title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003

text: Abstract Background Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that caused an outbreak in south China in 2003. The cause of SARS was identified as a novel coronavirus (CoV). The existence of asymptomatic seroconvertors and the detection of the SARS-CoV RNA in plasma during the course of infection all suggest that SARS could, as least theoretically, be transmitted by transfusion. An estimate of the risk of SARS transmission through blood transfusion will contribute to decisions concerning blood safety monitoring and may be useful in the design of strategies to decrease the risk of transfusion-transmitted infections. Study design and methods Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. Estimates of the asymptomatic-to-clinically confirmed SARS-CoV infection ratio, the proportion of asymptomatic infections reported in a seroprevalence survey in Hongkong, and the population size of Shenzhen are used to infer the SARS-CoV transfusion–transmission risk. Statistical resampling methods are used. Results Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. The estimated risk peaked on April 02, 2003. Conclusions Although there are currently no confirmed reports of the transmission of SARS-CoV from asymptomatic individuals, recent research data indicate that transfusion-transmitted SARS-CoV is at least theoretically possible. Although the risk is low, with its rapid spread of the disease, appearance of alarmingly high infectivity and high fatality rate, public health authorities need to consider strategies for blood donor recruitment and virus inactivation during an epidemic to further ensure blood safety.


title: Knowledge of inter-facility transport among emergency nurses in Hong Kong: A questionnaire survey

text: Abstract Introduction Inter-facility transport (IFT) is a dynamic process and its quality largely depends on pre-transport preparation, emergency equipment support and recognition of possible en route adverse events. This study aims to evaluate knowledge of IFT among emergency nurses of three Accident and Emergency Departments in Hong Kong. Methods Questionnaires were distributed to registered nurses of the three departments. Data was sought on participants’ characteristics, knowledge on equipment preparation and management of en route adverse events. Four clinical IFT scenarios were set for participants and answers were scored. Measured outcomes were defined as (1) relationships between clinical experience and relevant training in IFT with questionnaire results, (2) staff knowledge of the equipment carried routinely in ambulances and (3) the en route adverse events encountered according to the participants’ past experience. Results Participants’ test scores ranged from 24 to 37 (out of 40) with a mean of 30.6 (95% confidence interval 29.7–31.5). Participants with more clinical experience demonstrated significantly better test scores (p <0.05). Most participants were familiar with the monitoring devices carried in ambulances but were less familiar with the pharmacologic agents and airway devices available routinely in Hong Kong ambulances. Thirty participants (59%) had encountered en route adverse events in the past. Conclusion Nurses in emergency departments in Hong Kong have good knowledge of IFT. Extensive clinical experience is related to better IFT knowledge. IFT training for nurses should emphasize available ambulance service resources and capabilities.


title: Avian viral surveillance in Victoria, Australia, and detection of two novel avian herpesviruses

text: Viruses in avian hosts can pose threats to avian health and some have zoonotic potential. Hospitals that provide veterinary care for avian patients may serve as a site of exposure of other birds and human staff in the facility to these viruses. They can also provide a useful location to collect samples from avian patients in order to examine the viruses present in wild birds. This study aimed to investigate viruses of biosecurity and/or zoonotic significance in Australian birds by screening samples collected from 409 birds presented to the Australian Wildlife Health Centre at Zoos Victoria’s Healesville Sanctuary for veterinary care between December 2014 and December 2015. Samples were tested for avian influenza viruses, herpesviruses, paramyxoviruses and coronaviruses, using genus- or family-wide polymerase chain reaction methods coupled with sequencing and phylogenetic analyses for detection and identification of both known and novel viruses. A very low prevalence of viruses was detected. Columbid alphaherpesvirus 1 was detected from a powerful owl (Ninox strenua) with inclusion body hepatitis, and an avian paramyxovirus most similar to Avian avulavirus 5 was detected from a musk lorikeet (Glossopsitta concinna). Two distinct novel avian alphaherpesviruses were detected in samples from a sulphur-crested cockatoo (Cacatua galerita) and a tawny frogmouth (Podargus strigoides). Avian influenza viruses and avian coronaviruses were not detected. The clinical significance of the newly detected viruses remains undetermined. Further studies are needed to assess the host specificity, epidemiology, pathogenicity and host-pathogen relationships of these novel viruses. Further genome characterization is also indicated, and would be required before these viruses can be formally classified taxonomically. The detection of these viruses contributes to our knowledge on avian virodiversity. The low level of avian virus detection, and the absence of any viruses with zoonotic potential, suggests low risk to biosecurity and human health.


title: Mass spectral profiling: An effective tool for quality control of herbal medicines

text: Abstract Quality control of herbal medicines (HMs) is a big big headache because of the high complexity and unknown mechanism on disease treatment. In this work, mass spectral profiling, a new tool for data processing is proposed to help a lot in solving this problem as gas chromatography–mass spectroscopy (GC–MS) is used to detect both the active and non-active ingredients buried in HMs. The main idea of mass spectral profiling is employment of target m/z points of GC–MS data on the extraction of chromatographic profiles of pure and/or mixed compositions concerned. Further, the absolute or relative abundance at these m/z points can be utilized for results interpretation. With the help of this tool, the qualitative and quantitative information of chemical components within complicated HMs will be mined out effectively. It can then be recommended as reference indices to assess the importance of target compositions in HMs, such as efficacy evaluation on disease treatment of the active constituents. Mass spectral profiling with less data points significantly improves the possibility to get the rich information with no strong requirements of data preprocessing procedures, like alignment of shift of retention times among different chromatographic profiles. It is powerful for quality control of HMs coupled with pattern recognition techniques on high-throughput data sets. In this study, a commonly used herbal medicine, Houttuynia cordata Thunb and its finished injection products, were used to deliver the strategies. Absolutely, the working principles can be extended to the investigation of metabonomics with gas chromatography–time-of-flight–mass spectrometry (GC–MS–TOF). The good performance of mass spectral profiling shows that it can be a promising tool in the future studies of complex mixture systems.


title: Effect of mismatch repair on the mutation rate of bacteriophage ϕX174

text: Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli. Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capacity over the short term. However, the efficacy of mismatch repair in the presence of GATC sites is limited by inefficient methylation of the viral DNA. Therefore, both GATC avoidance and DNA under-methylation elevate the mutation rate of the phage relative to that of the host. We also found that the effects of GATC sites on the phage mutation rate vary extensively depending on their specific location within the phage genome. Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis.


title: Experiences with infectious cDNA clones of equine arteritis virus: Lessons learned and insights gained

text: Abstract The advent of recombinant DNA technology, development of infectious cDNA clones of RNA viruses, and reverse genetic technologies have revolutionized how viruses are studied. Genetic manipulation of full-length cDNA clones has become an especially important and widely used tool to study the biology, pathogenesis, and virulence determinants of both positive and negative stranded RNA viruses. The first full-length infectious cDNA clone of equine arteritis virus (EAV) was developed in 1996 and was also the first full-length infectious cDNA clone constructed from a member of the order Nidovirales. This clone was extensively used to characterize the molecular biology of EAV and other Nidoviruses. The objective of this review is to summarize the characterization of the virulence (or attenuation) phenotype of the recombinant viruses derived from several infectious cDNA clones of EAV in horses, as well as their application for characterization of the molecular basis of viral neutralization, persistence, and cellular tropism.


title: Ein einziger Patient befeuerte die MERS-Epidemie

text: Wie bei SARS vor 14 Jahren wurde jetzt auch bei MERS in Südkorea ein Superverbreiter identifiziert: Ein Mann hat wohl einen Großteil der Patienten angesteckt.


title: Positive natural selection in the evolution of human metapneumovirus attachment glycoprotein

text: Abstract Human metapneumovirus (hMPV), a newly discovered virus of the family Paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. The putative attachment (G) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. Using a maximum likelihood-based codon substitution model of sequence evolution, here we report that sequences of extracellular domain of 8 amino acid sites in lineage 1a, and 3 amino acid sites each in lineage 1b, 2a, and 2b have a higher rate of nonsynonymous substitutions (dN) than the synonymous substitutions (dS) with a posterior probability above 0.95, thus suggesting the evidence of adaptive evolution driven by Darwinian selection. Although it is unclear whether these amino acid adaptations are driven by differential immune pressure or some other factors, identification of these positively selected amino acid sites would help in better screening using epitope mapping technology to identify and localize the sites that can be recognized by the immune system. We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV.


EMERGING RESPIRATORY DISEASE - CORONAVIRUSES


title: Norovirus in Captive Lion Cub (Panthera leo)

text: African lions (Panthera leo) are susceptible to viral diseases of domestic carnivores, including feline calicivirus infection. We report the identification of a novel enteric calicivirus, genetically related to human noroviruses of genogroup IV, in a lion cub that died of severe hemorrhagic enteritis.


title: Positive mental health-related impacts of the SARS epidemic on the general public in Hong Kong and their associations with other negative impacts

text: Summary Objectives To investigate 2 positive impacts (better family/social support and lifestyle changes) and their associations with other negative impacts. Study design and participants A telephone survey using random telephone numbers and a structured questionnaire was conducted in Hong Kong general population. Eight hundred and eighteen Hong Kong residents of age 18–60 years completed the interview (response rate: 65%) at around end of June 2003, the early ending phase of the epidemic. Results Over 60% of the respondents stated that they cared more about the family members' feelings; about 30%–40% stated that they found their friends, their family members more supportive or having more sharing with others when not feeling happy; only a few percent felt the opposite. Further, about 2/3 of the respondents paid more attention to their mental health. About 35%–40% took more time to rest, for relaxation or doing exercise. These items were, in general, negatively associated with post-traumatic stress, perception of stress and other perceptions that were related to SARS. Conclusions SARS have brought some positive impacts on social/family support, mental health awareness and lifestyle changes. These positive impacts were associated with other relevant negative impacts and might be important cushions of the negative impact.


title: Multiantibody Strategies for HIV

text: Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.


title: Chapter Three Type I interferons and endoplasmic reticulum stress in health and disease

text: Abstract Type I interferons (IFNs) comprise of pro-inflammatory cytokines created, as well as sensed, by all nucleated cells with the main objective of blocking pathogens-driven infections. Owing to this broad range of influence, type I IFNs also exhibit critical functions in many sterile inflammatory diseases and immunopathologies, especially those associated with endoplasmic reticulum (ER) stress-driven signaling pathways. Indeed, over the years accumulating evidence has indicated that the presence of ER stress can influence the production, or sensing of, type I IFNs induced by perturbations like pattern recognition receptor (PRR) agonists, infections (bacterial, viral or parasitic) or autoimmunity. In this article we discuss the link between type I IFNs and ER stress in various diseased contexts. We describe how ER stress regulates type I IFNs production or sensing, or how type I IFNs may induce ER stress, in various circumstances like microbial infections, autoimmunity, diabetes, cancer and other ER stress-related contexts.


title: Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection.


title: IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity

text: BACKGROUND: Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. RESULTS: In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. CONCLUSIONS: The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0103-y) contains supplementary material, which is available to authorized users.


The Challenge of Laypeople Cardio-pulmonary Resuscitation Training during and after COVID-19 Pandemic


title: Immunophysiology and Pathology of Inflammation in the Testis and Epididymis

text: ABSTRACT: The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood‐testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.


title: What Macromolecular Crowding Can Do to a Protein

text: The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.


title: Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review

text: Abstract Egg yolk constitutes a relevant alternative source of antibodies. It presents some advantages over mammalian serum immunoglobulins regarding productivity, animal welfare and specificity. The main immunoglobulin present in avian blood (IgY) is transmitted to their offspring and accumulates in egg yolks, which enables the non-invasive harvesting of high amounts of antibodies. Moreover, due to structural differences and phylogenetic distance, IgY is more suitable for diagnostic purposes than mammalian antibodies, since it does not react with certain components of the human immune system and displays greater avidity for mammalian conserved proteins. IgY has been extensively used in health researches, as both therapeutic and diagnostic tool. This article aims to review its applications in both human and veterinary health.


title: Immunogenetic Variation and Differential Pathogen Exposure in Free-Ranging Cheetahs across Namibian Farmlands

text: BACKGROUND: Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. METHODOLOGY/PRINCIPAL FINDINGS: Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.


title: Quasispecies as a matter of fact: Viruses and beyond

text: Abstract We review the origins of the quasispecies concept and its relevance for RNA virus evolution, viral pathogenesis and antiviral treatment strategies. We emphasize a critical point of quasispecies that refers to genome collectivities as the unit of selection, and establish parallels between RNA viruses and some cellular systems such as bacteria and tumor cells. We refer also to tantalizing new observations that suggest quasispecies behavior in prions, perhaps as a result of the same quantum-mechanical indeterminations that underlie protein conformation and error-prone replication in genetic systems. If substantiated, these observations with prions could lead to new research on the structure–function relationship of non-nucleic acid biological molecules.


title: Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study

text: BACKGROUND: : Tocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin-6 (IL-6) receptor, has been proposed for the treatment of COVID-19 patients; however, limited data are available on the safety and efficacy. METHODS: : We performed a retrospective study on severe COVID-19 patients with hyper-inflammatory features admitted outside intensive care units (ICUs). Patients treated with intravenous TCZ in addition to standard of care were compared to patients treated with standard of care alone. Safety and efficacy were assessed over a 28-day follow-up. RESULTS: : 65 patients were included, 32 were of whose treated with TCZ. At baseline, all patients were on high-flow supplemental oxygen and most (78% of TCZ patients and 61% of standard treatment patients) were on non-invasive ventilation. During the 28-day follow-up, 69% of TCZ patients experienced a clinical improvement compared to 61% of standard treatment patients (p = 0.61). Mortality was 15% in the tocilizumab group and 33% in standard treatment group (p = 0.15). In TCZ group, at multivariate analysis, older age was a predictor of death, whereas higher baseline PaO2:FiO2 was a predictor of clinical improvement at day 28. The rate of infection and pulmonary thrombosis was similar between the two groups. CONCLUSIONS: : At day 28, clinical improvement and mortality were not statistically significant different between tocilizumab and standard treatment patients in our cohort. Bacterial or fungal infections were recorded in 13% of tocilizumab patients and in 12% of standard treatment patients. Confirmation of efficacy and safety will require ongoing controlled trials.


title: Sequencing of coronavirus IBV genomic RNA: a 195-base open reading frame encoded by mRNA B

text: Abstract DNA sequencing of genomic cDNA clones of avian infectious bronchitis virus (IBV) has been carried out. 770 bases have been determined which include genomic sequences spanning the 5' termini of the two smallest mRNAs of the 3'-coterminal “nested” set: mRNA A and mRNA B. This region contains the complete coding sequences for mRNA B which are additional to those present in mRNA A. Two open reading frames are present, predicting proteins of M rs 7500 and 9500.


title: High-level ribosomal frameshifting directs the synthesis of IS150 gene products.

text: IS150 contains two tandem, out-of-phase, overlapping genes, ins150A and ins150B, which are controlled by the same promoter. These genes encode proteins of 19 and 31 kD, respectively. A third protein of 49 kD is a transframe gene product consisting of domains encoded by both genes. Specific -1 ribosomal frameshifting is responsible for the synthesis of the large protein. Expression of ins150B also involves frameshifting. The IS150 frameshifting signals operate with a remarkably high efficiency, causing about one third of the ribosomes to switch frame. All of the signals required for this process are encoded in a 83-bp segment of the element. The heptanucleotide A AAA AAG and a potential stem-loop-forming sequence mark the frameshifting site. Similar sequence elements are found in -1 frameshifting regions of bacterial and retroviral genes. A mutation within the stem-loop sequence reduces the rate of frameshifting by about 80%. Artificial transposons carrying this mutation transpose at a normal frequency, but form cointegrates at a approximately 100-fold reduced rate.


title: Systematic review of the impact of point‐of‐care testing for influenza on the outcomes of patients with acute respiratory tract infection

text: Acute respiratory tract infections are a major cause of morbidity and mortality and represent a significant burden on the health care system. Laboratory testing is required to definitively distinguish infecting influenza virus from other pathogens, resulting in prolonged emergency department (ED) visits and unnecessary antibiotic use. Recently available rapid point‐of‐care tests (POCT) may allow for appropriate use of antiviral and antibiotic treatments and decrease patient lengths of stay. We undertook a systematic review to assess the effect of POCT for influenza on three outcomes: (1) antiviral prescription, (2) antibiotic prescription, and (3) patient length of stay in the ED. The databases Medline and Embase were searched using MeSH terms and keywords for influenza, POCT, antivirals, antibiotics, and length of stay. Amongst 245 studies screened, 30 were included. The majority of papers reporting on antiviral prescription found that a positive POCT result significantly increased use of antivirals for influenza compared with negative POCT results and standard supportive care. A positive POCT result also led to decreased antibiotic use. The results of studies assessing the effect of POCT on ED length of stay were not definitive. The studies assessed in this systematic review support the use of POCT for diagnosis of influenza in patients suffering an acute respiratory infection. Diagnosis using POCT may lead to more appropriate prescription of treatments for infectious agents. Further studies are needed to assess the effect of POCT on the length of stay in ED.


title: Using internet search queries for infectious disease surveillance: screening diseases for suitability

text: BACKGROUND: Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. METHODS: Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. RESULTS: Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. CONCLUSIONS: The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0690-1) contains supplementary material, which is available to authorized users.


title: Family caregivers in public tertiary care hospitals in Bangladesh: Risks and opportunities for infection control

text: BACKGROUND: Family caregivers are integral to patient care in Bangladeshi public hospitals. This study explored family caregivers’ activities and their perceptions and practices related to disease transmission and prevention in public hospitals. METHODS: Trained qualitative researchers conducted a total of 48 hours of observation in 3 public tertiary care hospitals and 12 in-depth interviews with family caregivers. RESULTS: Family caregivers provided care 24 hours a day, including bedside nursing, cleaning care, and psychologic support. During observations, family members provided 2,065 episodes of care giving, 75% (1,544) of which involved close contact with patients. We observed family caregivers washing their hands with soap on only 4 occasions. The majority of respondents said diseases are transmitted through physical contact with surfaces and objects that have been contaminated with patient secretions and excretions, and avoiding contact with these contaminated objects would help prevent disease. CONCLUSION: Family caregivers are at risk for hospital-acquired infection from their repeated exposure to infectious agents combined with their inadequate hand hygiene and knowledge about disease transmission. Future research should explore potential strategies to improve family caregivers’ knowledge about disease transmission and reduce family caregiver exposures, which may be accomplished by improving care provided by health care workers.


title: Flagging and Docking: dual roles for N-glycans in protein quality control and cellular proteostasis

text: Nascent polypeptides entering the endoplasmic reticulum (ER) are covalently modified with pre-assembled oligosaccharides. The terminal glucose and mannose residues are immediately removed after the transfer of the oligosaccharide onto newly synthesized polypeptides. This processing determines whether the polypeptide will be retained in the ER, transported along the secretory pathway, or dislocated across the ER membrane for destruction. Recently, new avenues of research and some issues of controversy have been opened by the discovery that lectin-oligosaccharide interactions stabilize supramolecular complexes between regulators of ER-associated degradation (ERAD). In this Opinion, we propose a unified model that depicts carbohydrates acting both as flags signaling the fitness of a maturing protein, and as docking sites that regulate assembly and stability of the ERAD machinery.


title: C reactive protein level may predict the risk of COVID-19 aggravation

text: BACKGROUND: Clinical findings indicated that a fraction of Corona Virus Disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study was to describe the clinical characteristics of these patients, analyze related factors and explore predictive markers of the disease aggravation. METHODS: Clinical and laboratory data of non-severe adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. Receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP). RESULTS: About 7.7% (16/209) non-severe adult COVID-19 patients progressed to severe cases after admission. Compared with non-severe patients, the aggravated patients had much higher levels of CRP (median, 43.8 mg/L [range: 12.3-101.9] vs 12.1 mg/L [range: 0.1-91.4]; P = 0.000). The regression analysis showed CRP was significantly associated with the aggravation of non-severe COVID-19 patients, with an area under the curves (AUC) of 0.844 (95% CI, 0.761 - 0.926) and the optimal threshold value of 26.9 mg/L. CONCLUSIONS: CRP could be a valuable marker to anticipate the possibility of aggravation of non-severe adult COVID-19 patients, with the optimal threshold value of 26.9 mg/L.


title: Microorganism-ionizing respirator with reduced breathing resistance suitable for removing airborne bacteria

text: Abstract In this paper, we have demonstrated the feasibility of using microorganism-ionizing respirators with reduced breathing resistance to remove airborne bacteria. Using a miniaturized corona ionizer and two pairs of separator electrodes, airborne bacteria were ionized and removed from the airflow. Two microorganism-ionizing respirator designs were experimentally evaluated with flow rates ranging from ∼10 to 20 L/min and yielded airborne bacterial removal efficiencies of ∼75%–100%. Further, they were in close agreement with the analytical airborne particle removal efficiencies, at a similar range of flow rates. These flow rates also correspond to the breathing rates of standing and walking adults. More importantly, the breathing resistance could be reduced by more than 50% for flow rates of ∼200 L/min. Using manganese (IV) oxide coated mesh, the ozone concentration in the air outflow was reduced to less than 0.1 ppm, at a flow rate of ∼20 L/min, thus enabling safe use. The power consumption was less than 1 W.


Lockdown—the only solution to defeat COVID-19


title: Management of ST‐segment‐elevation myocardial infarction during the coronavirus disease 2019 (COVID‐19) outbreak: Iranian“247” National Committee's position paper on primary percutaneous coronary intervention

text: World Health Organization has designated coronavirus disease 2019 (COVID‐19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST‐segment‐elevation myocardial infarction during the outbreak of COVID‐19 and outlines a practical algorithm for it.


title: The interferon response circuit: Induction and suppression by pathogenic viruses

text: Abstract Type I interferons (IFN-α/β) are potent antiviral cytokines and modulators of the adaptive immune system. They are induced by viral infection or by double-stranded RNA (dsRNA), a by-product of viral replication, and lead to the production of a broad range of antiviral proteins and immunoactive cytokines. Viruses, in turn, have evolved multiple strategies to counter the IFN system which would otherwise stop virus growth early in infection. Here we discuss the current view on the balancing act between virus-induced IFN responses and the viral counterplayers.


title: Consistent Detection of 2019 Novel Coronavirus in Saliva

text: The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.


title: La espectrometría de masas en el laboratorio de microbiología clínica

text: Infectious diseases are still a cause of high mortality and morbidity rates. Current microbiological diagnostic methods are based on culture and phenotypic identification of isolated microorganisms, which can be obtained in about 24-48 h. Given that the microbiological identification is of major importance for patient management, new diagnostic methods are needed in order to detect and identify microorganisms in a timely and accurate manner. Over the last few years, several molecular techniques based on the amplification of microbial nucleic acids have been developed with the aim of reducing the time needed for the identification of the microorganisms involved in different infectious processes. On the other hand, mass spectrometry has emerged as a rapid and consistent alternative to conventional methods for microorganism identification. This review describes the most widely used mass spectrometry technologies —matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization time-of-flight (ESI-TOF)—, both for protein and nucleic acid analysis, as well as the commercial platforms available. Related publications of most interest in clinical microbiology are also reviewed.


title: A survey of travel behaviour among scientists in Germany and the potential for change

text: Awareness of the environmental impact of conferences is growing within the scientific community. Here we report the results of a survey in which scientists in Germany were asked about their attendance at conferences, their reasons for attending, and their willingness to explore new approaches that would reduce the impact of conferences on the environment. A majority of respondents were keen to reduce their own carbon footprint and were willing to explore alternatives to the traditional conference.


title: Evaluation of reverse transcription and polymerase chain reaction (RT/PCR) for the detection of rota viruses: applications of the assay

text: Summary Our aim was to evaluate the reverse transcription and polymerase chain reaction (RT/PCR) technique for the detection of rotavirus shedding by infected children as a routine diagnostic procedure, in comparison to the enzyme-linked immunosorbent assay (ELISA), electron microscopy (EM) and polyacrylamide gel etectrophoresis (PAGE) of rotavirus double stranded RNA. Two-hundred and twenty stool specimens were collected from infants and young children with diarrhoea, and 10–20% faecal suspensions were made. Several methods of rotavirus dsRNA extraction were assayed. Electrophoretic analysis of viral RNA was carried out on 10% polyacrylamide gols followed by silver staining. RT/PCR was performed using oligonucleotide primers specific for both 3′ and 5′ ends of the rotavirus gene encoding VP7 which ere highly conserved among group A rotaviruses. Following RNA extraction with phenol-chloroform and ethanol precipitation, RT/PCR could detect rotaviral RNA in only 11 of 25 samples known to contain rotaviruses by conventional methods. The purification of RNA extracts by CF11 cellulose and the application of the RNAID method were equally effective in extracting RNA and/or removing inhibitory substances from the faecal samples. RT/PCR led to the detection of 66 positive samples from 220 specimens tested (30%). whilst 64 specimens were positive by EUSA (29%), 59 (26.3%) by PAGE and 56 (25.4%) by EM. In our study, RT/PCR was 100 times more sensitive than the ELISA test in detecting rotaviruses serially diluted in a faecal suspension. Although RT/PCR is theoretically much more sensitive than ELISA, PAGE and EM for detection of rotaviruses, great care must be taken to remove inhibitory substances from the enzymatic reactions. We do not consider that RT/PCR should replace immunoassays with high sensitivity and specificity for rotavirus testing in faecal samples, although this technique has other applications, like the search for rotavirus in different clinical specimens (sera, cerebrospinal fluid, respiratory secretions, etc.) and in environmental samples, as well as the typing of viral strains using serotype-specific primers.


title: CMV viral load in bronchoalveolar lavage for diagnosis of pneumonia in allogeneic hematopoietic stem cell transplantation

text: The objective of this report is to analyze the value of CMV viral load (VL) in bronchoalveolar lavage (BAL) in recipients of allogeneic hematopoietic stem cell transplantation (AHSCT) and to analyze the concordance between CMV quantification in plasma and BAL samples. Fifty-six patients were included; in 16 (28.6%) patients with symptoms of lung disease a BAL sample was collected, 7 (43.7%) patients had a VL >150 copies/mL (six had probable CMV pneumonia). Patients with CMV pneumonia were female (100%), of median age 53.5 years, and the median time from transplantion to onset of symptoms was 67.5 days. Pneumonia was early in three cases (incidence 5.4%). Median BAL VL was 53 250 copies/mL and plasma VL was 538 copies/mL (in one patient, the plasma VL was negative). Three (50.0%) patients had an improvement in the first week of treatment, and plasma VL became negative; the other 3 (50.0%) patients died with a CMV pneumonia refractory to treatment. Therefore, any value of CMV VL in BAL, especially if it is greater than plasma, with compatible signs or symptoms, should be considered suggestive of CMV pneumonia in recipients of AHSCT and they should receive specific treatment.


title: Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1

text: Bovine herpesvirus-1 (BHV-1) is a major cause of respiratory tract diseases in cattle. Vaccination of cattle against BHV-1 is a high priority. A major concern of currently modified live BHV-1 vaccines is their ability to cause latent infection and subsequent reactivation resulting in many outbreaks. Thus, there is a need for alternative strategies. We generated two recombinant Newcastle disease viruses (NDVs) expressing the glycoprotein D (gD) of BHV-1 from an added gene. One recombinant, rLaSota/gDFL, expressed gD without any modification. The other recombinant, rLaSota/gDF, expressed a chimeric gD in which the ectodomain of gD was fused with the transmembrane domain and cytoplasmic tail of the NDV fusion F glycoprotein. Remarkably, the native gD expressed by rLaSota/gDFL virus was incorporated into the NDV virion 2.5-fold more efficiently than the native NDV proteins, whereas the chimeric gD was not detectably incorporated even though it was abundantly expressed on the infected cell surface. The expression of gD did not increase the virulence of the rNDV vectors in chickens. A single intranasal and intratracheal inoculation of calves with either recombinant NDV elicited mucosal and systemic antibodies specific to BHV-1, with the responses to rLaSota/gDFL being higher than those to rLaSota/gDF. Following challenge with BHV-1, calves immunized with the recombinant NDVs had lower titers and earlier clearance of challenge virus compared to the empty vector control, and reduced disease was observed with rLaSota/gDFL. Following challenge, the titers of serum antibodies specific to BHV-1 were higher in the animals immunized with the rNDV vaccines compared to the rNDV parent virus, indicating that the vaccines primed for secondary responses. Our data suggest that NDV can be used as a vaccine vector in bovines and that BHV-1 gD may be useful in mucosal vaccine against BHV-1 infection, but might require augmentation by a second dose or the inclusion of additional BHV-1 antigens.


title: Sars‐CoV‐2 in the context of past coronaviruses epidemics: Consideration for prenatal care

text: Since December 2019, the novel SARS‐CoV‐2 outbreak has resulted in millions of cases and more than 200,000 deaths worldwide. The clinical course among non‐pregnant women has been described but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes and maternal deaths. For COVID‐19 infection, only 9 cases of maternal death have been reported as of April 22, 2020 and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress and stillbirth among newborns have been reported. The SARS‐CoV‐2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS and SARS‐CoV‐2) risks and consequences on pregnancies and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by RCOG, ACOG and the WHO to give an overview of prenatal management which should be utilized until future data appear. This article is protected by copyright. All rights reserved.


title: Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid

text: High consequence human pathogenic viruses must be handled at biosafety level 2, 3 or 4 and must be rendered non-infectious before they can be utilized for molecular or immunological applications at lower biosafety levels. Here we evaluate psoralen-inactivated Arena-, Bunya-, Corona-, Filo-, Flavi- and Orthomyxoviruses for their suitability as antigen in immunological processes and as template for reverse transcription PCR and sequencing. The method of virus inactivation using a psoralen molecule appears to have broad applicability to RNA viruses and to leave both the particle and RNA of the treated virus intact, while rendering the virus non-infectious.


title: Understanding protein domain-swapping using structure-based models of protein folding

text: Abstract In domain-swapping, two or more identical protein monomers exchange structural elements and fold into dimers or multimers whose units are structurally similar to the original monomer. Domain-swapping is of biotechnological interest because inhibiting domain-swapping can reduce disease-causing fibrillar protein aggregation. To achieve such inhibition, it is important to understand both the energetics that stabilize the domain-swapped structure and the protein dynamics that enable the swapping. Structure-based models (SBMs) encode the folded structure of the protein in their potential energy functions. SBMs have been successfully used to understand diverse aspects of monomer folding. Symmetrized SBMs model interactions between two identical protein chains using only intra-monomer interactions. Molecular dynamics simulations of such symmetrized SBMs have been used to correctly predict the domain-swapped structure and to understand the mechanism of domain-swapping. Here, we review such models and illustrate that monomer topology determines key aspects of domain-swapping. However, in some proteins, specifics of local energetic interactions modulate domain-swapping and these need to be added to the symmetrized SBMs. We then summarize some general principles of the mechanism of domain-swapping that emerge from the symmetrized SBM simulations. Finally, using our own results, we explore how symmetrized SBMs could be used to design domain-swapping in proteins.


title: Internalization of cystatin C in human cell lines

text: Altered protease activity is considered important for tumour invasion and metastasis, processes in which the cysteine proteases cathepsin B and L are involved. Their natural inhibitor cystatin C is a secreted protein, suggesting that it functions to control extracellular protease activity. Because cystatins added to cell cultures can inhibit polio, herpes simplex and coronavirus replication, which are intracellular processes, the internalization and intracellular regulation of cysteine proteases by cystatin C should be considered. The extension, mechanism and biological importance of this hypothetical process are unknown. We investigated whether internalization of cystatin C occurs in a set of human cell lines. Demonstrated by flow cytometry and confocal microscopy, A‐431, MCF‐7, MDA‐MB‐453, MDA‐MB‐468 and Capan‐1 cells internalized fluorophore‐conjugated cystatin C when exposed to physiological concentrations (1 μm). During cystatin C incubation, intracellular cystatin C increased after 5 min and accumulated for at least 6 h, reaching four to six times the baseline level. Western blotting showed that the internalized inhibitor was not degraded. It was functionally intact and extracts of cells exposed to cystatin C showed a higher capacity to inhibit papain and cathepsin B than control cells (decrease in enzyme activity of 34% and 37%, respectively). The uptake of labelled cystatin C was inhibited by unlabelled inhibitor, suggesting a specific pathway for the internalization. We conclude that the cysteine protease inhibitor cystatin C is internalized in significant quantities in various cancer cell lines. This is a potentially important physiological phenomenon not previously described for this group of inhibitors.


COVID-19 and the RAAS—a potential role for angiotensin II?


title: Investigating the Emerging COVID-19 Research Trends in the Field of Business and Management: A Bibliometric Analysis Approach

text: The COVID-19 pandemic has been labeled as a black swan event that caused a ripple effect on every aspect of human life. Despite the short time span of the pandemic—only four and half months so far—a rather large volume of research pertaining to COVID-19 has been published (107 articles indexed in Scopus and the Web of Science). This article presents the findings of a bibliometric study of COVID-19 literature in the business and management domain to identify current areas of research and propose a way forward. The analysis of the published literature identified four main research themes and 18 sub-themes. The findings and propositions of this study suggest that COVID-19 will be the catalyst of several long- and short-term policy changes and requires the theoretical and empirical attention of researchers. The offered propositions will act as a roadmap to potential research opportunities.


title: Crossing barriers: infections of the lung and the gut

text: Although known as respiratory pathogens, severe acute respiratory syndrome (SARS) and its sister coronaviruses frequently cause enteric symptoms. In addition, other classically non-enteric viruses (such as HIV and influenza) may also have enteric effects that are crucial in their pathogeneses. These effects can be due to direct infection of the gut mucosa, but can also be because of decreased antibacterial defenses, increased mucosal permeability, bacterial translocation, and systemic leak of endotoxin. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2008.79) contains supplementary material, which is available to authorized users.


title: Virus diseases of farmed shrimp in the Western Hemisphere (the Americas): A review

text: Abstract Penaeid shrimp aquaculture is an important industry in the Americas, and the industry is based almost entirely on the culture of the Pacific White Shrimp, Litopenaeus vannamei. Western Hemisphere shrimp farmers in 14 countries in 2004 produced more than 200,000 metric tons of shrimp, generated more than $2 billion in revenue, and employed more than 500,000 people. Disease has had a major impact on shrimp aquaculture in the Americas since it became a significant commercial entity in the 1970s. Diseases due to viruses, rickettsial-like bacteria, true bacteria, protozoa, and fungi have emerged as major diseases of farmed shrimp in the region. Many of the bacterial, fungal and protozoan caused diseases are managed using improved culture practices, routine sanitation, and the use of chemotherapeutics. However, the virus diseases have been far more problematic to manage and they have been responsible for the most costly epizootics. Examples include the Taura syndrome pandemic that began in 1991–1992 when the disease emerged in Ecuador, and the subsequent White Spot Disease pandemic that followed its introduction to Central America from Asia in 1999. Because of their socioeconomic significance to shrimp farming, seven of the nine crustacean diseases listed by the World Animal Organization (OIE) are virus diseases of shrimp. Of the seven virus diseases of penaeid shrimp, five are native to the Americas or have become enzootic following their introduction. The shrimp virus diseases in the Americas are increasingly being managed by exclusion using a combination of biosecurity and the practice of culturing domesticated specific pathogen-free (SPF) stocks or specific pathogen-resistant (SPR) stocks. Despite the significant challenges posed by disease, the shrimp farming industry of the Americas has responded to the challenges posed by disease and it has developed methods to manage its diseases and mature into a sustainable industry.


title: COVID-19 and mental health: A review of the existing literature

text: Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16–28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.


title: Decreased sialylation of the acute phase protein α1-acid glycoprotein in feline infectious peritonitis (FIP)

text: Abstract Feline infectious peritonitis (FIP) is an immune-mediated disease of domestic and exotic felides infected with feline coronavirus. FIP is characterized by the overexpression of an acute phase protein, the α1-acid glycoprotein (AGP). In humans, AGP is a heavily glycosylated protein that undergoes several modifications of its glycan moiety during acute and chronic inflammatory pathologies. We studied the changes in AGP glycosylation in the course of FIP. Specifically, we focussed our attention on the degree of sialylation, fucosylation and branching. This study presents a purification method for feline AGP (fAGP) from serum, using an ion exchange chromatography strategy. The glycosylation pattern was analyzed in detail by means of interaction of purified fAGP with specific lectins. In particular, Sambucus nigra agglutinin I and Maackia amurensis agglutinin lectins were used to detect sialic acid residues, Aleuria aurantia lectin was used to detect l-fucose residues and Concanavalin A was used to evaluate the branching degree. By this method we showed that fAGP did not present any l-fucose residues on its surface, and that its branching degree was very low, both in normal and in pathological conditions. In contrast, during FIP disease, fAGP underwent several modifications in the sialic acid content, including decreased expression of both α(2–6)-linked and α(2–3)-linked sialic acid (76 and 44%, respectively when compared to non-pathological feline AGP).


SARS-CoV-2-(„Severe acute respiratory syndrome coronavirus 2“)-Pandemie und Neurologie: Digitalisierung und DGN-Kongress


title: Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas

text: Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so‐called catechins, and the methyl‐xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme‐catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.


title: In vitro evaluation of anthraquinones from Aloe vera (Aloe barbadensis Miller) roots and several derivatives against strains of influenza virus

text: Abstract Aloe vera is a crop of wide economic value of worldwide distribution, and a rich source of quinone components. Recently, antiviral aloe anthraquinones had been reported against human influenza virus. In the present work two anthraquinones, aloesaponarin-I (1) and aloesaponarin-II (2) were isolated from A. vera roots, and six derivatives were obtained by methylation (3), acetylation (4) and O-glycosyl (5-6) reactions starting from (1). Additionally, a new Tetra-O-acetyl-β-d-glucopyranosyl derivative from 2 was also prepared. All compounds were evaluated against two strains of influenza virus AH1N1 by cytopathic effect reduction assay (CPE). The antiviral activity was determined by the ability of compounds to inhibit virus replication on Madin Darby Canine Kidney cells (MDCK). New derivatives 3-(2´,3´,4´,6´-Tetra-O-acetyl-β-d-glucopyranosyl-aloesaponarin-I (5) and 3-(2´,3´,4´,6´-Tetra-O-acetyl-β-d-glucopyranosyl- aloesaponarin-II (7) showed a cytopathic reduction effect against influenza strain A/Yucatán/2370/09 with IC50 of 30.77 and 13.70 μM, and against the virus A/Mexico/InDRE797/10 with IC50 of 62.28 and 19.47 μM, respectively. To assess the effect of derivatives 5 and 7 during one cycle of replication (0–10 h), a time-of-addition experiment was performed. As a result it was found that both compounds were most effective when added 6–10 h post-infection and significantly inhibited viral titre (> 70%) at the concentrations of 50 and 100 μM. Based on the structural analysis of the compounds, it was suggested that the Tetra-O-acetyl-β-d-glucopyranosyl substituent at the C3 position of the anthraquinone might have an effect against the influenza AH1N1 virus.


title: A study of the glycoproteins of Autographa californica nuclear polyhedrosis virus (AcNPV)

text: Abstract Pulse labeling with tritiated mannose was used to follow the time course of Autographa californica nuclear polyhedrosis virus (AcNPV) glycoprotein synthesis in Spodoptera frugiperda IPLB-21 cells. Nine viral-induced intracellular glycoproteins were first detected from as early as 2 hr postinoculation (67K, early phase) to as late as 14 hr (36K and 19K glycoproteins, intermediate phase). Glycosylation of these proteins was observed to continue to the end of the experiment (28 hr postinoculation). Seven of these intracellular glycoproteins could also be detected in infected Trichoplusia ni TN-368 cells 24 hr postinoculation. When the glycosylation inhibitor tunicamycin was present (from 0 hr postinoculation) there was no detectable glycosylation of any of these viral-induced glycoproteins. Metabolic labeling of the nonoccluded virus budded from IPLB-21 and TN-368 with tritiated mannose or N-acetylglucosamine identified 11 structural glycoproteins, 8 of which were identical in both virus preparations. All of these structural glycoproteins were sensitive to the inhibitory action of tunicamycin. A single 42K structural glycoprotein was detected (with acetylglucosamine only) in the occluded form of AcNPV. Glycosylation of this structural protein appeared to be insensitive to tunicamycin. Lactoperoxidase-catalyzed radioiodination was used to determine which of the virus structural glycoproteins are exposed on the virion surface.


title: Emerging Infectious Diseases

text: Emerging infectious diseases (EID) and reemerging infectious diseases are increasing globally. Zoonotic diseases are transmitted from animals to humans through direct contact or through food, water, and the environment. Vector-borne diseases are major sources of mortality and morbidity globally. Three mosquito-borne viruses are yellow fever, chikungunya virus, and dengue virus. Recent EIDs include Candida auris, Elizabethkingia anopheles, The Lone Star tick, and avian influenza H7N2. In addition, mcr-1 may contribute to the dissemination of drug resistance to gram-negative bacteria. Nurses play a major role in the identification and prevention of EID within health care settings.


title: Gastric cancer patients display a distinctive population of IFNg+IL10+ double positive CD8 T cells, which persists longer during prolonged activation

text: Abstract IL10 is generally regarded as a broad-spectrum regulatory cytokine. However, the role of IL10 in CD8 T cells remains controversial. In this study, we investigated the characteristics of endogenous IL10 by CD8 T cells in gastric cancer (GC) patients. Using intracellular staining, we found that in both GC patients and healthy controls, the majority of IL10-expressing CD8 T cells also presented concurrent IFNg expression. Interestingly, the frequency of IFNg+IL10+ CD8 T cells was significantly higher in GC patients than in healthy controls, while the frequency of IFNg+IL10- CD8 T cells was significantly lower in GC patients than in healthy controls. Compared to the IFNg-IL10- CD8 T cells, both IFNg+IL10- and IFNg+IL10+ CD8 T cells presented significantly higher expression of activation/inhibitory markers. Interestingly, the IFNg+IL10+ cells presented lower PD1 and TIM3 and higher KLRG1 than the IFNg+IL10- CD8 T cells. Remarkably, the IFNg+IL10+ CD8 T cells, but not the IFNg+IL10- CD8 T cells, were highly enriched in the CD45RO+CXCR5+ subset. Prolonged activation resulted in significant enrichment of IFNg+IL10+ CD8 T cells over time. Interestingly, compared to the CD45RO+CXCR5- CD8 T cells, the CD45RO+CXCR5+ CD8 T cells presented stronger proliferation capacity at later stages of stimulation, and higher viability throughout the stimulation process. Overall, our investigation demonstrated that GC patients were enriched with a distinctive population of IFNg+IL10+ double positive CD8 T cells, which resembled T follicular cytotoxic cells and could persist longer during prolonged activation.


title: 2019 Novel Coronavirus Disease (COVID-19): Paving the Road for Rapid Detection and Point-of-Care Diagnostics

text: We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well as factors for the preparedness and response to the outbreak of the COVID-19.


title: 20 Infection Prevention and Control in the Tropics

text: Abstract Tropical settings present unique challenges to the practice of infection prevention and control. These are multi-faceted due to differences in the climate, culture, social, and political milieu of low- and middle-income countries situated in the tropics, as well as the lack of resources. The emergence of communicable diseases and low vaccination coverage also lead to nosocomial augmentation of community outbreaks, further increasing the economic burden of hospital management. Addressing these challenges requires innovative, low-cost, and tailored solutions suited to the tropical environment.


title: Engineering large viral DNA genomes using the CRISPR‐Cas9 system

text: Manipulation of viral genomes is essential for studying viral gene function and utilizing viruses for therapy. Several techniques for viral genome engineering have been developed. Homologous recombination in virus‐infected cells has traditionally been used to edit viral genomes; however, the frequency of the expected recombination is quite low. Alternatively, large viral genomes have been edited using a bacterial artificial chromosome (BAC) plasmid system. However, cloning of large viral genomes into BAC plasmids is both laborious and time‐consuming. In addition, because it is possible for insertion into the viral genome of drug selection markers or parts of BAC plasmids to affect viral function, artificial genes sometimes need to be removed from edited viruses. Herpes simplex virus (HSV), a common DNA virus with a genome length of 152 kbp, causes labialis, genital herpes and encephalitis. Mutant HSV is a candidate for oncotherapy, in which HSV is used to kill tumor cells. In this study, the clustered regularly interspaced short palindromic repeat‐Cas9 system was used to very efficiently engineer HSV without inserting artificial genes into viral genomes. Not only gene‐ablated HSV but also gene knock‐in HSV were generated using this method. Furthermore, selection with phenotypes of edited genes promotes the isolation efficiencies of expectedly mutated viral clones. Because our method can be applied to other DNA viruses such as Epstein–Barr virus, cytomegaloviruses, vaccinia virus and baculovirus, our system will be useful for studying various types of viruses, including clinical isolates.


title: Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of Goose parvovirus in vivo

text: BACKGROUND: Goose parvovirus (GPV) is a Dependovirus associated with latent infection and mortality in geese. Currently, it severely affects geese production worldwide. The objective of this study was to develop a fluorescent quantitative real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate quantification of GPV DNA in infected goslings, which can aid in the understanding of the regular distribution pattern and the nosogenesis of GPV in vivo. RESULTS: The detection limit of the assay was 2.8 × 10(1 )standard DNA copies, with a sensitivity of 3 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intraassay and interassay coefficients of variation. CONCLUSION: The high sensitivity, specificity, simplicity, and reproducibility of the GPV fluorogenic PCR assay, combined with a high throughput, make this method suitable for a broad spectrum of GPV etiology-related applications.


title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses

text: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al ., Xiao et al .) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.


title: 18 Omics, Bioinformatics, and Infectious Disease Research

text: Bioinformatics and the ‘omics’ studies are rapidly changing the way scientific research is conducted. The genomics, proteomics, and metabolomics revolutions all have changed the quantity of the information available and have necessitated the embracement of bioinformatics as an integral part of modern-day science. This is no different in the infectious disease field where, arguably, most genome sequences originate. Here, we present large-scale studies that have resulted in vaccines that would not have been possible using the classical research approach. In addition, we provide an overview of methods available for those venturing into the area of next-generation sequencing.


NMR assignment of the SARS-CoV protein nsp1


title: A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras

text: siRNA-aptamer chimeras have emerged as one of the most promising approaches for targeted delivery of siRNA due to the modularity of their diblock RNA structure, relatively lower cost over other targeted delivery approaches, and, most importantly, the outstanding potential for clinical translation. However, additional challenges must be addressed for efficient RNA interference (RNAi), in particular, endosomal escape. Currently, vast majority of siRNA delivery vehicles are based on cationic materials, which form complexes with negatively charged siRNA. Unfortunately, these approaches complicate the formulations again by forming large complexes with heterogeneous sizes, unfavorable surface charges, colloidal instability, and poor targeting ligand orientation. Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. The protein selectively tags along the siRNA block of individual chimera, rendering the overall size of the complex small, desirable for deep tissue penetration, and the aptamer block accessible for target recognition. More interestingly, we found that extending the c-terminal polyhistidine segment in the protein tag to 18 amino acids completely abolishes the RNA binding function of dsRBD.


title: Intracellular accumulation of punta toro virus glycoproteins expressed from cloned cDNA

text: Abstract The Punta Toro virus (PTV) middle size (M) RNA encodes two glycoproteins, G1 and G2, and possibly a nonstructural protein, NSM. A partial cDNA clone of the M segment which contains G1 and G2 glycoprotein coding sequences but lacks most of the NSM sequences was inserted into the genome of vaccinia virus under the control of an early vaccinia promoter. Cells infected with the recombinant virus were found to synthesize two polypeptides with molecular weights of 65,000 (G1) and 55,000 (G2) that reacted specifically with antibody against PTV. Studies using indirect immunofluorescence microscopy revealed that these proteins accumulated intracellularly in the perinuclear region. The results of endoglycosidase H digestion of these glycoproteins suggested that both G1 and G2 glycoproteins were transported from the RER to the Golgi complex. These proteins were not chased out from the Golgi region during a 6-hr incubation in the presence of cycloheximide. Surface immune precipitation and 125I-protein A binding assays also demonstrated that the majority of the G1 and G2 glycoproteins are retained intracellularly. These results indicate that the PTV glycoproteins contain the necessary information for retention in the Golgi apparatus.


title: Antiviral activities against influenza virus (FM1) of bioactive fractions and representative compounds extracted from Banlangen (Radix Isatidis)

text: Abstract Objective To study the antiviral activities of clemastanin B (CB), epigoitrin, phenylpropanoids portion (PEP) and the mixture of phenylpropanoids, alkaloids and organic acid fractions (PEP + ALK + OA) from Banlangen (Radix Isatidis). Methods The experiment consisted of four parts: therapeutic action, prophylaxsis action, inhibition of virus attachment, and direct virucidal action. Cytopathic effect (CPE) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) were used to assess antiviral activity. Results CB, epigoitrin, PEP and PEP + ALK + OA fractions from Banlangen (Radix Isatidis) extract significantly increased the viability of MDCK cells pre-infected with the virus compared with the virus control group in all the dilutions (P < 0.01). Pretreated with either pure compounds or chemical fractions of Banlangen (Radix Isatidis) extract in all the dilutions significantly improved the viability of MDCK cells (P < 0.01). The inhibition of virus absorption to the host cells by CB, epigoitrin and PEP was in a dose dependent manner. Conclusion CB, epigoitrin, PEP and PEP + ALK + OA exert their anti-influenza activity by inhibiting the virus multiplication, prophylaxsis and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effects on virus attachment and multiplication are the main modes for epigoitrin.


title: Chapter 33 Animal Models of Human Viral Diseases

text: Abstract As the threat of exposure to emerging and reemerging viruses within a naïve population increases, it is vital that the basic mechanisms of pathogenesis and immune response be thoroughly investigated. Recent outbreaks of Middle East respiratory syndrome corona virus, Ebola virus, Chikungunya virus, and Zika virus illustrate the emerging threats that are encountered. By utilizing animal models in this endeavor, the host response to viruses can be studied in a more complex and integrated context to identify novel drug targets, and assess the efficacy and safety of new products rapidly. This is especially true in the advent and implementation of the FDA animal rule. Although no one animal model is able to recapitulate all aspects of human disease, understanding the current limitations allows for a more targeted experimental design. Important facets to consider prior to an animal study are route of viral exposure, species of animal, biomarkers of disease, and a humane endpoint. This chapter covers the current animal models for medically important human viruses, and demonstrates where the gaps in knowledge exist.


Susceptibility of selected domestic animals to COVID-19


title: COVID-19 Pandemic: Power Law Spread and Flattening of the Curve

text: In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to May 04, 2020. South Korea, China, Italy, France, Spain, and Germany have either flattened or close to flattening their epidemic curves. USA and Japan have transitioned to a linear regime, while India is still in a power-law phase. We argue that the transition from an exponential regime to a succession of power-law regimes is a good indicator for flattening of the epidemic curve. We also argue that lockdowns, long-term community transmission, and the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic.


title: Racial Differences in Long-Term Cardiovascular Outcomes: The Need to Move From Description to Action

text: [Figure: see text]


title: Breast radiotherapy under COVID-19 pandemic resource constraints -- approaches to defer or shorten treatment from a Comprehensive Cancer Center in the United States

text: Abstract Introduction Breast radiotherapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice. In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered. Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiotherapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization. Methods Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens. Results Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of breast cancer patients and for abbreviating or accelerating regimens among others. For those who require either whole-breast or post-mastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective. Conclusion In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at infection risk, the parsimonious application of breast radiotherapy may alleviate a significant clinical burden without compromising long term oncologic outcomes. The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic.


title: Streptococcus pneumoniae and community-acquired pneumonia: A cause for concern

text: Abstract Community-acquired pneumonia (CAP) is the sixth most common cause of death in the United States and the leading cause of death from infectious diseases. It is associated with significant morbidity and mortality, and poses a major economic burden to the healthcare system. Streptococcus pneumoniae is the leading cause of CAP. Other common bacterial causes include Haemophilus influenzae as well as atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species). Increasing resistance to a variety of antimicrobial agents has been documented in S pneumoniae and is common in H influenzae as well. Successful empiric therapy is paramount to the management of CAP to avoid treatment failure and subsequent associated costs. Given that resistance is increasing among respiratory pathogens, and S pneumoniae is the most common etiologic agent identified in CAP, strategies for antimicrobial therapy should be based on the likely causative pathogen, the presence of risk factors for infection with resistant bacteria, and local resistance patterns.


title: Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review

text: Studies have shown that the predictive value of “clinical diagnoses” of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence‐based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus‐1, coronaviruses, or parainfluenza virus: (a) systematic review and meta‐analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data‐driven analysis of an inception cohort of 6073 children with ILI (aged 0‐18 years, 56% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our “real‐world” dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms.


title: Virtual Ophthalmology: Telemedicine in a Covid-19 Era

text: Abstract Purpose To discuss the effects of the SARS-Cov-2 betacoronavirus on ambulatory ophthalmology practices, the value proposition of telemedicine, tele-ophthalmology implementation methodologies, and the accelerated future of telemedicine. Design Review of the current telehealth landscape including usage, policies, and techniques for ambulatory practice integration. Methods We provide author-initiated review of recent trends in telehealth, governmental recommendations for healthcare delivery during the COVID-19 pandemic, and a PubMed Central query for telemedicine in ophthalmology or tele-ophthalmology. In addition, authors’ comprehensive experience in telemedicine design and implementation is provided. Results A summary describing the present state of telehealth, tele-ophthalmology modeling, care delivery, and the proposed impact of telehealth surges on the future of ophthalmology practice. Conclusion Recent patient and provider interest in telemedicine, the relaxation of regulatory restrictions, increased remote care reimbursement, and ongoing social distancing practices compels many ophthalmologists to consider virtualizing services.


Rational perioperative utilization and management during the COVID-19 pandemic


title: A comparative evaluation of modelling strategies for the effect of treatment and host interactions on the spread of drug resistance

text: Abstract The evolutionary responses of infectious pathogens often have ruinous consequences for the control of disease spread in the population. Drug resistance is a well-documented instance that is generally driven by the selective pressure of drugs on both the replication of the pathogen within hosts and its transmission between hosts. Management of drug resistance therefore requires the development of treatment strategies that can impede the emergence and spread of resistance in the population. This study evaluates various treatment strategies for influenza infection as a case study by comparing the long-term epidemiological outcomes predicted by deterministic and stochastic versions of a homogeneously mixing (mean-field) model and those predicted by a heterogeneous model that incorporates spatial pair-wise correlation. We discuss the importance of three major parameters in our evaluation: the basic reproduction number, the population level of treatment, and the degree of clustering as a key parameter determining the structure of heterogeneous interactions. The results show that, as a common feature in all models, high treatment levels during the early stages of disease outset can result in large resistant outbreaks, with the possibility of a second wave of infection appearing in the pair-approximation model. Our simulations demonstrate that, if the basic reproduction number exceeds a threshold value, the population-wide spread of the resistant pathogen emerges more rapidly in the pair-approximation model with significantly lower treatment levels than in the homogeneous models. We tested an antiviral strategy that delays the onset of aggressive treatment for a certain amount of time after the onset of the outbreak. The findings indicate that the overall disease incidence is reduced as the degree of clustering increases, and a longer delay should be considered for implementing the large-scale treatment.


title: Acute Pulmonary Embolism in SARS-CoV-2 Infection Treated with Surgical Embolectomy

text: Abstract A cluster of pneumonia cases caused by the novel SARS-CoV-2 has spread rapidly throughout China, Europe and USA. The pneumonia might evolve in ARDS requiring assisted mechanical-ventilation. The prolonged immobilization combined with respiratory failure, sepsis and dehydration might expose SARS-CoV-2/patients to increased risk of complication including pulmonary embolism. We report the first case of SARS-CoV-2 complicated by massive pulmonary embolism underwent successfully surgical embolectomy. We believe that maintaining the same pro-active attitude suggested by current Guidelines might help in reducing morality and improving survival in SARS-COV-2/patients.


title: Other viral infections in solid organ transplantation

text: Abstract Viral infections are a major cause of morbidity and even mortality in solid organ transplant recipients. This article reviews key aspects of infections in solid organ transplant recipients from respiratory viruses, such as influenza, polyomavirus, erythrovirus B19 and measles.


Microvascular alterations in patients with SARS-COV-2 severe pneumonia


title: Maximising application of the aerosol box in protecting healthcare workers during the COVID‐19 pandemic

text: We report the rapid evolution of the Aerosol Box, originally designed by Dr Hsien Yung Lai, Mennonite Christian Hospital, Taiwan [1]. The Aerosol Box was intended to protect healthcare workers performing aerosol generating procedures (AGPs), specifically tracheal intubation, by providing a physical barrier to droplet and/or aerosol exposure [2]. An increased infection rate has been reported in healthcare workers internationally, particularly when the level of personal protective equipment (PPE) has been inadequate or when the supply of PPE has been depleted [3]. The Aerosol Box can be made of transparent acrylic or polycarbonate sheeting, and is re-usable after careful decontamination with an appropriate cleansing agent. The original model was based on a simple cuboid design, with two access ports for arms.


title: In vitro antiviral activity of Griffithsin against porcine epidemic diarrhea virus

text: Griffithsin is a lectin with potent antiviral activity against enveloped viruses. The objective of this study was to assess Griffithsin’s inhibitory effect on porcine epidemic diarrhea virus (PEDV). The results showed that Griffithsin reduced PEDV infection of Vero cells by approximately 82.8%. Moreover, using time-of-addition assays and RT-qPCR, we found that delayed addition of Griffithsin had a weaker inhibitory effect on PEDV than earlier treatment. The mechanism of Griffithsin’s action against PEDV involved both preventing viral attachment to host cells and disrupting cell-to-cell transmission; its dual mode of action distinguished Griffithsin from most other antiviral drugs. In conclusion, Griffithsin was identified as a potent PEDV inhibitor and may represent a candidate drug for preventing PEDV infection.


title: Characterization of the specificity and genetic restriction of human CD4+ cytotoxic T cell clones reactive to capsid antigen of rubella virus

text: Abstract Using 11 overlapping synthetic peptides covering more than 95% of the amino acid sequence of capsid protein of rubella virus, 7 CD4+ T cell clones (R10, R11, R18, A2, A10, A1, and A12) isolated from 2 rubella seropositive donors reacted strongly to rubella capsid peptides C6 (residues 119–152), C9 (residues 205–233), or C11 (residues 255–280), respectively, in both proliferation and cytotoxicity assay. Truncated peptides C6E (residues 125–139), C9B (residues 205–216), and C11E (residues 260–272) were shown to be involved directly to the T cell determinants of C6, C9, and C11, respectively. Genetic restriction of these T cell clones was analyzed by using human cell lines with various HLA-DR phenotypes as targets and/or antigen-presenting cells in cytotoxicity assay and/or proliferation assays. The results indicated that the recognition of peptide C6 by T cell clones (R11 and R18) was associated with DRw9 molecule, while the HLA restriction element of the responses of other T cell clones (A2 and A11, A10, and A12) that reacted with peptide C9 or C11 was DR4 molecule. However, there may be a cross-recognition by the T cell clone (A12) between DR1 and DR4 subtypes.


title: Regulation of RIG-I Activation by K63-Linked Polyubiquitination

text: RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5′-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then triggers the signal to induce the innate immune responses. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates the CTD. The physiological significance of each ubiquitin ligases has been shown by knockout and knockdown studies, but there appears to be contradictory to evidence reported in the literature. In this review, we summarize recent findings related to K63-linked polyubiquitination and propose a model that could reconcile current contradictory theories. We also discuss the physiological significance of the ubiquitin ligases in the immune system against viral infection.


title: Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020

text: We evaluated SARS-CoV-2 RNA and neutralising antibodies in blood donors (BD) residing in the Lodi Red Zone, Italy. Of 390 BDs recruited after 20 February 2020 − when the first COVID-19 case in Lombardy was identified, 91 (23%) aged 19–70 years were antibody positive. Viral RNA was detected in an additional 17 (4.3%) BDs, yielding ca 28% (108/390) with evidence of virus exposure. Five stored samples collected as early as 12 February were seropositive.


title: COVID‐19 related collapse of transplantation systems: a heterogeneous recovery?

text: The coronavirus disease‐2019 (COVID‐19) pandemic has pushed healthcare systems to the limit worldwide. Hospital resources have been compromised, especially in intensive care units (ICUs). Regarding that, some nephrologists have alerted about the potential shortages of our ability to deliver kidney replacement therapy to all patients who need it (1). Simultaneously, two reports have highlighted the collapse of organ transplantation figures in several countries such as France (91%), the US (51%) and Spain (87%), mainly due to a reduction in the number of transplants from deceased donors.


The Public Health Response to COVID-19: Balancing Precaution and Unintended Consequences


Applications of artificial intelligence in the emergency department


title: SARS‐CoV protease inhibitors design using virtual screening method from natural products libraries

text: Two natural products databases, the marine natural products database (MNPD) and the traditional Chinese medicines database (TCMD), were used to find novel structures of potent SARS‐CoV protease inhibitors through virtual screening. Before the procedure, the databases were filtered by Lipinski's ROF and Xu's extension rules. The results were analyzed by statistic methods to eliminate the bias in target‐based database screening toward higher molecular weight compounds for enhancing the hit rate. Eighteen lead compounds were recommended by the screening procedure. They were useful for experimental scientists in prioritizing drug candidates and studying the interaction mechanism. The binding mechanism was also analyzed between the best screening compound and the SARS protein. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 484–490, 2005


title: Dealing with Corona virus anxiety and OCD

text: Abstract The world is reeling under the crisis caused by corona virus disease (COVID-19), print, electronic and social media are flooded with numerous advisories issued by governments and other national & international agencies. While all this is being done with best of intentions so as to contain the spread of this viral disease, this is causing a significant negative impact on mental health of people specially person of obsessive-compulsive disorder with fear of contamination and excessive washing of hands.


title: Committee Recommendations for Resuming Cardiac Surgery Activity in the SARS-CoV-2 Era: Guidance from an International Cardiac Surgery Consortium

text: Abstract Recommendations for the safe and optimized resumption of cardiac surgery care, research and education during the SARS-CoV-2 era were developed by a cardiovascular research consortium, based in 19 countries and representing a wide spectrum of experience with COVID-19. This guidance document provides a framework for restarting cardiac surgery in the outpatient and inpatient settings, in accordance with the current understanding of SARS-CoV-2, the risks posed by interrupted cardiovascular care, and the available recommendations from major societies.


title: Managing Obstetrical Patients During Severe Acute Respiratory Syndrome Outbreak

text: Abstract Severe Acute Respiratory Syndrome (SARS) is a newly described infectious disease caused by a coronavirus. Two outbreaks occurred in Toronto in the spring of 2003, resulting in the closure of 3 hospitals, including 2 obstetrical units. Strategies, devised using information about the coronavirus available at the time as well as epidemiologic and infectious disease containment measures were initiated to protect obstetrical patients and staff. In the first outbreak, the obstetrical unit of an affected Toronto hospital was kept open while other clinical services were closed. In the second outbreak, the obstetrical unit was closed along with all other clinical activities. This report details the stepwise processes used to make decisions during the SARS outbreaks and the implementation of the decisions made. It is recommended that these or similar protocols be used when an obstetrical unit is confronted with a large-scale nosocomial infectious outbreak that has a mechanism of transmission similar to that of SARS.