title: A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong

text: We conducted a six-year epidemiological study on human coronaviruses (HCoVs) circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77 (0.93%) of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43 (0.58%), followed by HCoV-229E (0.15%), HCoV-HKU1 (0.13%) and HCoV-NL63 (0.07%). HCoVs were detected throughout the study period (September 2008–August 2014), with the highest detection rate from September 2010 to August 2011 (22/1500, 1.47%). Different seasonal patterns of each HCoV species in Hong Kong were noted. HCoV-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years (range, 22 days to 95 years). Intriguingly, the detection rate of HCoV-OC43 in the age group of > 80 years (26/2380, 1.09%) was significantly higher than that in the age group of 0–10 years (12/2529, 0.47%) (P < 0.05). These data provides new insight into the epidemiology of coronaviruses. [Image: see text]


title: Prudently conduct the engineering and synthesis of the SARS-CoV-2 virus

text: Abstract Regarding to the recent work of engineering SARS-CoV-19 virus and the publication “Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform” by researchers at University of Bern, this paper comments on the “dual-use” problem and regulation issue of synthetic biology from the perspective of responsible (research and) innovation, biosafety and biosecurity. Based on the ethical and legal framework, the authors suggest to conduct such research with high potential risks prudently and responsibly.


title: An in silico map of the SARS-CoV-2 RNA Structurome

text: SARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis.


title: Leading and managing an emergency department—A personal view

text: Abstract The emergency department (ED) is a “unique operation, optimized to exist at the edge of chaos”. It is the responsibility of the leaders and managers of the ED to ensure that their teams work in an environment where they can deliver the best care to their patients. This environment is defined by people, system and place. People are the most important asset of the ED. One of the most important responsibilities of the ED leaders and managers (senior management) is to foster teamwork. They will also have to ensure that communication between team members is optimal and that there is a structure in place for conflict resolution. ED senior management should be aware of their team dynamics and know the “movers and shakers” in their organization. ED systems should be kept simple. One of the core businesses of an ED is contingency planning. ED senior management must plan, prepare, practice, review, analyze, assess and strategize for unexpected events. The ED physical environment has an impact on the flow of care being delivered to her patients. ED senior management must manage change. Change works only if it takes root in the hearts and minds of the organization's people. The quality of the leaders and managers of the ED will determine whether or not, their teams work in an environment where they can deliver the best care to their patients.


title: Proteinaceous cysteine protease inhibitors

text: Studies of proteinaceous cysteine protease inhibitors originated with the discovery of cystatins in the 1960s. Since that time, a rich and fascinating world of proteins that control and regulate a multitude of important physiological processes, ranging from the basics of protein turnover to development and brain function, has been uncovered. Failures in such important and complex systems inevitably lead to pathologies. Many threatening diseases such as cancer or neurological disorders, to mention only some, are attributed to deregulation of proteaseinhibitor balance. Moreover, important aspects of infection pathology and host defense rely on proteolysis and protease inhibition. Recent advances in the field of protease inhibitors have drawn attention to the possible use of this collected knowledge to control related pathological processes. This review attempts to familiarize the reader with proteinaceous cysteine protease inhibitors by providing an overview of current knowledge. The work primarily highlights biological processes in which the inhibitors are involved and focuses on pathologies resulting from aberrant protease-inhibitor balance, pointing out emerging possibilities for their correction.


title: Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization

text: Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.


title: Palliative care in the time of COVID-19

text: Abstract After covid-19 crisis in Italy, serious restrictions have been introduced for relatives, with limitations or prohibitions on hospital visits. To partially overcome these issues “WhatsApp” has been adopted to get family members to participate in clinical rounds. Family members of patients admitted to the acute palliative care unit and hospice were screened for a period of 2 weeks. Four formal questions were posed: 1) Are you happy to virtually attend the clinical round? 2) Are you happy with the information gained in this occasion? 3) Do you think that your loved one was happy to see you during the clinical rounds? 4) This technology may substitute your presence during the clinical rounds? The scores were 0 = no, 1 = a little bit, 2 = much, 3 = very much. Relatives were free to comment about these points. Sixteen of 25 screened family members were interviewed. Most family members had a good impression, providing scores of 2 or 3 for the first three items. However, the real presence bedside (forth question) was considered irreplaceable. They perceived that their loved one, when admitted to hospice, had to say good-bye before dying.


title: Pathogen prevalence in commercially reared bumble bees and evidence of spillover in conspecific populations

text: Abstract Worldwide, wild bumble bees (Bombus spp.) are experiencing marked declines, with potentially up to 11% of species currently under threat. Recent studies from North America suggest that disease transmission from commercially reared bumble bees to wild populations has led to marked range contractions in some species. In Europe, data on the prevalence of pathogen spillover from commercial to wild bumble bee populations is lacking, despite the widespread production and transport of hives within the EU since the early 1980s. We determined the permeability of cropping systems to commercial bumble bees, and quantified the prevalence of four pathogens in commercial Bombus terrestris hives and adjacent conspecific populations at increasing distances from greenhouses in Ireland. Commercial bumble bees collected from 31% to 97% of non-crop pollen, depending on the cropping system, and hives had markedly higher frequencies of two gut parasites, Crithidia spp. and Nosema bombi, compared to adjacent populations, but were free of tracheal mites. The highest prevalence of Crithida was observed within 2km of greenhouses and the probability of infection declined in a host sex- and pathogen-specific manner up to 10km. We suggest implementing measures that prevent the interaction of commercially reared and wild bumble bees by integrating the enforcement of national best management practices for users of commercial pollinators with international legislation that regulates the sanitation of commercial hives in production facilities.


title: Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

text: The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02787-2) contains supplementary material, which is available to authorized users.


title: NCI’s Work to Advance Cancer Research while Responding to the COVID-19 Pandemic

text: Abstract During the COVID-19 pandemic, the National Cancer Institute (NCI) is bringing to bear its considerable expertise and capabilities to understand, treat, and prevent the disease. While responding to the pandemic, NCI’s priority remains the advancement of cancer research. NCI has implemented many flexibilities for grantees and trainees.


title: Coronavirus surveillance of wildlife in the Lao People’s Democratic Republic detects viral RNA in rodents

text: Coronaviruses can become zoonotic, as in the case of COVID-19, and hunting, sale, and consumption of wild animals in Southeast Asia increases the risk for such incidents. We sampled and tested rodents (851) and other mammals and found betacoronavirus RNA in 12 rodents. The sequences belong to two separate genetic clusters and are closely related to those of known rodent coronaviruses detected in the region and distantly related to those of human coronaviruses OC43 and HKU1. Considering the close human-wildlife contact with many species in and beyond the region, a better understanding of virus diversity is urgently needed for the mitigation of future risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04683-7) contains supplementary material, which is available to authorized users.


Prevalence of coronavirus


title: Using the COVID-19 to influenza ratio to estimate the numbers of symptomatic COVID-19 cases in Wuhan prior to the lockdown

text: A recent study tested 45 throat swabs taken from adults over age 30 who sought outpatient care at one of two central Wuhan hospitals for influenza-like-illness between December 30, 2019 and January 19, 2020. Although none were confirmed COVID-19 cases, nine retrospectively tested positive for the virus. Using the fact that Wuhan has 393 other hospitals, we extrapolate the total number of undetected cases of symptomatic COVID-19 in adults during this period. we estimate that there were 5,558 [95% CI: 2,761-9,864] adults with symptomatic COVID-19 infections in Wuhan between December 30th and January 19th, 2020.


title: Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) Viral Spike Protein-Angiotensin Converting Enzyme-2 (ACE2) interaction

text: Commonly used drugs for treating many conditions are either natural products or derivatives. In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein. Here we argue that the oral route of administration of quercetin is unlikely to be effective in clinical trials owing to biotransformation during digestion, absorption and metabolism, but suggest that agents could be administered directly by alternative routes such as a nasal or throat spray.


Adaptation: An Interventional Radiology Residency Response to COVID-19


title: Impact of RNA Virus Evolution on Quasispecies Formation and Virulence

text: RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.


title: Protein Microarrays and Biomarkers of Infectious Disease

text: Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.


title: A systems approach to natural disaster resilience

text: Abstract The frequency, social, and economic impacts of natural disasters show exponential increases in recent decades. Cities and countries around the world have begun to realize that these events are no longer “hundred year” storms, but repeat within a few years. As urbanisation continues throughout this century, more and more people and more economic activity will be concentrated in at-risk areas; especially as new arrivals in cities throughout Asia and Africa are likely to be concentrated in the highest risk districts, much as they often are in North America and Europe today. This article reviews recent growth of natural disasters and considers how a systems approach can improve approaches to mitigation and adaptation of these risks and to recovery from such events.


Whose responsibility? COVID‐19 in a homeless shelter in the UK


title: Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin

text: Abstract Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors (5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a replication model for severe acute respiratory syndrome (SARS) infections (Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K., Packard, M., Shieh, W.J., Zaki, S., Murphy, B., 2004. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in the respiratory tract of mice. J. Virol. 78, 3572–3577). Ribavirin given at 75mg/kg 4h prior to virus exposure and then given twice daily for 3 days beginning at day 0 was found to increase virus lung titers and extend the length of time that virus could be detected in the lungs of mice. Other IMP dehydrogenase inhibitors administered near maximum tolerated doses using the same dosing regimen as for ribavirin were found to slightly enhance virus replication in the lungs. In addition, ribavirin treatment seemed also to promote the production of pro-inflammatory cytokines 4 days after cessation of treatment, although after 3 days of treatment ribavirin inhibited pro-inflammatory cytokine production in infected mice, significantly reducing the levels of the cytokines IL-1α, interleukin-5 (IL-5), monocyte chemotactic protein-1 (MCP-1), and granulocyte-macrophage colony stimulating factor (GM-CSF). These findings suggest that ribavirin may actually contribute to the pathogenesis of SARS-CoV by prolonging and/or enhancing viral replication in the lungs. By not inhibiting viral replication in the lungs of infected mice, ribavirin treatment may have provided a continual source of stimulation for the inflammatory response thought to contribute to the pathogenesis of the infection. Our data do not support the use of ribavirin or other IMP dehydrogenase inhibitors for treating SARS infections in humans.


title: Characterization of a coronavirus I. Structural proteins: Effects of preparative conditions on the migration of protein in polyacrylamide gels

text: Abstract Coronavirus A59 possesses four size classes of structural proteins which have apparent molecular weights measured by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of 23,000 (GP23), 50,000 (VP50), 90,000 (GP90), and 180,000 (GP180). VP50 is the only structural protein which is completely unaffected by protease treatment of intact virions. This species is the most highly labeled by polar amino acids such as glutamic acid and arginine and it is probably associated with the viral nucleocapsid. GP90, GP180, and GP23 are membrane-associated proteins. However, after protease treatment of virions, only 20% of the GP23 molecule is digested, whereas all of the GP90 and GP180 are removed. GP90 and GP180 appear to comprise most of the prominent layer of characteristic projections on the external surface of the viral envelope. The major portion of GP23 is presumed to lie within the lipid envelope, protected from protease digestion. GP23 and the protease resistant portion, p∗18, exhibit anomalous behavior on SDS-PAGE. After heating to 100° in SDS the electrophoretic mobility of these polypeptides is altered and several new forms of lower mobility are produced. β-Mercaptoethanol and dithiothreitol exaggerate the effects of heating.


title: Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy

text: Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.


title: The Mongoose, the Pheasant, the Pox, and the Retrovirus

text: Paleovirology is the study of ancient viruses. The existence of a paleovirus can sometimes be detected by virtue of its accidental insertion into the germline of different animal species, which allows one to date when the virus actually existed. However, the ancient and the modern often connect, as modern viruses have unexpected origins that can be traced to ancient infections. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. REV apparently spread to poultry through a circuitous route involving the isolation of malaria parasites from a pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV. Repeated passage of this virus in poultry adapted the virus to its new host. At some point, the virus got inserted into another virus, called fowlpox virus, which has spread back into the wild. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20(th) century. These lessons of ancient and modern viruses have implications for modern human pandemics from viral reservoirs and for human interventions that may come with unintended consequences.


Renilla Luciferase as a Reporter to Assess SARS-CoV mRNA Transcription Regulation and Efficacy of ANTI-SARS-CoV Agents


title: Development of antibodies to feline IFN-γ as tools to elucidate the cellular immune responses to FeLV

text: Abstract An understanding of the nature of immune protection and the role of immune effector products such as interferon-γ (IFN-γ) in the control of infectious disease is fundamental to the rational design of effective vaccines and immunotherapeutic reagents. Murine monoclonal and sheep polyclonal antibodies (mAbs and pAbs) to feline IFN-γ (fIFN-γ) were generated firstly to facilitate further research into the role of cellular immune responses in the control of feline infectious disease, and secondly to enable evaluation of the efficacy of novel immunotherapeutic approaches. A hybridoma clone, D9, secreting IgG1 antibodies was selected for expansion and the mAbs affinity purified in vitro. Polyclonal antibodies were raised in a sheep against recombinant fIFN-γ and affinity purified. The sensitivity of the D9 mAb and the sheep anti-fIFN-γ pAb was determined using an indirect fIFN-γ enzyme-linked immunosorbent assay (ELISA) and immunoblots. These antibodies were assessed for their ability to detect the production of fIFN-γ by specific feline T cell populations ex vivo following coculture with mitogen or feline leukaemia virus (FeLV) antigens for 4 h in the presence of the protein secretion inhibitor brefeldin A (BFA). Production of fIFN-γ was evaluated using flow cytometry to simultaneously detect PE-labelled surface molecules and fluorescein isothiocyanate (FITC)-labelled intracellular fIFN-γ. Using this approach, our initial studies revealed an upregulation in virus-specific fIFN-γ-secreting CD4+T cells in the lymph nodes of FeLV latently infected cats.


title: Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases

text: Summary Background Acute exacerbation (AE) is currently established as a distinct condition with acute deterioration of respiratory status in idiopathic pulmonary fibrosis (IPF). Recently, several studies have reported that AE also occurred in interstitial pneumonias other than IPF, such as collagen vascular disease-associated interstitial pneumonia (CVD-IP). However, the incidence of AE in CVD-IP and its clinical characteristics remain to be fully determined. This study was conducted to elucidate cumulative incidence of AE in CVD-IP and its clinical features. Methods We reviewed 83 biopsy-proven CVD-IP patients, estimated cumulative incidence of AE, and examined its clinical characteristics. Results Among 83 CVD-IP patients, six patients with a mean age of 65.7 years developed AE (overall incidence, 7.2%; 1-year incidence, 1.25%). Underlying CVDs included rheumatoid arthritis (RA) (n =5; overall incidence, 20.0%) and primary Sjögren syndrome (n =1; overall incidence, 5.9%). Patients with AE showed acute respiratory deterioration with severe hypoxemia (mean PaO2/FiO2 ratio, 131). Radiologically, ground-glass opacity was superimposed on the underlying reticular abnormalities. Preexisting histological patterns included three usual interstitial pneumonia (UIP) and two non-specific interstitial pneumonia (NSIP). Five (83.3%) of six patients died of respiratory failure despite intensive therapy. Univariate Cox's proportional hazards analysis showed that age and RA diagnosis were significantly associated with AE. Multivariate Cox's proportional hazards analysis indicated that age was an independent significant factor predicting AE. Conclusions These data suggest that AE can occur in CVD-IP, and this condition is closely similar to that of IPF with poor prognosis. AE is most common in RA, and associated with higher ages.


title: Genetic, antigenic, and pathogenic characteristics of avian infectious bronchitis viruses genotypically related to 793/B in China

text: Abstract In this study, 20 infectious bronchitis virus (IBV) strains, which were genotypically related to 793/B, as assessed by an S1 gene comparison and a complete genomic sequence analysis, were isolated and identified from 2009 to 2014 in China. Phylogenetic analysis, network tree, similarity plot analysis, Recombination Detection Program 4(RDP4) and sequence comparison revealed that 12 of the 20 isolates were likely the reisolated vaccine virus. One isolate, ck/CH/LSD/110857, was shown to have originated from recombination events between H120- and 4/91-like vaccine strains that did not result in changes of antigenicity and pathogenicity. The remaining seven IBV isolates were shown to have originated from recombination events between a 4/91-like vaccine strain and a GX-LY9-like virus, which were responsible for the emergence of a novel serotype. A vaccination-challenge test found that vaccination with the 4/91 vaccine strain did not provide protection against challenge with the recombinant viruses. In addition, the results showed that the recombination events between the vaccine and field strains resulted in altered genetics, serotype, antigenicity, and pathogenicity compared with those of their deduced parental viruses. The results are important not only because this virus is of economic importance to poultry industry, but also because it is important for elucidating the origin and evolution of other coronaviruses.


title: Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

text: Abstract Objective The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n =29, 27.4%), with unilateral or bilateral consolidation (n =50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p <0.01, χ 2 test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S-OIV (H1N1).


title: Bioexclusion of diseases from dairy and beef farms: Risks of introducing infectious agents and risk reduction strategies

text: Abstract Infectious disease represents a major threat to the productivity and welfare of cattle herds throughout the world. The introduction of infectious agents into dairy and beef farms may be through direct transmission (purchased cattle, reintroduced resident cattle and contact with contiguous cattle) or indirect transmission (fomites, visitors, other species, and biological materials) and this article reviews the evidence supporting these transmission routes. In the absence of eradication programmes for many endemic infectious diseases, bioexclusion is the key management process for risk reduction. Various ameliorative bioexclusion strategies have been recommended and the evidence supporting these protocols is considered.


title: Chapter 9 Rabies Virus as a Research Tool and Viral Vaccine Vector

text: Abstract Until recently, single-stranded negative sense RNA viruses (ssNSVs) were one of only a few important human viral pathogens, which could not be created from cDNA. The inability to manipulate their genomes hindered their detailed genetic analysis. A key paper from Conzelmann's laboratory in 1994 changed this with the publication of a method to recover rabies virus (RABV) from cDNA. This discovery not only dramatically changed the broader field of ssNSV biology but also opened a whole new avenue for studying RABV pathogenicity, developing novel RABV vaccines as well a new generation of RABV-based vaccine vectors, and creating research tools important in neuroscience such as neuronal tracing.


title: Structural Factors of the Middle East Respiratory Syndrome Coronavirus Outbreak as a Public Health Crisis in Korea and Future Response Strategies

text: The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak has originated from a failure in the national quarantine system in the Republic of Korea as most basic role of protecting the safety and lives of its citizens. Furthermore, a number of the Korean healthcare system’s weaknesses seem to have been completely exposed. The MERS-CoV outbreak can be considered a typical public health crisis in that the public was not only greatly terrorized by the actual fear of the disease, but also experienced a great impact to their daily lives, all in a short period of time. Preparedness for and an appropriate response to a public health crisis require comprehensive systematic public healthcare measures to address risks comprehensively with an all-hazards approach. Consequently, discussion regarding establishment of post-MERS-CoV improvement measures must focus on the total reform of the national quarantine system and strengthening of the public health infrastructure. In addition, the Korea Centers for Disease Control and Prevention must implement specific strategies of action including taking on the role of “control tower” in a public health emergency, training of Field Epidemic Intelligence Service officers, establishment of collaborative governance between central and local governments for infection prevention and control, strengthening the roles and capabilities of community-based public hospitals, and development of nationwide crisis communication methods.


title: Emerging and Zoonotic Infections in Women

text: Emerging infections, many of them zoonotic, are caused by a wide variety of pathogens with global distribution. Their impact on women is similarly diverse. Pathogens that were previously rare are emerging in recent years to cause disease in new populations, and global travel facilitates their rapid spread across continents. Finally, human encroachment on previously remote areas has brought people into contact with zoonotic diseases and vectors never before characterized. Although systematic study of rare outbreaks can be challenging, our knowledge of emerging pathogens and their differential effects on women, including those who are pregnant, has started to accumulate. We discuss the effects on women of lymphocytic choriomeningitis virus, West Nile virus, SARS coronavirus, avian influenza A (H5N1), virus, and the viral hemorrhagic fevers. We also explore the spirochetal illnesses and Chagas disease as they pertain to the pregnant patient. Finally, we review the potential impact of candidate bioterror agents on the female population, and address related issues of prophylaxis and therapy.


title: An extended outbreak of infectious peritonitis in a closed colony of european wildcats (Felis silvestris)

text: Summary Feline infectious peritonitis is a multisystemic disease of domestic and exotic cats caused by a coronavirus. An outbreak of feline infectious peritonitis was investigated in a closed colony of European wildcats (Felis silvestris) at a zoological garden. Over a six-year period, a putative fading kitten syndrome occurred in six of 11 litters born and severe lesions of infectious peritonitis occurred in five of the eight wildcats retained in the colony during this period. Lesions were more acute in the early stages of the outbreak and included perivascular pyogranulomatous inflammation with exudative serositis. Lesions occurred only in males. Vascular lesions were common in the liver of all affected wildcats, serositis occurred in the abdominal and thoracic cavities in most cases and meningeal lesions were present in two cases. Immunohistochemistry with specific antisera detected viral antigen within macrophages in all lesions. This outbreak demonstrates that the lesions of feline infectious peritonitis can become modified over time and that the virus can persist in a closed colony, possibly via carrier wildcats.


title: Natural and artificial hyperimmune solutions: Impact on health in puppies

text: Colostrum and milk are complex mammary secretions providing the puppy with many nutritional and immunological factors, which play a crucial role for its correct development and survival. In the case of colostrum and/or milk intake deficiency, puppies are at increased risk of infectious diseases. This work reviews the various nutritional hyperimmune supplementations proposed to provide a passive immune protection and to positively impact puppies’ health. Some strategies rely on canine immunoglobulins: canine colostrum banking and canine serum/plasma supplementation. Others involve heterologous sources of antibodies and other immune factors: bovine colostrum or hyperimmune egg powder. Among the different solutions evaluated from birth to weaning, canine plasma and hyperimmune egg powder showed promising beneficial effect on puppies’ health. Canine plasma seems to positively impact not only growth (increased growth during the neonatal period), but also digestive health (higher species richness of intestinal microbiota) and the general health (tendency of lower morbidity). Puppies supplemented with hyperimmune egg powder presented increased neonatal growth and decreased risk of canine parvovirus infection. Nevertheless, natural canine maternal colostrum and milk ingestion remains the optimal guarantee for puppies’ health and survival, as a source of immunity, energy and growth factors.


title: Infecciones neonatales (II)

text: Resumen Las infecciones neonatales son un problema de salud pública mundial. Su incidencia se aproxima al 1 % de los nacimientos en los países industrializados, pero es más elevada en los países en desarrollo. En 1996, las infecciones aparecidas en el primer mes de vida eran responsables de cinco millones de fallecimientos anuales. Casi todos los microorganismos patógenos (bacterias, hongos y virus) pueden ser causantes de infecciones en el recién nacido. La epidemiología bacteriana varía según las épocas, los países e incluso las regiones, lo que impide extrapolar las propuestas terapéuticas formuladas a partir de la expenencia de un centro, tanto en lo que se refiere a los protocolos curativos como a los preventivos.


title: Coronavirus disease 2019: initial chest CT findings

text: OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20–91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4–7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: • Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. • The halo sign may be a special CT feature in the early-stage COVID-19 patients. • Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.


title: Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?

text: Abstract SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.


title: Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays

text: BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.


title: Emerging Trends in Clinical Tropical Medicine Research

text: The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.


title: Transport and deposition of hygroscopic particles in asthmatic subjects with and without airway narrowing

text: Abstract This study numerically investigates the effect of hygroscopicity on transport and deposition of particles in severe asthmatic lungs with distinct airway structures. The study human subjects were selected from two imaging-based severe asthmatic clusters with one characterized by non-constricted airways and the other by constricted airways in the lower left lobe (LLL). We compared the deposition fractions of sodium chloride (NaCl) particles with a range of aerodynamic diameters (1–8 μm) in cluster archetypes under conditions with and without hygroscopic growth. The temperature and water vapor distributions in the airways were simulated with an airway wall boundary condition that accounts for variable temperature and water vapor evaporation at the interface between the lumen and the airway surface liquid layer. On average, the deposition fraction increased by about 6% due to hygroscopic particle growth in the cluster subjects with constricted airways, while it increased by only about 0.5% in those with non-constricted airways. The effect of particle growth was most significant for particles with an initial diameter of 2 μm in the cluster subjects with constricted airways. The effect diminished with increasing particle size, especially for particles with an initial diameter larger than 4 μm. This suggests the necessity to differentiate asthmatic subjects by cluster in engineering the aerosol size for tailored treatment. Specifically, the treatment of severe asthmatic subjects who have constricted airways with inhalation aerosols may need submicron-sized hygroscopic particles to compensate for particle growth, if one targets for delivering to the peripheral region. These results could potentially inform the choice of particle size for inhalational drug delivery in a cluster-specific manner.


title: Point‐of‐care diagnostic assay for rapid detection of porcine deltacoronavirus using the recombinase polymerase amplification method

text: Porcine deltacoronavirus (PDCoV) has emerged and spread throughout the porcine industry in many countries over the last 6 years. PDCoV caused watery diarrhoea, vomiting and dehydration in newborn piglets. A sensitive diagnostic method would be beneficial to the prevention and control of PDCoV infection. Recombinase polymerase amplification (RPA) is an isothermal amplification method which has been widely used for virus detection. A probe‐based reverse transcription RPA (RT‐RPA) assay was developed for real‐time detection of PDCoV. The amplification can be finished in 20 min and fluorescence monitoring was performed by a portable device. The lowest detection limit of the PDCoV RT‐RPA assay was 100 copies of RNA molecules per reaction; moreover, the RT‐RPA assay had no cross‐reaction with other common swine viruses. The clinical performance of the RT‐RPA assay was evaluated using 108 clinical samples (54 intestine specimens and 54 faecal swab specimens). The coincidence rate of the detection results for clinical samples between RT‐RPA and RT‐qPCR was 97.2%. In summary, the real‐time RT‐RPA assay offers a promising alternative to RT‐qPCR for point‐of‐care detection of PDCoV.


title: Role of CD151, A tetraspanin, in porcine reproductive and respiratory syndrome virus infection

text: BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus causing respiratory and reproductive diseases in swine. The susceptibility for PRRSV varies between the different breeds of swine. In cell culture, PRRSV virus can be propagated in primary porcine alveolar macrophages and some African green monkey kidney cell lines, such as MARC-145 cells. Previous studies have shown that 3' untranslated region (UTR) RNAs of the arteriviruses play an important role in the replication of the virus through interactions with cellular proteins. To better understand the differences in the replication capability of PRRSV in different cell lines, we sought to identify the host cellular proteins interacting with PRRSV 3' UTR RNA. We constructed a cDNA library of MARC-145 cell line in lambda ZAP Express vector and screened the library with the positive sense 3' UTR RNA of PRRSV. RESULTS: We found that CD151, a host cellular protein, interacting with PRRSV 3' UTR RNA. The specificity of the interaction between CD151 and PRRSV 3' UTR RNA was examined by gel shift assay as well as North-Western hybridization. The transfection of CD151 expression clone into BHK-21 rendered these cells susceptible to PRRSV infection, and the transfection of siRNA against CD151 into MARC-145 significantly reduced the level of PRRSV infection. Also, anti-CD151 antibody treatment to MARC-145 completely blocked PRRSV infection. CONCLUSION: Based on our results, we suggest that CD151 should cooperate in PRRSV infection in vitro in MARC-145 and BHK-21 cells.


title: Follow-up of the health conditions of an urban colony of free-roaming cats (Felis catus Linnaeus, 1758) in the city of Rio de Janeiro, Brazil

text: Abstract Similar to other urban areas where food and shelter are abundant, the zoological garden of Rio de Janeiro has dealt for years with a colony of feral or semi-feral domestic cats. A survey was conducted during 2002–2004 as a follow-up to a previous study in 2001 of the cat colony to identify pathogens circulating among the population and to annually follow the status of the cats to analyze morbidity coefficients and associations among infections and infestations identified in the colony. During the 3 years of the present study, 75 cats were sampled at least once, including 44 that were caught and examined only once, 14 that were examined twice, and 17 that were examined three times. For each cat that was caught, records were kept regarding sex, age, general health, and the presence of ectoparasites. Each year, a blood sample was taken for hematologic testing, platelet count, hemoparasite detection, antibodies to Toxoplasma gondii, and retrovirus detection. Blood counts were within normal range for the majority of cats tested. Feline immunodeficiency virus, fleas, and lice were detected in all years; however, incidence rates for each of these varied significantly throughout the years. Prevalence of Cytauxzoon spp., Mycoplasma spp., T. gondii infections were variable among the 3 years, although differences were not significant. Prevalence of feline leukemia virus increased significantly over the 3 years. Mycoplasma spp. and flea infestations were significantly associated, but no other associations among the pathogens were detected. Over the 3 years, the rate of new cat introductions decreased, and the pathogens showed a tendency to disseminate throughout the colony; however, there was virtually no evidence of clinically detectable disease. Therefore, it seems that stabilizing the population by a judicious control program facilitated the distribution of the pathogens throughout the colony, while the general well-being of the cats was not seriously affected.


title: Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

text: The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.


title: Development of a Rapid Automated Influenza A, Influenza B, and Respiratory Syncytial Virus A/B Multiplex Real-Time RT-PCR Assay and Its Use during the 2009 H1N1 Swine-Origin Influenza Virus Epidemic in Milwaukee, Wisconsin

text: Rapid, semiautomated, and fully automated multiplex real-time RT-PCR assays were developed and validated for the detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV) from nasopharyngeal specimens. The assays can detect human H1N1, H3N2, and swine-origin (S-OIV) H1N1 Flu A viruses and were effectively used to distinguish Flu A infections (of all subtypes) from Flu B and RSV infections during the current S-OIV outbreak in Milwaukee, WI. The analytical limits of detection were 10(−2) to 10(1) TCID(50)/ml depending on the platform and analyte and showed only one minor cross-reaction among 23 common respiratory pathogens (intermittent cross-reaction to adenovirus at >10(7) TCID(50)/ml). A total of 100 clinical samples were tested by tissue culture, both automated assays, and the US Food and Drug Administration-approved ProFlu+ assay. Both the semiautomated and fully automated assays exhibited greater overall (Flu A, Flu B, and RSV combined) clinical sensitivities (93 and 96%, respectively) and individual Flu A sensitivities (100%) than the Food and Drug Administration-approved test (89% overall sensitivity and 93% Flu A sensitivity). All assays were 99% specific. During the S-OIV outbreak in Milwaukee, WI, the fully automated assay was used to test 1232 samples in 2 weeks. Flu A was detected in 134 clinical samples (126 H1N1 S-OIV, 5 H1N1 [human], and 1 untyped) with 100% positive agreement compared with other “in-house” validated molecular assays, with only 2 false-positive results. Such accurate testing using automated high-throughput molecule systems should allow clinicians and public health officials to react quickly and effectively during viral outbreaks.


COVID-19 and the Air We Breathe


title: Various computed tomography findings of 2009 H1N1 influenza in 17 patients with relatively mild illness

text: PURPOSE: We retrospectively analyzed the computed tomography (CT) findings of H1N1 virus infection in 17 patients with relatively mild illness. MATERIALS AND METHODS: From September 2009 to January 2010, a total of 17 patients with confirmed H1N1 infection were included in the study (mean age 30.7 years). All patients were managed as outpatients or required short hospitalization without ventilation assistance. The CT scans were assessed for the presence of nodules, ground glass opacity (GGO), consolidation, bronchial wall thickening, reticulation, effusion, and lymph node enlargement. Location and distribution were evaluated. RESULTS: The most frequent manifestation was a mixture of nodules, consolidation, and GGO (5/17, 29.4%). In one case there was a focal area of bronchiolitis (centrilobular nodules with tree-in-bud appearance), and 10 of 17 cases (58.8%) showed bronchial wall thickening (findings of bronchitis/peribronchitis) and/or other abnormalities. In 16 of the 17 cases (94.1%) there were CT abnormalities with bilateral and random distribution without zonal predominance. Pleural effusions were seen in eight cases (47.1%). CONCLUSION: In contrast to several reports so far, CT findings of H1N1 virus infection in patients with mild illness are variable, including suggestive findings of inflammation involving large and/or small airways. This study showed various CT findings overlapping with other viral, atypical, or bacterial pneumonia and even cryptogenic organizing pneumonia.


title: ‘Healthcare Heroes’: problems with media focus on heroism from healthcare workers during the COVID-19 pandemic

text: During the COVID-19 pandemic, the media have repeatedly praised healthcare workers for their ‘heroic’ work. Although this gratitude is undoubtedly appreciated by many, we must be cautious about overuse of the term ‘hero’ in such discussions. The challenges currently faced by healthcare workers are substantially greater than those encountered in their normal work, and it is understandable that the language of heroism has been evoked to praise them for their actions. Yet such language can have potentially negative consequences. Here, I examine what heroism is and why it is being applied to the healthcare workers currently, before outlining some of the problems associated with the heroism narrative currently being employed by the media. Healthcare workers have a clear and limited duty to treat during the COVID-19 pandemic, which can be grounded in a broad social contract and is strongly associated with certain reciprocal duties that society has towards healthcare workers. I argue that the heroism narrative can be damaging, as it stifles meaningful discussion about what the limits of this duty to treat are. It fails to acknowledge the importance of reciprocity, and through its implication that all healthcare workers have to be heroic, it can have negative psychological effects on workers themselves. I conclude that rather than invoking the language of heroism to praise healthcare workers, we should examine, as a society, what duties healthcare workers have to work in this pandemic, and how we can support them in fulfilling these.


title: Silencing Viral Infection

text: The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.


title: Inhibition of SARS-CoV-2 main protease 3CL(pro) by means of α-ketoamide and pyridone-containing pharmaceuticals using in silico molecular docking

text: The coronavirus disease infections (COVID-19) caused by a new type of coronavirus (SARS-CoV-2) have been emerging in the entire world. Therefore, it is necessary to find out potential therapeutic pharmaceuticals for this disease. This study investigates the inhibitory effect of the 3-chymotrypsin-like protease of SARS-CoV-2 (3CL(pro)) using pharmaceuticals containing α-ketoamide group and pyridone ring based on molecular docking. Of these, eight pharmaceuticals approved by US-Food and Drug Administration have shown good contact with the catalytic residues of 3CL(pro). They are telaprevir, temsirolimus, pimecrolimus, aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide. Their binding affinity score ranged from -5.6 to -7.4 kcal/mol. Hydrogen bonds were observed and reported. To the knowledge, this study report for the first time a compound that could be binding to ALA(285), the new residue resulting from genetic modification of 3CL(pro) of SARS-CoV-2 that has increased its catalytic activity 3.6-fold compared with its predecessor 3CL(pro) of SARS-CoV. It is recommended that telaprevir, and pyridone-containing pharmaceuticals including aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide be repurposed for COVID-19 treatment after suitable validation and clinical trials.


title: Care of the Pregnant Woman with COVID-19 in Labor and Delivery: Anesthesia, Emergency cesarean delivery, Differential diagnosis in the acutely ill parturient, Care of the newborn, and Protection of the healthcare personnel

text: COVID-19 in pregnancy can cause severe maternal morbidity in up to 9% of affected gravidae. Chest imaging is helpful in pregnant women who have a high pretest probability of COVID-19, but are RT-PCR negative. Vertical transmission is unlikely, but active measures are needed to prevent neonatal infection. We present an algorithm of care for the acutely ill parturient. We present a protocol for intrapartum care of the pregnant woman in labor.


Vaccination schedule for infants and COVID-19


title: Morbidity and Mortality Associated With Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplant: Too Little Defense or Harmful Immunity?

text: The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.


title: Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits

text: Abstract Steroid-associated osteonecrosis (SAON) may lead to joint collapse and subsequent joint replacement. Poly lactic-co-glycolic acid/tricalcium phosphate (P/T) scaffold providing sustained release of icaritin (a metabolite of Epimedium-derived flavonoids) was investigated as a bone defect filler after surgical core-decompression (CD) to prevent femoral head collapse in a bipedal SAON animal model using emu (a large flightless bird). The underlying mechanism on SAON was evaluated using a well-established quadrupedal rabbit model. Fifteen emus were established with SAON, and CD was performed along the femoral neck for the efficacy study. In this CD bone defect, a P/T scaffold with icaritin (P/T/I group) or without icaritin (P/T group) was implanted while no scaffold implantation was used as a control. For the mechanistic study in rabbits, the effects of icaritin and composite scaffolds on bone mesenchymal stem cells (BMSCs) recruitment, osteogenesis, and anti-adipogenesis were evaluated. Our efficacy study showed that P/T/I group had the significantly lowest incidence of femoral head collapse, better preserved cartilage and mechanical properties supported by more new bone formation within the bone tunnel. For the mechanistic study, our in vitro tests suggested that icaritin enhanced the expression of osteogenesis related genes COL1α, osteocalcin, RUNX2, and BMP-2 while inhibited adipogenesis related genes C/EBP-ß, PPAR-γ, and aP2 of rabbit BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in vitro and in vivo but a higher expression of migration related gene VCAM1 was only found in P/T/I group in vitro. In conclusion, both efficacy and mechanistic studies show the potential of a bioactive composite porous P/T scaffold incorporating icaritin to enhance bone defect repair after surgical CD and prevent femoral head collapse in a bipedal SAON emu model.


title: Survey of acute hospital infection control resources and services in the Republic of Ireland

text: Summary Following the development of national guidelines on the control of antimicrobial resistance in 2001, a survey was carried out in 2003 of all 68 acute hospitals in the Republic of Ireland on resources available and current practice to control and prevent nosocomial infection. Completed questionnaires were received from 66 hospitals (97%). The median number of acute inpatient beds per hospital was 156; this was 522 in regional/tertiary referral centres. Only 31 (47%) hospitals had on-site consultant microbiologist sessions, and there was an infection control nurse in 56 (85%) hospitals. Eighteen (29%) hospitals had an occupational health physician, and 48 (73%) hospitals had an infection control committee. There was a median of one isolation room for every 16 acute beds, and a median of five rooms with en-suite bathroom facilities per hospital in those hospitals that provided data. All hospitals had documented infection control policies, and these were available in electronic format in 25 (38%) hospitals. Fifty-five (83%) hospitals undertook surveillance of nosocomial infection, and alcohol-based hand hygiene facilities were available, either at a handwashing sink or at the entrance to a ward, in 57 (86%) hospitals. In the Republic of Ireland, there remains a significant shortage of microbiologists/infection control doctors, occupational health physicians and infection control nurses. Isolation facilities are also inadequate. Although there is much agreement internationally on the importance of nosocomial infection and the priorities for surveillance, there are no agreed basic minimum standards for the resources and facilities necessary to control and prevent nosocomial infection.


title: Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort

text: BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3–2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per μL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.


title: Determinants of translational fidelity and efficiency in vertebrate mRNAs

text: Abstract This article reviews current knowledge on the mechanisms affecting the fidelity of initiation codon selection, and discusses the effects of structural features in the 5′-non-coding region on the efficiency of translation of messenger RNA molecules.


title: Modelling the spreading rate of controlled communicable epidemics through an entropy-based thermodynamic model

text: A model based on a thermodynamic approach is proposed for predicting the dynamics of communicable epidemics in a city, when the epidemic is governed by controlling efforts of multiple scales so that an entropy is associated with the system. All the epidemic details are factored into a single parameter that is determined by maximizing the rate of entropy production. Despite the simplicity of the final model, it predicts the number of hospitalized cases with a reasonable accuracy, using the data of SARS of the year 2003, once the inflexion point characterizing the effect of multiple controlling efforts is known. This model is supposed to be of potential usefulness since epidemics such as avian influenza like H7H9 in China this year have the risk to become communicable among human beings.


title: Chapter 39 Viral Syndromes

text: Abstract The chapters in this textbook deal with those viruses causing human disease, and the various modes of replication, transmission, and disease-causing processes that contribute to a particular clinical presentation. This final chapter focuses on each of the major clinical syndromes and outlines the contribution of particular viruses to each one, thereby serving as a pointer to elsewhere among earlier chapters where more specific information can be found. These virus–disease associations have been presented in tabular form for ease of reference.


title: Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection

text: BACKGROUND: Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach. RESULTS: Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points. CONCLUSION: This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum.


The explosion in scabies cases during COVID‐19 pandemic


title: Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent

text: Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this review we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2.


Predicting severe outcomes in COVID-19


title: Japanese encephalitis virus: A multi-epitope loaded peptide vaccine formulation using reverse vaccinology approach

text: Abstract Japanese encephalitis (JE) is a serious leading health complication emerging expansively that has severely affected the survival rate of human beings. This fatal disease is caused by JE Virus (JEV). The current study was carried out for designing a multi-epitope loaded peptide vaccine to prevent JEV. Based on reverse vaccinology and in silico approaches, octapeptide B-cell and hexapeptide T-cell epitopes belonging to five proteins, viz. E, prM, NS1, NS3 and NS5 of JEV were determined. Hydrophilicity, antigenicity, immunogenicity and aliphatic amino acids of the epitopes were estimated. Further, the epitopes were analyzed for different physicochemical parameters, e.g. total net charges, amino acid composition and Boman index. Out of all the epitopes, a total of four T-cell epitopes namely KRADSS, KRSRRS, SKRSRR and KECPDE and one B-cell epitope i.e. PKPCSKGD were found to have potential for raising immunity in human against the pathogen. Taking into account the outcome of this study, the pharmaceutical industries could initiate efforts to combine the identified epitopes together with adjuvant or carrier protein to develop a multi-epitope-loaded peptide vaccine against JEV. The peptide vaccine, being cost effective, could be administered as a prophylactic measure and in JEV infected individuals to combat the spread of this virus in human population. However, prior to administration into human beings, the vaccine must pass through several clinical trials.


title: Surveillance and Preparedness for Ebola Virus Disease — New York City, 2014

text: In July 2014, as the Ebola virus disease (Ebola) epidemic expanded in Guinea, Liberia, and Sierra Leone, an air traveler brought Ebola to Nigeria and two American health care workers in West Africa were diagnosed with Ebola and later medically evacuated to a U.S. hospital. New York City (NYC) is a frequent port of entry for travelers from West Africa, a home to communities of West African immigrants who travel back to their home countries, and a home to health care workers who travel to West Africa to treat Ebola patients. Ongoing transmission of Ebolavirus in West Africa could result in an infected person arriving in NYC. The announcement on September 30 of an Ebola case diagnosed in Texas in a person who had recently arrived from an Ebola-affected country further reinforced the need in NYC for local preparedness for Ebola.


title: Regional localization of virus in the central nervous system of mice persistently infected with murine coronavirus JHM

text: Abstract Suckling C57BU6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop either a fatal acute encephalomyelitis or a late onset demyelinating disease, depending on whether they are nursed by unimmunized or immunized dams. To determine the localization of virus-specific RNA, serial sections of brains from infected and uninfected mice were annealed with a 35S-labeled antisense RNA probe and analyzed by film autoradiography. In the mice with acute encephalomyelitis, viral RNA was present in the mesencephalon, hypothalamus, hippocampus, basal ganglia, subcortical white matter, and thalamus. Viral RNA was detected in the spinal cords of all mice with the late onset, demyelinating encephalomyelitis, but was distributed into three different patterns in the brains of these mice, even though all had the same clinical disease. In the first group, viral RNA was detected only in the brainstem. In the second group, viral RNA was detected in the brainstem, thalamus, and cerebral grey matter. This distribution was consistent with viral spread along well-defined tracts connecting these parts of the brain. In the third group, viral RNA could be detected both in the brainstem and in several white matter tracts within close physical proximity to the optic chiasm. This distribution was consistent with viral spread by an extracellular route from one white matter tract to other tracts which were physically close, but which were not part of the same pathways. These results suggest that MHV-JHM spreads through the central nervous system both along well-defined neuronal pathways and by spread from contiguous structures, but also suggest that viral replicates preferentially in a limited number of areas of the brain. The technique of in situ hybridization with film autoradiography should be generally useful for analyzing macroscopic movements of virus within infected organs.


title: 8 Electrospinning and microfluidics An integrated approach for tissue engineering and cancer

text: Abstract Progress in microfluidic technology has enabled precise manipulation of small volumes of fluids, leading to the development of low-cost and portable systems that have shown considerable promise in biomedicine. Although these functional devices have gained a great deal of attention over the past decades, a new fascinating trend concerns the integration of microfluidics with other fabrication techniques, with particular regard to electrospinning and additive manufacturing.In this chapter, the attention will be focused on integrative approaches obtained combining microfluidics and electrospinning, highlighting the recent advances and challenges in the tissue-engineering framework. Indeed, although this innovative trend is still at its beginning, significant results have been achieved both in the microfluidic-aided fabrication of novel microstructured materials and in the development of new biosensors and analytical devices for point-of-care diagnostics.


“The Art of War” in the Era of Coronavirus Disease 2019 (COVID-19)


title: Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study

text: BACKGROUND: The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. METHODS: After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996–March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. RESULTS: Since receiving marketing authorization (February 21, 1996), ∼647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ∼31 000) is in line with the incidence observed with other four-factor PCCs. CONCLUSIONS: In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.


title: Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay

text: We report the discovery of a series of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N′-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC(50) value of 0.24 μM in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N′-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.056 μM in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC(50) values of 0.17, 0.088 and 0.14 μM in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization.


title: Airflow and droplet spreading around oxygen masks: A simulation model for infection control research

text: BACKGROUND: Respiratory assist devices, such as oxygen masks, may enhance the potential to spread infectious aerosols from patients with respiratory infections. METHODS: A technique was developed to visualize exhaled aerosols during simulated patients' use of oxygen masks in a health care setting and tested using the simple, the nonrebreathing, and the Venturi oxygen masks. A smoke tracer was introduced into one of the lungs of the model to enable it to mix with the incoming oxygen and then to be further inhaled/exhaled by the model according to a variety of realistic respiratory settings (14, 24, and 30 breaths per minute, with tidal volumes of 500, 330, 235 mL, respectively) and oxygen supply flow rates (between 6 and 15 liters per minute). Digital recordings of these exhaled airflow patterns allowed approximate distances to be estimated for the extent of the visible exhaled air plumes emitted from each oxygen mask type at these settings. RESULTS: It was found that the simple, the nonrebreathing, and the Venturi-type oxygen masks produced exhaled smoke plumes over minimum distances of 0.08 to 0.21 m, 0.23 to 0.36 m, and 0.26 to 0.40 m, respectively. CONCLUSION: Health care workers may therefore consider any area within at least 0.4 m of a patient using such oxygen masks to be a potential nosocomial hazard zone.


title: Coronaviruses: General Features

text: Coronaviruses have the largest known RNA genomes (∼30kb), which are of positive sense. Together with toroviruses, they are classified in the family Coronaviridae, order Nidovirales. All coronaviruses have four common proteins, three in the envelope and one associated with the genome. Assembly of virus particles occurs at internal membranes. The genes for the structural proteins are at the 3′ end of the genome. Most of the genome (∼20kb) is gene 1, which encodes 15–16 proteins associated with RNA replication and transcription. Translation of gene 1 involves ribosomal frameshifting. Transcription is by a discontinuous process which results in a 3′ co-terminal nested set of mRNAs, each of which has a common leader sequence transcribed from the 5′ terminus of the genome. Only the most 5′-proximal gene of each mRNA is translated. Recombination is a feature of coronavirus evolution. The outbreak of severe acute respiratory syndrome (SARS) has resulted in the discovery of more coronaviruses in humans, other mammals, and avian species, and the realization that the host range of coronaviruses is wider than previously acknowledged. Coronaviruses are associated with a wide range of diseases, including the respiratory and enteric systems, though not necessarily restricted to these, for example, some coronaviruses affect the central nervous system, kidneys, and gonads. The most widely used coronavirus vaccine (billions of doses annually) is against infectious bronchitis virus, which affects chickens.


title: Pathology of the thyroid in severe acute respiratory syndrome

text: Summary The severe acute respiratory syndrome (SARS) epidemic started in November 2002 and spread worldwide. The pathological changes in several human organs of patients with SARS have been extensively described. However, to date, little has been reported about the effects of this infection on the thyroid gland. Femoral head necrosis and low serum triiodothyronine and thyroxine levels, commonly found in patients with SARS, raise the possibility of thyroid dysfunction. We have undertaken this study to evaluate for any potential injury to the thyroid gland caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay was performed to identify apoptotic cells. The follicular epithelium was found to be damaged with large numbers of cells exfoliated into the follicle. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay demonstrated many cells undergoing apoptosis. Follicular architecture was altered and showed distortion, dilatation, and collapse. No distinct calcitonin-positive cells were detectable in the SARS thyroids. In conclusion, both parafollicular and follicular cells were injured. This may provide an explanation both for low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients with SARS. Apoptosis may play a role in the pathogenesis of SARS associated coronavirus infection in the thyroid gland.


title: Effects of environmental disinfection on the isolation of vancomycin-resistant Enterococcus after a hospital-associated outbreak of Middle East respiratory syndrome

text: Environmental disinfection with sodium hypochlorite and hydrogen peroxide vapor was performed after a hospital-associated outbreak of Middle East respiratory syndrome. Although only 11% of total beds were disinfected, the isolation and vancomycin-resistance rates of Enterococcus spp significantly decreased for 2 months, whereas other multidrug-resistant organisms did not.


title: Virogenomics: the virus–host interaction revisited

text: Genomics tools allow us to assess gene expression ‘genome wide’ providing an unprecedented view on the host-side of the virus–host interaction. The success of the application of these tools crucially depends on our ability to reduce the total information load while increasing the information density of the data collected. In addition to the advanced data analysis algorithms, gene annotation-pathway databases, and theoretical models, specifically designed sets of complementary experiments are crucial in translating the collected genomics data into palatable knowledge. A better understanding of the molecular basis of virus–host interactions will support the rational design of improved and novel intervention strategies for viral infections.


Heart Rhythm Society Expert Consensus Statement on Electrophysiology Laboratory Standards: Process, Protocols, Equipment, Personnel, and Safety


title: Enigmatic Histamine Receptor H(4) for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases

text: The histamine H(4) receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H(4)R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H(4)R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H(4)R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.


title: Contributions of Farm Animals to Immunology

text: By their very nature, great advances in immunology are usually underpinned by experiments carried out in animal models and inbred lines of mice. Also, their corresponding knock-out or knock-in derivatives have been the most commonly used animal systems in immunological studies. With much credit to their usefulness, laboratory mice will never provide all the answers to fully understand immunological processes. Large animal models offer unique biological and experimental advantages that have been and continue to be of great value to the understanding of biological and immunological processes. From the identification of B cells to the realization that γδ T cells can function as professional antigen presenting cells, farm animals have contributed significantly to a better understanding of immunity.


title: Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013

text: AIM: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa. METHODS: The study included 680 South African patients randomly selected in age‐defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real‐time polymerase chain reaction assay was used to detect hBoV; hCoV‐OC43, hCoV‐229E, hCoV‐NL63, and hCoV‐HKU1; and Washington University hPyV (hPyV‐WU) and Karolinska Insitute hPyV (hPyV‐KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real‐time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B. RESULTS: Human bocavirus, hCoV‐229E, and hPyV‐WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%‐60.7%), followed by adenovirus (21.4%‐39.3%), and respiratory syncytial virus (10.7%‐24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680). CONCLUSION: Inclusion of laboratory tests for hBoV, hCoV‐229E, and hPyV‐WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons.


Global Health Security Alliance (GloHSA)


title: 4 Smart durable and self-healing textile coatings

text: Abstract The durability of textiles can be endangered in different ways. Various treatments are used to protect textiles against degradation or damage or even to restore or repair the initial properties. Other technologies are still under investigation. In this chapter an overview is presented of the work done in our laboratory in the area of smart coatings protecting textiles.


Nuevo coronavirus (2019-nCov): ¿tiene suficientes unidades de cuidados intensivos?


title: Feline gut microbiota composition in association with feline coronavirus infection: A pilot study

text: Abstract Feline coronaviruses (FCoV) colonize the intestinal tract, however, due to not fully understood mutations, they can spread systemically and cause feline infectious peritonitis (FIP). Recent studies on human medicine report that gut microbiota is involved in the development of systemic disorders and could influence the immune response to viral diseases. The aim of this study was to provide preliminary data on the fecal microbiota composition in healthy cats compared to FCoV-infected cats, with and without FIP. Cats were equally grouped as healthy FCoV-negative, healthy FCoV-positive or FIP affected (total n = 15). Fecal sample were evaluated for the microbiota composition. A total of 3,231,916 sequences were analyzed. The samples' alpha-diversity curves did not reach a proper plateau and, for the beta-diversity, the samples seemed not to group perfectly by category, even if the healthy FCoV-positive group showed a hybrid microbial composition between FCoV-negative and FIP groups. Although there were no taxa significantly linked to the different conditions, some peculiar patterns were recognized: Firmicutes was always the most represented phylum, followed by Bacteroidetes and Actinobacteria. In FCoV-positive cats, the Firmicutes and Bacteroidetes were respectively over- and under-represented, compared to the other groups. Among FIP cats, three subjects shared a similar microbiome, one cat showed a different microbial profile and the other one had the lowest number of diverse phyla. Despite the limited number of animals, some differences in the fecal microbiome between the groups were observed, suggesting to further investigate the possible correlation between gut microbiota and FCoV infection in cats.


title: A possible link between recurrent upper respiratory tract infections and lower cytokine production in patients with Q fever fatigue syndrome

text: Besides fatigue, many Q fever fatigue syndrome (QFS) patients also complain of frequently recurring upper respiratory tract infections with severe symptoms. We investigated whether immunologic dysregulation contributes to these complaints. Cytokine and chemokine production was measured after stimulating monocytes of QFS patients and age‐ and sex‐matched healthy controls with LPS and several viral ligands. The H3K4me3 mark of open chromatin was measured at the promoter regions of cytokines and chemokines that differed significantly from healthy controls. Monocytes of QFS patients produced significantly less TNF‐α (p = 0.032), IL‐1β (0.004, 0.024, and 0.008), IL‐6 (0.043), RANTES (0.033), IP‐10 (0.049), MCP‐1 (0.022), IL‐ 13 (0.029), and IL‐10 (0.026) than healthy controls when stimulated with various ligands. H3K4me3 expression was significantly lower in QFS patients than in healthy controls on the promoter regions of IL‐1β (p = 0.004), MCP‐1 (<0.001 and <0.001), IP‐10 (<0.001), IL‐10 (0.041), and IL‐13 (<0.001, <0.001, and 0.001). QFS patients showed diminished cytokine responses to various stimuli compared to age‐ and sex‐matched healthy controls, likely due to epigenetic remodeling and long‐term memory as a result from the acute Q fever infection. This might explain the upper respiratory tract ailments in QFS.


title: Antivirales (a excepción del VIH y la hepatitis)

text: Los antivirales son en la actualidad un sector esencial de la farmacopea antiinfecciosa. Incluso si no se tienen en cuenta los antirretrovirales y los antivirales dirigidos contra los virus de la hepatitis B y C, que constituyen una parte muy importante, existen varias moléculas que se utilizan en la práctica clínica que permiten luchar eficazmente contra las infecciones por virus herpes, adenovirus, poxvirus, virus del papiloma y virus de la gripe. La mayoría de estas moléculas se dirigen contra las enzimas virales implicadas en la replicación de los genomas virales. La mayoría de los análogos nucleosídicos (de los que el arquetipo es el aciclovir) y los análogos nucleotídicos (cuyo arquetipo es el cidofovir) requieren una fosforilación previa para inhibir, por un mecanismo de competición y, en ocasiones de terminación, la actividad de una polimerasa de ADN (ácido desoxirribonucleico). El foscarnet, análogo de pirofosfato, ejerce esta inhibición directamente sin modificación. En la actualidad, se dispone de menos antivirales para los virus ARN (ácido ribonucleico) que para los de ADN, aunque los inhibidores de la neuraminidasa han demostrado su eficacia contra los virus de la gripe. La especificidad de los antivirales suele ser estrecha, limitada por lo general para cada molécula a unos pocos virus relacionados. Las otras limitaciones del uso actual de los antivirales son la imposibilidad de erradicar las infecciones virales latentes, la aparición de resistencia, los efectos indeseables relacionados en gran parte con la toxicidad celular relativa de las moléculas y su coste. Se esperan avances tanto en la eficacia de los antivirales como en su tolerabilidad clínica y el número de las enfermedades virales tratadas. Es esencial que las exigencias económicas no restrinjan la dinámica de uno de los ámbitos más innovadores de la medicina contemporánea.