title: Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application

text: In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis.


title: Metagenomics reshapes the concepts of RNA virus evolution by revealing extensive horizontal virus transfer

text: Abstract Virus metagenomics is a young research filed but it has already transformed our understanding of virus diversity and evolution, and illuminated at a new level the connections between virus evolution and the evolution and ecology of the hosts. In this review article, we examine the new picture of the evolution of RNA viruses, the dominant component of the eukaryotic virome, that is emerging from metagenomic data analysis. The major expansion of many groups of RNA viruses through metagenomics allowed the construction of substantially improved phylogenetic trees for the conserved virus genes, primarily, the RNA-dependent RNA polymerases (RdRp). In particular, a new superfamily of widespread, small positive-strand RNA viruses was delineated that unites tombus-like and noda-like viruses. Comparison of the genome architectures of RNA viruses discovered by metagenomics and by traditional methods reveals an extent of gene module shuffling among diverse virus genomes that far exceeds the previous appreciation of this evolutionary phenomenon. Most dramatically, inclusion of the metagenomic data in phylogenetic analyses of the RdRp resulted in the identification of numerous, strongly supported groups that encompass RNA viruses from diverse hosts including different groups of protists, animals and plants. Notwithstanding potential caveats, in particular, incomplete and uneven sampling of eukaryotic taxa, these highly unexpected findings reveal horizontal virus transfer (HVT) between diverse hosts as the central aspect of RNA virus evolution. The vast and diverse virome of invertebrates, particularly nematodes and arthropods, appears to be the reservoir, from which the viromes of plants and vertebrates evolved via multiple HVT events.


docid: resfrcep

title: Ignorance, Orientalism and Sinophobia in Knowledge Production on COVID‐19

text: In this commentary, based on a close readi ng of media reports and our everyday experiences as overseas Chinese researchers, we examine the production of ignorance surrounding the COVID‐19. Specifically, we focus on ignorance caused by selective inattention and power plays. We challenge the dominant dualistic frame of authoritarianism versus democracy and the role it plays in overly simplifying and even distorting the responses of Chinese authorities in handling this public health emergency. We maintain that this binary thinking is reflective of the conflation of orientalism, sinophobia and statephobia in the West, which also intersects with sexism and racism within and outside academic sites of knowledge production. The consequence is that knowledge accumulated by experts from China as well as other Asian countries about the virus and mitigation strategies are marginalised, discredited, distrusted, if not dismissed altogether.


Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness


Chen Zhu: from barefoot doctor to China's Minister of Health


title: Coordinated multi-sectoral efforts needed to address the COVID-19 pandemic: lessons from China and the United States

text: The COVID-19 pandemic has caused staggering human and economic costs. We outline four key lessons learned from efforts to address the pandemic in China and the US. First, effective surveillance, reporting, and contact tracing are needed to contain an epidemic at its emergence and to mitigate its impact at a later stage. Second, multi-sectoral efforts to offer incentives for those with no or minor symptoms to seek care and to quarantine themselves are critical, which would need concerted efforts from payers, providers, and public health. Third, sustained and routine prevention efforts involving both the public and the health systems will prove to be useful in times of a pandemic. Fourth, a strong public health system is essential and will be appreciated at times of urgency. Concerted multi-sectoral efforts are required to address COVID-19 pandemic with strong leadership from the public health sector.


title: Vitamin A deficiency alters airway resistance in children with acute upper respiratory infection

text: OBJECTIVE: To assess whether vitamin A deficiency alters the recovery of total respiratory resistance (TRR) following acute upper respiratory tract infection (URI). METHODS: This is a case control study of children, age 4–6 years and grouped as: URI, (n = 74), URI and wheezing, (URI‐wheezing, n = 52), and healthy controls (n = 51). Vitamin A and total respiratory resistance (TRR) were assessed using the modified relative dose response (MRDR) and forced oscillometry, respectively. RESULTS: Children with URI and URI‐wheezing had lower retinol, 32.4 ± 13.12 and 18.3 ± 6.83 µg/dl respectively, compared to controls, 56.9 ± 29.82 µg/dl (ANOVA, P < 0.001). The MRDR was elevated in children in the URI or URI‐wheezing groups 0.066 ± 0.045 and 0.021 ± 0.021, respectively, compared to controls 0.007 ± 0.006 (ANOVA, P < 0.0001). The TRR in the URI and URI‐wheezing groups differed from controls. During convalescence, the TRR failed to decline in the URI‐group only when the MRDR was >0.06. In the URI‐wheezing group, TRR declined independently of retinol and MRDR. CONCLUSION: Vitamin A contributes to preservation of airway function during and in recovery after upper respiratory infection in children. Pediatr Pulmonol. 2013; 48:481–489. © 2012 Wiley Periodicals, Inc.


title: Assembly of the silk fibroin elementary unit in endoplasmic reticulum and a role of L‐chain for protection of α1,2‐mannose residues in N‐linked oligosaccharide chains of fibrohexamerin/P25

text: Silk fibroin of Bombyx mori is secreted from the posterior silk gland (PSG) as a 2.3‐MDa elementary unit, consisting of six sets of a disulfide‐linked heavy chain (H‐chain)–light chain (L‐chain) heterodimer and one molecule of fibrohexamerin (fhx)/P25. Fhx/P25, a glycoprotein, associates noncovalently with the H–L heterodimers. The elementary unit was found and purified from the endoplasmic reticulum (ER) extract of PSG cells. A substantial amount of fhx/P25 unassembled into the elementary unit was also present in ER. In normal‐level fibroin‐producing breeds (J‐139 and C108), the elementary unit contained fhx/P25 of either 30 kDa (major) or 27 kDa (minor). The 27‐kDa fhx/P25 was produced from the 30‐kDa form by digestion with the bacterial α1,2‐mannosidase in vitro. The elementary unit in the ER extract contained only the 30‐kDa fhx/P25, whereas both 30‐ and 27‐kDa forms of fhx/P25 were present in the ER plus Golgi mixed extracts. In naked‐pupa mutants [Nd(2), Nd‐s and Nd‐s (D)], extremely small amounts of fibroin were produced and they consisted of one molecule of 27‐kDa fhx/P25 and six molecules of H‐chain but no L‐chain. When the Nd‐s (D) mutant was subjected to transgenesis with the normal L‐chain gene, the (H‐L)(6)fhx(1)‐type elementary unit containing the 30‐kDa fhx/P25, was produced. These results suggest that fhx/P25 in the elementary unit is largely protected from digestion with Golgi α1,2‐mannosidases when L‐chains are present in the unit. Models suggesting a role of L‐chain for the protection of α1,2‐mannose residues of fhx/P25 are presented.


docid: ptvaopgj

title: The Data set for Patient Information Based Algorithm to Predict Mortality Cause by COVID-19

text: Abstract The data of COVID-19 disease in China and then in South Korea were collected daily from several different official websites. The collected data included 33 death cases in Wuhan city of Hubei province during early outbreak as well as confirmed cases and death toll in some specific regions, which were chosen as representatives from the perspective of the coronavirus outbreak in China. Data were copied and pasted onto Excel spreadsheets to perform data analysis. A new methodology, Patient Information Based Algorithm (PIBA) [1], has been adapted to process the data and used to estimate the death rate of COVID-19 in real-time. Assumption is that the number of days from inpatients to death fall into a pattern of normal distribution and the scores in normal distribution can be obtained by observing 33 death cases and analysing the data [2]. We selected 5 scores in normal distribution of these durations as lagging days, which will be used in the following estimation of death rate. We calculated each death rate on accumulative confirmed cases with each lagging day from the current data and then weighted every death rate with its corresponding possibility to obtain the total death rate on each day. While the trendline of these death rate curves meet the curve of current ratio between accumulative death cases and confirmed cases at some points in the near future, we considered that these intersections are within the range of real death rates. Six tables were presented to illustrate the PIBA method using data from China and South Korea. One figure on estimated rate of infection and patients in serious condition and retrospective estimation of initially occurring time of CORID-19 based on PIBA.


title: Association between rhinovirus species and nasopharyngeal microbiota in infants with severe bronchiolitis

text: Among 774 infants with severe bronchiolitis, rhinovirus species related to distinct nasopharyngeal microbiota. Infants with rhinovirus-A were more likely to have Haemophilus-dominant microbiota profile, while those with rhinovirus-C were more likely to have Moraxella-dominant profile.


title: Airflow analysis of Pyeongtaek St Mary's Hospital during hospitalization of the first Middle East respiratory syndrome patient in Korea

text: Middle East respiratory syndrome (MERS) is known to be transmitted through close contact. However, epidemiological surveys of MERS in Korea indicated that some secondary patients were infected without close contact. Therefore, the possibility of other transmission routes must be identified. In this study, the possibility of MERS spreading through airflow was investigated on the eighth floor of Pyeongtaek St Mary's Hospital. Computational fluid dynamics was used to analyse the indoor airflow and passive tracer diffusion during the index patient's stay. Six cases were simulated for different outdoor wind directions and indoor mechanical ventilation operations. When a passive tracer was released in ward 8104, where the index patient was hospitalized, the passive tracer spread through the indoor airflow, which was created by the outdoor airflow. Ward 8109, which had the largest number of infected cases and was far distant from ward 8104, showed passive tracer concentration in all cases. This result indicates that MERS may have spread through airflow. The study results do not imply that the infection pathway of MERS is airborne. However, the results show the possibility of MERS spreading through airflow in specific environments such as poor ventilation environments.


title: Purification of the extra-cellular domain of Nipah virus glycoprotein produced in Escherichia coli and possible application in diagnosis

text: Abstract The glycoprotein (G) of Nipah virus (NiV) is important for virus infectivity and induction of the protective immunity. In this study, the extra-cellular domain of NiV G protein was fused with hexahistidine residues at its N-terminal end and expressed in Escherichia coli. The expression under transcriptional regulation of T7 promoter yielded insoluble protein aggregates in the form of inclusion bodies. The inclusion bodies were solubilized with 8M urea and the protein was purified to homogeneity under denaturing conditions using nickel–nitrilotriacetic acid (Ni–NTA) affinity chromatography. The denatured protein was renatured by gradual removal of the urea. Light scattering analysis of the purified protein showed primarily monodispersity. The purified protein showed significant reactivity with the antibodies present in the sera of NiV-infected swine, as demonstrated in Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Taken together, the data indicate the potential usefulness of the purified G protein for structural or functional studies and the development of immunoassay for detection of the NiV antibodies.


title: Characteristics of pregnant COVID-19 patients with liver injury

text: • Liver injury is not very severe in pregnant COVID-19 patients. • Pregnant COVID-19 patients with liver injury had higher inflammation. • Newborns of COVID-19 patients with liver injury were negative for SARS-CoV-2.


title: Effect of effort‐reward imbalance and burnout on infection control among Ecuadorian nurses

text: BACKGROUND: Nurses are frequently exposed to transmissible infections, yet adherence to infection control measures is suboptimal. There has been inadequate research into how the psychosocial work environment affects compliance with infection control measures, especially in low‐ and middle‐income countries. AIM: To examine the association between effort‐reward imbalance, burnout and adherence to infection control measures among nurses in Ecuador. INTRODUCTION: A cross‐sectional study linking psychosocial work environment indicators to infection control adherence. METHODS: The study was conducted among 333 nurses in four Ecuadorian hospitals. Self‐administered questionnaires assessed demographic variables, perceived infection risk, effort‐reward imbalance, burnout and infection control adherence. RESULTS: Increased effort‐reward imbalance was found to be a unique incremental predictor of exposure to burnout, and burnout was a negative unique incremental predictor of nurses' self‐reported adherence with infection control measures. DISCUSSION: Results suggest an effort‐reward imbalance‐burnout continuum, which, at higher levels, contributes to reduce adherence to infection control. The Ecuadorean government has made large efforts to improve universal access to health care, yet this study suggests that workplace demands on nurses remain problematic. CONCLUSION: This study highlights the contribution of effort‐reward‐imbalance‐burnout continuum to the chain of infection by decreased adherence to infection control of nurses. IMPLICATIONS FOR NURSING POLICY: Health authorities should closely monitor the effect of new policies on psychosocial work environment, especially when expanding services and increasing public accessibility with limited resources. Additionally, organizational and psychosocial interventions targeting effort‐reward imbalance and burnout in nurses should be considered part of a complete infection prevention and control strategy. Further study is warranted to identify interventions that best ameliorate effort‐reward imbalance and burnout in low‐ and middle‐income settings.


Mental Wellness system for COVID-19


title: Recombinant protein vaccines produced in insect cells

text: The baculovirus-insect cell expression system is a well known tool for the production of complex proteins. The technology is also used for commercial manufacture of various veterinary and human vaccines. This review paper provides an overview of how this technology can be applied to produce a multitude of vaccine candidates. The key advantage of this recombinant protein manufacturing platform is that a universal “plug and play” process may be used for producing a broad range of protein-based prophylactic and therapeutic vaccines for both human and veterinary use while offering the potential for low manufacturing costs. Large scale mammalian cell culture facilities previously established for the manufacturing of monoclonal antibodies that have now become obsolete due to yield improvement could be deployed for the manufacturing of these vaccines. Alternatively, manufacturing capacity could be established in geographic regions that do not have any vaccine production capability. Dependent on health care priorities, different vaccines could be manufactured while maintaining the ability to rapidly convert to producing pandemic influenza vaccine when the need arises.


title: Fatal SARS-CoV-2 infection in a renal transplant recipient

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15–20% have lung involvement, 5–10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.


title: Detection of respiratory pathogens in pediatric acute otitis media by PCR and comparison of findings in the middle ear and nasopharynx

text: Abstract We conducted a series of polymerase chain reactions (PCRs) in order to detect bacteria (7 species) and viruses (17 species) in middle ear fluid (MEF) and nasopharynx (Nph) of children with acute otitis media (AOM; n=179). Bacterial and viral nucleic acids were detected in MEF of 78.8% and 14.5% patients, respectively. The prevalence was as follows: Streptococcus pneumoniae, 70.4%; Haemophilus influenzae, 17.9%; Staphylococcus aureus, 16.8%; Streptococcus pyogenes, 12.3%; Moraxella catarrhalis, 9.5%; rhinovirus, 9.5%; and adenovirus, 3.4%. The overall rate of PCR-positive specimens for bacterial pathogens was 2.6 times higher, compared to culture results. The rate of PCR-positive results and the distribution of pathogens in the Nph were similar to those in the MEF. Nph PCR results had variable positive predictive values and high negative predictive values in predicting MEF findings. Our results indicate that Nph PCR could be a practical tool for examining respiratory pathogens in children with acute infections.


title: Emergency response to the outbreak of COVID-19: the Korean case

text: Abstract This letter aims to describe how Korea can improve its emergency response to the outbreak of COVID-19. The key finding is that the nation has to shift from a self-interest–oriented response to a shared-interest–oriented response. Similarly, neighboring nations could form a national framework of networks among stakeholders.


title: Attenuation of murine coronavirus infection by ammonium chloride

text: Abstract Ammonium chloride at a concentration of 20 mM delayed by 4–5 hr the production of virus progeny in mouse L-2 cells infected at high multiplicity with mouse hepatitis virus (MHV). This delay was seen in the production of both intracellular and extracellular virus. However, the final titers were similar to those produced by MHV-infected cells maintained in normal medium. The manifestation of virus-induced cell fusion was similarly found to be delayed, but not otherwise decreased in severity, when ammonium chloride was present in the culture medium. Ammonium chloride caused similar delays in production of virus-specific, positive-sense RNAs and of viral polypeptides. The relative proportions and apparent molecular weights of viral RNAs and polypeptides were similar to those found in MHV-infected cells cultured in normal medium. In vitro translation of endogenously produced viral RNAs in cell extracts, prepared from MHV-infected cells, was not inhibited by ammonium chloride. Thus, ammonium chloride has no specific, inhibitory effect on viral protein synthesis. Ammonium chloride did not reduce the number of virus-infected cells in culture, as monitored by infectious center assay. Analysis of early events in MHV infection showed that ammonium chloride did not affect adsorption or internalization of MHV by L-2 cells. However, the subsequent eclipse phase, as monitored by decline in infectivity of internalized virus inoculum proceeded less efficiently in the presence of ammonium chloride. On the basis of the known inhibitory effects of ammonium chloride on lysosomal/endosomal functions, the results suggest an endosomal mechanism of MHV uncoating. Thus the primary effect of ammonium chloride on MHV infection of L-2 cells is to attenuate virus uncoating, thereby chronologically displacing all subsequent virus-encoded functions.


title: Animal models of Multiple Sclerosis

text: Abstract Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which involves a complex interaction between immune system and neural cells. Animal modeling has been critical for addressing MS pathogenesis. The three most characterized animal models of MS are (1) the experimental autoimmune/allergic encephalomyelitis (EAE); (2) the virally-induced chronic demyelinating disease, known as Theiler׳s murine encephalomyelitis virus (TMEV) infection and (3) the toxin-induced demyelination. All these models, in a complementary way, have allowed to reach a good knowledge of the pathogenesis of MS. Specifically, EAE is the model which better reflects the autoimmune pathogenesis of MS and is extremely useful to study potential experimental treatments. Furthermore, both TMEV and toxin-induced demyelination models are suitable for characterizing the role of the axonal injury/repair and the remyelination process in MS. In conclusion, animal models, despite their limitations, remain the most useful instrument for implementing the study of MS.


docid: dnsxxgcd

title: Role of Human Factors Engineering in Infection Prevention: Gaps and Opportunities

text: Human factors engineering (HFE), with its focus on studying how humans interact with systems, including their physical and organizational environment, the tools and technologies they use, and the tasks they perform, provides principles, tools, and techniques for systematically identifying important factors, for analyzing and evaluating how these factors interact to increase or decrease the risk of Healthcare-associated infections (HAI), and for identifying and implementing effective preventive measures. We reviewed the literature on HFE and infection prevention and control and identified major themes to document how researchers and infection prevention staff have used HFE methods to prevent HAIs and to identify gaps in our knowledge about the role of HFE in HAI prevention and control. Our literature review found that most studies in the healthcare domain explicitly applying (HFE) principles and methods addressed patient safety issues not infection prevention and control issues. In addition, most investigators who applied human factors principles and methods to infection prevention issues assessed only one human factors element such as training, technology evaluations, or physical environment design. The most significant gap pertains to the limited use and application of formal HFE tools and methods. Every infection prevention study need not assess all components in a system, but investigators must assess the interaction of critical system components if they want to address latent and deep-rooted human factors problems.


title: The first wheezing episode: respiratory virus etiology, atopic characteristics, and illness severity

text: BACKGROUND: Susceptibility to early rhinovirus‐induced wheezing has been recognized as an important risk factor for childhood asthma, but data on the first wheezing episode are limited. The aim of this selected population study was to investigate virus etiology, atopic characteristics, and illness severity, as well as their interrelation, among first‐time wheezing children. METHODS: We studied 111 first‐time wheezing children aged between 3 and 23 months (88/23 in‐/outpatients). The investigated factors included atopy, food, perennial and aeroallergen sensitization, eczema, atopic eczema, elevated blood eosinophil count, and parental allergic rhinitis, asthma, and smoking. Nasopharyngeal aspirates were analyzed for adenovirus, coronaviruses, enteroviruses, bocavirus‐1 (also serologically confirmed), influenza viruses, metapneumovirus, parainfluenza viruses, rhinovirus, and respiratory syncytial virus using PCR methods. RESULTS: The mean age of the study patients was 12 months (standard deviation 6.0). Atopic characteristics could be found in 56%, atopic eczema in 16%, and sensitization in 23% of the cases. In all samples (100%), ≥1 viruses were detected as follows: rhinovirus (76%), respiratory syncytial virus (29%), bocavirus (18%, acute infections), and other viruses <10% each. Virus coinfections occurred in 38% of the children. Rhinovirus infection was positively associated with age, blood eosinophil count, eczema, and duration of cough, as well as parental allergic rhinitis and smoking but negatively associated with virus coinfection (all p < 0.05). CONCLUSIONS: A respiratory virus infection can be detected in all first‐time wheezing children. Rhinovirus dominated the findings and was linked to atopic characteristics, prolonged cough, and parental smoking.


title: Thermal effect of human body on cough droplets evaporation and dispersion in an enclosed space

text: Abstract This study numerically investigated the thermal effect of human body on the time-dependent dispersion of cough droplets with evaporation process. The thermal flow of human body was imitated using a 3D thermal manikin with real body features, while a recent developed multi-component Eulerian-Lagrangian approach was used to address the effects of inhomogeneous temperature and humidity fields on droplet evaporation. By comparing the results yielded without and with the human body heat, the outcomes demonstrated strong impact of human body heat on the droplets mass fraction and local air velocity distributions. Inspirable droplets could potentially drop into respirable droplets by evaporation, although the evaporation rate was not significantly affected by body heat. The thermal effect of human body revealed its vital impacts on the time-dependent droplets dispersion. Due to the buoyancy driven thermal flow, both the vertical velocity and displacement of small droplets (≤20 μm) were completely reversed from descending to ascending, while the deposition time of large droplets (≥50 μm) were significantly delayed. With the reduced droplet size by evaporation and droplets lifted into breathing zone by human thermal effect, the inhalability and infection risks of cough droplets would be much higher in real occupied indoor spaces.


title: Evaluation of single and dual siRNAs targeting rabies virus glycoprotein and nucleoprotein genes for inhibition of virus multiplication in vitro

text: Small interfering RNAs (siRNAs) targeting rabies virus (RV) glycoprotein (G) and nucleoprotein (N) genes were evaluated as antiviral agents against rabies virus in vitro in BHK-21 cells. To select effective siRNAs targeting RV-G, a plasmid-based transient co-transfection approach was used. In this, siRNAs were expressed as short hairpin RNAs (shRNAs), and their ability to inhibit RV-G gene expression was evaluated in cells transfected with a plasmid expressing RV-G. The nine different siRNAs designed to target RV-G exhibited varying degrees of knockdown of RV-G gene expression. One siRNA (si-G7) with considerable effect in knockdown of RV-G expression also demonstrated significant inhibition of RV multiplication in BHK-21 cells after in vitro challenge with the RV Pasteur virus-11 (PV-11) strain. A decrease in the number of fluorescent foci in siRNA-treated cells and a reduction (86.8 %) in the release of RV into infected cell culture supernatant indicated the anti-rabies potential of siRNA. Similarly, treatment with one siRNA targeting RV-N resulted in a decrease in the number of fluorescent foci and a reduction (85.9 %) in the release of RV. As a dual gene silencing approach where siRNAs targeting RV-G and RV-N genes were expressed from single construct, the anti-rabies-virus effect was observed as an 87.4 % reduction in the release of RV. These results demonstrate that siRNAs targeting RV-G and N, both in single and dual form, have potential as antiviral agent against rabies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-013-1738-z) contains supplementary material, which is available to authorized users.


docid: sdqbhhcf

title: Rethinking testing

text: Instead of just testing people with symptoms, many countries could benefit from weekly testing of all key workers, reports Michael Le Page


title: COVID-19 and ENT surgery: a brief review of essential precautions and triage

text: PURPOSE: This study is a brief review of the existing knowledge on the ENT surgeon’s approach towards management of patients during the COVID-19 pandemic. While it is being recommended to carry out only the emergent procedures and to postpone the non-urgent ones to a later date, this article is meant to provide an insight into triage of the ENT procedures and the various precautions to be taken into account by the ENT surgeons while carrying out a procedure during the COVID-19 pandemic. METHODS: The ENT Cochrane, Pubmed and Web of Science databases were searched without a time limit using the terms ‘COVID-19 and SARS-CoV-2 in conjunction with ENT surgery. RESULTS: Elective and non urgent cases are best avoided during this time. Only absolutely essential and emergent procedures need to be carried out with the use of Personal protective equipment comprising of safety gown, N95 mask, safety goggles, disposable gloves and caps. There is a possibility of transmission of the SARS- CoV-2 through asymptomatic patients and hence all patients, even with an unknown COVID-19 status, need to undergo a preoperative screening. As all procedures under general anesthesia are aerosol generating, the use of Personal protective equipment (PPE) is recommended for all the health care workers present in the operation theater. CONCLUSION: A proper knowledge of triage would be of immense help to the ENT surgeon in minimizing the exposure to health care workers and patients during this pandemic. All patients with an unknown COVID-19 status should be considered suspects and essential precautions for their management be taken accordingly.


title: Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic and has caused illness to many people worldwide. This review aimed to summarize and analyze the herbal formulae provided by the guidelines for their pattern identifications (PIs) and compositions of herbs to treat patients with COVID-19. METHODS: We searched 7 data sources for eligible traditional medicine guidelines up to March 6, 2020 and found a total of 28 traditional medicine guidelines that provide treatment measures for COVID-19. RESULTS: Of the 28 guidelines, there were 26 government-issued Chinese guidelines and 2 Korean guidelines. After standardizing the terminology of the PIs and herbal formulae, there were 8 PIs and 23 herbal formulae for the mild stage, 11 PIs and 31 herbal formulae for the moderate stage, 8 PIs and 21 herbal formulae for the severe stage, and 6 PIs and 23 herbal formulae for the recovery stage in the Chinese guidelines. In the Korean guidelines, there were 4 PIs and 15 herbal formulae for the mild stage, 3 PIs and 3 herbal formulae for the severe stage, and 2 PIs and 2 herbal formulae for the recovery stage. In the frequency analysis of herbs, Glycyrrhizae Radix et Rhizoma was found to be the herb with the highest frequency of usage in the Chinese guidelines. CONCLUSION: This review can be used as guidance for the traditional medicine treatment of COVID-19. Clinical evidence is needed in the future to evaluate the efficacy of traditional medicine.


title: COVID‐19: Thoughts and comments from a tertiary liver transplant center in France

text: We read with interest the analysis on modern approaches to organ transplantation during the COVID-19 pandemic by Kumar et al.1 . Following the December 2019 SARS-CoV-2 outbreak in China, France is now fifth in number of deaths worldwide while at the same time hosting one of the biggest European liver transplantation programs.


title: Genetic diversity of group A rotaviruses associated with repeated outbreaks of diarrhea in a farrow-to-finish farm: identification of a porcine rotavirus strain bearing a novel VP7 genotype, G26

text: Group A rotaviruses (GARs) are one of the most common causes of diarrhea in suckling pigs. Although a number of G and P genotypes have been identified in porcine GARs, few attempts have been made to study the molecular epidemiology of these viruses associated with diarrhea outbreaks within a farm over an extended period of time. Here, we investigated the molecular characteristics of GARs that caused four outbreaks of diarrhea among suckling pigs in a farrow-to-finish farm over the course of a year. G and P genotyping of GARs detected at each outbreak demonstrated genetic diversity in this farm as follows: G9P[23] was detected at the first outbreak, G9P[13]/[22] and G9P[23] at the second, G3P[7] at the third, and G9P[23], G5P[13]/[22], and P[7] combined with an untypeable G genotype at the fourth. Sequence analysis of the detected GARs revealed that such genetic diversity could have resulted not only from the introduction of new GAR strains, but also from gene reassortment between GAR strains within the farm. Further, the GAR strain carrying the untypeable G genotype was shown to be a novel porcine GAR bearing a new G26 genotype, as confirmed by the Rotavirus Classification Working Group.


title: Phylogeny of Viruses

text: Biological species, including viruses, change through generations and over time in the process known as evolution. Viruses may evolve at high, uneven, and fluctuating rates among genome sites. The accumulated changes, through either mutation or recombination with other species, are first fixed in the genome of successful individuals that give rise to genetic lineages. The relationship between biological lineages related by common descent is called ‘phylogeny’. For inferring phylogeny, the differences between aligned sequences of genomes and proteins are quantified and depicted in the form of a tree, in which contemporary species and their intermediate and common ancestors occupy, respectively, the terminal nodes, internal nodes, and the root. The tree is characterized by a topology, length of branches, shape, and the root position. A complex mathematical apparatus has been developed for phylogeny inference that can evaluate inter-species differences, facilitate tree building and comparison of trees, and assess the fit between data and tree through, typically, computationally intensive calculations. A reconstructed tree is an approximation of the true phylogeny that practically remains unknown. The phylogenetic analysis is used in applied and fundamental virus research, including epidemiology, diagnostics, forensic studies, phylogeography, evolutionary studies, and virus taxonomy. It can provide an evolutionary perspective on variation of any trait that can be measured for a group of viruses.


COVID-19 associated encephalopathy: is there a specific EEG pattern?


title: Bench-to-bedside review: Adjuncts to mechanical ventilation in patients with acute lung injury

text: Mechanical ventilation is indispensable for the survival of patients with acute lung injury and acute respiratory distress syndrome. However, excessive tidal volumes and inadequate lung recruitment may contribute to mortality by causing ventilator-induced lung injury. This bench-to-bedside review presents the scientific rationale for using adjuncts to mechanical ventilation aimed at optimizing lung recruitment and preventing the deleterious consequences of reduced tidal volume. To enhance CO(2 )elimination when tidal volume is reduced, the following are possible: first, ventilator respiratory frequency can be increased without necessarily generating intrinsic positive end-expiratory pressure; second, instrumental dead space can be reduced by replacing the heat and moisture exchanger with a conventional humidifier; and third, expiratory washout can be used for replacing the CO(2)-laden gas present at end expiration in the instrumental dead space by a fresh gas (this method is still experimental). For optimizing lung recruitment and preventing lung derecruitment there are the following possibilities: first, recruitment manoeuvres may be performed in the most hypoxaemic patients before implementing the preset positive end-expiratory pressure or after episodes of accidental lung derecruitment; second, the patient can be turned to the prone position; third, closed-circuit endotracheal suctioning is to be preferred to open endotracheal suctioning.


title: Initial ELSO Guidance Document: ECMO for COVID-19 Patients with Severe Cardiopulmonary Failure

text: Disclaimer: ECMO has, and will certainly continue, to play a role in the management of COVID-19 patients. It should be emphasized that this initial guidance is based on the current best evidence for ECMO use during this pandemic. Guidance documents addressing additional portions of ECMO care are currently being assembled for rapid publication and distribution to ECMO centers worldwide.


title: A randomised controlled trial of the effectiveness of an exercise training program in patients recovering from severe acute respiratory syndrome

text: The aim of this study was to evaluate the effectiveness of an exercise training program on cardiorespiratory and musculoskeletal performance and health-related quality of life of patients who were recovering from severe acute respiratory syndrome (SARS). A 6-week supervised exercise training program was carried out in the physiotherapy department of a university teaching hospital. One hundred and thirty-three patients referred from a SARS Review Clinic solely for physiotherapy were included. Cardiorespiratory fitness (6-minute walk test, Chester Step Test for predicting VO2max), musculoskeletal performance (isometric deltoid and gluteal muscles strength, handgrip strength, 1-minute curl-up and push-up tests) and health-related quality of life (SF-36) were measured and evaluated. Patients were assigned randomly to either a control group (standardised educational session about exercise rehabilitation) or an exercise group. After 6 weeks, significantly greater improvement was shown in the exercise group in the 6-minute walk test (77.4 m vs 20.7 m, p < 0.001), VO2max (3.6 ml/kg/min vs 1 ml/kg/min, p = 0.04), and musculoskeletal performance (handgrip strength, curl-up and push-up tests, p < 0.05). Effects on health-related quality of life were not statistically significant. It was concluded that the exercise training program was effective in improving both the cardiorespiratory and musculoskeletal fitness in patients recovering from SARS. However, health-related quality of life was not affected by physical training.


Developing a curriculum in artificial intelligence for emergency radiology


Summary of Suggestions From the Task Force for Mass Critical Care Summit, January 26–27, 2007


title: “Conscious proning: An introduction of a proning protocol for non‐intubated, awake, hypoxic Emergency Department COVID‐19 patients”

text: The novel coronavirus, or COVID‐19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID‐19 has been the worsening hypoxia which, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, as it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a system‐wide multi‐institutional (New York‐Presbyterian Hospital enterprise) protocol for placing awake, non‐intubated, Emergency Department patients with suspected or confirmed COVID‐19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID‐19 cases with respiratory symptoms.


title: Rapid detection of influenza A virus infection utilizing an immunomagnetic bead-based microfluidic system()

text: This study reports a new immunomagnetic bead-based microfluidic system for the rapid detection of influenza A virus infection by performing a simple two-step diagnostic process that includes a magnetic bead-based fluorescent immunoassay (FIA) and an end-point optical analysis. With the incorporation of monoclonal antibody (mAb)-conjugated immunomagnetic beads, target influenza A viral particles such as A/H(1)N(1) and A/H(3)N(2) can be specifically recognized and are bound onto the surface of the immunomagnetic beads from the specimen sample. This is followed by labeling the fluorescent signal onto the virus-bound magnetic complexes by specific developing mAb with R-phycoerythrin (PE). Finally, the optical intensity of the magnetic complexes can be analyzed immediately by the optical detection module. Significantly, the limit of detection (LOD) of this immunomagnetic bead-based microfluidic system for the detection of influenza A virus in a specimen sample is approximately 5 × 10(−4) hemagglutin units (HAU), which is 1024 times better than compared to conventional bench-top systems using flow cytometry. More importantly, the entire diagnostic protocol, from the purification of target viral particles to optical detection of the magnetic complexes, can be automatically completed within 15 min in this immunomagnetic bead-based microfluidic system, which is only 8.5% of the time required when compared to a manual protocol. As a whole, this microfluidic system may provide a powerful platform for the rapid diagnosis of influenza A virus infection and may be extended for diagnosis of other types of infectious diseases with a high specificity and sensitivity.


title: Infectious triggers of asthma

text: There is abundant evidence that asthma is frequently exacerbated by infectious agents. Several viruses have been implicated in the inception and exacerbation of asthma. Recent attention has been directed at the role of infections with the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae as agents capable of triggering asthma exacerbations and potentially as inciting agents for asthma. This article examines the evidence for interaction between specific infectious agents and exacerbations of asthma, including the immunopathology of infection-triggered asthma, and the current therapeutic options for management.


docid: rjthvtul

title: Origins and evolution of viruses of eukaryotes: The ultimate modularity

text: Abstract Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes.


title: An improved particle swarm optimization method for locating time-varying indoor particle sources

text: Abstract The indoor transmission of airborne particles can spread disease and have health-related and even life-threatening effects on occupants, thus necessitating effective ways to locate indoor particle sources. The identification of particle sources from concentration distributions is a difficult task because particles are often released at a time-varying rate, and particle transport mechanisms are more complex than those of gas. This study proposes an improved multi-robot olfactory search method for locating two types of time-varying indoor particle sources: 1) periodic sources such as occupants’ respiratory activities and 2) decaying sources such as laboratory leaky containers with hazardous chemicals. The method considers both particle concentrations and indoor air velocities by including an upwind term in the standard particle swarm optimization (PSO) algorithm, preventing robots from becoming trapped into a local optimum, which occurs when using other algorithms. We also considered two ventilation types (mixing ventilation and displacement ventilation) when particles are emitted from different source types, comprising four scenarios. For each scenario, particle concentration and air velocity were simulated using computational fluid dynamics (CFD) and then fed to the PSO algorithm for source localization. In addition, we validated the CFD approach for one scenario by comparing experimental data (e.g., velocities and particle concentrations) under laboratory settings. The results showed that the proposed method can locate the two types of particle sources within approximately 55 s, and the success rates of source localization exceeding 96%, which is a much higher level than levels achieved from the standard PSO and wind utilization II algorithms.


title: Fatalness of virus depends upon its cell fractal geometry

text: Abstract Why do more complex viruses (e.g., HIV, AIDS-virus and SARS coronavirus) tend to be more fatal? The paper concludes that the cell fractal geometry of viruses is the key. This paper also suggests two possible new approaches using nanotechnology and temperature to cure or prevent virus infection.


title: Fusion of Enveloped Viruses in Endosomes

text: Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH, and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion triggering mechanisms. A key take home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors, and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion.


Chapter 8 Digestive Disorders


title: Further Characterization of the Coronavirus Infectious Bronchitis Virus 3C-like Proteinase and Determination of a New Cleavage Site

text: Abstract Coronavirus infectious bronchitis virus (IBV) encodes a trypsin-like proteinase (3C-like proteinase) by ORF 1a, which has been demonstrated to play a pivotal role in proteolytic processing of gene 1-encoded polyproteins. In our previous studies, the proteinase was identified as a 33-kDa protein in IBV-infected cells, and its catalytic center was shown to consist of H2820 and C2922 residues. It is released from the 1a and 1a/1b polyproteins by autoprocessing at two Q–S dipeptide bonds (Q2779–S2780 and Q3086–S3087). In this report, further characterization of the two cleavage sites demonstrates that the N-terminal Q2779–S2780 site is tolerant to mutations at the P1 position. Deletion of the C-terminal region of the proteinase shows that a significant amount of the enzymatic activity is maintained upon deletion of up to 67 amino acids, suggesting that the extreme C-terminal region may be dispensable for the proteolytic activity of the proteinase. Analysis of the autoprocessing kinetics in vitro reveals that proteolysis at the Q2779–S2780 site is the first cleavage event mediated by this proteinase. This is followed by cleavage at the Q3086–S3087 site. The occurrence of both cleavage events in intact cells is potentially rapid and efficient, as no intermediate cleavage products covering the proteinase were detected in either IBV-infected or transfected cells. Immunofluorescence microscopy and subcellular fractionation studies further show differential subcellular localization of the proteinase in IBV-infected cells and in cells expressing the 3C-like proteinase alone, indicating that additional roles in viral replication might be played by this protein. Finally, a Q–A (Q3379–A3380) dipeptide bond encoded by nucleotides 10,663 to 10,668 was demonstrated to be a cleavage site of the proteinase.


title: Les séquelles de virose en pneumopédiatrie

text: Résumé L’immaturité du système immunitaire explique une part de la vulnérabilité aux pathogènes respiratoires durant l’enfance. Une infection virale respiratoire aiguë chez l’enfant peut être secondaire à 1 des 200 virus génétiquement différents et identifiables par les outils moléculaires. Les cellules ciliées distribuées tout au long de l’épithélium des voies respiratoires sont la cible des virus. Les études épidémiologiques rapportent une diminution de la fonction respiratoire chez l’adulte indépendamment de facteurs confondants lorsqu’une pneumonie est survenue avant l’âge de 2 voire 7 ans. Cette réduction de la fonction respiratoire est le reflet probable de l’atteinte initiale malgré les processus de réparation (altération potentielle de croissance pulmonaire) et à l’âge adulte d’une accélération du déclin physiologique des capacités ventilatoires. Les études portant sur l’origine des dilatations des bronches retrouvent des antécédents de pneumopathies infectieuses plus d’une fois sur deux. Les infections à adénovirus sont particulièrement en cause. Une bronchiolite obstructive post-infectieuse peut survenir même chez l’enfant immunocompétent ; le tableau initial est très souvent pseudo-grippal, puis est marqué par une dissociation entre des signes fonctionnels importants et un examen clinique pauvre. L’évolution au long cours est peu prévisible mais peut conduire à l’insuffisance respiratoire chronique létale. Les pneumopathies infiltratives diffuses sont caractérisées par une infiltration diffuse de la charpente conjonctivale du poumon par des cellules inflammatoires et de la fibrose. Le rôle des virus dans son développement a été évoqué en raison de la présence d’inclusions cellulaires évoquant des particules virales dans le poumon d’enfants atteints. Enfin la plupart des études épidémiologiques soulignent l’association entre une symptomatologie sifflante secondaire à une agression virale durant l’enfance et le risque ultérieur de développement d’un asthme. Summary Community-acquired viral bronchopneumonia is frequent, particularly in children, and can be associated with all types of respiratory viruses. Immature immunity explains the vulnerability to respiratory pathogens during childhood. Epithelial cells distributed throughout the airway epithelium are the target of viruses. Epidemiological studies report a decrease in respiratory function in adults, regardless of confounding factors, who had pneumonia before the age of 2 or even 7years. This reduction in respiratory function is a consequence of the initial involvement and of the accelerated physiological decline in adulthood. Studies on the origin of bronchial dilatation have found a history of infectious pneumonia in more than 50% of cases. Adenoviral infections in particular are involved. Postinfectious obstructive bronchiolitis can occur even in immunocompetent children. The initial clinical picture is often flu-like, and is subsequently marked by a dissociation between important functional signs and a poor clinical presentation. The long-term course is not predictable but can lead to lethal chronic respiratory failure. Diffuse infiltrative pneumonitis is characterized by pulmonary diffuse infiltration with inflammatory cells and fibrosis. The role of viruses in its development has been mentioned due to the presence of cellular inclusions evoking viral particles in the lungs of affected children. Finally, most epidemiological studies emphasize the association between wheezing symptoms secondary to viral infection in childhood and the subsequent risk of developing asthma.


title: Prolonged grief disorder following the Coronavirus (COVID-19) pandemic

text: • Prolonged grief disorder (PGD) cases will rise following the COVID-19 pandemic; • The pandemic shows similarities to natural disasters which increase PGD prevalence. • The circumstances of death during the pandemic likely increase PGD prevalence. • Evidence-based interventions for PGD should be made more accessible. • Internet-based interventions for PGD should be further developed and disseminated.


title: Infectious diseases – A global challenge

text: Abstract Infectious diseases represent a continuous and increasing threat to human health and welfare. Due to emerging diseases, increasing resistances, international travelling, and the risk of bioterroristic attacks, infectious diseases concern the whole world and can only be combated by internationally coordinated and interdisciplinary approaches. When assessing the worldwide publication activities on infectious diseases in the years 1994–2004 accessible via the ISI Science Citation Index Expanded®, an overall increase by 24% can be monitored. Furthermore, it becomes evident that highest research priorities are given to HIV/AIDS, hepatitis C, tuberculosis, respiratory infections, and sepsis. Ten countries – including the USA, the UK, France, Germany, and Japan – contributed to more than 80% of these publications; nation-specific research priorities focusing on the current problems in the respective country can be estimated. Countries with the highest disease burdens are still not given the opportunity to contribute adequately to the scientific field. Based on our data, relatively increasing publication activities include those on respiratory infections, tuberculosis, malaria, hepatitis, and sepsis, whereas decreasing activities were determined for AIDS, diarrhoea, meningitis, schistosomiasis, and other diseases. Accordingly, the prevalence of many infectious diseases occurring in tropical countries is not clearly reflected in the worldwide publication activities.


title: Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19

text: Abstract Background & Aims We compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea. Methods We performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR. Results Of the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P<.05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P<.001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P=.010), during these patients’ hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P=.039). Conclusions At a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.


title: The human virome: new tools and concepts

text: The human virome is the viral component of the microbiome. Its composition, and interindividual and temporal variability are not precisely known. Its impact on human health has received less attention than that of the bacterial microbiome, but is likely to be equally important, both in homeostasis and disease. Here we review the recent advances in this field and the questions that arise in the context of our rapidly increasing knowledge regarding the composition and function of the human virome. With the ever-extending use of next-generation sequencing (NGS) on a variety of clinical samples, rapid progress on the composition of the human virome and its impact upon human health are to be expected in the coming years.


title: COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice

text: Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002–2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and other epithelia and have shown to develop a rapidly lethal infection after intranasal inoculation with SARS-CoV, the pathogen of SARS. This literature review aims to present the importance of utilizing the human ACE2 transgenic mouse model to better understand the pathogenesis of COVID-19 and develop both therapeutics and vaccines.


title: Development and evaluation of a panel of multiplex one‐tube nested real time PCR assay for simultaneous detection of 14 respiratory viruses in five reactions

text: Multiplex real‐time quantitative polymerase chain reaction (mRT‐qPCR) assay is commonly used to detect respiratory viruses, however, the sensitivity is limited for most reports. A panel of locked nucleic acid based multiplex closed one‐tube nested real‐time PCR (mOTNRT‐PCR) assay consisting of five separate internally controlled RT‐qPCR assays was developed for detection of 14 respiratory viruses. The sensitivity and reproducibility of mOTNRT‐PCR panel were evaluated using plasmid standards and the specificity was evaluated using clinical samples. The clinical performance of mOTNRT‐PCR panel was further evaluated with 468 samples collected from patients with an acute respiratory infection and compared with individual real‐time PCR (RT‐qPCR) assay. The analytical sensitivities of mOTNRT‐PCR panel ranged from 2 to 20 copies/reaction, and no cross‐reaction with common respiratory viruses was observed. The coefficients of variation of intra‐assay and inter‐assay were between 0.35% and 8.29%. Totally 35 clinical samples detected by mOTNRT‐PCR assay panel were missed by RT‐qPCR and confirmed true positive by sequencing of nested PCR products. The mOTNRT‐PCR assay panel provides a more sensitive and high‐throughput method for the detection of 14 respiratory viruses.


title: Pandemic (H1N1) 2009 influenza

text: The clinical picture in severe cases of pandemic (H1N1) 2009 influenza is markedly different from the disease pattern seen during epidemics of seasonal influenza, in that many of those affected were previously healthy young people. Current predictions estimate that, during a pandemic wave, 12–30% of the population will develop clinical influenza (compared with 5–15% for seasonal influenza) with 4% of those patients requiring hospital admissions and one in five requiring critical care. This review covers the background, clinical presentation, diagnosis, and treatment. The role of immunization and antiviral drugs is discussed. Experience from the first wave of pandemic (H1N1) 2009 influenza suggests that a number of infected patients become critically ill and require intensive care admission. These patients rapidly develop severe progressive respiratory failure which is often associated with failure of other organs, or marked worsening of underlying airways disease. The critical care management of these patients and the implications for resources is reviewed. Guidance from a range of bodies has been produced in a relatively short period of time in response to pandemic (H1N1) 2009 influenza. Disease severity has the potential to change, especially if there is virus mutation. Clinicians must be prepared for the unexpected and continue to share their experiences to maximize patient outcomes.


title: COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – also known as COVID-19 – is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.


title: Epidemiological and clinical characteristics of discharged patients infected with SARS‐CoV‐2 on the Qinghai plateau

text: Since the outbreak of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was first reported in Wuhan, a series of confirmed cases of COVID‐19 were found on the Qinghai‐Tibet plateau. We aimed to describe the epidemiological, clinical characteristics, and outcomes of all confirmed cases in Qinghai, a province at high altitude. The region had no sustained local transmission. Of all 18 patients with confirmed SARS‐CoV‐2 infection, 15 patients comprising 4 transmission clusters were identified. Three patients were infected by direct contact without travel history to Wuhan. Of 18 patients, 10 patients showed bilateral pneumonia and 2 patients showed no abnormalities. Three patients with comorbidities such as hypertension, liver diseases or diabetes developed severe illness. High C‐reactive protein levels and elevations of both ALT and AST were observed in 3 severely ill patients on admission. All 18 patients were eventually discharged, including the 3 severe patients who recovered after treatment with non‐invasive mechanical ventilation, convalescent plasma and other therapies. Our findings confirmed human‐to‐human transmission of SARS‐CoV‐2 in clusters. Patients with comorbidities are more likely to develop severe illness. This article is protected by copyright. All rights reserved.


title: Modulation of angiogenesis with siRNA inhibitors for novel therapeutics

text: Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are currently focused on understanding gene function, as well as proof-of-concept for siRNA-mediated anti-angiogenesis. The prospects for siRNA therapeutics, both advantages and looming hurdles, are evaluated.


title: Fluoroscopy-guided balloon dilation of a proximal urethral stricture caused by a urethral membrane in a female cat

text: CASE SUMMARY: A proximal urethral stricture was diagnosed by retrograde urethrogram in a 2-year-old female neutered cat, which was referred following a 2-month history of stranguria, pollakiuria and urinary incontinence. Cystoscopic examination confirmed the presence of a severe narrowing of the proximal urethra near to the bladder neck, consisting of a membrane arising from the urethral mucosa. Fluoroscopy-guided balloon dilation was performed. Twelve months after the procedure, the cat did not show any recurrence of clinical signs. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of a proximal urethral stricture in a cat. Management by fluoroscopy-guided balloon dilation proved to be a successful and minimally invasive option with an excellent outcome.


title: Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Interactome Reveals Inhibition of Virus Replication by Cellular VPS36 Protein

text: The accessory protein ORF3 of porcine epidemic diarrhea virus (PEDV) has been proposed to play a key role in virus replication. However, our understanding of its function regarding virus and host interaction is still limited. In this study, we employed immunoprecipitation and mass spectrometry to screen for cellular interacting partners of ORF3. Gene ontology analysis of the host interactome highlighted the involvement of ORF3 in endosomal and immune signaling pathways. Among the identified ORF3-interacting proteins, the vacuolar protein-sorting-associated protein 36 (VPS36) was assessed for its role in PEDV replication. VPS36 was found to interact with ORF3 regardless of its GLUE domain. As a result of VPS36–ORF3 interaction, PEDV replication was substantially suppressed in cells overexpressing VPS36. Interestingly, the ORF3 protein expression was diminished in VPS36-overexpressing cells, an effect that could not be restored by treatment of lysosomal inhibitors. In addition, disruption of endogenously-expressed VPS36 by siRNA could partially augment PEDV replication. Taken together, our study provides mechanistic insights into the contribution of ORF3 in PEDV replication.


title: Coronavirus Disease 2019 (COVID-19) in Children: Vulnerable or Spared? A Systematic Review

text: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has affected people from all cultures, religions, gender, and age groups around the world. In the last few months, several studies have been conducted on various aspects of COVID-19. Our goal was to see if the pediatric population is vulnerable to this infection. In this review, we conducted extensive research mainly by using the PubMed database. We used Medical Subject Headings (MeSH) and associated keywords to engage in an extensive search focussing on COVID-19 in the pediatric population. We discovered that most of the studies were from China, and some of them were in the Chinese language. However, English translations of many of the studies were available. For accessing the relevant statistical data, we relied on the World Health Organization (WHO) resources and the official website of the Ontario Government (ontario.ca). Most of the studies showed that the virus has affected the pediatric population. However, we found some differences among these studies regarding the severity of symptoms in children affected by COVID-19. While a few studies stated that the virus has presented with milder symptoms in the pediatric population, some studies have presented data of children who have suffered life-threatening complications due to COVID-19. Although the data is limited, we have been able to conclude from the studies we reviewed that COVID-19 does indeed affect children the same way as any other age group. Moreover, children can act as carriers of the virus and can endanger the lives of other individuals. Besides, neonates and infants can easily acquire the infection from family members without having any exposure to the outside world. Hence, utmost care should be taken while handling this population. More trials and studies should be conducted to analyze the impact of early diagnosis of infection in children and its management.


title: Differential Diagnosis of Common Acute Toxicologic Versus Nontoxicologic Illness

text: This table outlines common toxicologic versus nontoxicologic rule outs based on clinical abnormalities seen in an acutely ill animal. The purpose is to provide an initial guideline for considering toxicologic versus nontoxicologic rule outs when a patient is presented to a practicing veterinarian. Major clinical abnormalities followed by common toxicologic rule outs and non-toxicologic rule outs have been listed so that practicing veterinarians can narrow down an etiology quickly. Based on history, physical examination findings, and blood work changes, once a reasonable etiology has been narrowed down or established, the reader is encouraged to review a more detailed discussion on management of the particular poisoning or disease listed in this or other references.


title: Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients

text: Abstract An outbreak of new coronavirus SARS-CoV-2 was occurred in Wuhan, China and rapidly spread to other cities and nations. The standard diagnostic approach that widely adopted in the clinic is nucleic acid detection by real-time RT-PCR. However, the false-negative rate of the technique is unneglectable and serological methods are urgently warranted. Here, we presented the colloidal gold-based immunochromatographic (ICG) strip targeting viral IgM or IgG antibody and compared it with real-time RT-PCR. The sensitivity of ICG assay with IgM and IgG combinatorial detection in nucleic acid confirmed cases were 11.1%, 92.9% and 96.8% at the early stage (1–7 days after onset), intermediate stage (8–14 days after onset), and late stage (more than 15 days), respectively. The ICG detection capacity in nucleic acid-negative suspected cases was 43.6%. In addition, the concordance of whole blood samples and plasma showed Cohen's kappa value of 0.93, which represented the almost perfect agreement between two types of samples. In conclusion, serological ICG strip assay in detecting SARS-CoV-2 infection is both sensitive and consistent, which is considered as an excellent supplementary approach in clinical application.


title: Hospital biosecurity capacitation: Analysis and recommendations from the prevention and control of COVID-19

text: The outbreak of COVID-19 epidemic in December 2019 has highlighted issues with hospital biosafety capacitation in the People’s Republic of China, although the epidemic has been controlled now. This study examined the primary issues, including an absence of hospital emergency system, inadequate management and control of nosocomial infection, limited hospital laboratory capacity, and poor hospital admission capacity. Accordingly, the study put forward the following countermeasures and suggestions for hospitals to deal with future biosecurity events, such as a major epidemic: first, there is a need to build biosecurity management systems and emergency response mechanisms in hospitals; second, the investment and guarantee mechanisms for hospital biosecurity construction should be improved; third, the capacity building of biosecurity incident treatment needs attention in general hospitals; and fourth, comprehensive plans need to be developed for the integrated construction of medical treatment and prevention facilities through disease-control systems.


title: Global dynamics of a general vector-borne disease model with two transmission routes

text: In this paper, we study the dynamics of a vector-borne disease model with two transmission paths: direct transmission through contact and indirect transmission through vector. The direct transmission is considered to be a non-monotone incidence function to describe the psychological effect of some severe diseases among the population when the number of infected hosts is large and/or the disease possesses high case fatality rate. The system has a disease-free equilibrium which is locally asymptomatically stable when the basic reproduction number (R0) is less than unity and may have up to four endemic equilibria. Analytical expression representing the epidemic growth rate is obtained for the system. Sensitivity of the two transmission pathways were compared with respect to the epidemic growth rate. We numerically find that the direct transmission coefficient is more sensitive than the indirect transmission coefficient with respect to R0 and the epidemic growth rate. Local stability of endemic equilibria is studied. Further, the global asymptotic stability of the endemic equilibrium is proved using Li and Muldowney geometric approach. The explicit condition for which the system undergoes backward bifurcation is obtained. The basic model also exhibits the hysteresis phenomenon which implies diseases will persist even when R0 < 1 although the system undergoes a forward bifurcation and this phenomenon is rarely observed in disease models. Consequently, our analysis suggests that the diseases with multiple transmission routes exhibit bi-stable dynamics. However, efficient application of temporary control in bi-stable regions will curb the disease to lower endemicity. In addition, increase in transmission heterogeneity will increase the chance of disease eradication.


title: Glycosylation of Zika Virus is Important in Host–Virus Interaction and Pathogenic Potential

text: Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.


title: Thiol-based angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1 subsite

text: Abstract Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P1 benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP.


title: Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation

text: Abstract As antiviral drug resistance develops and new viruses emerge there is a pressing need to develop strategies to rapidly develop antiviral therapeutics. Here we use phospho-specific flow cytometry to assess perturbations of many different cellular signaling pathways during treatment with drug combinations that are highly effective in blocking Herpes simplex virus type 1 (HSV-1) infection. We discovered two antiviral drug combinations act on distinct signaling pathways, either STAT1 or S6 phosphorylation, to block HSV-1 infection. We focused on upregulation of S6 phosphorylation by HSV-1 infection, and our subsequent finding that ribavirin antagonizes this upregulation of S6 phosphorylation. We go on to show that the S6 kinase inhibitor SL0101 blocks HSV-1 replication in vitro and in an in vivo animal model of HSV-1 infection. Overall, we have used an unbiased analysis of cellular signaling pathways during treatment by antiviral drug combinations to discover a novel antiviral drug target against HSV-1 infection. The outcomes of the approach we present highlight the importance of analyzing how antiviral drugs modulate cellular and pathogen-induced signaling as a method to discover new drug therapy targets.


title: Willingness of Chinese nurses to practice in Hubei combating the coronavirus disease 2019 epidemic: A cross‐sectional study

text: AIMS: To investigate the willingness of Chinese nurses to practice in Hubei combating the coronavirus disease 2019 and to explore the associated factors. DESIGN: A cross‐sectional survey. METHODS: Clinical nurses were conveniently recruited by an online link in three provinces out of Hubei, including Hunan (Central south), Chongqing (Southwest) and Xinjiang (Northwest) during 4‐10 February 2020. A structured questionnaire was distributed by an online investigation system. Information on sociodemographic characteristics, willingness, possible influencing factors (previous experience, health status, training conditions, perceptions on volunteering to practice in Hubei, family attitude and insurance) were collected. Binary logistic regression was conducted to explore the association of different factors with the willingness decision of nurses. RESULTS: A total of 11,183 nurses participated in this survey and a high proportion of them were willing to volunteer to practice in Hubei combating the epidemic. Nurses who were likely to volunteer had the following characteristics: younger, unmarried, members of the Communist Party of China, with senior professional qualification, working in critical care departments, with support from their families, with adequate training and learning, with good health status and low levels of anxiety. The regression model could explain 31.1% of the variances of the willingness decision of nurses. CONCLUSIONS: A high proportion of nurses in China were willing to practice in Hubei during the coronavirus disease 2019 epidemic. Adequate training and psychological support would facilitate nurses to volunteer during the outbreak of an infectious disease. IMPACT: The study identified a high proportion of nurses in China were willing to to practice in Hubei combating the coronavirus disease 2019 epidemic. The findings will provide valuable references for nurses and decision makers to formulate better plans for increasing nursing workforce during such kind of public health crisis.


title: Commentary: Performing Cardiac Surgery in the COVID-19 Era: What is the New Normal?

text: The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the COVID-19 pandemic crisis have significantly changed the landscape of cardiac surgical practice. There is a sense of urgency that is all the more intensified given the many unanswered questions surrounding virus transmission. Furthermore, the cardiac surgeon’s primary responsibility is to assure patient safety and excellent outcome. There remains a huge gap between the different aspects of this biopsychosocial viral crisis and our current knowledge.


title: Pandemic Influenza and Pregnant Women

text: Planning for a future influenza pandemic should include considerations specific to pregnant women. First, pregnant women are at increased risk for influenza-associated illness and death. The effects on the fetus of maternal influenza infection, associated fever, and agents used for prophylaxis and treatment should be taken into account. Pregnant women might be reluctant to comply with public health recommendations during a pandemic because of concerns regarding effects of vaccines or medications on the fetus. Guidelines regarding nonpharmaceutical interventions (e.g., voluntary quarantine) also might present special challenges because of conflicting recommendations about routine prenatal care and delivery. Finally, healthcare facilities need to develop plans to minimize exposure of pregnant women to ill persons, while ensuring that women receive necessary care.


title: Gastrointestinal Disease in Exotic Small Mammals

text: Abstract Exotic small mammal medicine is a relatively new specialty area within veterinary medicine. Ferrets, rabbits, and rodents have long been used as animal models in human medical research investigations, resulting in a body of basic anatomic and physiologic information that can be used by veterinarians treating these species. Unfortunately, there is a paucity of veterinary articles that describe clinical presentation, diagnosis, and treatment options of gastrointestinal (GI) disease as it affects exotic small mammals. Although there is little reference material relating to exotic small mammal GI disease, patients are commonly presented to veterinary hospitals with digestive tract disorders. This article provides the latest information available for GI disease in ferrets (Helicobacter mustelae gastritis, inflammatory bowel disease [IBD], GI lymphoma, systemic coronavirus, coccidiosis, and liver disease), rabbits (GI motility disorders, liver lobe torsion, astrovirus, and coccidiosis), guinea pigs (gastric dilatation volvulus [GDV]), rats (Taenia taeniaeformis), and hamsters (Clostridium difficile). Both noninfectious diseases and emerging infectious diseases are reviewed as well as the most up-to-date diagnostics and treatment options.


title: Mathematical prediction in infection

text: Abstract It is now increasingly common for infectious disease epidemics to be analysed with mathematical models. Modelling is possible because epidemics involve relatively simple processes occurring within large populations of individuals. Modelling aims to explain and predict trends in disease incidence, prevalence, morbidity or mortality. Epidemic models give important insight into the development of an epidemic. Following disease establishment, epidemic growth is approximately exponential. The rate of growth in this phase is primarily determined by the basic reproduction number, R 0, the number of secondary cases per primary case when the population is susceptible. R 0 also determines the ease with which control policies can control an epidemic. Once a significant proportion of the population has been infected, not all contacts of an infected individual will be with susceptible people. Infection can now continue only because new births replenish the susceptible population. Eventually an endemic equilibrium is reached where every infected person infects one other individual on average. Heterogeneity in host susceptibility, infectiousness, human contact patterns and in the genetic composition of pathogen populations introduces substantial additional complexity into this picture, however – and into the models required to model real diseases realistically. This chapter concludes with a brief review of the recent application of mathematical models to a wide range of emerging human or animal epidemics, most notably the spread of HIV in Africa, the 2001 foot and mouth epidemic in British livestock, bioterrorism threats such as smallpox, the SARS epidemics in 2003 and most recently the use of modelling as a tool for influenza pandemic preparedness planning.


title: The Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Healthcare Network in the United States

text: BACKGROUND: Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results. RESULTS: Of 7256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients aged 18–21 years had the highest test positive rate (11.2%), while those aged 1–5 years had the lowest (3.9%). By race, 10.6% (226/2132) of black children tested positive vs 3.3% (117/3592) of white children. By indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs 3.8% (53/1410) of those undergoing preprocedural or preadmission testing. Of 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbidities, 87 (20.5%) had asthma, and 55 (13.0%) were obese. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2–positive patients were hospitalized, of whom 24 (31.2%) required respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2-positive patients required mechanical ventilation, and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low but varied by testing indication. The majority of cases were mild and few children had critical illness.


title: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus : Brief Review

text: Feline aminopeptidase N (fAPN) has been shown to serve as a receptor for feline, canine, porcine and human coronaviruses. Our objective was to determine if fAPN can serve as a receptor for infectious bronchitis virus (IBV). Feline kidney cells that express fAPN and hamster kidney fibroblasts that do not express fAPN were inoculated with IBV and monitored for replication by indirect fluorescent assay and confocal microscopy and in chicken embryonated eggs. The results showed that the feline cells were permissive to IBV but the hamster cells were not. The hamster cells became permissive to IBV after transfection with a fAPN cDNA suggesting that the feline APN molecule plays a role in IBV entry.


title: Flavivirus reverse genetic systems, construction techniques and applications: A historical perspective

text: Abstract The study of flaviviruses, which cause some of the most important emerging tropical and sub-tropical human arbovirus diseases, has greatly benefited from the use of reverse genetic systems since its first development for yellow fever virus in 1989. Reverse genetics technology has completely revolutionized the study of these viruses, making it possible to manipulate their genomes and evaluate the direct effects of these changes on their biology and pathogenesis. The most commonly used reverse genetics system is the infectious clone technology. Whilst flavivirus infectious clones provide a powerful tool, their construction as full-length cDNA molecules in bacterial vectors can be problematic, laborious and time consuming, because they are often unstable, contain unwanted induced substitutions and may be toxic for bacteria due to viral protein expression. The incredible technological advances that have been made during the past 30years, such as the use of PCR or new sequencing methods, have allowed the development of new approaches to improve preexisting systems or elaborate new strategies that overcome these problems. This review summarizes the evolution and major technical breakthroughs in the development of flavivirus reverse genetics technologies and their application to the further understanding and control of these viruses and their diseases.


title: Adaptation of the Fear of COVID-19 Scale: Its Association with Psychological Distress and Life Satisfaction in Turkey

text: The world is currently experiencing a pandemic of an infectious disease called COVID-19 which has drawn global intensive attention. While global attention is largely focusing on the effects of the coronavirus on physical health, the impacts of the coronavirus on psychological health cannot be overlooked. Therefore, this study aims to adapt the Fear of COVID-19 Scale into Turkish and investigate the relationships between fear of COVID-19, psychological distress, and life satisfaction. Data were collected by convenience sampling method, which allowed us to reach total 1304 participants, aged between 18 and 64 years, from 75 cities in Turkey. In the adaptation process of the Fear of COVID-19 Scale, confirmatory factor analysis, Item Response Theory, convergent validity, and reliability (Cronbach’s α, McDonald’s ω, Guttmann’s λ6, and composite reliability) analyses were performed. Additionally, the mediating role of psychological distress on the relationship between fear of COVID-19 and life satisfaction was tested. The uni-dimensionality of the 7-item scale was confirmed on a Turkish sample. Item Response Theory revealed that all items were coherent and fit with the model. The results indicated that the Turkish version of the scale had satisfactory reliability coefficients. The fear of COVID-19 was found to be associated with psychological distress and life satisfaction. Results indicated that the Turkish version of the Fear of COVID-19 Scale had strong psychometric properties. This scale will allow mental health professionals to do research on the psychological impacts of COVID-19 in Turkey.


title: Use Incentive Approach to Promote BAT/BEP for Centralized Incineration Facilities of Medical Waste in China

text: Abstract The GEF project of environmental sustainability management for medical waste in China has been developed and implemented. The overall objectives of the project are to incorporate the concept of overall-process management in life cycle of medical waste into medical waste management and disposal of China, facilitate BAT/BEP application and promotion, improve China's abilities of medical waste management and disposal, promote reduction of medical waste and realize the target of harmlessness, by introducing the advanced experiences in medical waste management and disposal from foreign countries. Currently, most of the activities in demonstration stage have already been completed, and it is expected to reach the dioxin concentration of 0.1 ngTEQ/m3 in flue gas of 15 incineration (including pyrolysis) facilities. Hence, the project decides to implement the incentive plan among eligible medical waste incineration facilities in China. In this plan, a process with steps as application, review, examination, technical transformation, verification and award was designed. To standardize and externalize the process, an entire package of files including principles, guidelines, quota and criteria, table and checklist templates were developed, considering all the involved stakeholders. As a result, with active involvements and contribution of the MEP, local governments, enterprises, experts and monitoring instructions, the incentive plan vigorously guided and promoted BAT/BEP replication and application for medical waste disposal, avoided and reduced the generation and emission of dioxin POPs and other toxic substances. Currently, there are 8 incinerators which realized the aim of controlling their dioxins emission under limited concentration of 0.1ng TEQ/m3 in the flue gas.


title: Viral channel forming proteins — Modeling the target

text: Abstract The cellular and subcellular membranes encounter an important playground for the activity of membrane proteins encoded by viruses. Viral membrane proteins, similar to their host companions, can be integral or attached to the membrane. They are involved in directing the cellular and viral reproduction, the fusion and budding processes. This review focuses especially on those integral viral membrane proteins which form channels or pores, the classification to be so, modeling by in silico methods and potential drug candidates. The sequence of an isolate of Vpu from HIV-1 is aligned with host ion channels and a toxin. The focus is on the alignment of the transmembrane domains. The results of the alignment are mapped onto the 3D structures of the respective channels and toxin. The results of the mapping support the idea of a ‘channel–pore dualism’ for Vpu.


title: Antibody-dependent NK cell degranulation as a marker for assessing antibody-dependent cytotoxicity against pandemic 2009 influenza A(H1N1) infection in human plasma and influenza-vaccinated transchromosomic bovine intravenous immunoglobulin therapy

text: Abstract This study describes an antibody-dependent NK cell degranulation assay, as a biomarker to assess antibody-dependent cellular cytotoxicity (ADCC) response in influenza plasma and for antibody therapies against influenza infection. The concentration of neutralizing antibodies (NAbs) against the hemagglutinin receptor of influenza viruses is a current determinant in protection against infection, particularly following receipt of the seasonal influenza vaccine. However, this is a limited assessment of protection, because: (i) NAb titers that incur full protection vary; and (ii) NAb titers do not account for the entire breadth of antibody responses against viral infection. Previous reports have indicated that antibodies that prime ADCC play a vital role in controlling influenza infections, and thus should be quantified for assessing protection against influenza. This report demonstrates a non-radioactive assay that assesses NK cell activation as a marker of ADCC, in which NK cells interact with opsonized viral antigen expressed on the surface of infected Raji target cells resulting in effector cell degranulation (surrogate CD107a expression). A positive correlation was determined between HAI titers and sustained NK cell activation, although NK cell activation was seen in plasma samples with HAI titers below 40 and varied amongst samples with high HAI titers. Furthermore, sustained NK cell degranulation was determined for influenza-vaccinated transchromosomic bovine intravenous immunoglobulin, indicating the potential utility of this therapy for influenza treatment. We conclude that this assay is reproducible and relevant.


Comment on “Antipsoriatic treatments during COVID‐19 outbreak”


title: Chinese medicine diagnosis and treatment for COVID-2019: Is China ready for implementing a national guideline?

text: OBJECTIVES: COVID-19 sparked a pandemic in December 2019 and is currently posing a huge impact globally. Chinese herbal medicine is incorporated into the Chinese national guideline for COVID-19 management, emphasising the individualisation of herbal treatment guided by pattern differentiation, which is an ICD-11-endorsed approach. However, this was not widely implemented with many provincial governments and hospitals developing their own guideline, suggesting the use of standardised herbal formulae and herbal active ingredients without pattern differentiation. METHODS: Through the case study of COVID-19 guideline implementation, we compared the three approaches of developing Chinese herbal medicine, namely pattern differentiation-guided prescription, standardised herbal formulae, and herbal active ingredients, in terms of their strengths, limitations, and determinants of adoption. RESULTS: Pattern differentiation-guided prescription is the practice style taught in the national syllabus among universities of Traditional Chinese Medicine in China, yet the lack of relevant diagnostic research reduces its reliability and hinders its implementation. Application of standardised herbal formulae is straightforward since the majority of clinical evidence on Chinese herbal medicine is generated using this approach. Nevertheless, it is downplayed by regulatory bodies in certain jurisdictions where the use of pattern differentiation is required in routine practice. Although herbal active ingredients may have clear in vitro therapeutic mechanisms, this may not be translated into real world clinical effectiveness. CONCLUSIONS: Multiple COVID-19 clinical trials evaluating the effectiveness and safety of Chinese herbal medicine prescribed using one of the three approaches described above are progressing. These results will demonstrate the comparative effectiveness among these approaches. Forthcoming clinical evidence from these trials should inform the updating process of the national guideline, such that its recognition and compliance may be strengthened. For longer-term development Chinese herbal medicine, serious investment for establishing high-quality clinical research infrastructure is urgently needed.