title: Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23

text: Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1.


title: Association of Increased Bcl‐2 Expression with Rescue from Tumor Necrosis Factor‐α‐Induced Cell Death in the Oligodendrocyte Cell Line OLN‐93

text: Abstract: The present study investigated the effects of flupirtine(Katadolon) on tumor necrosis factor (TNF)‐α‐mediated cell death andBcl‐2 expression in the permanent rat oligodendrocyte cell line OLN‐93 (OLNcells). TNF‐α (500 U/ml) induced apoptosis of OLN cells, which wasconfirmed by DNA fragmentation using an in situ end‐labeling technique andultrastructural analysis. Flupirtine significantly reduced the rate ofspontaneous cell death of OLN cells already at low concentrations;TNF‐α‐mediated apoptosis was suppressed only with higher concentrationsof flupirtine (100 μM). Expression of Bcl‐2 protein and mRNA inOLN cells was detected by immunocytochemistry, western blot, and RT‐PCR.Quantitative analysis of western blots revealed an ∼2.5‐fold up‐regulationof Bcl‐2 protein during TNF‐α treatment. Furthermore, addition of 10 or100 μM flupirtine before incubation with TNF‐α led to anapproximately threefold increase of Bcl‐2 expression. Exposure of OLN cells toflupirtine alone moderately augmented the expression of Bcl‐2 protein. Ourdata demonstrate that flupirtine up‐regulates the expression of Bcl‐2 proteinin OLN cells; this Bcl‐2 induction is associated with a reduced rate ofTNF‐α‐induced cell death.


title: Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection

text: Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.


title: A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis

text: The multi-omic integration of microbiota data with metabolomics has gained popularity. This protocol is based on a human multi-omics study, integrating cervicovaginal microbiota, HPV status and neoplasia, with urinary metabolites. Indeed, to understand the biology of the infections and to develop adequate interventions for cervical cancer prevention, studies are needed to characterize in detail the cervical microbiota and understand the systemic metabolome. This article is a detailed protocol for the multi-omic integration of cervical microbiota and urine metabolome to shed light on the systemic effects of cervical dysbioses associated with Human Papillomavirus (HPV) infections. This methods article suggests detailed sample collection and laboratory processes of metabolomics, DNA extraction for microbiota, HPV typing, and the bioinformatic analyses of the data, both to characterize the metabolome, the microbiota, and joint multi-omic analyses, useful for the development of new point-of-care diagnostic tests based on these approaches.


Reply to: ‘Younger patients with MAFLD are at increased risk of severe COVID-19 illness: A multicenter preliminary analysis’


title: Smart campus—A sketch

text: Abstract Smart campus is an emerging trend that allows educational institutions to combine smart technologies with physical infrastructure for improved services, decision making, campus sustainability etc. Under the umbrella of smart campus, various solutions have been implemented on campus levels such as smart microgrid, smart classrooms, controlling visual and thermal properties of the buildings, taking students attendance through face recognition/smart cards and so forth. Though these small-scale solutions contribute in parts to the realization of a smart campus, a generic model for smart campus is yet to be established. In this work, we study existing literature and propose a sketch of smart campus based on the smart city concepts. We create a list of smart campus initiatives that can be prioritized as per a university needs and geographical location. The work aims at propagating and providing an insight to the administration of higher educational institutions in evaluating and positioning their existing infrastructure against the smart campus concept. Whilst the vision, available resources and strategic goals of a university may emphasis on a different set of initiatives, in most of the cases, the generic model established in this work for a smart campus remains valid.


title: Vaccines and Vaccination for Veterinary Viral Diseases: A General Overview

text: A high number of infectious diseases affecting livestock and companion animals are caused by pathogens of viral etiology. Ensuring the maximum standards of quality and welfare in animal production requires developing effective tools to halt and prevent the spread of those infectious diseases affecting animal husbandry. To date, one of the best strategies is to implement vaccination policies whenever possible. However many of the currently manufactured vaccines relies in classical vaccine technologies (killed or attenuated vaccines) which, under some circumstances, may not be optimal in terms of safety or adequate for widespread application in disease-free countries at risk of disease introduction. One step ahead is needed to improve and adapt vaccine manufacturing to the use of new generation vaccine technologies already tested in experimental settings. Here we present in the context of animal viral diseases of veterinary interest, an overview of some current vaccine technologies that can be approached for virus pathogens with a brief insight in the type of immunity elicited.


docid: uhjtilve

title: Collaborative accountability for sustainable public health: A Korean perspective on the effective use of ICT-based health risk communication

text: Abstract The sustainability of public health practices requires collaboration between the government and its citizens. On the government's side, social media can provide a conduit for communicating health risk information in an effective and timely fashion, while also engaging citizens in informed decision-making. On the citizen's side, information communication technology (ICT)-based practices cannot function unless citizens recognize and act on their responsibility to actively engage with government social media platforms. Despite an increasing interest in understanding the adoption of ICT practices and e-government services for health risk communication, there remains a crucial need for a comprehensive framework to explain which factors determine citizen use of digital government resources. The purpose of this study is to investigate how to increase government accountability for motivating citizens to engage in ICT-based health risk communication, thereby attaining sustainable public health practices through collaborative governance. By integrating trust and health risk information into the e-government adoption model (GAM), this research examines factors that influence citizens' likelihood of using government social media resources. Survey data from 700 Korean citizens were analyzed using structural equation modeling. The results indicated that individuals with higher social media competency are more likely to (a) seek risk information through social media and (b) perceive the government's social media sites as easy to use. Consistent with the GAM, intentions to use the government's social media sites for information and interactions appear to increase as citizens perceive more value in using them regarding information quality, ease of use, functional benefit, and security. Furthermore, perceived trust in the government's social media resources appears to function as a mediator of this process. Initial trust in the government is an important determinant of perceptions of its digital resources. Citizens who trust the government tend to evaluate new initiatives positively and are more likely to accept and make use of them. The results of this study can inform policy design and implementation by elucidating the mechanisms that determine citizens' adoption and usage of digital government services. Theoretically, this work expands the GAM to include health risk communication and adds empirical evidence to the small yet growing body of knowledge of e-government initiatives. These findings also highlight the importance of public trust in the government, as this encourages citizens to seek health risk information and assistance from the government. Overall, the data and model generated in this investigation represent an important step toward the successful and sustainable modernization of public services.


title: Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line.

text: • Clinicians are looking for a reliable prognostic marker for patients with COVID-19; • In our cohort, clinical improvement was predicted by younger age and a NLR below 3; • Transfer to ICU was instead predicted by a NLR over 4 (p=0.046); • NLR is a fast, widely available and relatively inexpensive assessment; • NLR may be a useful tool in the early screening of patients with COVID-19.


title: A case series of chest imaging manifestation of COVID-19

text: Abstract Coronavirus disease 2019 (COVID-19) is caused by a infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It started in Wuhan, China, in December 2019, after which quickly spread to many other countries around the world. Chest radiography (CXR) and computed tomography (CT) play key roles in managment and diagnosis of COVID-19. In this case series we are presenting three patients with predominant left-sided changes caused by COVID-19 infection.


docid: bvcahbbi

title: The role of post-Golgi transport pathways and sorting motifs in the plasmodesmal targeting of the movement protein (MP) of Ourmia melon virus (OuMV)

text: Plants have a highly sophisticated endomembrane system that is targeted by plant viruses for cell-to-cell movement. The movement protein (MP) of Ourmia melon virus (OuMV) is targeted to plasmodesmata (PD) and forms tubules to facilitate cell-to-cell movement. Despite a number of functionally important regions for correct subcellular localization of OuMV MP has been identified, little is known about the pathways OuMV MP hijacks to reach PD. Here, we demonstrate that OuMV MP localizes to the trans-Golgi network (TGN), but not to the multivesicular body/prevacuolar compartment or Golgi, and carries two putative sorting motifs, a tyrosine (Y) and a dileucine (LL) motif, near its N-terminus. Introducing glycine substitutions in these motifs results in loss of OuMV infectivity in Nicotiana benthamiana and Arabidopsis (Arabidopsis thaliana). Live cell imaging of GFP-labeled sorting motif mutants shows that Y motif mutants fail to localize to the TGN, plasma membrane, and PD. Mutations in the LL motif do not impair plasma membrane targeting of MP, but affect its ability to associate with callose deposits at PD. Taken together, these data suggest that both Y and LL motifs are indispensable for targeting of OuMV MP to PD and for efficient systemic infection, but show differences in functionality. This study provides new insights into the role of sorting motifs in intracellular targeting of MPs and vesicle trafficking pathways that plant viruses hijack for cell-to-cell movement.


title: Inferring generation-interval distributions from contact-tracing data

text: Generation intervals, defined as the time between when an individual is infected and when that individual infects another person, link two key quantities that describe an epidemic: the initial reproductive number, [Formula: see text] , and the initial rate of exponential growth, r. Generation intervals can be measured through contact tracing by identifying who infected whom. We study how realized intervals differ from ‘intrinsic’ intervals that describe individual-level infectiousness and identify both spatial and temporal effects, including truncating (due to observation time), and the effects of susceptible depletion at various spatial scales. Early in an epidemic, we expect the variation in the realized generation intervals to be mainly driven by truncation and by the population structure near the source of disease spread; we predict that correcting realized intervals for the effect of temporal truncation but not for spatial effects will provide the initial forward generation-interval distribution, which is spatially informed and correctly links r and [Formula: see text]. We develop and test statistical methods for temporal corrections of generation intervals, and confirm our prediction using individual-based simulations on an empirical network.


docid: oqwevkrb

title: Blood Screening for Influenza

text: Influenza viruses, including highly pathogenic avian influenza virus (H5N1), could threaten blood safety. We analyzed 10,272 blood donor samples with a minipool nucleic acid amplication technique. Analytical sensitivity of the method was 804 geq/mL and 444 geq/mL for generic influenza primers and influenza (H5N1) subtype–specific primers. This study demonstrates that such screening for influenza viruses is feasible.


title: Balkan endemic nephropathy—current status and future perspectives

text: Balkan endemic nephropathy (BEN), originally described in 1956, is a unique familial, chronic renal disease encountered with a high-prevalence rate in Serbia, Bulgaria, Romania, Croatia and Bosnia and Herzegovina. The most prominent features of the disease are its endemic nature, long-incubation period, familial clustering of the disease and an unusually high incidence of associated upper urothelial cancer (UUC). There are no clear-cut data on BEN incidence and prevalence, since the studies carried out in different endemic areas yielded contradictory information. In spite of intermittent variations, the incidence of new cases has remained stable over time. It has been estimated that almost 100 000 people are at risk of BEN, whereas 25 000 have the disease. The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years. There are no pathognomonic diagnostic features of BEN, but the set of epidemiological, clinical and biochemical data along with the pattern of pathologic injury in the absence of any other renal diseases are highly suggestive of this entity. Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN. Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs). In light of these later studies, one can raise the question whether AAs could be responsible for previously and currently widespread unrecognized global renal disease and UUC.


Striding Toward Malaria Elimination in China


title: Thoughts on the pathophysiology of nonallergic rhinitis

text: Nonallergic noninfectious rhinitis is a diagnosis by exclusion, meaning that a number of poorly defined nasal conditions that have in common allergy and infection as a cause of the rhinitis have been excluded. The etiology of some subgroups of nonallergic noninfectious rhinitis, like nonallergic rhinitis with eosinophilia (NARES) and drug-induced rhinitis, are quite well defined, but in the majority of the patients, the etiology and pathophysiology are unknown. These patients are classified as idiopathic rhinitis patients. A careful determination of the intensity of the symptoms combined with modern diagnostic tools enables us to discriminate idiopathic rhinitis patients from normal controls. This review discusses the possible pathophysicologic mechanisms of nonallergic noninfectious rhinitis, with emphasis on idiopathic rhinitis.


title: Bilirubin levels in patients with mild and severe Covid‐19: A pooled analysis

text: The letter comments on a recent commentary published in Liver International entitled "COVID-19 and liver disease" by Sun et al., and describes a pooled analysis of data on bilirubin levels in patients with and without severe Covid-19. This is the first pooled analysis of data on bilirubin in Covid-19 patients. The results evidence that bilirubin levels are significantly associated with the severity of the disease.


title: Methodology and application of Escherichia coli F4 and F18 encoding infection models in post-weaning pigs

text: The enterotoxigenic Escherichia coli (ETEC) expressing F4 and F18 fimbriae are the two main pathogens associated with post-weaning diarrhea (PWD) in piglets. The growing global concern regarding antimicrobial resistance (AMR) has encouraged research into the development of nutritional and feeding strategies as well as vaccination protocols in order to counteract the PWD due to ETEC. A valid approach to researching effective strategies is to implement piglet in vivo challenge models with ETEC infection. Thus, the proper application and standardization of ETEC F4 and F18 challenge models represent an urgent priority. The current review provides an overview regarding the current piglet ETEC F4 and F18 challenge models; it highlights the key points for setting the challenge protocols and the most important indicators which should be included in research studies to verify the effectiveness of the ETEC challenge. Based on the current review, it is recommended that the setting of the model correctly assesses the choice and preconditioning of pigs, and the timing and dosage of the ETEC inoculation. Furthermore, the evaluation of the ETEC challenge response should include both clinical parameters (such as the occurrence of diarrhea, rectal temperature and bacterial fecal shedding) and biomarkers for the specific expression of ETEC F4/F18 (such as antibody production, specific F4/F18 immunoglobulins (Igs), ETEC F4/F18 fecal enumeration and analysis of the F4/F18 receptors expression in the intestinal brush borders). On the basis of the review, the piglets’ response upon F4 or F18 inoculation differed in terms of the timing and intensity of the diarrhea development, on ETEC fecal shedding and in the piglets’ immunological antibody response. This information was considered to be relevant to correctly define the experimental protocol, the data recording and the sample collections. Appropriate challenge settings and evaluation of the response parameters will allow future research studies to comply with the replacement, reduction and refinement (3R) approach, and to be able to evaluate the efficiency of a given feeding, nutritional or vaccination intervention in order to combat ETEC infection.


title: High time for ease the doctor-patient relationship in China

text: Abstract As doctors, we find it disturbing to read the paper “Burnout in physicians who are exposed to workplace violence” (January 2020).1 Workplace violence experienced by doctors has been documented both in developed and developing countries. Reports show that Chinese medical professionals are being injured, disabled, or even killed by patients or their family members.2,3 The killing of a doctor in Beijing in 2019 attracted national attention. China's top legislative body has approved the first fundamental and comprehensive law to protect health-care professionals. The bill will take effect on June 1, 2020. However, the law alone will not solve the problem. We need to treat it from the root and address the issues that have led to this health-care-related violence. A multi-faceted action must be launched to reduce violence against doctors in China urgently.


title: Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels

text: Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl(−)) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl(−) to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl(−) to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.


docid: scvbkmrq

title: Crises drive innovation

text: Crises often drive innovation. The COVID 19 pandemic has led to the necessary postponement of much planned surgical activity with the cancellation of outpatient, diagnostic and operative work. These measures have been designed to 'flatten the curve' and delay the spread of coronavirus whilst also freeing up capacity within hospitals for patients affected with the virus. This inevitable postponement of routine activity will create challenges to health care systems when normal business resumes and in many healthcare settings, which are often already resource constrained. This will impose an additional burden on patients whose diagnoses and treatment will be delayed.


Re: “Proposal for International Standardization of the Use of Lung Ultrasound for Patients With COVID‐19: A Simple, Quantitative, Reproducible Method”—Could Telementoring of Lung Ultrasound Reduce Health Care Provider Risks, Especially for Paucisymptomatic Home‐Isolating Patients?


title: Population-based Surveillance for Medically Attended Human Parainfluenza Viruses From the Influenza Incidence Surveillance Project, 2010–2014

text: BACKGROUND: Parainfluenza viruses (PIV) have been shown to contribute substantially to pediatric hospitalizations in the United States. However, to date, there has been no systematic surveillance to estimate the burden among pediatric outpatients. METHODS: From August 2010 through July 2014, outpatient health care providers with enumerated patient populations in 13 states and jurisdictions participating in the Influenza Incidence Surveillance Project conducted surveillance of patients with influenza-like illness (ILI). Respiratory specimens were collected from the first 10 ILI patients each week with demographic and clinical data. Specimens were tested for multiple respiratory viruses, including PIV1–4, using reverse transcriptase–polymerase chain reaction assays. Cumulative incidence was calculated using provider patient population size as the denominator. RESULTS: PIVs 1–3 were detected in 8.0% of 7716 ILI-related outpatient specimens: 30% were PIV1, 26% PIV2 and 44% PIV3. PIV circulation varied noticeably by year and type, with PIV3 predominating in 2010–2011 (incidence 110 per 100,000 children), PIV1 in 2011–2012 (89 per 100,000), dual predominance of PIV2 and PIV3 (88 and 131 per 100,000) in 2012–2013 and PIV3 (100 per 100,000) in 2013–2014. The highest incidence of PIV detections was among patients aged <5 years (259–1307 per 100,000). The median age at detection for PIV3 (3.4 years) was significantly lower than the median ages for PIV1 (4.5 years) and PIV2 (7.0 years; P < 0.05). CONCLUSIONS: PIVs 1–3 comprise a substantial amount of medically attended pediatric ILI, particularly among children aged <5 years. Distinct seasonal circulation patterns as well as significant differences in rates by age were observed between PIV types.


docid: iropfzgs

title: Identification of Alpha and Beta Coronavirus in Wildlife Species in France: Bats, Rodents, Rabbits, and Hedgehogs

text: Coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-coronavirus (MERS-CoV), are known to cross the species barrier and eventually to move from wildlife to humans. Knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. This study explored the presence of coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs, and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The results obtained suggest the circulation of potentially evolving virus strains, with the potential to cross the species barrier.


title: Chapter 44 Experimental Models of Virus-Induced Demyelination

text: Publisher Summary This chapter reviews two of the most widely studied animal models of virus-induced demyelinating disease. These are Theiler's murine encephalomyelitis virus and murine hepatitis virus. Both viruses produce acute inflammatory encephalitis that is followed by chronic central-nervous-system (CNS) demyelinating disease. The clinical and pathologic correlates of virus-induced demyelination are largely immune mediated. Furthermore, several pathologic mechanisms have been proposed to explain the development of myelin damage and neurologic deficits, and each of the proposed mechanisms may play a role in disease progression depending on the genetic constitution of the infected animal. The induction of demyelinating disease by virus may be directly relevant to human MS. Several viruses are known to cause demyelination in humans and viral infection is an epidemiologic factor that is consistently associated with clinical exacerbation of MS. It is suggested that viral infection may be a cause of MS, although no specific virus has been identified as a causative agent.


title: What’s the Deal? Trump, Fichte’s Closed Commercial State, and the Perverse Dialectic of Neoliberal Risk

text: The following paper seeks to understand Donald Trump as a “dialectical image” for the contradictions of neoliberal capitalism. Trump’s management style, as described in his Art of the Deal, combines a fetishizing of entrepreneurial risk as a “lifestyle” with the insistence that it is not the entrepreneur but his targets who are ultimately exposed to risk. This suggests that we might understand the elevation of “deal-making” to a lifestyle as a characteristic of modernity that, with neoliberalism, is increasingly coming to the fore. Such a critique of modernity, I further argue, is anticipated by Fichte’s Closed Commercial State with its intriguing dialectic of risk. I conclude by arguing that Trump’s politics marks the rise of a new, specifically American style of Fascism—one that demands identification not with the state as supra-individual collective, but with an impersonal system governing over individual lives and rendering them precarious.


More Competences than You Knew? The Web of Health Competence for European Union Action in Response to the COVID-19 Outbreak


title: PEGylated Adenoviruses: From Mice to Monkeys

text: Covalent modification with polyethylene glycol (PEG), a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models.


title: Public health in Canada: Evolution, meaning and a new paradigm for respiratory therapy

text: Chronic disease burden in Canada poses an imminent public health threat. The impact of respiratory disease in Canada alone is significant, affecting one in five and leading any other cause of repeat hospitalization in all age groups. Public health action is considered to be an important means of addressing these issues. Historical understanding of health has evolved to support the adoption of paradigms by professions that recognize the limitations of medical intervention in addressing the fundamental basis of disease when compared with the broader public health perspective. Several key historical events have shaped this understanding in the Canadian context including the Lalonde and Epp reports, and public health emergencies such as the severe acute respiratory syndrome outbreak in 2003. The profession of respiratory therapy has historically existed within a medicalized paradigm of practice; however, forces both internal and external to the profession are pressuring it to consider adopting broader social-and population-based approaches. As a rapidly evolving profession, there is a need to explore emerging areas of practice opportunities in the discipline. Investigating alternative knowledge and ideology can ensure that effective strategies for addressing the contemporary respiratory heath needs of Canadians are undertaken. The present article explores the rationale for a public health- and population-based approach to health in general, and its applicability to the respiratory therapist’s role in addressing respiratory health-related issues in Canada.


title: The putative etiology and prevention of autism

text: Since the initial psychological report by Leo Kanner in 1943, relatively little formal biochemical/neurological research on the cause of autism, other than peripheral searches for genomic mutations, had been carried until the end of the 20th century. As a result of studies on twin sets and the conclusion that autism was largely a hereditary defect, numerous investigations have sought various genetic faults in particular. However, such studies were able to reveal a plausible etiology for this malady in only a small percentage of instances. Key bio-molecular characteristics of this syndrome have been uncovered when the potential roles of the glia were studied in depth. Findings related to biochemical deficiencies appearing early in the newborn, such as depressed IGF-1 (insulin-like growth factor #1) in neurogenesis/myelination, are becoming emphasized in many laboratories. Progress leading to timely diagnoses and subsequent prevention of central nervous system dysconnectivity now seems plausible. The tendency for an infant to develop autism may currently be determinable and preventable before irreversible psychosocial disturbances become established. These discussions about glial function will be inter-spersed with comments about their apparent relevance to autism. The concluding portion of this presentation will be a detailed review and summation of this diagnosis and prevention proposition.


title: Review of Randomized Controlled Trials Using e-Health Interventions for Patients With Eating Disorders

text: BACKGROUND: In a world of technological advancements, electronic devices and services seem to be a promising way to increase patients’ engagement in treatment and to help manage their symptoms. Here, we identified and analyzed the current evidence of RCTs to evaluate the effectiveness and acceptability of e-health interventions in the eating disorder (ED) field. METHODS: We screened an initial cluster of 581 papers. In the end, 12 RCTs in clinical ED cohorts were included. RESULTS: Some studies were conceived as stand-alone interventions, while others were presented as add-ons to ED-specific treatments. Studies varied in the type of EDs under investigation and in the e-health intervention applied (with vs. without therapist support vs. blended interventions; smartphone- vs. web-based). Only four studies reported explicit acceptability measures. Out of those, two reported high acceptability, one reported low acceptability, and one reported no significant difference in acceptability between groups. Four studies reported higher effectiveness of the e-health intervention compared to the control condition, e.g., reduction in maladaptive eating behaviors. Regarding control groups, three used a wait list design and nine had another kind of intervention (e.g., face-to-face CBT, or treatment as usual) as control. DISCUSSION: So far, the evidence for acceptability and effectiveness of e-health interventions in EDs is very limited. There is also a lack of studies in older patients, adolescents, men, sexual and ethnic minorities. Shame/stigma is discussed in the context of e-health interventions for EDs. It remains unclear how severity of EDs affects the effectiveness of e-health interventions, how patients can channel the knowledge they acquire from e-health interventions into their actual behaviors, and how such interventions can better fit the needs of the individual patient to increase acceptability and effectiveness.


title: Coronavirus disease 2019 (COVID-19): latest developments in potential treatments

text: Many viral respiratory infections can cause severe acute respiratory symptoms leading to mortality and morbidity. In the spring of 2003, the severe acute respiratory syndrome (SARS) outbreak caused by SARS-CoV spread globally. In the summer of 2012, the Middle East respiratory syndrome (MERS) outbreak caused by MERS-CoV occurred in Saudi Arabia. In the winter of 2019, the coronavirus disease 2019 (COVID-19) outbreak caused by a novel coronavirus SARS-CoV-2 occurred in China which rapidly spread worldwide causing a global pandemic. Up until 27 May 2020, there are 5.5 million confirmed cases of COVID-19 and 347,587 COVID-19 related deaths worldwide, and there has also been an unprecedented increase in socioeconomic and psychosocial issues related to COVID-19. This overview aims to review the current developments in preventive treatments and therapies for COVID-19. The development of vaccines for SARS-CoV-2 is ongoing and various clinical trials are currently underway around the world. It is hoped that existing antivirals including remdesivir and lopinavir-ritonavir might have roles in the treatment of COVID-19, but results from trials thus far have not been promising. COVID-19 causes a mild respiratory disease in the majority of cases, but in some cases, cytokine activation causes sepsis and acute respiratory distress syndrome, leading to morbidity and mortality. Immunomodulatory treatments and biologics are also being actively explored as therapeutics for COVID-19. On the other hand, the use of steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) has been discouraged based on concerns about their adverse effects. Over the past two decades, coronaviruses have caused major epidemics and outbreaks worldwide, whilst modern medicine has been playing catch-up all along.


title: Contextualizing covid-19 spread: a county level analysis, urban versus rural, and implications for preparing for the next wave

text: Paraphrasing [Morano and Holt, 2017], contextual determinants of health including social, environmental, healthcare and others, are a so-called deck of cards one is dealt. The ability to modify health outcomes varies then based upon how one's hand is played. It is thus of great interest to understand how these determinants associate with the emerging pandemic covid-19. To this end, we conducted a deep-dive analysis into this problem using a recently curated public dataset on covid-19 that connects infection spread over time to a rich collection of contextual determinants for all counties of the U.S and Washington, D.C. Using random forest machine learning methodology, we identified a relevant constellation of contextual factors of disease spread which manifest differently for urban and rural counties. The findings also have clear implications for better preparing for the next wave of disease.


title: Current research for a vaccine against Lassa hemorrhagic fever virus

text: Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical.


title: Experimental Teschovirus Encephalomyelitis in Gnotobiotic Pigs

text: Summary A central nervous system (CNS) disorder characterized by non-suppurative encephalomyelitis with neurological signs was induced experimentally in gnotobiotic pigs by intravenous and oral or intranasal inoculation of the porcine teschovirus (PTV) Toyama 2002 strain isolated from breeding pigs in Japan. Lesions consisting of perivascular cuffing of mononuclear cells, focal gliosis, neuronal necrosis and neuronophagia were observed in the brainstem, cerebellum and spinal cord. Non-suppurative ganglionitis in the spinal ganglion and neuritis in the spinal root were also observed. Regardless of the route of inoculation, all pigs infected experimentally with PTV showed a similar distribution of CNS lesions. Histological lesions in the CNS caused by oral or intranasal inoculation of the virus were mild compared with those induced by intravenous infection. Immunohistochemically, the distribution of PTV antigens corresponded closely with the distribution of brain lesions. PTV particles were detected via electron microscopy in the cytoplasm of nerve cells and the endothelial cells of blood vessels in the spinal cord of inoculated pigs. Polymerase chain reaction analysis demonstrated the presence of PTV RNA in the CNS, tonsils and large intestines of 21 of the 22 pigs inoculated. Direct CNS invasion via the blood vessels appears to be a major route of infection for PTV. The gnotobiotic pig provides a useful model for further study of PTV pathogenesis.


title: Routine molecular point-of-care testing for respiratory viruses in adults presenting to hospital with acute respiratory illness (ResPOC): a pragmatic, open-label, randomised controlled trial

text: Summary Background Respiratory virus infection is a common cause of hospitalisation in adults. Rapid point-of-care testing (POCT) for respiratory viruses might improve clinical care by reducing unnecessary antibiotic use, shortening length of hospital stay, improving influenza detection and treatment, and rationalising isolation facility use; however, insufficient evidence exists to support its use over standard clinical care. We aimed to assess the effect of routine POCT on a broad range of clinical outcomes including antibiotic use. Methods In this pragmatic, parallel-group, open-label, randomised controlled trial, we enrolled adults (aged ≥18 years) within 24 h of presenting to the emergency department or acute medical unit of a large UK hospital with acute respiratory illness or fever higher than 37·5°C (≤7 days duration), or both, over two winter seasons. Patients were randomly assigned (1:1), via an internet-based allocation sequence with random permuted blocks, to have a molecular POC test for respiratory viruses or routine clinical care. The primary outcome was the proportion of patients who received antibiotics while hospitalised (up to 30 days). Secondary outcomes included duration of antibiotics, proportion of patients receiving single doses or brief courses of antibiotics, length of stay, antiviral use, isolation facility use, and safety. Analysis was by modified intention to treat, excluding patients who declined intervention or were withdrawn for protocol violations. This study is registered with ISRCTN, number 90211642, and has been completed. Findings Between Jan 15, 2015, and April 30, 2015, and between Oct 1, 2015, and April 30, 2016, we enrolled 720 patients (362 assigned to POCT and 358 to routine care). Six patients withdrew or had protocol violations. 301 (84%) of 360 patients in the POCT group received antibiotics compared with 294 (83%) of 354 controls (difference 0·6%, 95% CI −4·9 to 6·0; p=0·84). Mean duration of antibiotics did not differ between groups (7·2 days [SD 5·1] in the POCT group vs 7·7 days [4·9] in the control group; difference −0·4, 95% CI −1·2 to 0·4; p=0·32). 50 (17%) of 301 patients treated with antibiotics in the POCT group received single doses or brief courses of antibiotics (<48 h) compared with 26 (9%) of 294 patients in the control group (difference 7·8%, 95% CI 2·5 to 13·1; p=0·0047; number needed to test=13). Mean length of stay was shorter in the POCT group (5·7 days [SD 6·3]) than in the control group (6·8 days [7·7]; difference −1·1, 95% CI −2·2 to −0·3; p=0·0443). Appropriate antiviral treatment of influenza-positive patients was more common in the POCT group (52 [91%] of 57 patients) than in the control group (24 [65%] of 37 patients; difference 26·4%, 95% CI 9·6 to 43·2; p=0·0026; number needed to test=4). We found no differences in adverse outcomes between the groups (77 [21%] of 360 patients in the POCT group vs 88 [25%] of 354 patients in the control group; −3·5%, −9·7 to 2·7; p=0·29). Interpretation Routine use of molecular POCT for respiratory viruses did not reduce the proportion of patients treated with antibiotics. However, the primary outcome measure failed to capture differences in antibiotic use because many patients were started on antibiotics before the results of POCT could be made available. Although POCT was not associated with a reduction in the duration of antibiotics overall, more patients in the POCT group received single doses or brief courses of antibiotics than did patients in the control group. POCT was also associated with a reduced length of stay and improved influenza detection and antiviral use, and appeared to be safe. Funding University of Southampton.


title: Mental well-being of international migrants to Japan: a systematic review

text: BACKGROUND: Migration is a stressful process of resettlement and acculturation that can often negatively impact the mental health of migrants. International migration to Japan, a country with dominant ethnic homogeneity, is growing steadily amid an ageing domestic population and severe labour shortages. OBJECTIVES: To identify the contemporary barriers to, and facilitators of, mental well-being among the migrant population in Japan. DESIGN: Systematic review DATA SOURCES: PubMed, ProQuest, Web of Science, Ichushi and J-Stage ELIGIBILITY CRITERIA: Research articles examining the mental well-being of international migrants in Japan that were published in English or Japanese between January 2000 and September 2018 were included. DATA EXTRACTION AND SYNTHESIS: Full texts of relevant articles were screened and references of the included studies were hand-searched for further admissible articles. Study characteristics, mental well-being facilitators and barriers, as well as policy recommendations were synthesised into categorical observations and were then thematically analysed. RESULTS: Fifty-five studies (23 published in English), surveying a total of 8649 migrants, were identified. The most commonly studied migrant nationalities were Brazilian (36%), followed by Chinese (27%) and Filipino (8%). Thematic analysis of barriers to mental well-being among migrants chiefly identified ‘language difficulties’, ‘being female’ and ‘lack of social support’, whereas the primary facilitators were ‘social networks’ followed by ‘cultural identity’. Policy recommendations for authorities generally described more migrant support services and cross-cultural awareness among the Japanese public. CONCLUSION: Access to social support networks of various types appears to be an influential factor affecting the mental well-being of international migrants in Japan. More research is necessary on how to promote such connections to foster a more inclusive and multicultural Japanese society amid rapid demographic change. PROSPERO REGISTRATION NUMBER: CRD42018108421.


title: Epidemiologic characteristics of traumatic fractures during the outbreak of coronavirus disease 2019 (COVID-19) in China: A retrospective & comparative multi-center study

text: PURPOSE: Amid the outbreak of coronavirus disease 2019 (COVID-19), effective measures have been taken in China to suggest people wearing masks and staying at home. The majority of the people stayed at home, which had an obvious impact on the occurrence of traumatic fractures. This study aimed to describe the epidemiologic characteristics of traumatic fractures during the COVID-19, and provide reference for targeted control measures for the whole world by proposing China's experiences. METHODS: This was a retrospective & comparative multi-center study with data obtained from 11 hospitals in five provinces of China. Patients were enrolled into this study, who sustained fractures from 20 January to 19 February 2020 and the same period in 2019 (based on Chinese lunar calendar). All patients were divided into two groups: epidemic group (admitted in 2020) and control group (admitted in 2019). The data of patients' demographics (age and gender), injury related data (fracture type, fractured site, osteoporosis fracture, concurrent fractures, injury mechanism, places where fracture occurred, ISS score, Gustilo-Anderson Classification for open fracture), mortality and treatment modality were compared between the two groups. RESULTS: A total of 2,489 patients with 2,590 fractures were included. In the epidemic group, there were 865 patients, including 483 (55.8%) males and 382 (44.2%) females with an average age of 53.1 ± 23.1 years (range, 1 to 105). In the control group, there were 1,624 patients, including 876 (53.9%) males and 748 (46.1%) females with an average age of 51.2 ± 21.5 years (range, 1 to 98). Patients in the epidemic group was significantly older than those in the control group (t=-2.046, P = 0.045). For epidemic group, the mostly commonly involved age group was elderly patients, whereas it was middle-aged adults for the control group (χ(2) = 14.642, P = 0.002). For epidemic group, a total of 576 (66.6%) patients had their fracture occurring at home, while in the control group there was 183 (11.3%). The proportion rates of low energy injuries (79.1%, 684/865), osteoporotic fractures (32.5%, 294/906) and closed fractures (94.5%, 817/865) in the epidemic group were significantly higher when compared to the control group, respectively (34.4%, 559/1624; 26.9%, 453/1684; 91.9%, 1,493/1692; all P<0.05). The proportion rates of Gustilo-Anderson classification (5.5%, 16/865), concurrent fractures (2.3%, 20/865), and injury severity score (15.6 ± 6.7) in epidemic group were significantly lower than those in the control group, respectively (52.8%, 199/1624; 3.9%, 63/1624; 20.1 ± 8.7; all P<0.05). No positive case with COVID-19 was diagnosed in the epidemic group. The mortality rate in the epidemic group (0.46%) was similar with that in the control group (0.43%). CONCLUSIONS: Our findings confirmed the importance of the measures to restrict people's movement and wear masks in the prevention of the spread of COVID-19. The epidemiological characteristics of traumatic fractures amid the epidemic changes dramatically, and more attempts should be focused on the prevention of low energy injuries of elderly population.


title: Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

text: Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.


title: Peptide microarrays with site-specifically immobilized synthetic peptides for antibody diagnostics

text: Abstract Peptide microarrays bear the potential to discover molecular recognition events on protein level, particularly in the field of molecular immunology, in a manner and with an efficiency comparable to the performance of DNA microarrays. We developed a novel peptide microarray platform for the detection of antibodies in liquid samples. The system comprises site-specific solution phase coupling of biotinylated peptides to NeutrAvidin, localized microdispensing of peptide–NeutrAvidin conjugates onto activated glass slides and a fluorescence immuno sandwich assay format for antibody capture and detection. Our work includes synthetic peptides deduced from amino acid sequences of immunodominant linear epitopes, such as the T7 phage capsid protein, Herpes simplex virus glycoprotein D, c-myc protein and three domains of the Human coronavirus 229E polymerase polyprotein. We demonstrate that our method produces peptide arrays with excellent spot morphology which are capable of specific and sensitive detection of monoclonal antibodies from fluid samples.


CoronARTvirus


title: Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015

text: OBJECTIVES: As of 1 November 2015, the Saudi Ministry of Health had reported 1273 cases of Middle East respiratory syndrome (MERS); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. This study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of MERS contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in Saudi Arabia. DESIGN: Data from the Saudi Ministry of Health of confirmed outbreak and non-outbreak cases of MERS coronavirus (CoV) infections from September 2012 through October 2015 were abstracted and analysed. Univariate and descriptive statistical analyses were conducted, and the time between disease onset and confirmation, onset and notification and onset and death were examined. RESULTS: A total of 1250 patients (aged 0–109 years; mean, 50.825 years) were reported infected with MERS-CoV. Approximately two-thirds of all MERS cases were diagnosed in men for outbreak and non-outbreak cases. Healthcare workers comprised 22% of all MERS cases for outbreak and non-outbreak cases. Nosocomial infections comprised one-third of all Saudi MERS cases; however, nosocomial infections occurred more frequently in outbreak than non-outbreak cases (p<0.001). Patients contracting MERS during an outbreak were significantly more likely to die of MERS (p<0.001). CONCLUSIONS: To date, nosocomial infections have fuelled MERS outbreaks. Given that the Kingdom of Saudi Arabia is a worldwide religious travel destination, localised outbreaks may have massive global implications and effective outbreak preventive measures are needed.


title: 31 days of COVID-19—cardiac events during restriction of public life—a comparative study

text: AIMS: The coronavirus SARS-CoV-2 outbreak led to the most recent pandemic of the twenty-first century. To contain spread of the virus, many nations introduced a public lockdown. How the pandemic itself and measures of social restriction affect hospital admissions due to acute cardiac events has rarely been evaluated yet. METHODS AND RESULTS: German public authorities announced measures of social restriction between March 21st and April 20th, 2020. During this period, all patients suffering from an acute cardiac event admitted to our hospital (N = 94) were assessed and incidence rate ratios (IRR) of admissions for acute cardiac events estimated, and compared with those during the same period in the previous three years (2017–2019, N = 361). Admissions due to cardiac events were reduced by 22% as compared to the previous years (n = 94 vs. an average of n = 120 per year for 2017–2019). Whereas IRR for STEMI 1.20 (95% CI 0.67–2.14) and out-of-hospital cardiac arrest IRR 0.82 (95% CI 0.33–2.02) remained similar, overall admissions with an IRR of 0.78 (95% CI 0.62–0.98) and IRR for NSTEMI with 0.46 (95% CI 0.27–0.78) were significantly lower. In STEMI patients, plasma concentrations of high-sensitivity troponin T at admission were significantly higher (644 ng/l, IQR 372–2388) compared to 2017–2019 (195 ng/l, IQR 84–1134; p = 0.02). CONCLUSION: The SARS-CoV-2 pandemic and concomitant social restrictions are associated with reduced cardiac events admissions to our tertiary care center. From a public health perspective, strategies have to be developed to assure patients are seeking and getting medical care and treatment in time during SARS-CoV-2 pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00392-020-01681-2) contains supplementary material, which is available to authorized users.


title: Where are we now with COVID‐19?

text: As a practicing front line clinician in the acute adult general medical field, I read Dr Stein's recent insightful article on novel coronavirus (COVID 19)1 with great interest. News reports in the UK and around the world carry daily updates and increasing speculation about the potential global impact as the virus spreads much as Dr Stein predicted. However, a number of questions appear to be emerging that were not covered when Dr Stein published his editorial in IJCP.


title: Differential response to frameshift signals in eukaryotic and prokaryotic translational systems.

text: The genomic RNA of beet western yellows virus (BWYV) contains a potential translational frameshift signal in the overlap region of open reading frames ORF2 and ORF3. The signal, composed of a heptanucleotide slippery sequence and a downstream pseudoknot, is similar in appearance to those identified in retroviral RNAs. We have examined whether the proposed BWYV signal functions in frameshifting in three translational systems, i.c. in vitro in a reticulocyte lysate or a wheat germ extract and in vivo in E. coli. The efficiency of the signal in the eukaryotic system is low but significant, as it responds strongly to changes in either the slip sequence or the pseudoknot. In contrast, in E. coli there is hardly any response to the same changes. Replacing the slip sequence to the typical prokaryotic signal AAAAAAG yields more than 5% frameshift in E. coli. In this organism the frameshifting is highly sensitive to changes in the slip sequence but only slightly to disruption of the pseudoknot. The eukaryotic assay systems are barely sensitive to changes in either AAAAAAG or in the pseudoknot structure in this construct. We conclude that eukaryotic frameshift signals are not recognized by prokaryotes. On the other hand the typical prokaryotic slip sequence AAAAAAG does not lead to significant frameshifting in the eukaryote. In contrast to recent reports on the closely related potato leafroll virus (PLRV) we show that the frameshifting in BWYV is pseudoknot-dependent.


title: Political will and international collaborative frameworks in infectious diseases

text: The last few decades have been marked by a rapid expansion in the world?s population, along with an increasingly dynamic mobility of individuals. This accelerated global inter‐connectedness enabled microorganisms to reach virtually any location worldwide more rapidly and efficiently than ever before, reshaping the global dynamics of pathogens. As a result, a local infectious disease outbreak anywhere in the world may almost instantaneously assume global dimensions, and should therefore be considered a global priority. The history of several infectious diseases illustrates that in addition to prophylactic and therapeutic medical interventions, the interplay of social, economic, and political factors makes a fundamental contribution to the outcome of infectious disease outbreaks. Furthermore, this multi‐ and cross‐disciplinary interconnectedness is a key determinant of the outcome of efforts to eradicate vaccine‐preventable infectious diseases. A combined framework that incorporates teachings provided by previous outbreaks, and integrates medical and biomedical interventions with contributions made by social, economic, and political factors, emerges as vital requirement of successful global public health initiatives.


title: A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01)

text: The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS-associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the M protein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s).


Assessing the skillset of surgeons facing the COVID‐19 pandemic


title: Validation and Psychometric Properties of the Japanese Version of the Fear of COVID-19 Scale Among Adolescents

text: In the context of the global outbreak of COVID-19, there is an urgent need to explore the effects of this pandemic on the mental health of adolescents. The present study aims to adapt and validate a Japanese-version Fear of COVID-19 Scale (FCV-19S) with a sample of adolescent students from Japan. To this end, the Japanese-version FCV-19S, Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire for Adolescents (PHQ-A), and Perceived Vulnerability to Disease Scale (PVDS) were administered to a sample of Japanese adolescents in schools. The results of statistical analyses revealed that the Japanese-version FCV-19S has a bi-factor model consisting of the emotional response factor and the physiological response factor, with high reliability (emotional: α = .71; physiological: α = .82). Constructive validity was shown by the significant positive correlation between the GAD-7 and emotional (r = .11) and physiological response (r = .25), between PHQ-A and physiological response (r = .19), and between both factors and the PVDS subscale (rs > .16). Taken together, these results indicate that the Japanese-version FCV-19S has a high internal consistency and a moderately good construct validity.


title: The pathogen receptor liver and lymph node sinusoidal endotelial cell C‐type lectin is expressed in human Kupffer cells and regulated by PU.1

text: Human LSECtin (liver and lymph node sinusoidal endothelial cell C‐type lectin, CLEC4G) is a C‐type lectin encoded within the L‐SIGN/DC‐SIGN/CD23 gene cluster. LSECtin acts as a pathogen attachment factor for Ebolavirus and the SARS coronavirus, and its expression can be induced by interleukin‐4 on monocytes and macrophages. Although reported as a liver and lymph node sinusoidal endothelial cell‐specific molecule, LSECtin could be detected in the MUTZ‐3 dendritic‐like cell line at the messenger RNA (mRNA) and protein level, and immunohistochemistry analysis on human liver revealed its presence in Kupffer cells coexpressing the myeloid marker CD68. The expression of LSECtin in myeloid cells was further corroborated through the analysis of the proximal regulatory region of the human LSECtin gene, whose activity was maximal in LSECtin+ myeloid cells, and which contains a highly conserved PU.1‐binding site. PU.1 transactivated the LSECtin regulatory region in collaboration with hematopoietic‐restricted transcription factors (Myb, RUNX3), and was found to bind constitutively to the LSECtin proximal promoter. Moreover, knockdown of PU.1 through the use of small interfering RNA led to a decrease in LSECtin mRNA levels in THP‐1 and monocyte‐derived dendritic cells, thus confirming the involvement of PU.1 in the myeloid expression of the lectin. Conclusion: LSECtin is expressed by liver myeloid cells, and its expression is dependent on the PU.1 transcription factor. (Hepatology 2009;49:287–296.)


title: Legal and Ethical Aspects of ‘Best Interests’ Decision-Making for Medical Treatment of Companion Animals in the UK

text: SIMPLE SUMMARY: Making decisions about medical treatment for animal patients involves two key decision-makers, the animal owner and the veterinary surgeon. We aim to show that these decisions should and can be based on the ‘best interests’ of the animal, with both human decision-makers acting as advocates for the animal requiring treatment. We suggest that the role of the animal owner is similar to that of a parent in making decisions for a child, drawing on legal cases to demonstrate the limits of parental (and owner) decision-making. To provide a firmer basis for ‘best interests’ decision-making, we adapt the factors included in the United Nations Convention on the Rights of the Child and demonstrate how these could be used with a typical clinical situation. Finally, we analyse the decisions from an ethical point of view. ABSTRACT: Medical decisions for young children are made by those with parental responsibility, with legal involvement only if the decision is potentially detrimental to the child’s welfare. While legally classified as property, some argue that animals are in a similar position to children; treatment decisions are made by their owners, posing a legal challenge only if the proposed treatment has the potential to cause harm or unnecessary suffering, as defined by animal protection legislation. This paper formulates the approach to a ‘best interests’ calculation, utilising the factors included in the United Nations Convention on the Rights of the Child and relying on exchange of information between the human parties involved. Although this form of decision-making must primarily protect the animal from unnecessary suffering, it recognises that the information provided by the owner is critical in articulating the animal’s non-medical interests, and hence in formulating what is in the animal’s best overall welfare interests. While statute law does not mandate consideration of ‘best interests’ for animals, this approach might reasonably be expected as a professional imperative for veterinary surgeons. Importantly, this version of a ‘best interests’ calculation can be incorporated into existing ethical frameworks for medical decision-making and the humane treatment of animals.


title: A virus that has gone viral: amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding, and thus, infectivity

text: Since 2002, β coronaviruses (CoVs) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019). Spike (S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the nCoV2019 takes its course throughout the world, more and more sequence analyses are being done and genome sequences are being deposited in various databases. From India, two clinical isolates have been sequenced and the full genome has been deposited in GenBank. We have performed sequence analyses of the Spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates, one was found to harbor a mutation in its receptor-binding domain (RBD) at position 407. At this site, arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-β branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor binding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.


title: The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis

text: Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9–18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4–15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3–41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7–13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0–4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.


title: Managing business relationships during a pandemic: Conducting a relationship audit and developing a path forward

text: Abstract During stable times, firms will generally aim to create reliable B2B relationships that provide increased efficiency and profitability. However, tumultuous times, such as the time during a major pandemic, cause many significant disruptions in both internal and external environmental domains. Thus, we argue that it is critical during this time to reevaluate the company's business relationships as a whole. While long-term partnerships are great for handling incremental changes during stable times, disruptive environmental changes may require managers to consider disruptive changes to their businesses. A pandemic may also present opportunities for establishing new relationships as there may be other partners/suppliers who are better equipped to help the company address urgent short-term needs and to capitalize on significant long-term opportunities. In this paper, we design a new relationship audit template to help B2B firms weather the immediate crisis at hand and position themselves more strategically for the future. We explore this idea in relation to the coronavirus outbreak, introduce the idea of a B2B crisis relationship audit, and offer potential steps forward for firms.


title: Evaluation of a Novel Non-Penetrating Electrode for Use in DNA Vaccination

text: Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination.


title: Human Coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana

text: BACKGROUND: Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. This study sought to determine whether human coronaviruses (HCoVs) are associated with upper respiratory tract infections among older children and adults in Ghana. METHODS: We conducted a case control study among older children and adults in three rural areas of Ghana using asymptomatic subjects as controls. Nasal/Nasopharyngeal swabs were tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-22E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. RESULTS: Out of 1,213 subjects recruited, 150 (12.4%) were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95%CI = 2.24–11.78), HCoV-OC43 (OR = 6.16, 95%CI = 1.77–21.65) and combine HCoVs (OR = 2.36, 95%CI = 1.5 = 3.72) were associated with upper respiratory tract infections. HCoVs were found to be seasonally dependent with significant detections in the harmattan season (mainly HCoV-229E) and wet season (mainly HCoV-NL63). A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. CONCLUSION: HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural areas of Ghana.


title: Bullous skin disease patients in a high‐epidemic COVID‐19 area, Bergamo, Italy

text: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are blistering disorders associated with barrier disruption, immune dysregulation and use of immunosuppressing systemic therapy. Patients with BP and PV have higher potential risk factors for infections secondary to skin alterations, comorbidity and chronic treatment with immunosuppressing agents.


title: A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3

text: The fusion glycoproteins of human respiratory syncytial virus (RSV) and human parainfluenza virus type-3 (PIV-3) mediate virus entry and syncytium formation. Interaction between the fusion protein of RSV and RhoA, a small GTPase, facilitates virus-induced syncytium formation. We show here a RhoA-derived peptide inhibits RSV and syncytium formation induced by RSV and PIV-3, both in vitro by inhibition of cell-to-cell fusion and in vivo by reduction of peak titer by 2 log(10) in RSV-infected mice. These findings indicate that the interaction between these two paramyxovirus fusion proteins and RhoA is an important target for new antiviral strategies.


title: Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing

text: Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the emergence of these viruses in humans. Next-generation sequencing (NGS) is currently the preferred methodology for virus discovery to ensure unbiased sequencing of bat CoVs, considering their high genetic diversity. However, unbiased NGS is an expensive methodology and is prone to missing low-abundance CoV sequences due to the high background level of nonviral sequences present in surveillance field samples. Here, we employ a capture-based NGS approach using baits targeting most of the CoV species. Using this technology, we effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them. IMPORTANCE Active surveillance is both urgent and essential to predict and mitigate the emergence of bat-origin CoV in humans and livestock. However, great genetic diversity increases the chance of homologous recombination among CoVs. Performing targeted PCR, a common practice for many surveillance studies, would not reflect this diversity. NGS, on the other hand, is an expensive methodology and is prone to missing low-abundance CoV sequences. Here, we employ a capture-based NGS approach using baits targeting all CoVs. Our work demonstrates that targeted, cost-effective, large-scale, genome-level surveillance of bat CoVs is now highly feasible.


title: ISOLATION AND CHARACTERIZATION OF AN EXOPOLYMER PRODUCED BY BACILLUS LICHENIFORMIS: IN VITRO ANTIVIRAL ACTIVITY AGAINST ENVELOPED VIRUSES

text: The exopolymer (EPSp) produced by the strain B. licheniformis IDN-EC was isolated and characterized using different techniques (MALDI-TOF, NMR, ATR-FTIR, TGA, DSC, SEM). The results showed that the low molecular weight EPSp contained a long polyglutamic acid and an extracellular teichoic acid polysaccharide. The latter was composed of poly(glycerol phosphate) and was substituted at the 2-position of the glycerol residues with a αGal and αGlcNH(2). The αGal O-6 position was also found to be substituted by a phosphate group. The antiviral capability of this EPSp was also tested on both enveloped (herpesviruses HSV, PRV and vesicular stomatitis VSV) and non-enveloped (MVM) viruses. The EPSp was efficient at inhibiting viral entry for the herpesviruses and VSV but was not effective against non-enveloped viruses. The in vivo assay of the EPSp in mice showed no signs of toxicity which could allow for its application in the healthcare sector.


title: Type 1 cytokines polarize thymocytes during T cell development in adult thymus organ cultures

text: Abstract Peripheral T cells can be polarized towards type 1 or type 2 cytokine immune responses during TCR engagement. Because T cell selection by peptide plus self-MHC in the thymus requires TCR engagement, we hypothesized that type 1 cytokines may polarize developing T cells. We cultured thymi from BBDR rats in adult thymus organ cultures (ATOC) under type 1 cytokine conditions in the absence of exogenous antigen. Type 1 cytokine-conditioned ATOC generated cells that spontaneously secreted high levels of IFNγ, but not IL-4. A second exposure to type 1 cytokines further increased IFNγ secretion by these cells, most of which were blasts that expressed the activation markers CD25, CD71, CD86, and CD134. Studies using blocking antibodies and pharmacological inhibitors suggested that both IL-18 and cognate TCR–MHC/ligand interactions were important for activation. Blocking anti-MHC class I plus anti-MHC class II antibodies, neutralizing anti-IL-18 antibody, and the p38 MAP-kinase inhibitor SB203580 each reduced IFNγ production by ∼75–80%. Cyclosporin A, which prevents TCR signaling, inhibited IFNγ production by ∼50%. These data demonstrate that exposure to type 1 cytokines during intrathymic development can polarize differentiating T cells, and suggest a mechanism by which intrathymic exposure to type 1 cytokines may modulate T cell development.


title: Upper airway viruses and bacteria in urban Aboriginal and Torres Strait Islander children in Brisbane, Australia: a cross-sectional study

text: BACKGROUND: Respiratory morbidity in Australian Indigenous children is higher than their non-Indigenous counterparts, irrespective of urban or remote residence. There are limited studies addressing acute respiratory illness (ARI) in urban Indigenous children, particularly those that address the upper airway microbiome and its relationship to disease. We aimed to describe the prevalence of upper airway viruses and bacteria in symptomatic and asymptomatic urban-based Australian Indigenous children aged less than 5 years. METHODS: A cross-sectional analysis of data collected at baseline in an ongoing prospective cohort study of urban Aboriginal and Torres Strait Islander children registered with a primary health care service in the northern suburbs of Brisbane, Australia. Clinical, demographic and epidemiological data and bilateral anterior nasal swabs were collected on enrolment. Polymerase chain reaction was performed on nasal swabs to detect 17 respiratory viruses and 7 bacteria. The primary outcome was the prevalence of these microbes at enrolment. Logistic regression was performed to investigate differences in microbe prevalence between children with and without acute respiratory illness with cough as a symptom (ARIwC) at time of specimen collection. RESULTS: Between February 2013 and October 2015, 164 children were enrolled. The median age at enrolment was 18.0 months (IQR 7.2–34.3), 49.4% were boys and 56 children (34.2%) had ARIwC. Overall, 133/164 (81%) nasal swabs were positive for at least one organism; 131 (79.9%) for any bacteria, 59 (36.2%) for any virus and 57 (34.8%) for both viruses and bacteria. Co-detection of viruses and bacteria was more common in females than males (61.4% vs 38.6%, p = 0.044). No microbes, alone or in combination, were significantly associated with the presence of ARIwC. CONCLUSIONS: The prevalence of upper airways microbes in asymptomatic children is similar to non-Indigenous children with ARIwC from the same region. Determining the aetiology of ARIwC in this community is complicated by the high prevalence of multiple respiratory pathogens in the upper airways. STUDY REGISTRATION: Australia New Zealand Clinical Trial Registry Registration Number: 12,614,001,214,628. Retrospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2349-1) contains supplementary material, which is available to authorized users.


title: Nucleic-Acid Testing, New Platforms and Nanotechnology for Point-of-Decision Diagnosis of Animal Pathogens

text: Accurate disease diagnosis in animals is crucial for animal well-being but also for preventing zoonosis transmission to humans. In particular, livestock diseases may constitute severe threats to humans due to the particularly high physical contact and exposure and, also, be the cause of important economic losses, even in non-endemic countries, where they often arise in the form of rapid and devastating epidemics. Rapid diagnostic tests have been used for a long time in field situations, particularly during outbreaks. However, they mostly rely on serological approaches, which may confirm the exposure to a particular pathogen but may be inappropriate for point-of-decision (point-of-care) settings when emergency responses supported on early and accurate diagnosis are required. Moreover, they often exhibit modest sensitivity and hence significantly depend on later result confirmation in central or reference laboratories. The impressive advances observed in recent years in materials sciences and in nanotechnology, as well as in nucleic-acid synthesis and engineering, have led to an outburst of new in-the-bench and prototype tests for nucleic-acid testing towards point-of-care diagnosis of genetic and infectious diseases. Manufacturing, commercial, regulatory, and technical nature issues for field applicability more likely have hindered their wider entrance into veterinary medicine and practice than have fundamental science gaps. This chapter begins by outlining the current situation, requirements, difficulties, and perspectives of point-of-care tests for diagnosing diseases of veterinary interest. Nucleic-acid testing, particularly for the point of care, is addressed subsequently. A range of valuable signal transduction mechanisms commonly employed in proof-of-concept schemes and techniques born on the analytical chemistry laboratories are also described. As the essential core of this chapter, sections dedicated to the principles and applications of microfluidics, lab-on-a-chip, and nanotechnology for the development of point-of-care tests are presented. Microdevices already applied or under development for application in field diagnosis of animal diseases are reviewed.


title: Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice

text: Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage‐ and pathogen‐associated molecular patterns contribute to a self‐perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM‐1) is a surface receptor that amplifies inflammation induced by toll‐like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM‐1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand‐independent TREM‐1 inhibitory peptides that were formulated into human high‐density lipoprotein (HDL)‐mimicking complexes GF9‐HDL and GA/E31‐HDL. As revealed in vitro, macrophages endocytosed these rationally designed complexes through scavenger receptors. A 5‐week alcohol feeding with the Lieber‐DeCarli diet in mice resulted in increased serum alanine aminotransferase (ALT), liver steatosis, and increased proinflammatory cytokines in the liver. TREM‐1 messenger RNA (mRNA) expression was significantly increased in alcohol‐fed mice, and TREM‐1 inhibitors significantly reduced this increase. TREM‐1 inhibition significantly attenuated alcohol‐induced spleen tyrosine kinase (SYK) activation, an early event in both TLR4 and TREM‐1 signaling. The TREM‐1 inhibitors significantly inhibited macrophage (epidermal growth factor‐like module‐containing mucin‐like hormone receptor‐like 1 [F4/80], clusters of differentiation [CD]68) and neutrophil (lymphocyte antigen 6 complex, locus G [Ly6G] and myeloperoxidase [MPO]) markers and proinflammatory cytokines (monocyte chemoattractant protein 1 [MCP‐1], tumor necrosis factor α [TNF‐α], interleukin‐1β [IL‐1β], macrophage inflammatory protein 1α [MIP‐1α]) at the mRNA level compared to the HDL vehicle. Administration of TREM‐1 inhibitors ameliorated liver steatosis and early fibrosis markers (α‐smooth muscle actin [αSMA] and procollagen1α [Pro‐Col1α]) at the mRNA level in alcohol‐fed mice. However, the HDL vehicle also reduced serum ALT and some cytokine protein levels in alcohol‐fed mice, indicating HDL‐related effects. Conclusion: HDL‐delivered novel TREM‐1 peptide inhibitors ameliorate early phases of inflammation and neutrophil and macrophage recruitment and activation in the liver and attenuate hepatocyte damage and liver steatosis. TREM‐1 inhibition represents a promising therapeutic approach for further investigations in ALD.


title: European Bats as Carriers of Viruses with Zoonotic Potential

text: Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.


title: MERS-coronavirus: From discovery to intervention

text: Middle East respiratory syndrome coronavirus (MERS-CoV) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. Here we describe the current epidemiological picture of MERS-CoV, focusing on humans and animals affected by this virus and propose specific intervention strategies that would be appropriate to control MERS-CoV. One-third of MERS-CoV patients develop severe lower respiratory tract infection and succumb to a fatal outcome; these patients would require effective therapeutic antiviral therapy. Because of the lack of such intervention strategies, supportive care is the best that can be offered at the moment. Limiting viral spread from symptomatic human cases to health care workers and family members, on the other hand, could be achieved through prophylactic administration of MERS-CoV neutralizing antibodies and vaccines. To ultimately prevent spread of the virus into the human population, however, vaccination of dromedary camels – currently the only confirmed animal host for MERS-CoV – may be the best option to achieve a sustained drop in human MERS cases in time. In the end, a One Health approach combining all these different efforts is needed to tackle this zoonotic outbreak.


title: A data-driven assessment of early travel restrictions related to the spreading of the novel COVID-19 within mainland China

text: Two months after it was firstly reported, the novel coronavirus disease COVID-19 spread worldwide. However, the vast majority of reported infections until February occurred in China. To assess the effect of early travel restrictions adopted by the health authorities in China, we have implemented an epidemic metapopulation model that is fed with mobility data corresponding to 2019 and 2020. This allows to compare two radically different scenarios, one with no travel restrictions and another in which mobility is reduced by a travel ban. Our findings indicate that i) travel restrictions might be an effective measure in the short term, however, ii) they are ineffective when it comes to completely eliminate the disease. The latter is due to the impossibility of removing the risk of seeding the disease to other regions. Furthermore, our study highlights the importance of developing more realistic models of behavioral changes when a disease outbreak is unfolding.


title: Development and validation of the HNC-LL score for predicting the severity of coronavirus disease 2019

text: BACKGROUND: Information regarding risk factors associated with severe coronavirus disease (COVID-19) is limited. This study aimed to develop a model for predicting COVID-19 severity. METHODS: Overall, 690 patients with confirmed COVID-19 were recruited between 1 January and 18 March 2020 from hospitals in Honghu and Nanchang; finally, 442 patients were assessed. Data were categorised into the training and test sets to develop and validate the model, respectively. FINDINGS: A predictive HNC-LL (Hypertension, Neutrophil count, C-reactive protein, Lymphocyte count, Lactate dehydrogenase) score was established using multivariate logistic regression analysis. The HNC-LL score accurately predicted disease severity in the Honghu training cohort (area under the curve [AUC]=0.861, 95% confidence interval [CI]: 0.800–0.922; P<0.001); Honghu internal validation cohort (AUC=0.871, 95% CI: 0.769–0.972; P<0.001); and Nanchang external validation cohort (AUC=0.826, 95% CI: 0.746–0.907; P<0.001) and outperformed other models, including CURB-65 (confusion, uraemia, respiratory rate, BP, age ≥65 years) score model, MuLBSTA (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hypertension, and age) score model, and neutrophil-to-lymphocyte ratio model. The clinical significance of HNC-LL in accurately predicting the risk of future development of severe COVID-19 was confirmed. INTERPRETATION: We developed an accurate tool for predicting disease severity among COVID-19 patients. This model can potentially be used to identify patients at risks of developing severe disease in the early stage and therefore guide treatment decisions. FUNDING: This work was supported by the National Nature Science Foundation of China (grant no. 81972897) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015).


title: Capillary Electrophoresis of PCR fragments with 5´-labelled primers for testing the SARS-Cov-2

text: Due to the huge demand for SARS-Cov-2 determination,alternatives to the standard qtPCRtestsare potentially useful for increasing the number of samples screened. Our aim was to develop a direct fluorescent PCR capillary-electrophoresis detection of the viral genome. We validated this approach on several SARS-Cov-2 positive and negative samples.We isolated the naso-pharingealRNA from 20 positive and 10 negative samples. The cDNA was synthesised and two fragments of the SARS-Cov-2 were amplified. One of the primers for each pair was 5´-end fluorochrome labelled. The amplifications were subjected to capillary electrophoresis in ABI3130 sequencers to visualize the fluorescent peaks.The two SARS-Cov-2 fragments were successfully amplified in the positive samples, while the negative samples did not render fluorescent peaks. In conclusion, we describe and alternative method to identify the SARS-Cov-2 genome that could be scaled to the analysis of approximately 100 samples in less than 5 hours. By combining a standard PCR with capillary electrophoresis our approach would overcome the limits imposed to many labs by the qtPCR and increase the testing capacity.


The genomes of three coronaviruses


title: Identification of New Respiratory Viruses in the New Millennium

text: The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001.