title: The direction of restructuring of a Korea field epidemiology training program through questionnaire survey among communicable disease response staff in Korea

text: We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.


title: Zinc lozenges as cure for the common cold – A review and hypothesis

text: Summary A 7-day reduction in duration of common colds was shown by Eby et al. in 1984 using 23mg zinc gluconate throat lozenges. Over the following 25years, 14 double-blind, placebo-controlled, randomized clinical trials produced widely differing results with about one-half showing success and the remainder showing failure. Positively charged, ionic zinc (iZn), but not bound zinc, is strongly astringent, antirhinoviral, increases interferon-gamma (IFN-γ) 10-fold, inhibits intercellular adhesion molecule-1 (ICAM-1) and inhibits the release of vasoactive ingredients from mast cell granules. Solution equilibrium chemistry analytical techniques showed lozenge iZn fraction varying from 0% to 100% of total lozenge zinc between trials, with zinc acetate (ZA) releasing 100% iZn, zinc gluconate (ZG) releasing 72% iZn and other zinc compounds releasing much less or none at physiologic pH 7.4. Since only iZn has in vitro benefits, iZn variations are hypothesized to have produced the widely varying clinical results. In support of the iZn hypothesis, lozenge iZn and total daily iZn in trials were found highly correlated with reductions in common cold durations with statistical significance for mean duration (P <0.001) and median duration (P <0.004), while total zinc (iZn plus bound) showed no correlation with changes in duration. Duration reductions (mean 0days, median 0.43days) for multi-ligand ZG and ZA lozenges differed significantly from duration reductions (mean 3.37days, median 2.9days) for single ligand ZA and ZG lozenges (P <0.001) showing that additive ligands as flavor-masks damaged or eliminated efficacy. Five of 6 trials with lozenges whose zinc compositions had a first stability constant of 1.7 or less succeeded, while only 2 of 9 trials of lozenges with higher stability succeeded (P <0.02). From the strong, multiple statistical relationships found, it is inferred that iZn is the active ingredient in zinc lozenges for colds, as it is in vitro against rhinoviruses, and that solution chemistry analytical techniques used at physiological pH are correct means for lozenge iZn analysis. Zinc lozenges slowly dissolving in the mouth over a 20–30min period releasing adequate iZn (⩾18mg) used each 2h are hypothesized to shorten common colds by 6–7days, which is a cure for the common cold. Due to inadequate lozenge iZn very few of more than 40 different brands of zinc lozenges on the US market are expected to have any effect on the duration or severity of common colds.


title: A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic

text: Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.


title: Novel Approach to Reduce Transmission of COVID-19 During Tracheostomy

text: ABSTRACT Severe infection involving the novel coronavirus 2019 (COVID-19) has been associated with acute respiratory distress syndrome that subsequently requires patients to be intubated and dependent on mechanical ventilation. In the setting of the recent pandemic, there is a greater need to perform tracheostomy for these patients. With the high transmissibility of the virus, there has been an increasing concern for the development of techniques to perform surgical intervention while mitigating the risk for infecting hospital staff. As more data emerge pertaining to viral shedding in various bodily fluids, it has become more important to give special attention to precautions. In this article, we submit a novel approach for better protection and thus reduced transmission for tracheostomy in a COVID-19 positive patient. Importantly, this technique is functional, easy to set up, and can be used for additional operations that involve risk of aerosolization or droplet exposure to operating room staff.


title: Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis

text: INTRODUCTION: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. METHOD: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. RESULT: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5% (95% CI 54.5–79, p < 0.001) of patients had a history of recent travel endemic area or contact with them. The most common symptoms among COVID-19 infected patients were fever 87% (95% CI 73–93, p < 0.001), and cough 68% (95% CI 55.5–74, p < 0.001)), respectively. The laboratory analysis showed that thrombocytosis was present in 61% (95% CI 41–78, p < 0.001) CRP was elevated in 79% (95% CI 65–91, p < 0.001), and lymphopenia in 57.5% (95% CI 42–79, p < 0.001). The most common radiographic signs were bilateral involvement in 81% (95% CI 62.5–87, p < 0.001), consolidation in 73.5% (95% CI 50.5–91, p < 0.001), and ground-glass opacity 73.5% (95% CI 40–90, p < 0.001) of patients. Case fatality rate (CFR) in <15 years old was 0.6%, in >50 years old was 39.5%, and in all range group was 6%. CONCLUSIONS: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.


title: Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID‐19 pandemic: The Princess Margaret experience and proposal

text: BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT‐hypo) during the COVID‐19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT‐hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT‐acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005‐2017 were included. Locoregional control (LRC) and distant control (DC) after RT‐hypo, RT‐acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus–positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT‐hypo, RT‐acc, and CCRT, respectively) and 1045 HPV– HNSCC cases (with 263, 451, and 331 receiving RT‐hypo, RT‐acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy‐alone patients were older. The median follow‐up was 4.6 years. RT‐hypo, RT‐acc, and CCRT produced comparable 3‐year LRC and DC for HPV+ T1‐2N0‐N2a disease (seventh edition of the TNM system [TNM‐7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1‐T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1‐2N2c/T3N0‐N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT‐hypo or RT‐acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV– HNSCC, 3‐year LRC and DC were similar with RT‐hypo, RT‐acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT‐hypo and RT‐acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT‐acc (62%) but not RT‐hypo (80%) or CCRT (92%; RT‐hypo vs CCRT: P = .270; RT‐acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT‐hypo or RT‐acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT‐hypo be considered in place of CCRT for HPV+ T1‐T3N0‐N2c (TNM‐7) HNSCCs, HPV– T1‐T2N0 HNSCCs, and select stage III HNSCCs during the COVID‐19 outbreak.


title: A rapid immunochromatographic test strip for detecting rabies virus antibody

text: Abstract An immunochromatographic test strip (ICTS) for detecting antibodies to rabies virus was developed, using colloidal gold particles labeled with rabies virus glycoprotein as the tracer. The assay was evaluated using sera from dogs immunized with various commercial rabies vaccines, or from dogs in the clinics and sera from dogs immunized with vaccines against pathogens other than rabies virus, and negative sera from a wide variety of animal sources, including dogs, mice, and cats which had never been vaccinated. The ICTS was found to be highly specific for antibodies against rabies virus, with a detection limit of 0.5IU/ml as measured by the fluorescent antibody virus neutralization (FAVN) test. Compared with the FAVN test, the specificity and sensitivity of ICTS were 98.2% and 90.4%, respectively. There was an excellent agreement between results obtained by the ICTS and FAVN tests (kappa=0.888). Strips stored at 4°C in a plastic bag with a desiccant retained their specificity and sensitivity for at least 15 months, and strips stored at ambient temperature remained stable for 12 months. The immunochromatographic test strip may therefore be useful for clinical laboratories lacking specialized equipment and for diagnosis in the field for rapid detection of rabies virus-specific antibodies.


title: Grouper TRIM13 exerts negative regulation of antiviral immune response against nodavirus

text: Abstract The tripartite motif (TRIM)-containing proteins have attracted particular attention to their multiple functions in different biological processes. TRIM13, a member of the TRIM family, is a RING domain-containing E3 ubiquitin ligase which plays critical roles in diverse cellular processes including cell death, cancer and antiviral immunity. In this study, a TRIM13 homolog from orange spotted grouper, Epinephelus coioides (EcTRIM13) was cloned and characterized. The full-length of EcTRIM13 cDNA encoded a polypeptide of 399 amino acids which shared 81% identity with TRIM13 homolog from large yellow croaker (Larimichthys crocea). Amino acid alignment analysis showed that EcTRIM13 contained conserved RING finger and B-box domain. Expression patterns analysis indicated that EcTRIM13 was abundant in liver, spleen, kidney, intestine and gill. Moreover, the transcript of EcTRIM13 in grouper spleen was differently regulated after injection with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C). Under fluorescence microscopy, we observed the tubular structure in wild type EcTRIM13 transfected cells, but the RING domain mutant resulted in the fluorescence distribution was changed and the bright punctate fluorescence was evenly situated throughout the cytoplasm, suggesting that the RING domain was essential for its accurate localization. Overexpression of EcTRIM13 in vitro obviously increased the replication of red spotted grouper nervous necrosis virus (RGNNV), and the enhancing effect of EcTRIM13 on virus replication was affected by the RING domain. Furthermore, the ectopic expression of EcTRIM13 not only negatively regulated the interferon promoter activity induced by interferon regulator factor (IRF) 3, IRF7, and melanoma differentiation-associated protein 5 (MDA5), but also decreased the expression of several interferon related factors. In addition, the overexpression of EcTRIM13 also differently regulated the transcription of pro-inflammatory factors. Together, our results firstly demonstrated that fish TRIM13 exerted negative regulation of antiviral response against nodavirus infection.


title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature

text: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.


title: The environmental and economic analysis of grid-connected photovoltaic power systems with silicon solar panels, in accord with the new energy policy in Iran

text: Abstract In recent years, authorities in Iran have introduced supporting policies for renewable energy resources but there is no comprehensive and updated survey from this perspective. The aim of this work is to give a comprehensive survey on the country background from energy outlook and its prominent policies for renewable energy resources. Due to the high CO2 emissions alongside with the high solar energy harvesting potential in Iran, We have presented a clear simulation on 20 kW and 1 MW grid-connected photovoltaic (PV) power plants using RETScreen software to determine the environmental and economic aspects based on the net greenhouse gases (GHG) emissions reduction, the annual electricity exported to the grid, the cumulative cash flows, and the payback period for the initial investment. According to this simulation, the annual GHG emissions reduction and the annual electricity exported to the grid for 20 kW and 1 MW PV power plants are 22.06 tCO2, 1103 tCO2, 39 MWh, and 1953 MWh, respectively. From the economic outlook, based on the new feed-in tariff for power plants and the supposed initial costs, the payback period for the initial investments are between 3 and 4, and 5 years for 20 kW and 1 MW PV power plants, respectively.


title: Homologous Recombination as an Evolutionary Force in African Swine Fever Viruses

text: Recent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.


title: The use of genomics in microbial vaccine development

text: Vaccination is one of the most effective tools for the prevention of infectious diseases. The availability of complete genome sequences, together with the progression of high-throughput technologies such as functional and structural genomics, has led to a new paradigm in vaccine development. Pan-genomic reverse vaccinology, with the comparison of sequence data from multiple isolates of the same species of a pathogen, increases the opportunity of the identification of novel vaccine candidates. Overall, the conventional empiric approach to vaccine development is being replaced by vaccine design. The recent development of synthetic genomics may provide a further opportunity to design vaccines.


title: Predicting Interactions between Virus and Host Proteins Using Repeat Patterns and Composition of Amino Acids

text: Previous methods for predicting protein-protein interactions (PPIs) were mainly focused on PPIs within a single species, but PPIs across different species have recently emerged as an important issue in some areas such as viral infection. The primary focus of this study is to predict PPIs between virus and its targeted host, which are involved in viral infection. We developed a general method that predicts interactions between virus and host proteins using the repeat patterns and composition of amino acids. In independent testing of the method with PPIs of new viruses and hosts, it showed a high performance comparable to the best performance of other methods for single virus-host PPIs. In comparison of our method with others using same datasets, our method outperformed the others. The repeat patterns and composition of amino acids are simple, yet powerful features for predicting virus-host PPIs. The method developed in this study will help in finding new virus-host PPIs for which little information is available.


Large-scale mapping of the Ebola NP and GP proteins reveals multiple immunoprevalent and conserved CD4 T-cell epitopes


title: Evaluación de la teleconsulta en el paciente urológico durante la pandemia COVID 19

text: Abstract Introduction: The global pandemic of COVID-19 has led to rapid implementation of telemedicine, but there is little information on patient satisfaction of this system as an alternative to face-to-face care. Objective. To evaluate urological patient satisfaction with teleconsultation during the COVID-19 pandemic. Material and methods: Observational, prospective, cross-sectional, non-interventional study carried out by telephone survey during the period considered as the peak of the pandemic (March-April 2020). A quality survey composed of 11 questions on urological care provided by physicians during the COVID-19 pandemic was conducted, selecting a representative sample of patients attended by teleconsultation. Results: Two hundred patients were contacted by telephone to answer a survey on the quality of teleconsultation. The distribution of patients surveyed among the specialized consultations was homogeneous with the number of consultations cited in the period;18% of them required assistance from family members. Sixty percent of patients avoided going to a medical center during the pandemic. Of the surveyed patients, 42% had cancelled diagnostic tests, 59% had cancelled medical consultations, 3.5% had cancelled treatments and 1%, had cancelled interventions. Ten percent reported a worsening of urological symptoms during confinement. According to physicians, consultations were effectively delivered in 72% of cases, with teleconsultation being carried out by their usual urologist in 81%. Teleconsultation overall satisfaction level was 9 (IQI 8-10), and 61.5% of respondents consider teleconsultation as a "health care option" after the healthcare crisis. Conclusion: Teleconsultation has been evaluated with a high level of satisfaction during the COVID-19 pandemic, offering continuous care to urological patients during the healthcare crisis. The perceived quality offers a field of optional telematic assistance in selected patients, which should be re-evaluated in a period without confinement measures.


title: Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion-associated protein

text: Abstract Eight accessory proteins have been identified in severe acute respiratory syndrome-associated coronavirus (SARS-CoV). They are believed to play roles in the viral life cycle and may contribute to the pathogenesis and virulence. ORF9b as one of these accessory proteins is located in subgenomic mRNA9 and encodes a 98 amino acid protein. However, whether 9b protein is a structural component of SARS-CoV particles remains unknown. In this study, we demonstrate that 9b protein is translated from bicistronic mRNA9 via leaky ribosome scanning and it is incorporated into both virus-like particles (VLPs) and purified SARS-CoV virions. Further analysis shows that sufficient incorporation of 9b protein into VLPs is dependent upon the co-expression of E and M proteins, but not upon the presence of either S or N protein. Our data indicate that 9b protein of SARS-CoV is another virion-associated accessory protein. This finding will lead to a better understanding of the properties of the SARS-CoV 9b protein.


title: Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

text: Abstract Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups.


title: Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance

text: Abstract Alarming situation has been caused due to the emergence of COVID-19 infection around the world. There is an urgency of developing a therapeutic strategy in order to control the spread of COVID-19. Towards that initiative, potential drugs like hydroxychloroquine, ivermectin and azithromycin have been tested by diverse group of researchers worldwide for their potential against novel coronavirus. The present report presents together the comprehensive knowledge derived from the major researches about the above drugs altogether in context of the current health emergency around the world. Hydroxychloroquine and ivermectin were known to act by creating the acidic environment and inhibiting the importin (IMPα/β1) mediated viral import. Azithromycin was found to act similar to the hydroxychloroquine as an acidotropic lipophilic weak base. All the three categories of drugs seemed to potentially act against novel coronavirus infection. However, their efficacies need to be studied in detail individually and in combination in-vivo in order to combat COVID-19 infection.


title: e-Tourism beyond COVID-19: a call for transformative research

text: This viewpoint article argues that the impacts of the novel coronavirus COVID-19 call for transformative e-Tourism research. We are at a crossroads where one road takes us to e-Tourism as it was before the crisis, whereas the other holds the potential to transform e-Tourism. To realize this potential, e-Tourism research needs to challenge existing paradigms and critically evaluate its ontological and epistemological foundations. In light of the paramount importance to rethink contemporary science, growth, and technology paradigms, we present six pillars to guide scholars in their efforts to transform e-Tourism through their research, including historicity, reflexivity, equity, transparency, plurality, and creativity. We conclude the paper with a call to the e-Tourism research community to embrace transformative research.


title: Initial events in the pathogenesis of acute tonsillitis caused by Streptococcus pyogenes 1 This paper was presented in part at the XVI World Congress of Otorhinolaryngology, Head and Neck Surgery, Sydney, Australia, March 2–7, 1997. 1

text: Abstract Bacterial and epithelial cell samples were obtained, within 24 h of onset of pharyngeal symptoms, from the palatine tonsils of nine patients (four female and five male; age range 10–40 years, median age 23) with acute tonsillitis, culture-positive for Streptococcus pyogenes. The specimens were examined using fluorescein isothiocyanate- (FITC) and gold-labelled antiserum to S. pyogenes and fluorescence, scanning electron and transmission electron microscopy. S. pyogenes could be identified both in the mucous layer covering the tonsils and attached to the surface epithelial cells. Long chains of coccus-shaped bacteria could be seen encroaching on the epithelial cell borders. S. pyogenes can apparently penetrate the mucous barrier, attach to the epithelial cells, spread from cell to cell and possibly penetrate into the outermost layer of the epithelial cells. These events in turn provoke cytokine production and/or complement activation, which induce inflammatory reaction in the tonsillar tissue.


title: Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

text: Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.


title: Relationship Between Clinical Features and Computed Tomographic Findings in Hospitalized Adult Patients With Community-Acquired Pneumonia

text: Abstract Background Data on the relationship between the clinical and microbiological features of community-acquired pneumonia (CAP) and its computed tomography (CT) findings are limited. The aim of the present study was to investigate the clinic-microbiological features of patients with CAP presenting with ground-glass opacity (GGO) and centrilobular nodules or tree-in-bud pattern on CT images. Methods Patients with CAP who underwent a CT scan at presentation were retrospectively classified using CT findings into consolidation, GGO and bronchiolitis groups. These 3 groups were compared in terms of clinical parameters and microbiological data. Results A total of 40 patients (2.4%) were allocated to the bronchiolitis group and 46 (2.8%) to the GGO group. The most common pathogen in the bronchiolitis group was Mycoplasma pneumoniae, which was significantly more frequently isolated in this group. The bronchiolitis group was characterized by a higher percentage of cough, a lower percentage of chest pain and lower blood levels of inflammatory markers. Common pathogens in the GGO group were not significantly different from those in the other 2 groups. Unlike that observed in the consolidation group, complicated parapneumonic effusion or empyema was not observed in the bronchiolitis or GGO group. Outcome variables were similar in the 3 groups. Conclusions The bronchiolitis group was characterized by a higher frequency of M. pneumoniae and a less severe form of CAP. The GGO and consolidation groups was similar with respect to causative microorganisms and the clinical features of CAP. No patient in the bronchiolitis or GGO group exhibited complicated parapneumonic effusion or empyema.


title: Applications of analytical ultracentrifugation to protein size-and-shape distribution and structure-and-function analyses

text: Abstract The rebirth of modern analytical ultracentrifugation (AUC) began in 1990s. Since then many advanced AUC detectors have been developed that provide a vast range of versatile choices when characterizing the physical and chemical features of macromolecules. In addition, there have been remarkable advances in software that allow the analysis of AUC data using more sophisticated models, including quaternary structures, conformational changes, and biomolecular interactions. Here we report the application of AUC to protein size-and-shape distribution analysis and structure-and-function analysis in the presence of ligands or lipids. Using band-sedimentation velocity, quaternary structural changes and an enzyme’s catalytic activity can be observed simultaneously. This provides direct insights into the correlation between quaternary structure and catalytic activity of the enzyme. On the other hand, also in this study, we have applied size-and-shape distribution analysis to a lipid-binding protein in either an aqueous or lipid environment. The sedimentation velocity data for the protein with or without lipid were evaluated using the c(s,f r) two-dimensional distribution model, which provides a precise and quantitative means of analyzing the protein’s conformational changes.


title: Tracking the origin of early COVID-19 cases in Canada

text: Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.


title: Small Animal Models of Respiratory Viral Infection Related to Asthma

text: Respiratory viral infections are strongly associated with asthma exacerbations. Rhinovirus is most frequently-detected pathogen; followed by respiratory syncytial virus; metapneumovirus; parainfluenza virus; enterovirus and coronavirus. In addition; viral infection; in combination with genetics; allergen exposure; microbiome and other pathogens; may play a role in asthma development. In particular; asthma development has been linked to wheezing-associated respiratory viral infections in early life. To understand underlying mechanisms of viral-induced airways disease; investigators have studied respiratory viral infections in small animals. This report reviews animal models of human respiratory viral infection employing mice; rats; guinea pigs; hamsters and ferrets. Investigators have modeled asthma exacerbations by infecting mice with allergic airways disease. Asthma development has been modeled by administration of virus to immature animals. Small animal models of respiratory viral infection will identify cell and molecular targets for the treatment of asthma.


Neonatal Diarrhea and Septicemia in an American Miniature Horse


title: Sequence analysis of the N, P, M and F genes of Canadian human metapneumovirus strains

text: Abstract The complete nucleotide sequences of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) genes of 15 Canadian human metapneumovirus (hMPV) isolates were determined. Phylogenetic analysis revealed two distinct genetic clusters, or groups for each gene with additional sequence variability within the individual groups. Comparison of the deduced amino acid sequences for the N, M and F genes of the different isolates revealed that all three genes were well conserved with 94.1–97.6% identity between the two distinct clusters The P gene showed more diversity with 81.6–85.7% amino acid identity for isolates between the two clusters, and 94.6–100% for isolates within the same cluster.


title: Pausing the Fight Against Malaria to Combat the COVID-19 Pandemic in Africa: Is the Future of Malaria Bleak?

text: Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In 2019, a Phase IV Expanded Programme on Immunization (EPI)-linked malaria vaccine implementation was underway. However, in December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many clinical, epidemiological, and biological parallels to malaria, was reported in Wuhan, China. COVID-19 is spreading rapidly, and, as of the 3rd of June, 2020, more than 382,507 persons had died from COVID-19. Children under 5 years who suffer high malaria-attributable mortalities are largely asymptomatic for COVID-19. Considering that the malaria burden is highest in low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hampered. Access to healthcare has generally been limited, while malaria interventions, such as seasonal malaria chemotherapy and distribution of insecticide-treated bed nets, have been suspended due to lockdowns. Likewise, the repurposing of antimalarials for treatment of COVID-19 shared symptoms and the shift in focus from the production of malaria rapid diagnostic tests (RDTs) to COVID-19 RDTs is a cause for concern in malaria-endemic regions. Children are less affected by the COVID-19 pandemic compared to the elderly. However, due to the fears of contracting SARS-CoV-2, the elderly who are worst affected by COVID-19 may not take children for malaria medication, resulting in high malaria-related mortalities among children. COVID-19 has disproportionately affected developed countries, threatening their donation capacity. These are likely to thwart malaria control efforts in low-income regions. Here, we present perspectives on the collateral impact of COVID-19 on malaria, especially in Africa.


title: Virus-induced secondary bacterial infection: a concise review

text: Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus–bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness.


title: Design of recombinant protein-based SARS-CoV entry inhibitors targeting the heptad-repeat regions of the spike protein S2 domain

text: Abstract Entry of SARS-CoV into a target cell is initiated by binding of the S1 domain of spike protein to a receptor, followed by conformational changes of the spike protein S2 domain, resulting in the formation of a six-helix bundle by the heptad-repeat (HR1 and HR2) regions. Our previous studies have demonstrated that peptides derived from HR2 region could inhibit SARS-CoV entry. However, synthesis of these peptides is at high cost. In this study, we designed two recombinant proteins, one containing two HR1 and one HR2 peptides (denoted HR121), and the other consisting of two HR2 and one HR1 peptides (designated HR212). These two proteins could be easily purified with the low cost of production, exhibiting high stability and potent inhibitory activity on entry of the HIV/SARS pseudoviruses with IC50 values of 4.13 and 0.95μM, respectively. These features suggest that HR121 and HR212 can serve as potent inhibitors of SARS-CoV entry.


title: Interpretation of CT signs of 2019 novel coronavirus (COVID-19) pneumonia

text: OBJECTIVES: To characterize and interpret the CT imaging signs of the 2019 novel coronavirus (COVID-19) pneumonia in China. MATERIALS AND METHODS: The CT images of 130 patients diagnosed as COVID-19 pneumonia from several hospitals in China were collected and their imaging features were analyzed and interpreted in detail. RESULTS: Among the 130 patients, we can see (1) distribution: 14 cases with unilateral lung disease and 116 cases with bilateral disease, the distribution was mainly lobular core (99 cases) and subpleural (102 cases); (2) number: 9 cases with single lesion, 113 cases with multiple lesions, and 8 cases with diffuse distribution; (3) density: 70 cases of pure ground glass opacity (GGO), and 60 cases of GGO with consolidation; (4) accompanying signs: vascular thickening (100 cases), “parallel pleura sign” (98 cases), “paving stone sign” (100 cases), “halo sign” (18 cases), “reversed halo sign” (6 cases), pleural effusion (2 cases), and pneumonocele (2 cases). After follow-up CT examination on 35 patients, 21 cases turned better and 14 became worse. There were signs of consolidation with marginal contraction, bronchiectasis, subpleural line, or fibrous streak. CONCLUSION: GGO and consolidation are the most common CT signs of COVID-19 pneumonia, mainly with lobular distribution and subpleural distribution. The main manifestations were tissue organization and fibrosis at late stage. The most valuable features are the parallel pleura sign and the paving stone sign. KEY POINTS: • The CT signs of the COVID-19 pneumonia are mainly distributed in the lobular core, subpleural and diffused bilaterally. • The CT signs include the “parallel pleura sign,” “paving stone sign,” “halo sign,” and “reversed halo sign.” • During the follow-up, the distribution of lobular core, the fusion of lesions, and the organization changes at late stage will appear.


title: Influenza B viral load analysis in patients with acute respiratory infection from a tertiary hospital in Brazil

text: Currently, 2 genotypes of Influenza B viruses (IFB) are cocirculating in humans: Victoria (VIC) and Yamagata (YAM). Infection and viral load (VL) were analyzed in 105 genotyped IFB (59 VIC and 46 YAM) out of 3452 respiratory samples from immunodepressed (ID), immunocompetent (IC) including outpatients (OP) and hospitalized patients (HP) attended during 2001‐2013 at São Paulo Hospital. VL (Log(10) RNA copies/mL) calculation was possible in 78 samples (47 VIC, 31 YAM). The age group of 12 to 18 years presented the highest detection (14.13%). Rates of infection among groups were of 3.67% (IC), 1.68% (ID), 3.50% (OP), 0.6% (HP), and VLs varied from 2.8 to 10.13 with no difference regarding age, immune status, and disease severity. From 10 OP vaccinated against influenza, 8 (7 children, 1 ID) received a matching strain shot (VIC), and 2 a monovalent influenza A H1N1pdm09. Those patients presented a VL of 6.31 ± 1.62 (mean ± SD). IFB infection rates follow an age pattern, but VL seems not to be related to frequency or clinical outcome. IFB patients with previous immunization could point to some protection for VIC infections since there was no HP. Other immunological aspects, such as lineage infection immune priming, previous infections, and vaccinations, should be further investigated.


title: Evolutionary dynamics of recent peste des petits ruminants virus epidemic in China during 2013–2014

text: Abstract Peste des petits ruminants virus (PPRV) causes a highly contagious disease, peste des petits ruminants (PPR), in sheep and goats which has been considered as a serious threat to the local economy in Africa and Asia. However, the in-depth evolutionary dynamics of PPRV during an epidemic is not well understood. We conducted phylogenetic analysis on genomic sequences of 25 PPRV strains from China 2013–2014 outbreaks. All these strains clustered into a novel clade in lineage 4. An evolutionary rate of 2.61 × 10−6 nucleotide substitutions per site per day was estimated, dating the most recent common ancestor of PPRV China 2013–2014 strains to early August 2013. Transmission network analysis revealed that all the virus sequences could be grouped into five clusters of infection, suggesting long-distance animal transmission play an important role in the spread of PPRV in China. These results expanded our knowledge for PPRV evolution to achieve effective control measures.


A tale of two cities: a comparison of Hong Kong and Singapore's early strategies for the Coronavirus Disease 2019 (COVID-19)


title: The health impacts of globalisation: a conceptual framework

text: This paper describes a conceptual framework for the health implications of globalisation. The framework is developed by first identifying the main determinants of population health and the main features of the globalisation process. The resulting conceptual model explicitly visualises that globalisation affects the institutional, economic, social-cultural and ecological determinants of population health, and that the globalisation process mainly operates at the contextual level, while influencing health through its more distal and proximal determinants. The developed framework provides valuable insights in how to organise the complexity involved in studying the health effects resulting from globalisation. It could, therefore, give a meaningful contribution to further empirical research by serving as a 'think-model' and provides a basis for the development of future scenarios on health.


title: Bid cleavage, cytochrome c release and caspase activation in canine coronavirus-induced apoptosis

text: Abstract A previous study demonstrated that infection of a canine fibrosarcoma cell line (A-72 cells) by canine coronavirus (CCoV) resulted in apoptosis (Ruggieri et al., 2007). In this study, we investigated the cell death processes during infection and the underlying mechanisms. We found that CCoV-II triggers apoptosis in A-72 cells by activating initiator (caspase-8 and -9) and executioner (caspase-3 and -6) caspases. The proteolytic cleavage of poly(ADP-ribose) polymerases (PARPs) confirmed the activation of executioner caspases. Furthermore, CCoV-II infection resulted in truncated bid (tbid) translocation from the cytosolic to the mitochondrial fraction, the cytochrome c release from mitochondria, and alterations in the pro- and anti-apoptotic proteins of bcl-2 family. Our data indicated that, in this experimental model, both intrinsic and extrinsic pathways are involved. In addition, we demonstrated that the inhibition of apoptosis by caspase inhibitors did not affect CCoV replication, suggesting that apoptosis does not play a role in facilitating viral release.


title: Clinical usefulness of pneumococcal urinary antigen test, stratified by disease severity and serotypes

text: Abstract Early diagnosis of pneumococcal pneumonia facilitates appropriate antibiotic therapy. The urinary antigen test (UAT) is known to be useful for the diagnosis of pneumococcal pneumonia. This study aimed to evaluate the usefulness of UAT in the 13-valent pneumococcal conjugated vaccine (PCV13) era. Community-acquired pneumonia (CAP) cases aged ≥19 years were reviewed retrospectively. This study evaluated the utility of Streptococcus pneumoniae UAT (BinaxNOW® assay) for diagnosis of pneumococcal CAP, and the relation of the UAT positive rate to age, comorbidities, pneumonia severity, and pneumococcal serotypes. Among 752 microbiologically identified CAP cases, S. pneumoniae (36.7%) was the most common isolate, and of those cases, 56.4% were positive for UAT. UAT positivity varied by pneumococcal serotype (serotype 3, 50%; 9V/9A, 85%; 11A/11E, 54%; 14, 36.4%; 19A, 50%; and 23F, 37.5%), and was significantly increased since 2012, two years after introduction of PCV13. The positive rate of UAT was significantly related to CRP level (P = 0.007) and lobar pneumonia (P = 0.006), but not to age, co-morbidities or prior antibiotic therapy. In conclusion, urinary antigen detection varied depending on the S. pneumoniae serotype. In the PCV13 era, the serotype distribution of pneumococcal pneumonia may be changing, and the clinical usefulness of UAT needs to be monitored. The positive rate of UAT may be influenced by a localized bacterial burden and host reactions.


title: Development of a pan-serotype reverse transcription loop-mediated isothermal amplification assay for the detection of dengue virus

text: Abstract During dengue outbreaks, acute diagnosis at the patient's point of need followed by appropriate supportive therapy reduces morbidity and mortality. To facilitate needed diagnosis, we developed and optimized a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that detects all 4 serotypes of dengue virus (DENV). We used a quencher to reduce nonspecific amplification. The assay does not require expensive thermocyclers, utilizing a simple water bath to maintain the reaction at 63°C. Results can be visualized using UV fluorescence, handheld readers, or lateral flow immunochromatographic tests. We report a sensitivity of 86.3% (95% confidence interval [CI], 72.7–94.8%) and specificity of 93.0% (95% CI, 83.0–98.1%) using a panel of clinical specimens characterized by DENV quantitative reverse transcription–polymerase chain reaction. This pan-serotype DENV RT-LAMP can be adapted to field-expedient formats where it can provide actionable diagnosis near the patient's point of need.


title: C-type lectin DC-SIGN: An adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity

text: The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II C-type lectin whose expression is restricted to the most potent antigen-presenting cells (APCs), the dendritic cells (DCs). In recent years, DC-SIGN has gained an exponential increase in attention because of its involvement in multiple aspects of immune function. Besides being an adhesion molecule, particularly in binding ICAM-2 and ICAM-3, it is also crucial in recognizing several endogenous and exogenous antigens. Additionally, the intracellular domain of DC-SIGN includes molecular motifs, which enable the activation of signal transduction pathways involving Raf-1 and subsequent modulation of DC-maturation status, through direct modification of nuclear factor Nf-κB in DCs. Upon DC-SIGN engagement by mannose- or fucose-containing oligosaccharides, the latter leads to a tailored Toll-like receptor signalling, resulting in an altered DC-cytokine profile and skewing of Th1/Th2 responses. In this article, we will discuss recent advances on a broad perspective concerning DC-SIGN structure, signalling and immune function.


title: The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p

text: INTRODUCTION: Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion. METHODS: LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism. RESULTS: The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 alpha, and IL-1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co-culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti-inflammatory ability against LPS-induced ALI. CONCLUSION: The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up-regulating IL-1 RA and sTNF RII expression.


title: Genetic diversity and evolution of SARS-CoV-2

text: Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.


title: Ligands, their receptors and … plasma membranes

text: Abstract Ligand–receptor interactions are customarily described by equations that apply to solutes. Yet, most receptors are present in cell membranes so that sufficiently lipophilic ligands could reach the receptor by a two-dimensional approach within the membrane. As summarized in this review, this may affect the ligand–receptor interaction in many ways. Biophysicians calculated that, compared to a three-dimensional approach from the liquid phase, such approach could alter the time the ligands need to find a receptor. Biochemists found that ligand incorporation in lipid bilayers modifies their conformation. This, along with the depth at which the ligands reside in the bilayer, will affect the probability of successful receptor interaction. Novel mechanisms were also introduced, including “exosite” binding and ligand translocation between the receptor's α-helical transmembrane domains. Pharmacologists focused attention at ligand concentrations in membrane, their adsorption and release rates and the effects thereof on ligand potency and residence time at the receptor.


title: Maternal, neonatal, and child health in southeast Asia: towards greater regional collaboration

text: Although maternal and child mortality are on the decline in southeast Asia, there are still major disparities, and greater equity is key to achieve the Millennium Development Goals. We used comparable cross-national data sources to document mortality trends from 1990 to 2008 and to assess major causes of maternal and child deaths. We present inequalities in intervention coverage by two common measures of wealth quintiles and rural or urban status. Case studies of reduction in mortality in Thailand and Indonesia indicate the varying extents of success and point to some factors that accelerate progress. We developed a Lives Saved Tool analysis for the region and for country subgroups to estimate deaths averted by cause and intervention. We identified three major patterns of maternal and child mortality reduction: early, rapid downward trends (Brunei, Singapore, Malaysia, and Thailand); initially high declines (sustained by Vietnam but faltering in the Philippines and Indonesia); and high initial rates with a downward trend (Laos, Cambodia, and Myanmar). Economic development seems to provide an important context that should be coupled with broader health-system interventions. Increasing coverage and consideration of the health-system context is needed, and regional support from the Association of Southeast Asian Nations can provide increased policy support to achieve maternal, neonatal, and child health goals.


title: COVID-19: A Brief Overview of the Discovery Clinical Trial.

text: The outbreak of COVID-19 is leading to a tremendous search for curative treatments. The urgency of the situation favors a repurposing of active drugs but not only antivirals. This short communication focuses on four treatments recommended by WHO and included in the first clinical trial of the European Discovery project.


title: Molecular characterization of Lelystad virus

text: Abstract Lelystad virus (LV), the prototype of porcine reproductive respiratory syndrome virus, is a small enveloped virus, containing a positive strand RNA genome of 15 kb. LV is tentatively classified in the family Arteriviridae, which consists of lactate dehydrogenase-elevating virus (LDV), equine arteritis virus (EAV) and simian hemorrhagic fever virus (SHFV). These viruses have a similar genome organization and replication strategy as coronaviruses, but the size of the genome is much smaller (12–15 kb) and they have different morphological and physicochemical properties. The genome of LV contains eight open reading frames (ORFs) that encode the replicase genes (ORFs 1a and 1b), envelope proteins (ORFs 2 to 6) and the nucleocapsid protein (ORF7). Genomic comparison of European and North American isolates has shown that the structural proteins encoded by ORFs 2 to 7 vary widely. The amino acid sequences of ORFs 2 to 7 of North American strains share only 55 to 79% identical amino acids with those of European strains. Using polyvalent porcine anti-LV serum, gene-specific anti-peptide sera and monoclonal antibodies, we have identified six structural proteins of LV and their corresponding genes. These are: the 15 kDa unglycosylated nucleocapsid protein (N) encoded by ORF7, an 18 kDa unglycosylated integral membrane protein M encoded by ORF6, a 25 kDa N-glycosylated protein encoded by ORF5, a 31–35 kDa N-glycosylated protein encoded by ORF4, a 45–50 kDa N-glycosylated protein encoded by ORF3 and a 29–30 kDa N-glycosylated protein encoded by ORF2. A nomenclature for these structural proteins is proposed.


title: Encephalomyelitis of Swine Caused by a Haemagglutinating Virus VI. Morphology of the Virus

text: SUMMARY Electron microscopic examinations were made on negatively stained preparations of supernatant fluids from cell cultures infected with haemagglutinating encephalomyelitis virus (HEV). The studies revealed that all related strains of the virus so examined were morphologically similar to coronaviruses. One strain, of similar origin, but known to differ serologically from the others, was shown to resemble the paramyxoviruses.


Respiratory infections in the Asia‐Pacific region


title: Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies

text: Abstract A capsid protein of porcine circovirus 2 (PCV 2) serves as a diagnostic antigen for the detection of PCV 2-associated disease known as a postweaning multisystemic wasting syndrome (PMWS). In this report, a bacterial expression system was developed for the expression and purification of the full-length PCV 2 capsid (Cap) protein from a codon-optimized cap gene. Replacement of rare arginine codons located at the 5′ end of the cap reading frame with codons optimal for E. coli was found to overcome the poor expression of the viral protein in the prokaryotic system. The Cap protein was purified to greater than 95% homogeneity by using a single cation-exchange chromatography at a yield of 10mg per litre of bacterial culture. Despite the failure of the E. coli-expressed Cap protein to self-assemble into virus-like particles (VLPs), the immunization of mice with recombinant Cap yielded antibodies with the same specificity as those raised against native PCV 2 virions. In addition, the antigenic properties of the purified Cap protein were employed in a subunit-based indirect ELISA to monitor the levels of PCV 2 specific antibodies in piglets originating from a herd which was experiencing PCV 2 infection. These results pave the way for a straightforward large-scale production of the recombinant PCV 2 capsid protein and its use as a diagnostic antigen or a PCV 2 subunit vaccine.


The Covid-19 pandemic stress the need to build resilient production ecosystems


title: Molecular mechanisms of coronavirus RNA capping and methylation

text: The 5′-cap structures of eukaryotic mRNAs are important for RNA stability, pre-mRNA splicing, mRNA export, and protein translation. Many viruses have evolved mechanisms for generating their own cap structures with methylation at the N7 position of the capped guanine and the ribose 2′-Oposition of the first nucleotide, which help viral RNAs escape recognition by the host innate immune system. The RNA genomes of coronavirus were identified to have 5′-caps in the early 1980s. However, for decades the RNA capping mechanisms of coronaviruses remained unknown. Since 2003, the outbreak of severe acute respiratory syndrome coronavirus has drawn increased attention and stimulated numerous studies on the molecular virology of coronaviruses. Here, we review the current understanding of the mechanisms adopted by coronaviruses to produce the 5′-cap structure and methylation modification of viral genomic RNAs. [Image: see text]


title: A structural perspective of RNA recognition by intrinsically disordered proteins

text: Protein-RNA recognition is essential for gene expression and its regulation, which is indispensable for the survival of the living organism at one hand, on the other hand, misregulation of this recognition may lead to their extinction. Polymorphic conformation of both the interacting partners is a characteristic feature of such molecular recognition that promotes the assembly. Many RNA binding proteins (RBP) or regions in them are found to be intrinsically disordered, and this property helps them to play a central role in the regulatory processes. Sequence composition and the length of the flexible linkers between RNA binding domains in RBPs are crucial in making significant contacts with its partner RNA. Polymorphic conformations of RBPs can provide thermodynamic advantage to its binding partner while acting as a chaperone. Prolonged extensions of the disordered regions in RBPs also contribute to the stability of the large cellular machines including ribosome and viral assemblies. The involvement of these disordered regions in most of the significant cellular processes makes RBPs highly associated with various human diseases that arise due to their misregulation.


title: Biopreparedness in the Age of Genetically Engineered Pathogens and Open Access Science: An Urgent Need for a Paradigm Shift

text: Our systems, thinking, training, legislation, and policies are lagging far behind momentous changes in science, and leaving us vulnerable in biosecurity. Synthetic viruses and genetic engineering of pathogens are a reality, with a rapid acceleration of dual-use science. The public availability of methods for dual-use genetic engineering, coupled with the insider threat, poses an unprecedented risk for biosecurity. Case studies including the 1984 Rajneesh salmonella bioterrorism attack and the controversy over engineered transmissible H5N1 influenza are analyzed. Simple probability analysis shows that the risks of dual-use research are likely to outweigh potential benefits, yet this type of analysis has not been done to date. Many bioterrorism agents may also occur naturally. Distinguishing natural from unnatural epidemics is far more difficult than other types of terrorism. Public health systems do not have mechanisms for routinely considering bioterrorism, and an organizational culture that is reluctant to consider it. A collaborative model for flagging aberrant outbreak patterns and referral from the health to security sectors is proposed. Vulnerabilities in current approaches to biosecurity need to be reviewed and strengthened collaboratively by all stakeholders. New systems, legislation, collaborative operational models, and ways of thinking are required to effectively address the threat to global biosecurity.


title: Vaccine Technologies: From Whole Organisms to Rationally Designed Protein Assemblies

text: Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development.


title: Coronavirus Disease 2019 (COVID-19) Infection Associated With Antiphospholipid Antibodies and Four-Extremity Deep Vein thrombosis in a Previously Healthy Female

text: Infection caused by novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been associated with coagulopathy. We present a case of a previously healthy 49-year-old female who was admitted to the hospital for coronavirus disease 2019 (COVID-19) pneumonia and later found to have extensive deep vein thrombosis (DVT) in all four extremities. This was accompanied by a steep rise in D-dimer levels and positive antiphospholipid antibodies (APLA) on further testing. She clinically improved on hydroxychloroquine and therapeutic anticoagulation. This is one of the first case reports describing APLA-associated DVT in a patient with COVID-19 pneumonia. Transient elevation of APLA from the viral illness may play a role in thrombosis associated with COVID-19.


A View From The Front-Line of the COVID-19 War


title: Occurrence of severe gastroenteritis in pups after canine parvovirus vaccine administration: A clinical and laboratory diagnostic dilemma

text: A total of 29 faecal samples collected from dogs with diarrhoea following canine parvovirus (CPV) vaccination were tested by minor groove binder (MGB) probe assays for discrimination between CPV vaccine and field strains and by diagnostic tests for detection of other canine pathogens. Fifteen samples tested positive only for CPV field strains; however, both vaccine and field strains were detected in three samples. Eleven samples were found to contain only the vaccine strain, although eight of them tested positive for other pathogens of dogs. Only three samples were found to contain the vaccine strain without evidence of canine pathogens. The present study confirms that most cases of parvovirus-like disease occurring shortly after vaccination are related to infection with field strains of canine parvovirus type 2 (CPV-2) rather than to reversion to virulence of the modified live virus contained in the vaccine.


title: Parental exposure to bisphenol A and its analogs influences zebrafish offspring immunity

text: Abstract Transgenerational effects of environmental pollutants on humans and animals are complex. Thus, we used zebrafish to evaluate the effects of parental whole-life cycle exposure to bisphenol A and its analogs (bisphenol S and F) on offspring innate immunity. At adulthood, offspring were examined with/without continued chemicals treatment until 72h post-fertilization (hpf). To measure offspring immune function, larvae at 72 hpf were expose for 24h with/without the viral mimic polyinosinic-cytidylic acid (Poly I:C) or the bacterial mimic Pam3Cys-Ser-Lys4 (PAM3CSK4). Data show modified immunity in offspring. Specifically, lysozyme activity was significantly induced in F1 larvae and respiratory burst response and oxidative defense genes were inhibited. Genes of the innate immune system including Toll-like receptors and their downstream molecules and inflammatory cytokines were significantly down-regulated, whereas matrix metalloproteinases were up-regulated in larvae. In addition, recombination-activating genes in the immature adaptive immune system were significantly reduced. Thus, immune defense is diminished by exposing parental generations of zebrafish to environmentally relevant concentration of bisphenols and this suggests that fish chronically exposed to bisphenols in the wild may be vulnerable to pathogens.


title: First detection and molecular identification of Borrelia species in Bactrian camel (Camelus bactrianus) from Northwest China

text: Abstract Comprehensive epidemiological surveys for Lyme disease have not been conducted for the Bactrian camel in China. In this study, a total of 138 blood specimens collected from Bactrian camels from Zhangye City in Gansu Province and Yili and Aksu in Xinjiang Province, China, were examined for the presence of Borrelia spp. Species-specificity nested PCR based on the 5S-23S rRNA, OspA, flaB and 16S rRNA genes revealed that the total positive rate of Borrelia spp. was 3.6% (5/138, 95% CI = 0.2–17.9). These results were confirmed by sequence analysis of the positive PCR products or positive colonies. This is the first report of Borrelia pathogens in camels in China. Two Borrelia species that cause Lyme disease and one that causes relapsing fever were identified in the camel blood samples by sequencing. The findings of this study indicate that the Bactrian camel may serve as a potential natural host of Lyme disease and/or relapsing fever in China.


The International Health Regulations 10 years on: the governing framework for global health security


title: The application of virus-like particles as vaccines and biological vehicles

text: Virus-like particles (VLPs) can be spontaneously self-assembled by viral structural proteins under appropriate conditions in vitro while excluding the genetic material and potential replication probability. In addition, VLPs possess several features including can be rapidly produced in large quantities through existing expression systems, highly resembling native viruses in terms of conformation and appearance, and displaying repeated cluster of epitopes. Their capsids can be modified via genetic insertion or chemical conjugation which facilitating the multivalent display of a homologous or heterogeneous epitope antigen. Therefore, VLPs are considered as a safe and effective candidate of prophylactic and therapeutic vaccines. VLPs, with a diameter of approximately 20 to 150 nm, also have the characteristics of nanometer materials, such as large surface area, surface-accessible amino acids with reactive moieties (e.g., lysine and glutamic acid residues), inerratic spatial structure, and good biocompatibility. Therefore, assembled VLPs have great potential as a delivery system for specifically carrying a variety of materials. This review summarized recent researches on VLP development as vaccines and biological vehicles, which demonstrated the advantages and potential of VLPs in disease control and prevention and diagnosis. Then, the prospect of VLP biology application in the future is discussed as well.


title: Racial, Economic and Health Inequality and COVID-19 Infection in the United States

text: Abstract Background: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. Methods: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). Findings: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Interpretation: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access. Keywords: Healthcare Disparities, Health Status Disparities, Socioeconomic Factors, COVID-19, Economic Inequality, Racial Disparity, United States, Population-Based Analysis.


title: Acute Respiratory Distress Syndrome: Bench‐to‐Bedside Approaches to Improve Drug Development

text: Despite 50 years of extensive research, no definite drug is currently available to treat acute respiratory distress syndrome (ARDS), and the supportive therapies remain the mainstay of treatment. To improve drug development for ARDS, researchers need to deeply analyze the “omics” approaches, reevaluate the suitable therapeutic targets, resolve the problems of inadequate animal modeling, develop the strategies to reduce the heterogeneity, and reconsider new therapeutic and analytical approaches for better designs of clinical trials.


title: Evaluation of commercial ResPlex II v2.0, MultiCode®-PLx, and xTAG® respiratory viral panels for the diagnosis of respiratory viral infections in adults

text: Abstract Background Commercial multiplex PCR panels for respiratory viruses (PRV) have been recently developed. ResPlex II Panel v2.0 (Qiagen), MultiCode®-PLx (EraGen Biosciences), and xTAG® (Luminex) PRV's were studied. All assays detect influenza A and B, adenovirus, parainfluenza 1–3, respiratory syncytial virus A and B, human metapneumovirus and human rhinovirus. The ResPlex II additionally detects coronavirus (229E, OC43, NL63, HKU1), coxsackie/echo virus, bocavirus and differentiates adenoviruses (B, E). The MultiCode-PLX assay detects 229E, OC43, and NL63, differentiates parainfluenza 4a, 4b and adenoviruses (B, C, E). The xTAG additionally subtypes influenza A as seasonal H1 and H3. Study design 202 specimens collected from adult patients with signs of respiratory infection from November, 2008 to May, 2009 were used for evaluating the performance of the three commercial PRV assays. Viral culture and xTAG were used as the standards to assess sensitivity and specificity. Results The PRV assays detected more viruses than culture. When compared to culture, the xTAG PRV showed a sensitivity and specificity of 100% and 91%, compared to MultiCode-PLx with 89% and 87%, and ResPlex II with 89% and 94%, respectively. Co-infection was detected in a small subset of patient specimens. Each panel showed differences in sensitivities for individual viruses. Conclusions While the ResPlex II and MultiCode-PLx offer a broader virus detection range and greater ease of use, the xTAG PRV showed increased sensitivity to common viral targets represented in the assays, and also had the ability to differentiate human from non-human influenza A H1.


title: Emerging infections—an increasingly important topic: review by the Emerging Infections Task Force

text: Abstract Objectives This paper review trends in emerging infections and the need for increased clinical and laboratory surveillance. Methods Factors that contributed to the emergence of recent outbreaks have been reviewed. Known, major outbreaks over the past two decades were reviewed. Results We identified at least four major drivers of emergent infections: (i) increasing density of the human population; (ii) stress from farmland expansion on the environment; (iii) globalization of the food market and manufacturing; (iv) environmental contamination. The factors creating new opportunities for emerging infections include: (i) population growth; (ii) spread in health care facilities; (iii) an ageing population; (iv) international travel; (v) changing and expanding vector habitats. Conclusions Emerging infections are unpredictable. In this review we argue that to discover new trends in infectious diseases, the clinicians have to look for the unusual and unexpected and ensure proper diagnostics and that syndromic surveillance must be supported by highly specialized laboratory services. Mathematical modeling has not been able to predict outbreaks More emphasis on the biology of evolution is needed. EID rarely stands out as unusual, and the continuous pressure on health care budgets forces clinicians and laboratories to prioritize their diagnostic work-up to common and treatable conditions. The European Society for Infectious Diseases and Clinical Microbiology, ESCMID, has established an Emerging Infections Task Force, EITaF, to strengthen the activities of the society on emerging infections and ensure that emerging infections is included in differential diagnostic considerations in everyday clinical practice.


title: Common Infections in the Lung Transplant Recipient

text: Infections are a major cause of morbidity and mortality after lung transplantation. Pretransplant assessments for infection risk and immunization updates may help reduce posttransplant infections. In addition careful choice of posttransplant prophylaxis for cytomegalovirus and fungal infections is critical. Because of the potential association of infections such as respiratory viral infections and gram-negative bacterial infections with bronchiolitis obliterans syndrome, prompt attention to these pathogens is critical. Choice of antimicrobials for prophylaxis and treatment should take into consideration both adverse effects and drug interactions associated with antimicrobial choice.


title: The administration of vaccines

text: Vaccines should only be administered following a complete risk/benefit analysis by a veterinarian in conjunction with the owner. The designation of “core” or “noncore” vaccines are not absolute and will depend upon specific circumstances. Vaccines must be administered by the correct route, at the correct time, in the correct manner. Vaccination schedules must take maternal immunity into account, and revaccination must take duration of immunity data into account. Serologic tests should be employed to determine the need for revaccination. Vaccines must be stored and administered correctly. They may be administered by diverse routes, in addition to injection. Intranasal and oral vaccination, intraocular and aerosolization are all possible routes.


title: Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3′-digallate (TF3)

text: SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS). The virally encoded 3C-like protease (3CL(Pro)) has been presumed critical for the viral replication of SARS-CoV in infected host cells. In this study, we screened a natural product library consisting of 720 compounds for inhibitory activity against 3CL(Pro). Two compounds in the library were found to be inhibitive: tannic acid (IC(50) = 3 µM) and 3-isotheaflavin-3-gallate (TF2B) (IC(50) = 7 µM). These two compounds belong to a group of natural polyphenols found in tea. We further investigated the 3CL(Pro)-inhibitory activity of extracts from several different types of teas, including green tea, oolong tea, Puer tea and black tea. Our results indicated that extracts from Puer and black tea were more potent than that from green or oolong teas in their inhibitory activities against 3CL(Pro). Several other known compositions in teas were also evaluated for their activities in inhibiting 3CL(Pro). We found that caffeine, (—)-epigallocatechin gallte (EGCg), epicatechin (EC), theophylline (TP), catechin (C), epicatechin gallate (ECg) and epigallocatechin (EGC) did not inhibit 3CL(Pro) activity. Only theaflavin-3,3′-digallate (TF3) was found to be a 3CL(Pro) inhibitor. This study has resulted in the identification of new compounds that are effective 3CL(Pro) inhibitors.


Although most patients with COVID-19 pneumonia have a good prognosis, some patients develop to severe or critical illness, and the mortality of critical cases is up to 61.5%. However, specific molecular information about immune response in critical patients with COVID-19 is poorly understood. A total of 54 patients were enrolled and divided into three groups, among which 34 were common, 14 were severe, and 6 were critical. The constitution of peripheral blood mononuclear cells (PBMC) in patients was analyzed by CyTOF. The profile of cytokines was examined in plasma of patients using luminex. The IL-2 signaling pathway was investigated in the PBMC of patients by qRT-PCR. The count and percentage of lymphocytes were significantly decreased in critical patients compared to common and severe patients with COVID-19 pneumonia. The count of T cells, B cells, and NK cells was remarkably decreased in critical patients compared to normal controls. The percentage of CD8(+) T cells was significantly lower in critical patients than that in common and severe patients with COVID-19 pneumonia. The expression of IL-2R, JAK1, and STAT5 decreased in PBMC of common, severe, and critical patients, but IL-2 level was elevated in severe patients and decreased in critical patients with COVID-19 pneumonia. The decrease of CD8(+) T cells in critical patients with COVID-19 pneumonia may be related to the IL-2 signaling pathway. The inhibition of IL-2/IL-2R gives rise to CD8(+) T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia.


title: Harnessing the immune system via FcγR function in immune therapy: a pathway to next‐gen mAbs

text: The human fragment crystallizable (Fc)γ receptor (R) interacts with antigen‐complexed immunoglobulin (Ig)G ligands to both activate and modulate a powerful network of inflammatory host‐protective effector functions that are key to the normal physiology of immune resistance to pathogens. More than 100 therapeutic monoclonal antibodies (mAbs) are approved or in late stage clinical trials, many of which harness the potent FcγR‐mediated effector systems to varying degrees. This is most evident for antibodies targeting cancer cells inducing antibody‐dependent killing or phagocytosis but is also true to some degree for the mAbs that neutralize or remove small macromolecules such as cytokines or other Igs. The use of mAb therapeutics has also revealed a “scaffolding” role for FcγR which, in different contexts, may either underpin the therapeutic mAb action such as immune agonism or trigger catastrophic adverse effects. The still unmet therapeutic need in many cancers, inflammatory diseases or emerging infections such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) requires increased effort on the development of improved and novel mAbs. A more mature appreciation of the immunobiology of individual FcγR function and the complexity of the relationships between FcγRs and antibodies is fueling efforts to develop more potent “next‐gen” therapeutic antibodies. Such development strategies now include focused glycan or protein engineering of the Fc to increase affinity and/or tailor specificity for selective engagement of individual activating FcγRs or the inhibitory FcγRIIb or alternatively, for the ablation of FcγR interaction altogether. This review touches on recent aspects of FcγR and IgG immunobiology and its relationship with the present and future actions of therapeutic mAbs.


title: The requirement of environmental acidification for Ibaraki virus infection to host cells

text: The effect of environmental acidification on Ibaraki virus (IBAV) infection was tested using endosomal inhibitory chemicals and low pH treatment. Treatment of target cells with endosomal inhibitors significantly decreased the progeny virus production. IBAV outer capsid proteins, VP5 and VP2, were removed from virion when purified IBAV was exposed to low pH environment. Further experiment showed that the exposure to low pH buffer facilitated IBAV infection when the cellular endosomal pathway was impaired by bafilomycin A1. Results obtained in this study suggest that acidic environment is essential to initiate IBAV infection.


title: Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

text: On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.


title: Traditional Chinese medicine treatments for upper respiratory tract infections/common colds in Taiwan

text: Abstract Introduction Traditional Chinese medicine (TCM) has been used to treat upper respiratory tract infections/common colds (URTIs) in Asian countries for over 2000 years. However, Chinese medicine doctors (CMDs) follow the traditional treatment rules to select or administer these diverse Chinese medicine formulae. The main purpose of our study was to explore data on the frequency of medication and medication habits by CMDs for the treatment of URTIs with Chinese herbs and Chinese medicine formulae. Methods The TCM treatments for patients consulting with an URTIs were analyzed from the National Health Insurance Research Database using the appropriate codes from the International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses for Taiwan in 2009. A data mining and association rules, were used to analyze co-prescriptions of TCM for patients with URTIs. Results For 472,005 patients who sought the treatment of URTIs, a total of 46,805 patients with URTIs received TCM treatments, of these 29,052 patients sought both TCM and Western medication treatments. Of the URTIs patients who had received a TCM treatment, 79% presented with an acute common cold, 9% had influenza, and 9% had acute upper respiratory infections. Furthermore, 53.89% of the sample were aged between 20 and 49 years, and 62.84% were women, 3.56% of the patients used Yin-Qiao-San and 2.76% used Jie-Geng. Yin-Qiao-San and Ma-Xing-Gan-Shi-Tang were the most commonly combinations of prescriptions for patients with URTIs. Conclusions The patients experiencing URTIs were more likely to request TCM treatment if their symptoms were mild and they were women. The Chinese medicine doctors treating URTIs generally followed TCM theory. A coding system for TCM diagnostic classifications could improve evaluations of TCM treatments.


title: Pharmacy Administration and Pharmaceutical Care Practice in a Module Hospital during the COVID-19 Epidemic

text: Abstract Objective To describe the pharmacy administration and pharmaceutical care in a module hospital during COVID-19 epidemic and provide reference for domestic and foreign pharmacists participating in the epidemic prevention and control. Design The new COVID-19 “module” pharmaceutical care model was equipped with new features such as pharmacy emergency command group, organizational structure for pharmacy administration, electronic control of drug prescription, and “zero contact” pharmaceutical care relying on the new media platform “WeChat”. This platform provided relevant pharmaceutical care for patients, such as ensuring drug supply, setting up critical care drug trolleys, designing specific drug packaging bags, creating a module radio station to broadcast rational drug use information to the patients, and other aspects. Setting and participants The study was performed in Jianghan module hospital constructed at the Wuhan Convention and Exhibition Center in Wuhan, China. This is one of the first three module hospitals. Outcome measures Pharmacists successfully completed the tasks of purchase, storage, and free distribution of 1033844.3 RMB worth of drugs (about $146,000 US dollars), reviewed about 20,000 electronic orders, provided one-on-one online medication consultation for 484 patients, and held five lectures on rational drug use knowledge, which could help reduce irrational drug use and minimize the risk involved. Results The pharmacists provided pharmaceutical care for 1848 patients with mild COVID-19 disease. They not only ensured the timely supply of the drugs but also reduced the incidence of drug-induced risks through medication review and guidance, thereby improving patient compliance and helping the patients rebuild their confidence in overcoming the disease. Conclusion The new COVID-19 “module” pharmaceutical care model has played an important role in overcoming the epidemic situation of COVID-19 in China and thus can be implemented on a broader scale.


title: Coronavirus disease 2019 (COVID-19): chest CT characteristics benefit to early disease recognition and patient classification-a single center experience

text: Background: The current outbreak of coronavirus disease 2019 (COVID-19), epi-centered in Wuhan, Hubei Province of the China, has become a global health emergency Several studies from China have recently provided the evidence of epidemiological, clinical, laboratory, and outcomes of COVID-19 patients Investigation on the role of chest CT in patient screening and management course in a large cohort remains paucity Methods: This was a retrospective observational study based on the data collected between January 19 and 2020 to February 15, 2020 A clinic workflow using chest CT and RT-PCR assay to screen suspected patient was reviewed Clinical data were evaluated and patients were classified to mild, common, severe and critical group Chest CT characteristics of each patient were evaluated and a CT scoring system was applied to grade the lung involvement Results: Of 98 enrolled patients, 1, 29, 51 and 17 were clinically classified into mild, common, severe and critical group, respectively Eighty-three patients (84 7%) demonstrated ground-glass opacity (GGO), 76 patients (77 5%) demonstrated consolidation and 18 patients (18 4%) demonstrated crazy-paving pattern on chest CT Based on the CT scoring, 2, 35, 55 and 6 patients were categorized to grade 0, grade 1, grade 2 and grade 3, respectively, which significantly consistent with clinical classification (kappa =0 638, P0 05) Twenty-nine patients admitted from fever clinic, with an average interval of 1 2 days (range, 0-4 days) between CT examination and onset of symptom Three of these patients had negative initial RT-PCR result while abnormalities displayed on the initial chest CT Conclusions: Peripheral lung distributed GGO and consolidation, without subpleural sparing, are the most common manifestations on chest CT of COVID-19 Abnormalities on chest CT can occur in an early stage of COVID-19, even when RT-PCR assay negative, which may help to early recognition and rapid diagnosis of this disease


title: A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children

text: Abstract Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that involves multifocal areas of the white matter, rarely the gray matter and spinal cord, mainly affecting children and mostly occurring 1–2weeks after infections or more rarely after vaccinations. Though a specific etiologic agent is not constantly identified, to evaluate carefully patient's clinical history and obtain adequate samples for the search of a potential ADEM causal agent is crucial. In the case of a prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with full recovery, but in the case of diagnostic delays or inappropriate treatment some patients might display neurological sequelae and persistent deficits or even show an evolution to multiple sclerosis. The suspicion of ADEM rises on a clinical basis and derives from systemic and neurologic signs combined with magnetic resonance imaging of the central nervous system. Other advanced imaging techniques may help an appropriate differential diagnosis and definition of exact disease extension. Although there is no standardized protocol or management for ADEM, corticosteroids, intravenous immunoglobulin, and plasmapheresis have been successfully used. There is no marker that permits to identify the subset of children with worse prognosis and future studies should try to detect any biological clue for prevision of neurologic damage as well as should optimize treatment strategies using an approach based on the effective risk of negative evolution.


title: A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations

text: The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B*15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A*01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.