title: Prevalence of porcine circovirus type 3 in pigs in the southeastern Chinese province of Zhejiang

text: BACKGROUND: Porcine circovirus type 3 (PCV3) was first reported in US in 2016. The virus was also identified later in China. Prevalence of PCV3 in Zhejiang province in southeastern China is not clear though it has been reported in many parts of China. RESULTS: PCV3 infection and its co-infection with other swine viral pathogens in pig herds of Zhejiang province were retrospectively investigated by quantitative PCR (qPCR) and its sero-prevalence by indirect ELISA. PCV3 was found positive in 67.1% of the 283 clinical samples taken from 2014 to 2017 as shown by qPCR. Single infection with PCV3 accounted for only one-third of the samples, and majority were of co-infections, predominantly with PEDV (41.6%) but generally low with other swine viruses. Indirect ELISA using the PCV3 capsid protein as the coating antigen revealed an average sero-positive rate of 52.6% (40.8 to 60.8%) in 2345 serum samples from 2011 to 2017, with earliest yet high positive findings in samples taken in 2012. Of 203 serum samples, the qPCR method showed more positive findings than ELISA (81.3% vs 56.2%). With 89 serum samples negative by ELISA, vast majority (n = 81) were found positive by qPCR. There was negative correlation in levels of PCV3 DNA and anti-capsid antibody response. ORF2-based phylogenetic analysis revealed three major groups (PCV3a, PCV3b and PCV3c) of the 200 strains, 38 from this study and 162 reference strains from GenBank. Most of the strains from this study were clustered into PCV3c. Of the putative signature residues of the capsid protein (aa 24, 27, 77 and 150) relative to the three groups, only the PCV3a group strains showed a distinct pattern of residues VKSI (95% of the strains), while the other two groups did not have such a ‘signature’ pattern. CONCLUSIONS: Results from this study provided further evidence that the novel virus PCV3 was widely distributed in China and might have emerged in Zhejiang province before 2014, most probably back in 2012 when there was high PCV3 sero-prevalence. PCV3 might be viremic in pigs and could spread by fecal shedding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1977-7) contains supplementary material, which is available to authorized users.


title: Co-infection with SARS-CoV-2 and influenza A virus

text: Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses.


title: The performance of chest CT in evaluating the clinical severity of COVID-19 pneumonia: identifying critical cases based on CT characteristics

text: OBJECTIVES: To assess the clinical severity of COVID-19 pneumonia using qualitative and/or quantitative chest CT indicators and identify the CT characteristics of critical cases. MATERIALS AND METHODS: Fifty-one patients with COVID-19 pneumonia including ordinary cases (group A, n=12), severe cases(group B, n=15) and critical cases (group C, n=24) were retrospectively enrolled. The qualitative and quantitative indicators from chest CT were recorded and compared using Fisher's exact test, one-way ANOVA, Kruskal-Wallis H test and receiver operating characteristic analysis. RESULTS: Depending on the severity of the disease, the number of involved lung segments and lobes, the frequencies of consolidation, crazy-paving pattern and air bronchogram increased in more severe cases. Qualitative indicators including total severity score for the whole lung and total score for crazy-paving and consolidation could distinguish groups B and C from A(69% sensitivity, 83% specificity and 73% accuracy) but were similar between group B and group C. Combined qualitative and quantitative indicators could distinguish these three groups with high sensitivity(B+C vs. A, 90%; C vs. B, 92%), specificity(100%, 87%) and accuracy(92%, 90%). Critical cases had higher total severity score(>10) and higher total score for crazy-paving and consolidation(>4) than ordinary cases, and had higher mean lung density(>-779HU) and full width at half maximum(>128HU) but lower relative volume of normal lung density(≦50%) than ordinary/severe cases. In our critical cases, eight patients with relative volume of normal lung density smaller than 40% received mechanical ventilation for supportive treatment, and two of them had died. CONCLUSION: A rapid, accurate severity assessment of COVID-19 pneumonia based on chest CT would be feasible and could provide help for making management decisions, especially for the critical cases.


title: Chapitre 10 Rhinites, sinusites et rhinosinusites

text: ■. Une douleur faciale unilatérale quotidienne à horaire fixe, s’accompagnant de congestion ou d’obstruction nasale ipsilatérale, évoque une sinusite aiguë. ■. Le diagnostic différentiel principal des sinusites aiguës est l’algie vasculaire de la face (cf. partie 2, fiche « Algie faciale »). ■. Les sinusites maxillaire, frontale et ethmoïdale antérieure se caractérisent par la présence de pus dans le méat moyen ipsilatéral. ■. La radiologie n’est pas nécessaire au diagnostic de sinusite aiguë, mais le devient si les signes ne régressent pas sous traitement en moins d’une semaine. ■. Chez un petit enfant, la présence d’un œdème à l’angle interne de l’œil, s’étendant à la paupière supérieure dans un contexte fébrile, est synonyme d’ethmoïdite aiguë extériorisée. ■. Une sinusite devient chronique après 12 semaines d’évolution. ■. Le diagnostic des sinusites chroniques repose sur l’interrogatoire, l’endoscopie nasale à l’optique et la tomodensitométrie (TDM). ■. Les rhinosinusites chroniques forment un ensemble de pathologies caractérisées par un infiltrat inflammatoire polymorphe auto-entretenu. ■. La polypose nasosinusienne ne constitue que le stade le plus sévère des rhinosinusites chroniques. ■. La maladie de Widal est une maladie métabolique associant polypose nasosinusienne, asthme et intolérance à l’aspirine. ■. Les formes unilatérales de rhinosinusite chronique relèvent plutôt du versant chirurgical du traitement (chirurgie endoscopique des sinus), tandis que les formes bilatérales relèvent plutôt du versant médical.


Comprehensive diagnostics for respiratory virus infections after transplantation or after potential exposure to swine flu A/H1N1: what else is out there?


title: Use of a multiplex real-time PCR to study the incidence of human metapneumovirus and human respiratory syncytial virus infections during two winter seasons in a Belgian paediatric hospital

text: ABSTRACT Viruses are an important cause of acute respiratory tract infection (ARTI) in children. This study aimed to develop and evaluate a rapid molecular diagnostic test (duplex real-time PCR) for human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), and to determine the frequency of these two viruses as causative agents of ARTI in Belgium. Nasopharyngeal aspirates were collected over two winter and spring seasons (November 2003 to May 2004 and November 2004 to May 2005) from children aged <5 years with ARTI (n = 778). The duplex real-time PCR showed a linear range of 104–1010 copies/mL for both hMPV and hRSV. Analysis of the stability of the hRSV and hMPV genomes revealed that nasopharyngeal aspirates could be stored at room temperature for up to 1 month without significant loss of detection. hRSV was detected by antigen testing and by real-time PCR; hMPV was detected by real-time PCR only. The hRSV antigen test was less sensitive than PCR, and failed to detect one-third of the hRSV infections. Overall, 54 (6.9%) and 306 (39.3%) of the 778 samples were positive for hMPV and hRSV, respectively. Both viruses infected young infants, but the mean age of infants infected by hRSV was lower than that of infants infected by hMPV (12 months vs. 17 months, respectively).


title: Viruses and thyroiditis: an update

text: Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.


Extracorporeal Oxygenation and Coronavirus Disease 2019 Epidemic: Is the Membrane Fail-Safe to Cross Contamination?


title: Membrane-anchored serine proteases in health and disease

text: Serine proteases of the trypsin-like family have long been recognized to be critical effectors of biological processes as diverse as digestion, blood coagulation, fibrinolysis, and immunity. In recent years, a subgroup of these enzymes has been identified that are anchored directly to plasma membranes, either by a carboxy-terminal transmembrane domain (Type I), an amino-terminal transmembrane domain with a cytoplasmic extension (Type II or TTSP), or through a glycosyl-phosphatidylinositol (GPI) linkage. Recent biochemical, cellular, and in vivo analyses have now established that membrane-anchored serine proteases are key pericellular contributors to processes vital for development and the maintenance of homeostasis. This chapter will review our current knowledge of the biological and physiological functions of these proteases, their molecular substrates, and their contributions to disease.


title: The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood–brain barrier

text: As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system includes neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-COV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is expressed throughout various caliber vessels in the frontal cortex. Additionally, ACE2 was also detectable in primary human brain microvascular endothelial (hBMVEC) maintained under cell culture conditions. Analysis for cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48hr exposure window. However, when the viral spike proteins were introduced into model systems that recapitulate the essential features of the Blood-Brain Barrier (BBB), breach to the barrier was evident in various degrees depending on the spike protein subunit tested. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluid model of the human BBB, a platform that most closely resembles the human physiological conditions at this CNS interface. Subsequent analysis also showed the ability for SARS-CoV-2 spike proteins to trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.


title: Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias

text: Resumen Introducción Las infecciones respiratorias virales que requieren hospitalización parecen conferir riesgo de desarrollar sibilancias recurrentes, pero existen pocos datos publicados en poblaciones no seleccionadas por tener factores de riesgo. Nuestro objetivo principal fue analizar si las infecciones respiratorias virales sintomáticas y asintomáticas, de diferente gravedad, durante el primer año de vida en una cohorte de recién nacidos, suponen un mayor riesgo de sibilancias recurrentes. Pacientes y métodos Se incluyeron 302 recién nacidos. Se recogió aspirado nasofaríngeo a los niños cuando presentaron una infección respiratoria y de forma periódica en los controles de salud (2, 4, 6 y 12 meses). Se estudiaron 16 virus respiratorios mediante reacción en cadena de polimerasa (PCR). Resultados Se analizaron 1.293 muestras (1.005 controles de salud y 288 infecciones respiratorias). El 30,8% de las muestras tomadas en los controles de salud fueron positivas, frente a un 77,8% en las infecciones respiratorias, p<0,001 (OR: 3, IC 95%: 2,4-3,8). Un total de 239 (79%) lactantes tuvieron al menos una detección viral positiva durante el primer año de vida. El virus más frecuentemente identificado (71%) fue el rinovirus (RV). En 27 lactantes (11%) se detectaron sibilancias recurrentes durante su primer año de vida (2,9 DE: 1,2 episodios). El 58,3% de los lactantes cuya primera infección respiratoria requirió hospitalización desarrollaron sibilancias de repetición, frente al 8,6% de los niños cuya primera infección fue leve o asintomática, p<0,001 (OR: 2,18; lC 95%: 1,05-4,5). Conclusiones En nuestra serie, las infecciones respiratorias virales graves en los primeros meses de vida supusieron un factor de riesgo para desarrollar sibilancias recurrentes. No ocurrió lo mismo con las infecciones respiratorias leves. Abstract Introduction It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. Patients and methods A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. Results A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P <.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P <.001 (OR: 2.18; 95% CI: 1.05-4.5). Conclusions In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections.


Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From the ACC’s Interventional Council and SCAI


title: Mechanisms for lyssavirus persistence in non-synanthropic bats in Europe: insights from a modeling study

text: Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk. Focusing on the European Bat Lyssavirus subtype 1 (EBLV-1), causing rabies disease, we develop a data-driven spatially explicit metapopulation model to investigate EBLV-1 persistence in Myotis myotis and Miniopterus schreibersii bat species in Catalonia. We find that persistence relies on host spatial structure through the migratory nature of M. schreibersii, on cross-species mixing with M. myotis, and on survival of infected animals followed by temporary immunity. The virus would not persist in the single colony of M. myotis. Our study provides for the first time epidemiological estimates for EBLV-1 progression in M. schreibersii. Our approach can be readily adapted to other zoonoses of public health concern where long-range migration and habitat sharing may play an important role.


Inaugural Lifestyle Medicine Editorial: Lifestyle medicine in the time of COVID‐19


title: Global response to pandemic flu: more research needed on a critical front

text: If and when sustained human-to-human transmission of H5N1 becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet Earth. Given that air transportation is the one feature that most differentiates present day transmission scenarios from those in 1918, our present inability to prevent spread of influenza by international air travel, as reckoned by the World Health Organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. Despite the lessons of SARS, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued.


COVID-19 Pandemic: New Challenge to Securing Mental Well-being in Conflict Settings


title: Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli.

text: Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.


title: Classification of COVID-19 patients from chest CT images using multi-objective differential evolution–based convolutional neural networks

text: Early classification of 2019 novel coronavirus disease (COVID-19) is essential for disease cure and control. Compared with reverse-transcription polymerase chain reaction (RT-PCR), chest computed tomography (CT) imaging may be a significantly more trustworthy, useful, and rapid technique to classify and evaluate COVID-19, specifically in the epidemic region. Almost all hospitals have CT imaging machines; therefore, the chest CT images can be utilized for early classification of COVID-19 patients. However, the chest CT-based COVID-19 classification involves a radiology expert and considerable time, which is valuable when COVID-19 infection is growing at rapid rate. Therefore, an automated analysis of chest CT images is desirable to save the medical professionals’ precious time. In this paper, a convolutional neural networks (CNN) is used to classify the COVID-19-infected patients as infected (+ve) or not (−ve). Additionally, the initial parameters of CNN are tuned using multi-objective differential evolution (MODE). Extensive experiments are performed by considering the proposed and the competitive machine learning techniques on the chest CT images. Extensive analysis shows that the proposed model can classify the chest CT images at a good accuracy rate.


title: Viral infections and multiple sclerosis

text: The etiology and pathogenesis of MS is likely to involve multiple factors interacting with each other, and the role of infectious and viral agents is still under debate, however a consistent amount of studies suggests that some viruses are associated with the disease. The strongest documentation has come from the detection of viral nucleic acid or antigen or of an anti-viral antibody response in MS patients. A further step for the study of the mechanism viruses might be involved in can be made using in vitro and in vivo models. While in vitro models, based on glial and neural cell lines from various sources are widely used, in vivo animal models present challenges. Indeed neurotropic animal viruses are currently used to study demyelination in well-established models, but animal models of demyelination by human virus infection have only recently been developed, using animal gammaherpesviruses closely related to Epstein Barr virus (EBV), or using marmosets expressing the specific viral receptor for Human Herpesvirus 6 (HHV-6). The present review will illustrate the main potential mechanisms of MS pathogenesis possibly associated with viral infections and viruses currently used to study demyelination in animal models. Then the viruses most strongly linked with MS will be discussed, in the perspective that more than one virus might have a role, with varying degrees of interaction, contributing to MS heterogeneity.


title: Bat-derived influenza-like viruses H17N10 and H18N11

text: Shorebirds and waterfowls are believed to be the reservoir hosts for influenza viruses, whereas swine putatively act as mixing vessels. The recent identification of two influenza-like virus genomes (designated H17N10 and H18N11) from bats has challenged this notion. A crucial question concerns the role bats might play in influenza virus ecology. Structural and functional studies of the two major surface envelope proteins, hemagglutinin (HA) and neuraminidase (NA), demonstrate that neither has canonical HA or NA functions found in influenza viruses. However, putative functional modules and domains in other encoded proteins are conserved, and the N-terminal domain of the H17N10 polymerase subunit PA has a classical structure and function. Therefore, potential genomic reassortments of such influenza-like viruses with canonical influenza viruses cannot be excluded at this point and should be assessed.


title: Susceptibility of porcine IPI-2I intestinal epithelial cells to infection with swine enteric coronaviruses

text: Abstract Swine enteric coronavirus (CoV) is an important group of pathogens causing diarrhea in piglets. At least four kinds of swine enteric CoVs have been identified, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and the emerging HKU2-like porcine enteric alphacoronavirus (PEAV). The small intestines, particularly the jejunum and ileum, are the most common targets of these four CoVs in vivo, and co-infections by these CoVs are frequently observed in clinically infected pigs. This study was conducted to investigate the susceptibility of the porcine ileum epithelial cell line, IPI-2I, to different swine enteric CoVs. We found that IPI-2I cells are highly susceptible to TGEV, PDCoV, and PEAV, as demonstrated by cytopathic effect and virus multiplication. However, only a small number of cells could be infected by PEDV, possibly due to the heterogeneity of IPI-2I cells. A homogeneous cell line, designated IPI-FX, obtained from IPI-2I cells by sub-cloning with limited serial dilutions, was found to be highly susceptible to PEDV. Furthermore, IPI-FX cells were also highly susceptible to TGEV, PDCoV, as well as PEAV. Thus, this sub-cloned IPI-FX cell line is an ideal cell model to study the mechanisms of infection, particularly co-infections of swine enteric CoVs.


title: Fever Screening and Detection of Febrile Arrivals at an International Airport in Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning, and Tympanic Temperature

text: OBJECTIVES: The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. METHODS: Data were retrieved from arrivals’ health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. RESULTS: Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (p<0.001). The difference between the thermal camera temperature (36.83°C) and tympanic (or ear) temperature (38.14°C) was not statistically significant. CONCLUSIONS: The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system.


title: Cryptosporidiosis in small ruminants

text: Abstract Cryptosporidiosis is an infection caused by protozoan parasites belonging to the genus Cryptosporidium which is responsible for a potentially severe disease in new-born ruminants. This infection is highly prevalent in small ruminants throughout the world, especially in pre-weaned animals. The clinical expression is different between goat kids and lambs, the infection being generally more severe in the former. Molecular data demonstrate geographical variations in the species of Cryptosporidium infecting small ruminants. They also support the possibility of transmission of zoonotic species from these hosts to humans. Studies are still needed on molecular epidemiology, especially in goats, and on ways to control infection.


title: A novel riccati equation grey model and its application in forecasting clean energy

text: and accurate prediction of clean energy can supply an important reference for governments to formulate social and economic development policies. This paper begins with the logistic equation which is the whitening equation of the Verhulst model, introduces the Riccati equation with constant coefficients to optimize the whitening equation, and establishes a grey prediction model (CCRGM(1,1)) based on the Riccati equation. This model organically combines the characteristics of the grey model, and flexibly improves the modelling precision. Furthermore, the nonlinear term is optimized by the simulated annealing algorithm. To illustrate the validation of the new model, two kinds of clean energy consumption in the actual area are selected as the research objects. Compared with six other grey prediction models, CCRGM(1,1) model has the highest accuracy in simulation and prediction. Finally, this model is used to predict the nuclear and hydroelectricity energy consumption in North America from 2019 to 2028. The results predict that nuclear energy consumption will keep rising in the next decade, while hydroelectricity energy consumption will rise to a peak and subsequently fall back, which offers important information for the governments of North America to formulate energy measures.


title: DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans

text: Abstract DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing α-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans.


title: Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection

text: BACKGROUND: Viral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler’s murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain-infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear. METHODS: Chemokine expression levels in the hippocampus were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte infiltration during acute TMEV infection was measured by flow cytometry. CCL2 levels were manipulated by immunodepletion and by specific removal from neurons in mice generated by crossing a line expressing the Cre recombinase behind the synapsin promoter to animals with floxed CCL2. RESULTS: Inoculation of the brain with TMEV induced hippocampal production of the proinflammatory chemokine CCL2 that peaked at 6 h postinfection, whereas inoculation with UV-inactivated TMEV did not elicit this response. Immunofluorescence revealed that hippocampal neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2 and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of inflammatory monocytes into the brain during acute infection. Specific genetic deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and inhibited inflammatory monocyte infiltration into the brain. CONCLUSIONS: We conclude that intracranial inoculation with infectious TMEV rapidly induces the expression of CCL2 in neurons, and this cellular source is necessary for CCR2-dependent infiltration of inflammatory monocytes into the brain during the most acute stage of encephalitis. These findings highlight a unique role for neuronal production of chemokines in the initiation of leukocytic infiltration into the infected central nervous system.


title: Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats

text: Abstract The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV), but the prophylactic treatment of SARS-CoV is still under investigation. We constructed a recombinant adenovirus containing a truncated N-terminal fragment of the SARS-CoV Spike (S) gene (from −45 to 1469, designated Ad-SN), which encoded a truncated S protein (490 amino-acid residues, a part of 672 amino-acid S1 subunit), and investigated whether this construct could induce effective immunity against SARS-CoV in Wistar rats. Rats were immunized either subcutaneously or intranasally with Ad-SN once a week for three consecutive weeks. Our results showed that all of the immunized animals generated humoral immunity against the SARS-CoV spike protein, and the sera of immunized rats showed strong capable of protecting from SARS-CoV infection in vitro. Histopathological examination did not find evident side effects in the immunized animals. These results indicate that an adenoviral-based vaccine carrying an N-terminal fragment of the Spike gene is able to elicit strong SARS-CoV-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV infection.


title: A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm)

text: The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.


Rol del estudiante de ciencias médicas frente a la COVID-19: el ejemplo de Cuba


Avian influenza and the threat of the next human pandemic


title: Démarche diagnostique et thérapeutique devant une suspicion d'infection bronchique et pulmonaire aiguë chez l'immunocompétent

text: Résumé Les infections respiratoires regroupent trois entités dont les indications thérapeutiques sont différentes et qu'il importe de reconnaître : les bronchites aiguës, les pneumopathies aiguës et les exacerbations de bronchite chronique. Les bronchites aiguës sont très fréquentes, de diagnostic facile et d'évolution bénigne. Leur étiologie est en règle virale. Elles ne justifient pas d'antibiothérapie. Les pneumopathies aiguës sont, à l'inverse, peu fréquentes, mais présentent un risque évolutif potentiellement grave et restent la sixième cause de mortalité. Leur étiologie est le plus souvent bactérienne chez l'adulte et elles requièrent toujours une antibiothérapie. Leur diagnostic clinique repose sur des signes de présomption : fièvre, tachycardie, tachypnée, douleur thoracique, râles crépitants en foyer et impression de gravité. Elles justifient la réalisation d'une radiographie pulmonaire. Les exacerbations de bronchite chronique peuvent être d'origine bactérienne, virale ou non infectieuse. Les indications de l'antibiothérapie dépendent de la probabilité de l'origine bactérienne (augmentation du volume et de la purulence de l'expectoration, apparition ou aggravation d'une dyspnée) et du stade de la bronchopathie chronique (simple, obstructive sans insuffisance respiratoire chronique, insuffisance respiratoire chronique). Abstract Respiratory infections include acute bronchitis, acute pneumonia and acute exacerbation of chronic bronchitis. Each of these diseases has its own therapeutic approach, making important a good differential diagnosis. Acute bronchitis are very frequent, easy to diagnose and have a benign evolution. The etiology is usually viral. The treatment doesn’t require antibiotics. Conversely, acute pneumonia is infrequent but has to be considered as a serious illness; it remains the sixth cause of death. In adults, pneumonia is usually due to bacteria and antibiotherapy is always required. Clinical diagnosis is based on presumption signs: fever, tachycardia, tachypnea, thoracic pain, localized rales and an overall feeling of severity. A chest X-ray is required. Acute exacerbation of chronic bronchitis can be due to bacteria, virus or a non infectious cause. Antibiotherapy indications are based on the probability of bacterial etiology (increased volume and purulence of sputum, apparition or increase of dyspnea) and on the severity of the chronic bronchitis (chronic bronchitis, chronic obstructive pulmonary disease without respiratory insufficiency or chronic respiratory insufficiency).


title: The Palm Subdomain-based Active Site is Internally Permuted in Viral RNA-dependent RNA Polymerases of an Ancient Lineage

text: Abstract Template-dependent polynucleotide synthesis is catalyzed by enzymes whose core component includes a ubiquitous αβ palm subdomain comprising A, B and C sequence motifs crucial for catalysis. Due to its unique, universal conservation in all RNA viruses, the palm subdomain of RNA-dependent RNA polymerases (RdRps) is widely used for evolutionary and taxonomic inferences. We report here the results of elaborated computer-assisted analysis of newly sequenced replicases from Thosea asigna virus (TaV) and the closely related Euprosterna elaeasa virus (EeV), insect-specific ssRNA+ viruses, which revise a capsid-based classification of these viruses with tetraviruses, an Alphavirus-like family. The replicases of TaV and EeV do not have characteristic methyltransferase and helicase domains, and include a putative RdRp with a unique C–A–B motif arrangement in the palm subdomain that is also found in two dsRNA birnaviruses. This circular motif rearrangement is a result of migration of ∼22 amino acid (aa) residues encompassing motif C between two internal positions, separated by ∼110aa, in a conserved region of ∼550aa. Protein modeling shows that the canonical palm subdomain architecture of poliovirus (ssRNA+) RdRp could accommodate the identified sequence permutation through changes in backbone connectivity of the major structural elements in three loop regions underlying the active site. This permutation transforms the ferredoxin-like β1αAβ2β3αBβ4 fold of the palm subdomain into the β2β3β1αAαBβ4 structure and brings β-strands carrying two principal catalytic Asp residues into sequential proximity such that unique structural properties and, ultimately, unique functionality of the permuted RdRps may result. The permuted enzymes show unprecedented interclass sequence conservation between RdRps of true ssRNA+ and dsRNA viruses and form a minor, deeply separated cluster in the RdRp tree, implying that other, as yet unidentified, viruses may employ this type of RdRp. The structural diversification of the palm subdomain might be a major event in the evolution of template-dependent polynucleotide polymerases in the RNA–protein world.


title: Increased plasma levels of leukotriene B4 and prostaglandin E2 in cats experimentally inoculated with feline infectious peritonitis virus

text: Specific-pathogen-free kittens experimentally infected with feline infectious peritonitis virus (FIPV) subsequently demonstrated increased plasma levels of the arachidonic acid metabolites, leukotriene (LT) B4 and prostaglandin (PG) E2. Significant increases (P<0.025) in LTB4 plasma levels occurred in all (5/5) FIPV-inoculated kittens on postchallenge-exposure days (PCD) 7 and 14 vs PCD 0. Significant increases (P<0.05) in PGE2 plasma levels occurred in 80% (4/5) of FIPV-infected kittens on PCD 7 and 14. Maximal mean plasma levels of LTB4 and PGE2 occurred on PCD 7 (502.5±45.6 pg/ml and 1108.0±247.9 pg/ml, respectively). A positive correlation was found between LTB4 plasma levels and body temperature (r=0.609, P<0.01). Mean survival time in FIPV-inoculated kittens was 19.4±3.2 days. Gross lesions, including peritoneal or pleural effusions (or both) and connective tissue edema, indicated an increased vascular permeability in the FIPV-infected kittens. Histologically, lesions were characterized by pyogranulomatous inflammation. Immunofluorescent studies of tissues from FIPV-infected kittens demonstrated foci of polymorphonuclear leukocytes and FIPV-positive macrophages oriented around dilated blood vessels. Seemingly, arachidonic acid metabolites, including LTB4 or PGE2 released from macrophages, neutrophils or other cells, may be involved in the pathogenesis of FIP vascular and inflammatory lesions and in some of the clinical disease manifestations.


title: Viral Induced Demyelination

text: Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell‐cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral‐induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non‐enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus‐specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the oligodendroglia or the myelin sheath; or 4) infection initiates activation of an immune response specific for either oligodendroglia or myelin components. Virus‐induced inflammation may be associated with the processing of myelin or oligodendroglial components and their presentation to the host's own T cell compartment. Alternatively, antigenic epitopes derived from the viral proteins may exhibit sufficient homology to host components that the immune response to the virus activates autoreactive T cells, i.e. molecular mimicry. Although it is not clear that each of these potential mechanisms participates in the pathogenesis of human demyelinating disease, analysis of the diverse demyelinating viral infections of both humans and rodents provides examples of many of these potential mechanisms.


title: The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry

text: Abstract This review summarizes the field's major findings related to the characterization of polyomavirus structures and to the characterization of virus receptors and mechanisms of host cell invasion. The four members of the family that have received the most attention in this regard are the mouse polyomavirus (mPyV), the monkey polyomavirus SV40, and the two human polyomaviruses, JCV and BKV. The structures of both the mPyV and SV40 alone and in complex with receptor fragments have been solved to high resolution. The majority of polyomaviruses recognize terminal sialic acid in either an α2,3 linkage or an α2,6 linkage to the underlying galactose. Studies on virus structure, receptor utilization and mechanisms of entry have led to new insights into how these viruses interact in an active way with cells to ensure the nuclear delivery and expression of their genomes. Critical work on virus entry has led to the discovery of a pH neutral endocytic compartment that accepts cargo from caveolae and to novel roles for endoplasmic reticulum (ER) associated factors in virus uncoating and penetration of ER membranes. This review will summarize the major findings and compare and contrast the mechanisms used by these viruses to infect cells.


title: Inflammatory Responses Regulating Alveolar Ion Transport during Pulmonary Infections

text: The respiratory epithelium is lined by a tightly balanced fluid layer that allows normal O(2) and CO(2) exchange and maintains surface tension and host defense. To maintain alveolar fluid homeostasis, both the integrity of the alveolar–capillary barrier and the expression of epithelial ion channels and pumps are necessary to establish a vectorial ion gradient. However, during pulmonary infection, auto- and/or paracrine-acting mediators induce pathophysiological changes of the alveolar–capillary barrier, altered expression of epithelial Na,K-ATPase and of epithelial ion channels including epithelial sodium channel and cystic fibrosis membrane conductance regulator, leading to the accumulation of edema and impaired alveolar fluid clearance. These mediators include classical pro-inflammatory cytokines such as TGF-β, TNF-α, interferons, or IL-1β that are released upon bacterial challenge with Streptococcus pneumoniae, Klebsiella pneumoniae, or Mycoplasma pneumoniae as well as in viral infection with influenza A virus, pathogenic coronaviruses, or respiratory syncytial virus. Moreover, the pro-apoptotic mediator TNF-related apoptosis-inducing ligand, extracellular nucleotides, or reactive oxygen species impair epithelial ion channel expression and function. Interestingly, during bacterial infection, alterations of ion transport function may serve as an additional feedback loop on the respiratory inflammatory profile, further aggravating disease progression. These changes lead to edema formation and impair edema clearance which results in suboptimal gas exchange causing hypoxemia and hypercapnia. Recent preclinical studies suggest that modulation of the alveolar–capillary fluid homeostasis could represent novel therapeutic approaches to improve outcomes in infection-induced lung injury.


title: Numerical modeling of exhaled droplet nuclei dispersion and mixing in indoor environments

text: Abstract The increasing incidence of indoor airborne infections has prompted attention upon the investigation of expiratory droplet dispersion and transport in built environments. In this study, a source (i.e. a patient who generates droplets) and a receiver (i.e. a susceptible object other than the source) are modeled in a mechanically ventilated room. The receiver's exposure to the droplet nuclei is analyzed under two orientations relative to the source. Two droplet nuclei, 0.1 and 10μm, with different emission velocities, are selected to represent large expiratory droplets which can still be inhaled into the human respiratory tracts. The droplet dispersion and mixing characteristics under well-mixed and displacement ventilation schemes are evaluated and compared numerically. Results show that the droplet dispersion and mixing under displacement ventilation is consistently poorer. Very low concentration regions are also observed in the displacement scheme. For both ventilation schemes, the intake dose will be reduced substantially if the droplets are emitted under the face-to-wall orientation rather than the face-to-face orientation. Implications of using engineering strategies for reducing exposure are briefly discussed.


title: Subviral Particle as Vaccine and Vaccine Platform

text: Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.


title: Work effort, readability and quality of pharmacy transcription of patient directions from electronic prescriptions: a retrospective observational cohort analysis

text: BACKGROUND: Free-text directions generated by prescribers in electronic prescriptions can be difficult for patients to understand due to their variability, complexity and ambiguity. Pharmacy staff are responsible for transcribing these directions so that patients can take their medication as prescribed. However, little is known about the quality of these transcribed directions received by patients. METHODS: A retrospective observational analysis of 529 990 e-prescription directions processed at a mail-order pharmacy in the USA. We measured pharmacy staff editing of directions using string edit distance and execution time using the Keystroke-Level Model. Using the New Dale-Chall (NDC) readability formula, we calculated NDC cloze scores of the patient directions before and after transcription. We also evaluated the quality of directions (eg, included a dose, dose unit, frequency of administration) before and after transcription with a random sample of 966 patient directions. RESULTS: Pharmacy staff edited 83.8% of all e-prescription directions received with a median edit distance of 18 per e-prescription. We estimated a median of 6.64 s of transcribing each e-prescription. The median NDC score increased by 68.6% after transcription (26.12 vs 44.03, p<0.001), which indicated a significant readability improvement. In our sample, 51.4% of patient directions on e-prescriptions contained at least one pre-defined direction quality issue. Pharmacy staff corrected 79.5% of the quality issues. CONCLUSION: Pharmacy staff put significant effort into transcribing e-prescription directions. Manual transcription removed the majority of quality issues; however, pharmacy staff still miss or introduce following their manual transcription processes. The development of tools and techniques such as a comprehensive set of structured direction components or machine learning–based natural language processing techniques may help produce clear directions.


title: Chapter 4 Antiviral Immunity and Virus Vaccines

text: Abstract This chapter describes mechanisms of antiviral immunity and prophylaxis, including innate and acquired host immunity and vaccination.


Applications of 3D Printing Technology to Address COVID-19 Related Supply Shortages


title: Evaluation of a rapid detection for Coxsackievirus B3 using one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP)

text: Abstract Coxsackievirus B3 (CVB3) is a member of the genus Enterovirus within the family Picornaviridae and is an important pathogen of viral myocarditis, which accounts for more than 50% viral myocarditis cases. VP1 is major capsid protein that this region has a low homology in both amino acid and nucleotide sequences among Enteroviruses. Therefore we have chosen this region for designed a set of RT-LAMP primers for CVB3 detection. For this the total RNA was extracted from 24-h post infected-HeLa cells with complete cytopathic effect (CPE), and applied to a one-step reverse transcription loop-mediated isothermal amplification reaction (RT-LAMP) using CVB3-specific primers. The optimization of RT-LAMP reaction was carried out with three variables factors including MgSO4 concentration, temperature and time of incubation. Amplification was analyzed by using 2% agarose gel electrophoresis and ethidium bromide and SYBR Green staining. Our results were shown the ladder-like pattern of the VP1 gene amplification. The LAMP reaction mix was optimized and the best result observed at 4mM MgSO4 and 60°C for 90min incubation. RT-LAMP had high sensitivity and specificity for detection of CVB3 infection. This method can be used as a rapid and easy diagnostic test for detection of CVB3 in clinical laboratories.


title: Electrospun Nanofibers-Based Face Masks

text: Textiles have proved to be very important materials to human beings since the time immemorial. And, fibers are the basic building units of these materials. In this perspective we substantiate the uniqueness and capability of nanofibers as active layers in face masks, to protect people against the novel coronavirus disease (COVID-19). This time-sensitive letter introduces the mechanisms based on which their active filters function, the uniqueness of electrospun nanofibers in face masks and do-it-yourself (DIY) steps to realize a fully functional face mask at home.


title: Serum α1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection

text: Previous studies have demonstrated that the concentration of α1-acid glycoprotein (AGP) transiently increases in asymptomatic cats infected with feline coronavirus (FCoV). In order to establish whether these fluctuations depend on the FCoV status, the serum concentration of AGP and anti-FCoV antibody titres and/or faecal shedding of FCoVs in clinically healthy cats from catteries with different levels of prevalence of FCoV infection were monitored over time. Serum AGP concentrations fluctuated over time in clinically healthy cats from the cattery with the highest prevalence of feline infectious peritonitis (FIP) and significantly increased just before an outbreak of FIP. Further studies are required to clarify whether the observed increase of AGP concentration is a consequence of the increased viral burden or a protective response against mutated viral strains. Nevertheless, the results of the present study suggest that AGP might be useful in monitoring FCoV–host interactions in FCoV-endemic catteries.


title: Clinical Outcomes in COVID‐19 Patients Treated with Tocilizumab: An Individual Patient Data Systematic Review

text: BACKGROUND: Current evidence suggests an important role of interleukin‐6 (IL‐6) pathway in SARS‐CoV‐2‐related cytokine release storm in severely ill COVID‐19 patients. Inhibition of the IL‐6 pathway with tocilizumab has been employed successfully in some of these patients but the data is mostly consistent of case reports and series. METHODS: We performed a systematic search of PubMed, Embase, and Medline from 22(nd) April 2020 and again on 27(th) April 2020 using the following search terms alone or in combination: “COVID‐19”, “coronavirus”, “SARS‐CoV‐2”, “COVID”, “anti‐interleukin 6 receptor antibodies”, “anti‐IL‐6”, “tocilizumab”, “sarilumab”, “siltuximab”. We included studies which reported individual patient data. We extracted and analyzed individual level data on baseline characteristics, laboratory findings, and clinical outcomes. Primary endpoint was in‐hospital mortality. Secondary endpoints included in‐hospital complications, recovery rates, effect of patient characteristics on the primary outcome and changes in levels of inflammatory markers. RESULTS: 352 records were identified through the systematic search of which 10 studies met the inclusion criteria. A single study currently under review was also added. Eleven observational studies encompassing 29 patients were included in the present review. There were more males (24 [82.8%]) and hypertension was the most common comorbidity (16 [48.3 %]). Over an average of 5.4 hospital days, the primary endpoint occurred in 6 (20.7%) patients. Among surviving patients, about 10% had worsened disease and 17% recovered. The most common complication was acute respiratory distress syndrome (8[27.6%]). IL‐6 level was significantly higher after the initiation of tocilizumab with median (IQR) of 376.6 (148‐900.6) pg/mL compared to the baseline of 71.1 (31.9‐122.8) pg/mL (p=0.002). Mean (SD) levels of c‐reactive protein (CRP) were significantly decreased following treatment 24.6 (26.9) mg/L compared to baseline 140.4 (77) mg/L (P< 0.0001). Baseline demographics were not significantly different amongst survivors and non‐survivors by Fisher's exact test. CONCLUSION: In COVID‐19 patients treated with tocilizumab, IL‐6 levels are significantly elevated which are supportive of cytokine storm. Following initiation of tocilizumab, there is elevation in the IL‐6 levels and CRP levels dramatically decrease suggesting an improvement in this hyper‐inflammatory state. Ongoing randomized control trials will allow for further evaluation of this promising therapy. IMPORTANCE: Recent data indicate that severe COVID 19 causes cytokine release storm and is associated with worse clinical outcomes and IL‐6 plays an important role. It is suggestive that anti‐IL6 results in the improvement of this hyperinflammatory state. However, to our knowledge, there is no individual patient data systematic review performed to summarize baseline characteristics and clinical outcomes of COVID 19 patients who received tocilizumab. This article is protected by copyright. All rights reserved.


title: Plant-based vaccines against viruses

text: Plant-made or “biofarmed” viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.


title: Clinical and CT findings of COVID-19: differences among three age groups

text: BACKGROUND: The novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) has spread around the world. We aimed to recapitulate the clinical and CT imaging features of COVID-19 and their differences in three age groups. METHODS: The clinical and CT data of patients with COVID-19 (n = 307) that had been divided into three groups (Group 1: < 40 years old; Group 2: 40 ≤ age < 60 years old; Group 3: ≥ 60 years old) according to age were analyzed retrospectively. RESULTS: Of all patients, 114 (37.1%) had histories of epidemiological exposure, 48 (15.6%) were severe/critical cases, 31 had hypertension (10.1%), 15 had diabetes mellitus (4.9%), 3 had chronic obstructive pulmonary disease (COPD, 1%). Among the three groups, severe/critical type, hypertension and diabetes occurred more commonly in the elderly group compared with Group 1&2 (P < 0.05, respectively). Cough and chest tightness/pain were more commonly appeared in Group 2&3 compared with Group 1 (P < 0.05, respectively). Compared with Group 1 and 2, there were more abnormal laboratory examination indexes (including CRP increase, abnormal percentage of lymphocytes, neutrophils and monocytes) in Group 3 (P < 0.05, respectively). CT images revealed that more lobes were affected and more subpleural lesions were involved in the elderly group, besides, crazy paving sign, bronchodilatation and pleural thickening were more commonly seen in the elderly group, with significant difference between Group 1&2, Group 2&3 (P < 0.05, respectively). CONCLUSIONS: COVID-19 presented representative clinical manifestations, laboratory examinations and CT findings, but three age groups possessed their own specific characteristics. Grasping the clinical and CT features stratified by age will be helpful for early definite diagnosis of COVID-19.


title: Coronavirus disease 2019 induces multi‐lineage, morphologic changes in peripheral blood cells

text: The clinical course of coronavirus disease 2019 (COVID‐19) varies from mild symptoms to acute respiratory distress syndrome, hyperinflammation, and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinflammation, particularly in severely ill patients. We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID‐19 patients. COVID‐19 associated morphologic changes were defined in a training cohort and subsequently validated in a second cohort (n = 45). Morphologic aberrations were further analyzed by electron microscopy (EM) and flow cytometry of lymphocytes was performed. We included 45 COVID‐19 patients in our study (median age 58 years; 82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi‐lineage aberrations in lymphocytes (80%) and monocytes (91%) of patients. Overall, 84%, 98%, and 98% exhibited aberrations in granulopoiesis, erythropoiesis, and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confirmed the multi‐lineage aberrations already seen by light microscopy. The morphologic pattern caused by COVID‐19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defined a hematologic COVID‐19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the hematologic system during the clinical course of COVID‐19 patients.


title: Serotype shift of a 793/B genotype infectious bronchitis coronavirus by natural recombination

text: Abstract An infectious bronchitis coronavirus, designated as ck/CH/LHLJ/140906, was isolated from an infectious bronchitis virus (IBV) strain H120-vaccinated chicken flock, which presented with a suspected infectious bronchitis virus (IBV) infection. A phylogenetic analysis based on the S1 gene clustered ck/CH/LHLJ/140906 with the 793/B group; however, a pairwise comparison showed that the 5′ terminal of the S1 gene (containing hypervariable regions I and II) had high sequence identity with the H120 strain, while the 3′ terminal sequence was very similar to that of IBV 4/91 strain. A SimPlot analysis of the complete genomic sequence, which was confirmed by a phylogenetic analysis and nucleotide similarities using the corresponding gene fragments, suggested that isolate ck/CH/LHLJ/140906 emerged from multiple recombination events between parental IBV strains 4/91 and H120. Although the isolate ck/CH/LHLJ/140906 had slightly higher S1 amino acid sequence identity to strain 4/91 (88.2%) than to strain H120 (86%), the serotype of the virus was more closely related to that of the H120 strain (32% antigenic relatedness) than to the 4/91 strain (15% antigenic relatedness). Whereas, vaccination of specific pathogen-free chickens with the 4/91 vaccine provided better protection against challenge with ck/CH/LHLJ/140906 than did vaccination with the H120 strain according to the result of virus re-isolation. As the spike protein, especially in the hypervariable regions of the S1 domain, of IBVs contains viral neutralizing epitopes, the results of this study showed that recombination of the S1 domain resulted in the emergence of a new serotype.


title: Long-term psychiatric morbidities among SARS survivors

text: Abstract Objective Severe acute respiratory syndrome (SARS) was the first massive infectious disease outbreak of the 21st century. However, it is unlikely that this outbreak will be the last. This study aimed to evaluate the long-term psychiatric morbidities in survivors of SARS. Method This is a cohort study designed to investigate psychiatric complications among SARS survivors treated in the United Christian Hospital 30 months after the SARS outbreak. Psychiatric morbidities were assessed by the Structured Clinical Interview for DSM-IV, the Impact of Events Scale–Revised and the Hospital Anxiety and Depression Scale. Functional outcomes were assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results Ninety subjects were recruited, yielding a response rate of 96.8%. Post-SARS cumulative incidence of DSM-IV psychiatric disorders was 58.9%. Current prevalence for any psychiatric disorder at 30 months post-SARS was 33.3%. One-fourth of the patients had post-traumatic stress disorder (PTSD), and 15.6% had depressive disorders. Conclusion The outbreak of SARS can be regarded as a mental health catastrophe. PTSD was the most prevalent long-term psychiatric condition, followed by depressive disorders. Our results highlight the need to enhance preparedness and competence of health care professionals in detecting and managing the psychological sequelae of future comparable infectious disease outbreaks.


title: COVID-19 Treatment: Close to a Cure? – A Rapid Review of Pharmacotherapies for the Novel Coronavirus

text: Currently, there is no approved therapy for COVID-19. The World Health Organization therefore endorse supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak in China. China's National Health Commission has issued the first COVID-19 Treatment Guideline with therapy suggestions (7(th) edition attached) which inspired following clinical studies worldwide. Major therapeutics are evaluated in this review. Key evidence from in vitro researches, animal models and clinical researches in emerging coronaviruses are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited to indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, and the studies on clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial.


title: Early T cell response in the central nervous system in canine distemper virus infection

text: The initial demyelinating lesions in canine distemper virus (CDV) infection develop during a period of severe immunosuppression in the absence of inflammation. In vitro and in vivo studies suggest that early demyelination is due to directly virus-induced oligodendroglial changes. In the present spatiotemporal study in experimentally CDV-infected dogs we observed diffuse up-regulation of T cells throughout the central nervous system (CNS) and T cell invasion in early demyelinating lesions. Invasion of T cells in the CNS occurred despite severe immunosuppression and without any perivascular cuffing. However, the major fraction of invading T cells correlated with sites of viral replication and coincided with the demonstration of an early immune response against the nucleocapsid protein of CDV. Activation of microglial cells was thought to have elicited the migration of T cells to the CNS by secretion of chemokines: marked IL-8 activity was found in the CSF of dogs with acute lesions. In areas of early demyelination, large numbers of CD3(+) cells accumulated in the tissue in the absence of any morphological sign of inflammation. Whether the T cells at lesion sites contribute to the development of acute demyelination remains uncertain at this stage. Antiviral cytotoxicity was not apparent since viral clearance in demyelinating lesions is only effective when B cells and concurring antiviral antibody production appeared in the subacute and chronic inflammatory stage of the disease. CD3(+) cells appear to persist for several weeks after infection since they were also found in recovered dogs that did not develop demyelination. Accumulation of immune cells, including a significant proportion of resting T cells (CD45RA(+)) in the CNS in the early stages of the disease may facilitate the later development of the intrathecal immune response and associated immunopathological complications.


title: Extracellular cyclophilins in health and disease

text: BACKGROUND: Extracellular cyclophilins (eCyPs) are pro-inflammatory factors implicated in pathogenesis of a number of inflammatory diseases. Most pathogenic activities of eCyPs are related to their chemotactic activity towards leukocytes, which is mediated by eCyP receptor on target cells, CD147, and involves peptydil-prolyl cis-trans isomerase activity of cyclophilins. This activity is inhibited by cyclosporine A (CsA) and non-immunosuppressive derivatives of this drug. Accumulating evidence for the role of eCyPs in disease pathogenesis stimulated research on the mechanisms of eCyP-initiated events, resulting in identification of multiple signaling pathways, characterization of a variety of effector molecules released from eCyP-treated cells, and synthesis of CsA derivatives specifically blocking eCyPs. However, a number of important questions related to the mode of action of eCyPs remain unanswered. SCOPE OF REVIEW: In this article, we integrate available information on release and function of extracellular cyclophilins into a unified model, focusing on outstanding issues that need to be clarified. MAJOR CONCLUSIONS: Extracellular cyclophilins are critical players in pathogenesis of a number of inflammatory diseases. Their mechanism of action involves interaction with the receptor, CD147, and initiation of a poorly characterized signal transduction process culminating in chemotaxis and production of pro-inflammatory factors. GENERAL SIGNIFICANCE: Extracellular cyclophilins present an attractive target for therapeutic interventions that can be used to alleviate symptoms and consequences of acute and chronic inflammation.


Subacute perimyocarditis in a young patient with COVID-19 infection


title: Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist

text: OBJECTIVE: In response to the American Academy of Otolaryngology – Head and Neck Surgery’s recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. With regulations for telemedicine loosened, new possibilities for the practice of otolaryngology have opened. To address the uncertain duration of this pandemic, a review was conducted of current literature on use of telemedicine services in the current SARS-CoV-2 pandemic and in previous national emergencies to reveal the role telemedicine can play for otolaryngology practices. DATA SOURCES: Pubmed articles with an independent search query were utilized. METHODS: Literature review performed by one author searched for all published English-language literature on telehealth in the SARS-CoV-2 era. Articles were considered for discussion if they provided relevant developments for telemedicine in the context of the SARS-CoV-2 pandemic. RESULTS: Telemedicine can be up-scaled in the current SARS-CoV-2 pandemic where exposure containment is of the utmost priority. With patient interaction possible through virtual communication, telemedicine allows continued patient care while minimizing the risk of viral spread. In the realm of otolaryngology, telemedicine has been used in the past during disasters with other studies demonstrating high diagnostic concordance with inpatient visits. Many institutions have recognized the potential for such care as they begin utilize both virtual visits and in-person care during this pandemic. CONCLUSION: To limit the spread of SARS-CoV-2, we support the AAO-HNS recommendation for the adoption of novel ways to employ telemedicine in this era. Many emergency departments and health care systems have the infrastructure necessary for synchronous video telemedicine visits that can be leveraged to provide quality care with patients. With the continued need to socially distance, telemedicine can protect both physicians and patients from unnecessary exposure to the virus.


title: Recommendations for Standards of Network Care for Patients with Parkinson’s Disease in Germany

text: Although our understanding of Parkinson’s disease (PD) has improved and effective treatments are available, caring for people with PD remains a challenge. The large heterogeneity in terms of motor symptoms, nonmotor symptoms, and disease progression makes tailored individual therapy and individual timing of treatment necessary. On the other hand, only limited resources are available for a growing number of patients, and the high quality of treatment cannot be guaranteed across the board. At this point, networks can help to make better use of resources and improve care. The working group PD Networks and Integrated Care, part of the German Parkinson Society, is entrusted to convene clinicians, therapists, nurses, researchers, and patients to promote the development of PD networks. This article summarizes the work carried out by the working group PD Networks and Integrated Care in the development of standards of network care for patients with PD in Germany.


Psoriasis and psoriatic arthritis: How to manage immunosuppressants in COVID‐19 days


Making sense of dictatorships and health outcomes


title: Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series

text: BACKGROUND: There is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights. METHODS: We present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center. FINDINGS: In seven patients (four female), regardless of anticoagulation status, all autopsies demonstrated platelet-rich thrombi in the pulmonary, hepatic, renal, and cardiac microvasculature. Megakaryocytes were seen in higher than usual numbers in the lungs and heart. Two cases had thrombi in the large pulmonary arteries, where casts conformed to the anatomic location. Thrombi in the IVC were not found, but the deep leg veins were not dissected. Two cases had cardiac venous thrombosis with one case exhibiting septal myocardial infarction associated with intramyocardial venous thrombosis, without atherosclerosis. One case had focal acute lymphocyte-predominant inflammation in the myocardium with no virions found in cardiomyocytes. Otherwise, cardiac histopathological changes were limited to minimal epicardial inflammation (n = 1), early ischemic injury (n = 3), and mural fibrin thrombi (n = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing. INTERPRETATION: In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis. FUNDING: None.


title: Altered regulatory cytokine profiles in cases of pediatric respiratory syncytial virus infection

text: Abstract Objectives Regulatory cytokines are associated with viral infection. The objective of this study was to evaluate the relation between serum regulatory cytokines concentrations and respiratory syncytial virus (RSV) disease. Methods We enrolled 325 children aged < 24 months who were diagnosed with acute respiratory tract infection. Twenty age-matched healthy children were enrolled as controls. Nasopharyngeal swabs were analyzed to identify virus by reverse transcription polymerase chain reaction, and blood samples were taken to quantify the regulatory cytokine concentrations, including interleukin (IL)-35, IL-10 and transforming growth factor (TGF)-β1 using the Bio-Plex immunoassay or enzyme-linked immunosorbent assay. Results RSV disease was associated with a great regulatory cytokine response than healthy children, among 89 RSV-infected patients, serum IL-35 (P = .0001) and IL-10 (P = .006) was significantly elevated in comparison with healthy controls. Young children (0< age ≤6 months) with RSV infection had significantly lower IL-35 and IL-10 expression but needed more oxygen therapy and more severe disease comparing with older children (12< age <24 months). Comparing with mild group, the expression levels of IL-10 were significantly lower in children with moderate and severe disease (P = .012 and P = .005, respectively). And levels of IL-10 was inversely associated with total duration of RSV infection symptoms (r = − 0.311, P = .019). Conclusion Children with RSV infected had increased serum regulatory cytokine IL-10 and IL-35 concentrations. Elevated expression of IL-10 and IL-35 were contributed to protect hypoxia and reduce the severity of disease.


title: Protein Microarrays for Personalized Medicine

text: Background: Over the last 10 years, DNA microarrays have achieved a robust analytical performance, enabling their use for analyzing the whole transcriptome or for screening thousands of single-nucleotide polymorphisms in a single experiment. DNA microarrays allow scientists to correlate gene expression signatures with disease progression, to screen for disease-specific mutations, and to treat patients according to their individual genetic profiles; however, the real key is proteins and their manifold functions. It is necessary to achieve a greater understanding of not only protein function and abundance but also their role in the development of diseases. Protein concentrations have been shown to reflect the physiological and pathologic state of an organ, tissue, or cells far more directly than DNA, and proteins can be profiled effectively with protein microarrays, which require only a small amount of sample material. Content: Protein microarrays have become well-established tools in basic and applied research, and the first products have already entered the in vitro diagnostics market. This review focuses on protein microarray applications for biomarker discovery and validation, disease diagnosis, and use within the area of personalized medicine. Summary: Protein microarrays have proved to be reliable research tools in screening for a multitude of parameters with only a minimal quantity of sample and have enormous potential in applications for diagnostic and personalized medicine.


title: Shuffling multivariate adaptive regression splines and adaptive neuro-fuzzy inference system as tools for QSAR study of SARS inhibitors

text: Abstract In this work, the inhibitory activity of pyridine N-oxide derivatives against human severe acute respiratory syndrome (SARS) is predicted in terms of quantitative structure–activity relationship (QSAR) models. These models were developed with the aid of multivariate adaptive regression spline (MARS) and adaptive neuro-fuzzy inference system (ANFIS) combined with shuffling cross-validation technique. A shuffling MARS algorithm is utilized to select the most important variables in QSAR modeling and then these variables were used as inputs of ANFIS to predict SARS inhibitory activities of pyridine N-oxide derivatives. A data set of 119 drug-like compounds was coded with over hundred calculated meaningful molecular descriptors. The best descriptors describing the inhibition mechanism were solvation connectivity index, length to breadth ratio, relative negative charge, harmonic oscillator of aromatic index, average molecular weight and total path count. These parameters are among topological, electronic, geometric, constitutional and aromaticity descriptors. The statistical parameters of R 2 and root mean square error (RMSE) are 0.884 and 0.359, respectively. The accuracy and robustness of shuffling MARS–ANFIS model in predicting inhibition behavior of pyridine N-oxide derivatives (pIC50) was illustrated using leave-one-out and leave-multiple-out cross-validation techniques and also by Y-randomization. Comparison of the results of the proposed model with those of GA-PLS-ANFIS shows that the shuffling MARS–ANFIS model is superior and can be considered as a tool for predicting the inhibitory behavior of SARS drug-like molecules.


title: The clinical characteristics of pediatric inpatients with SARS‐CoV‐2 infection: a meta‐analysis and systematic review

text: Millions of people were infected with the coronavirus disease 2019 (COVID‐19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID‐19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with SARS‐CoV‐2 infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS‐CoV‐2 infection which were published from 1‐January‐2020 to 21‐April‐2020. Studies with more than 5 pediatric inpatients were included in our meta‐analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS‐CoV‐2 infection and the other clinical characters such as Diarrhea, Vomiting, Nasal congestion, and Fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95%CI: 0.27‐0.59) and severe cases was 0.03(95%CI: 0.01‐0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase(AST) (19%), lymphopenia (16%), high alanine aminotransferase (ALT) (15%), high C‐reactive protein (CPR) (17%), lymphopenia (16%), leukocytosis (13%), high D‐dimer (12%) and high creatine kinase‐MB (CK‐MB)(5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS‐CoV‐2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS‐CoV‐2 infection in other countries should be conducted. This article is protected by copyright. All rights reserved.


title: Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways. It is unknown whether cellular infection by MERS-CoV activates the stress response pathway or whether the virus has evolved strategies to suppress this infection-limiting pathway. Here, we show that cellular infection with MERS-CoV does not lead to the formation of SGs. By transiently expressing the MERS-CoV accessory proteins individually, we identified a role of protein 4a (p4a) in preventing activation of the stress response pathway. Expression of MERS-CoV p4a impeded dsRNA-mediated PKR activation, thereby rescuing translation inhibition and preventing SG formation. In contrast, p4a failed to suppress stress response pathway activation that is independent of PKR and dsRNA. MERS-CoV p4a is a dsRNA binding protein. Mutation of the dsRNA binding motif in p4a disrupted its PKR antagonistic activity. By inserting p4a in a picornavirus lacking its natural PKR antagonist, we showed that p4a exerts PKR antagonistic activity also under infection conditions. However, a recombinant MERS-CoV deficient in p4a expression still suppressed SG formation, indicating the expression of at least one other stress response antagonist. This virus also suppressed the dsRNA-independent stress response pathway. Thus, MERS-CoV interferes with antiviral stress responses using at least two different mechanisms, with p4a suppressing the PKR-dependent stress response pathway, probably by sequestering dsRNA. MERS-CoV p4a represents the first coronavirus stress response antagonist described.


title: Assembly and immunogenicity of baculovirus-derived infectious bronchitis virus–like particles carrying membrane, envelope and the recombinant spike proteins

text: OBJECTIVE: To assemble infectious bronchitis virus (IBV)-like particles bearing the recombinant spike protein and investigate the humoral immune responses in chickens. RESULTS: IBV virus-like particles (VLPs) were generated through the co-infection with three recombinant baculoviruses separately encoding M, E or the recombinant S genes. The recombinant S protein was sufficiently flexible to retain the ability to self-assemble into VLPs. The size and morphology of the VLPs were similar to authentic IBV particles. In addition, the immunogenicity of IBV VLPs had been investigated. The results demonstrated that the efficiency of the newly generated VLPs was comparable to that of the inactivated M41 viruses in eliciting IBV-specific antibodies and neutralizing antibodies in chickens via subcutaneous inoculation. CONCLUSIONS: This work provides basic information for the mechanism of IBV VLP formation and develops a platform for further designing IBV VLP-based vaccines against IBV or other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-015-1973-3) contains supplementary material, which is available to authorized users.


title: No current evidence supporting risk of using Ibuprofen in patients with COVID‐19

text: SARS‐CoV‐2 is a novel RNA virus that infects cells expressing the angiotensin‐converting enzyme (ACE2) receptor and is associated with an acute respiratory disease named COVID‐19. It has been hypothesized that ACE2 expression can be increased by Ibuprofen leading to a higher risk for severe COVID‐19 (1). Despite the reasonable mechanistic background and results from studies suggesting that Ibuprofen may be associated with complications of community‐acquired pneumonia in children (2,3), there is no current evidence that this NSAID aggravates a SARS‐CoV‐2 infection in any age group.


title: Know your epidemic, know your response: Understanding and responding to the heterogeneity of the COVID‐19 epidemics across Southeast Asia

text: As living in the midst of the COVID‐19 pandemic becomes the new normal, the heterogeneity in the burden and secondary mortality across global epidemics has become increasingly evident. This is especially notable in Southeast Asia, a region with substantial variation in population density, income levels, access to healthcare, and public health infrastructure (Table). It has extensive travel exchanges with East Asia, but to date has experienced relatively limited local epidemics.


title: Pneumonia in the Emergency Department

text: Pneumonia remains one of the most common reasons for admission of emergency department (ED) patients to the hospital. Pneumonia also remains one of the most common causes of death in our patients. As with many emergent conditions, the ED management of these patients initiated by ED physicians contributes greatly to the survival and successful management of these patients. Specifically, the recognition of severe pneumonias, precise choice of diagnostic tests, and appropriate antibiotics can have an impact on the outcome.


title: Normalising the “new normal”: Changing tech-driven work practices under pandemic time pressure

text: The COVID-19 pandemic has had massive implications for the nature of work and the role technology plays in the workplace. Organisations have been forced into rapid ‘big bang’ introduction of technology and ‘tech-driven’ practices in an unprecedented and time pressured manner. In many cases there has been little training or reflection on how the practices and associated technology should be introduced and integrated or adapted to suit the new workplace context. We argue that there is a need for a more reflective ‘normalisation’ of work practices and the role technology plays. The paper draws on normalisation process theory (NPT) and its underlying components of cohesion, cognitive participation, collective action and reflexive monitoring. As an exemplar, we focus on the changing nature of work and adoption of remote working practices. The paper uses NPT to examine current thinking and approaches and offering some guidelines to inform research and practice.


Preparing for the unpredictable: The continuing need for pandemic influenza preparedness


title: Evaluation and Clinical Validation of Two Field–Deployable Reverse Transcription-Insulated Isothermal PCR Assays for the Detection of the Middle East Respiratory Syndrome–Coronavirus

text: Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean health care settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, the evaluation and validation of two newly developed reverse transcription–insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV are described. Compared with World Health Organization-recommended singleplex real-time quantitative RT-PCR (RT-qPCR) assays, both RT-iiPCR assays had comparable analytical sensitivity for the detection of MERS-CoV RNA in tissue culture fluid and in sputum samples spiked with infectious virus. Furthermore, clinical evaluation was performed with sputum samples collected from subjects with acute and chronic respiratory illnesses, including patients infected with MERS-CoV. The overall agreement values between the two RT-iiPCR assays and the reference RT-qPCR assays were 98.06% (95% CI, 94.43%–100%; κ = 0.96) and 99.03% (95% CI, 95.88%–100%; κ = 0.99) for ORF1a and upE assays, respectively. The ORF1a and upE MERS-CoV RT-iiPCR assays coupled with a field-deployable system provide a platform for a highly sensitive and specific on-site tool for diagnosis of MERS-CoV infections.


title: Anesthetic Management of Patients with COVID 19 Infections during Emergency Procedures

text: Objectives The aim of the present study was to prevent cross-infection in the operating room during emergency procedures for patients with confirmed or suspected 2019 novel coronavirus (2019-nCoV) by following anesthesia management protocols, and to document clinical- and anesthesia-related characteristics of these patients. Design This was a retrospective, multicenter clinical study. Setting This study used a multicenter dataset from 4 hospitals in Wuhan, China. Participants Patients and health care providers with confirmed or suspected 2019-nCoV from January 23 to 31, 2020, at the Wuhan Union Hospital, the Wuhan Children's Hospital, The Central Hospital of Wuhan, and the Wuhan Fourth Hospital in Wuhan, China. Interventions Anesthetic management and infection control guidelines for emergency procedures for patients with suspected 2019-nCoV were drafted and applied in 4 hospitals in Wuhan. Measurements and Main Results Cross-infection in the operating rooms of the 4 hospitals was effectively reduced by implementing the new measures and procedures. The majority of patients with laboratory-confirmed 2019-nCoV infection or suspected infection were female (23 [62%] of 37), and the mean age was 41.0 years old (standard deviation 19.6; range 4-78). 10 (27%) patients had chronic medical illnesses, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients presented with lymphopenia, and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on computed tomography scanning. Conclusions The present study indicates that COVID 19–specific guidelines for emergency procedures for patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating room. Most patients with confirmed or suspected COVID 19 presented with fever and dry cough and demonstrated bilateral multiple mottling and ground-glass opacity on chest computed tomography scans.


title: Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations

text: ABSTRACT Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = 6) genes. Four SAMD9 patients had features of MIRAGE syndrome. Median age at HCT was 2.8 years (range, 1.2 to 12.8 years). Conditioning was myeloablative in 9 cases and reduced intensity in 3 cases. Syndrome-related comorbidities (diarrhea, infections, adrenal insufficiency, malnutrition, and electrolyte imbalance) were present in MIRAGE syndrome cases. One patient with a familial SAMD9L mutation, MDS, and morbid obesity failed to engraft and died of refractory acute myeloid leukemia. The other 11 patients achieved neutrophil engraftment. Acute post-transplant course was complicated by syndrome-related comorbidities in MIRAGE cases. A patient with SAMD9L-associated MDS died of diffuse alveolar hemorrhage. The other 10 patients had resolution of hematologic disorder and sustained peripheral blood donor chimerism. Ten of 12 patients were alive with a median follow-up of 3.1 years (range, 0.1 to 14.7 years). More data are needed to refine transplant approaches in SAMD9/SAMD9L patients with significant comorbidities and to develop guidelines for their long-term follow-up.


title: Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay

text: Abstract Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis–trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS_1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micro-molar level (compounds 1–15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1–6, 15, 16a–q, 17a–d, and 18a–l), and four of which (compounds 16b, 16h, 16k, and 18g) showed high CypA PPIase inhibition activities with IC50s of 2.5–6.2μM. Pharmacological assay indicated that these four compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells.