged mesenteric lymph nodes (LNs), hyper echoic liver and splenomegaly. Cytology of fine needle aspirate of synovial fluid, spleen, liver, enlarged abdominal LNs and bone marrow supported a diagnosis of LGL leukemia with concurrent articular infiltration. A COP-based protocol was initiated with L-asparaginase (400 UI/kg intramuscularly) and prednisolone (1mg/kg/day orally). However, the cat presented 1 week later with obtundation and paresis, indicating the involvement of the central nervous system (CNS). LGL were also observed on cerebrospinal fluid analysis. Histologic examination noted LGL in the spleen, liver and LNs. Immunohistochemistry (IHC) yielded negative results for both B- and T-cells thus suggesting NK-cells. The diagnosis was LGL leukemia with concurrent articular and CNS involvement. Articular infiltration with LGL is rarely reported in small animals, whereas CNS involvement was previously only suspected in a cat at necropsy.


title: Metapneumovirus and acute wheezing in children

text: Summary A new respiratory virus, human metapneumovirus, was recently identified. We detected this virus by PCR in ten (8%) of 132 consecutive children admitted to Turku Hospital, Finland, for acute expiratory wheezing (median age 7 months, range 4–25). The mean duration of hospital stay was 2·5 days (SD 1·6) and mean duration of respiratory symptoms was 19 days (8). The white blood cell count, C-reactive protein, and regulated upon activation, normal T-cell-expressed and T-cell-secreted (RANTES) concentrations in nasal secretion remained low, whereas interleukin 8 concentrations in nasal secretion were high. Human metapneumovirus is a clinically important causative agent of acute wheezing in young children.