title: Corona Virus Disease 2019, a growing threat to children?

text: • COVID-19 was reported in Wuhan, China and spread rapidly to nationwide and 25 other countries. • Most of children COVID-19 are familial clusters with mild clinical symptoms. • Early isolation should be performed to protect underlying diseases children. • It is necessary to isolate the newborns immediately after delivery.


title: Adenoviral vector-based strategies against infectious disease and cancer

text: Adenoviral vectors are widely employed against infectious diseases or cancers, as they can elicit specific antibody responses and T cell responses when they are armed with foreign genes as vaccine carriers, and induce apoptosis of the cancer cells when they are genetically modified for cancer therapy. In this review, we summarize the biological characteristics of adenovirus (Ad) and the latest development of Ad vector-based strategies for the prevention and control of emerging infectious diseases or cancers. Strategies to circumvent the pre-existing neutralizing antibodies which dampen the immunogenicity of Ad-based vaccines are also discussed.


title: Distribution of a novel binding site for angiotensins II and III in mouse tissues

text: Abstract A novel binding site for angiotensins II and III that is unmasked by parachloromercuribenzoate has been reported in rat, mouse and human brains. Initial studies of this binding site indicate that it is not expressed in the adrenal, liver or kidney of the rat and mouse. To determine if this binding site occurs in other mouse tissues, 8 tissues were assayed for expression of this binding site by radioligand binding assay and compared with the expression of this binding site in the forebrain. Particulate fractions of homogenates of testis, epididymis, seminal vesicles, heart, spleen, pancreas, lung, skeletal muscle, and forebrain were incubated with 125I-sarcosine1, isoleucine8 angiotensin II in the presence or absence of 0.3mM parachloromercuribenzoate plus 10µM losartan and 10µM PD123319 (to saturate AT1 and AT2 receptors). Specific (3µM angiotensin II displaceable) high affinity binding occurred in the testis>forebrain>epididymis>spleen>pancreas>lung when parachloromercuribenzoate was present. Binding could not be reliably observed in heart, skeletal muscle and seminal vesicles. High affinity binding of 125I-sarcosine1, isoleucine8 angiotensin II was observed in the absence of parachloromercuribenzoate in the pancreas on occasion. This suggests that this novel angiotensin binding site may have a functional role in these tissues.


title: Control of asthma triggers in indoor air with air cleaners: a modeling analysis

text: BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.


title: Infections Caused by HRSV A ON1 Are Predominant among Hospitalized Infants with Bronchiolitis in São Paulo City

text: Human respiratory syncytial virus is the main cause of respiratory infections in infants. Several HRSV genotypes have been described. Goals. To describe the main genotypes that caused infections in São Paulo (2013–2015) and to analyze their clinical/epidemiological features. Methods. 94 infants (0–6 months) with bronchiolitis were studied. Clinical/epidemiological information was collected; a search for 16 viruses in nasopharyngeal secretion (PCR-real-time and conventional, sequencing, and phylogenetic analyses) was performed. Results. The mean age was 2.4 m; 48% were male. The mean length of hospital stay was 4.4 d (14% in the Intensive Care Unit). The positive rate of respiratory virus was 98.9%; 73 cases (77.6%) were HRSV (76,7% HRSVA). HRSVA formed three clusters: ON1 (n = 34), NA1 (n = 1), and NA2 (n = 4). All HRSVB were found to cluster in the BA genotype (BA9-n = 10; BA10-n = 3). Clinical analyses showed no significant differences between the genotype AON1 and other genotypes. Conclusion. This study showed a high rate of HRSV detection in bronchiolitis. HRSVA ON1, which has recently been described in other countries and has not been identified in previous studies in the southeast region of Brazil, was predominant. The clinical characteristics of the infants that were infected with AON1 were similar to infants with infections by other genotypes.


title: Human metapneumovirus-associated respiratory tract infections in the Republic of Ireland during the influenza season of 2003–2004

text: Human metapneumovirus (hMPV) is a newly identified paramyxovirus that has been associated with respiratory tract illness in children aged < 5 years, the elderly, and immunocompromised patients. This study determined the frequency of respiratory tract infections (RTIs) associated with hMPV in the Republic of Ireland. Bronchoalveolar lavage (BAL) samples from 168 adult patients and respiratory specimens from 122 children aged < 5 years were collected between September 2003 and May 2004. The virus was detected by reverse-transcription (RT)-PCR using hMPV polymerase (L) and matrix (M)-specific primers in four (2.4%) of 171 BAL specimens obtained from 168 adults. No other respiratory virus was detected in these specimens, and no hMPV RNA was detected in respiratory specimens from children during the same time period. In all four adult cases, two of whom had underlying disease, hMPV was associated with mild, self-limiting upper RTIs. The most common clinical findings included fever (3/4 patients), cough (4/4) and rhinorrhoea (3/4). No patient died as a result of these RTI episodes. Phylogenetic analysis was performed using the amplified regions of the Mand fusion (F) genes of hMPV. The Irish isolates belonged to cluster 1B, and did not show a separate Irish sub-lineage.


title: Recovery of severely ill COVID-19 patients by intravenous immunoglobulin (IVIG) treatment: A case series

text: INTRODUCTION: During the recent months, COVID-19 has turned to a global crisis claiming high mortality and morbidity among populations. Despite the high prevalence of the disease, it has currently no definitive treatment. We here reported the effects of intravenous immunoglobulin (IVIG) administration in severely ill COVID-19 patients diagnosed based on PCR and radiology tests. CASE PRESENTATION: Five severely ill COVID-19 patients in whom standard treatments failed were administrated with IVIG which prevented the deterioration of clinical symptoms. All the patients were treated with high-dose IVIG (0.3–0.5 g/kg) for 5 consecutive days so that no patient would receive lower than 25 g of the drug. All the patients showed a desirable therapeutic response and were discharged from the hospital with a stable clinical condition after being recovered. CONCLUSION: Treatment with IVIG at the therapeutic dose of 0.3–0.5 g/kg can improve the clinical condition and O2 saturation and prevent the progression of pulmonary lesions in COVID-19 patients with severe symptoms in whom standard treatments have failed.


title: One Group's Historical Reflections on DNA Vaccine Development

text: DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.


title: Canine kobuvirus infections in Korean dogs

text: To investigate canine kobuvirus (CaKoV) infection, fecal samples (n = 59) were collected from dogs with or without diarrhea (n = 21 and 38, respectively) in the Republic of Korea (ROK) in 2012. CaKoV infection was detected in four diarrheic samples (19.0 %) and five non-diarrheic samples (13.2 %). All CaKoV-positive dogs with diarrhea were found to be infected in mixed infections with canine distemper virus and canine parvovirus or canine adenovirus. There was no significant difference in the prevalence of CaKoV in dogs with and without diarrhea. By phylogenetic analysis based on partial 3D genes and complete genome sequences, the Korean isolates were found to be closely related to each other regardless of whether they were associated with diarrhea, and to the canine kobuviruses identified in the USA and UK. This study supports the conclusion that CaKoVs from different countries are not restricted geographically and belong to a single lineage.


title: Advancing translational research with next‐generation protein microarrays

text: Protein microarrays are a high‐throughput technology used increasingly in translational research, seeking to apply basic science findings to enhance human health. In addition to assessing protein levels, posttranslational modifications, and signaling pathways in patient samples, protein microarrays have aided in the identification of potential protein biomarkers of disease and infection. In this perspective, the different types of full‐length protein microarrays that are used in translational research are reviewed. Specific studies employing these microarrays are presented to highlight their potential in finding solutions to real clinical problems. Finally, the criteria that should be considered when developing next‐generation protein microarrays are provided.


title: n-Gram characterization of genomic islands in bacterial genomes

text: Abstract The paper presents a novel, n-gram-based method for analysis of bacterial genome segments known as genomic islands (GIs). Identification of GIs in bacterial genomes is an important task since many of them represent inserts that may contribute to bacterial evolution and pathogenesis. In order to characterize and distinguish GIs from rest of the genome, binary classification of islands based on n-gram frequency distribution have been performed. It consists of testing the agreement of islands n-gram frequency distributions with the complete genome and backbone sequence. In addition, a statistic based on the maximal order Markov model is used to identify significantly overrepresented and underrepresented n-grams in islands. The results may be used as a basis for Zipf-like analysis suggesting that some of the n-grams are overrepresented in a subset of islands and underrepresented in the backbone, or vice versa, thus complementing the binary classification. The method is applied to strain-specific regions in the Escherichia coli O157:H7 EDL933 genome (O-islands), resulting in two groups of O-islands with different n-gram characteristics. It refines a characterization based on other compositional features such as G+C content and codon usage, and may help in identification of GIs, and also in research and development of adequate drugs targeting virulence genes in them.


title: How the gut microbiome regulates host immune responses to viral vaccines

text: The co-evolution of the microbiota and immune system has forged a mutually beneficial relationship. This relationship allows the host to maintain the balance between active immunity to pathogens and vaccines and tolerance to self-antigens and food antigens. In children living in low-income and middle-income countries, undernourishment and repetitive gastrointestinal infections are associated with the failure of oral vaccines. Intestinal dysbiosis associated with these environmental influences, as well as some host-related factors, compromises immune responses and negatively impacts vaccine efficacy. To understand how immune responses to viral vaccines can be optimally modulated, mechanistic studies of the relationship between the microbiome, host genetics, viral infections and the development and function of the immune system are needed. We discuss the potential role of the microbiome in modulating vaccine responses in the context of a growing understanding of the relationship between the gastrointestinal microbiota, host related factors (including histo-blood group antigens) and resident immune cell populations.


title: Application of a cell-based protease assay for testing inhibitors of picornavirus 3C proteases

text: Abstract Proteolytical cleavage of the picornaviral polyprotein is essential for viral replication. Therefore, viral proteases are attractive targets for anti-viral therapy. Most assays available for testing proteolytical activity of proteases are performed in vitro, using heterologously expressed proteases and peptide substrates. To deal with the disadvantages associated with in vitro assays, we modified a cell-based protease assay for picornavirus proteases. The assay is based on the induction of expression of a firefly luciferase reporter by a chimeric transcription factor in which the viral protease and cleavage sites are inserted between the GAL4 binding domain and the VP16 activation domain. Firefly luciferase expression is dependent on cleavage of the transcription factor by the viral protease. This biosafe assay enables testing the effect of compounds on protease activity in cells while circumventing the need for infection. We designed the assay for 3C proteases (3Cpro) of various enteroviruses as well as of viruses of several other picornavirus genera, and show that the assay is amenable for use in a high-throughput setting. Furthermore, we show that the spectrum of activity of 3Cpro inhibitor AG7088 (rupintrivir) not only encompasses enterovirus 3Cpro but also 3Cpro of foot-and-mouth disease virus (FMDV), an aphthovirus. In contrary, AG7404 (compound 1), an analogue of AG7088, had no effect on FMDV 3Cpro activity, for which we provide a structural explanation.


The Importance of the Clinical Environment in the Transmission of Health Care-Associated Infections


title: Beyond the ‘nanny state’: Stewardship and public health

text: SUMMARY Background Some public health measures restrict personal freedom more than others, and deciding what type of measure will be appropriate and effective has long been a problem for policy makers. Existing bioethical frameworks are often not well suited to address the problems of public health. Methods The Nuffield Council on Bioethics set up an expert working party to examine the ethical issues surrounding public health in January 2006. Following evidence gathering and a public consultation exercise, the Council published its conclusions and recommendations in the report ‘Public health: ethical issues’ in November 2007. Results A spectrum of views exists on the relationship between the state's authority and the individual. The Council set out a proposal to capture the best of the libertarian and paternalistic approaches, in what it calls the ‘stewardship model’. This model suggests guiding principles for making decisions about public health policies, and highlights some key principles including Mill's harm principle, caring for the vulnerable, autonomy and consent. An ‘intervention ladder’ is also proposed, which provides a way of thinking about the acceptability of different public health measures. The report then applies these principles to a number of case studies: infectious diseases, obesity, alcohol and tobacco, and fluoridation of water supplies. Conclusions The idea of a ‘nanny state’ is often rejected, but the state has a duty to look after the health of everyone, and sometimes that means guiding or restricting people's choices. On the other hand, the state must consider a number of principles when designing public health programmes, and justification is required if any of these principles are to be infringed.


title: Antiviral potentials of medicinal plants

text: Abstract Medicinal plants have been widely used to treat a variety of infectious and non-infectious ailments. According to one estimate, 25% of the commonly used medicines contain compounds isolated from plants. Several plants could offer a rich reserve for drug discovery of infectious diseases, particularly in an era when the latest separation techniques are available on one hand, and the human population is challenged by a number of emerging infectious diseases on the other hand. Among several other ailments, viral infections, particularly infections associated with human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2), and newly emerging infectious viruses have challenged mankind survival. Of importance, a variety of medicinal plants have shown promise to treat a number of viral infections, and some of them possess broad-spectrum antiviral activity. In the past, exploration into the antiviral activity of various promising medicinal plants was limited due to: (a) highly infectious nature of viruses and (b) lack of appropriate separation techniques for the identification of antiviral components from plants. Development of vector-based strategies, in which non-infectious molecular clone of a virus could be used for antiviral screening purposes, and advancement in separation technologies offers promise for medicinal plants usage in modern drug discovery. This article describes potential antiviral properties of medicinal plants against a diverse group of viruses, and suggests screening the potential of plants possessing broad-spectrum antiviral effects against emerging viral infections.


title: Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis

text: Abstract Background Human rhinoviruses (HRVs) are some of the earliest identified and most commonly detected viruses associated with acute respiratory tract infections (ARTIs) and yet the molecular epidemiology and genomic variation of individual serotypes remains undefined. Objectives To molecularly characterise a novel HRV and determine its prevalence and clinical impact on a predominantly paediatric population. Study design Nucleotide sequencing was employed to determine the complete HRV-QPM coding sequence. Two novel real-time RT-PCR diagnostic assays were designed and employed to retrospectively screen a well-defined population of 1244 specimen extracts to identify the prevalence of HRV-QPM during 2003. Results Phylogenetic studies of complete coding sequences defined HRV-QPM as a novel member the genus Rhinovirus residing within the previously described HRV-A2 sub-lineage. Investigation of the relatively short VP1 sequence suggest that the virus is resistant to Pleconaril, setting it apart from the HRV A species. Sixteen additional HRV-QPM strains were detected (1.4% of specimens) often as the sole micro-organism present among infants with suspected bronchiolitis. HRV-QPM was also detected in Europe during 2006, and a closely related virus circulated in the United States during 2004. Conclusions We present the molecular characterisation and preliminary clinical impact of a newly identified HRV along with sequences representing additional new HRVs.


During COVID‐19, Outpatient Advance Care Planning Is Imperative: We Need All Hands on Deck


Multiplex PCR theranostics of severe respiratory infections


title: Deep learning in generating radiology reports: A survey

text: Substantial progress has been made towards implementing automated radiology reporting models based on deep learning (DL). This is due to the introduction of large medical text/image datasets. Generating radiology coherent paragraphs that do more than traditional medical image annotation, or single sentence-based description, has been the subject of recent academic attention. This presents a more practical and challenging application and moves towards bridging visual medical features and radiologist text. So far, the most common approach has been to utilize publicly available datasets and develop DL models that integrate convolutional neural networks (CNN) for image analysis alongside recurrent neural networks (RNN) for natural language processing (NLP) and natural language generation (NLG). This is an area of research that we anticipate will grow in the near future. We focus our investigation on the following critical challenges: understanding radiology text/image structures and datasets, applying DL algorithms (mainly CNN and RNN), generating radiology text, and improving existing DL based models and evaluation metrics. Lastly, we include a critical discussion and future research recommendations. This survey will be useful for researchers interested in DL, particularly those interested in applying DL to radiology reporting.


title: The effects of a celebrity suicide on suicide rates in Hong Kong

text: Abstract Background Deaths of celebrities, especially by suicide, can be followed by an increase in population suicide rates, particularly where there is extensive media reporting. We have examined the impact on suicides following the death of a famous Hong Kong pop singer whose death from suicide by jumping from a height, occurred on 1st April 2003, and resulted in extensive and often dramatic media coverage. Methods Data on suicides were obtained from the Hong Kong Census and Statistics Department and the Coroner's Court. The numbers of suicides in 2003 before and after the death of celebrity were compared to the same period in 1998–2002. The case files and suicide notes of people who died by suicide in 2003 were also studied qualitatively. Results There was a significant increase in suicides following the celebrity death, compared with the average over the preceding three months as well as the corresponding monthly average during 1998–2002. It was particularly marked in a subgroup comprising males, aged 25–39 years, many of whom died by jumping. The name of the celebrity was often mentioned in case files and suicide notes. Limitations The statistical results in showing the excess of suicides were based on aggregated data only. Conclusions This study provides further confirmation of the potential harmful consequences of sensational and excessive reporting of celebrity deaths.


title: Developing therapeutic monoclonal antibodies at pandemic pace

text: The time from discovery to proof-of-concept trials could be reduced to 5–6 months from a traditional timeline of 10–12 months.


title: Region‐resolved proteomics profiling of monkey heart

text: Nonhuman primates (NHPs) play an indispensable role in biomedical research because of their similarities in genetics, physiological, and neurological function to humans. Proteomics profiling of monkey heart could reveal significant cardiac biomarkers and help us to gain a better understanding of the pathogenesis of heart disease. However, the proteomic study of monkey heart is relatively lacking. Here, we performed the proteomics profiling of the normal monkey heart by measuring three major anatomical regions (vessels, valves, and chambers) based on iTRAQ‐coupled LC‐MS/MS analysis. Over 3,200 proteins were identified and quantified from three heart tissue samples. Furthermore, multiple bioinformatics analyses such as gene ontology analysis, protein–protein interaction analysis, and gene‐diseases association were used to investigate biological network of those proteins from each area. More than 60 genes in three heart regions are implicated with heart diseases such as hypertrophic cardiomyopathy, heart failure, and myocardial infarction. These genes associated with heart disease are mainly enriched in citrate cycle, amino acid degradation, and glycolysis pathway. At the anatomical level, the revelation of molecular characteristics of the healthy monkey heart would be an important starting point to investigate heart disease. As a unique resource, this study can serve as a reference map for future in‐depth research on cardiac disease‐related NHP model and novel biomarkers of cardiac injury.


The first detection of bovine coronavirus in calves diarrhea in west of Iran


The role of peer review and science for advancing public understanding


title: Longitudinal serological and virological study on porcine torovirus (PToV) in piglets from Spanish farms

text: Abstract A study was performed to evaluate porcine torovirus (PToV) seroprevalence and infection in three multi-site farms from the North-eastern region of Spain. Serum samples from 120 piglets and faecal samples from 36 piglets were longitudinally collected at 1, 3, 7, 11 and 15 weeks of age. Serum samples from their dams (n =30) were also taken 1-week post-farrowing. PToV antibodies in serum were monitored by ELISA, while viral infection was assessed by real-time RT-PCR in faeces. A high seroprevalence (about 100%) was observed in animals older than 11 weeks and in adult sows. Moreover, all 1-week-old animals were seropositive, indicating maternal antibody transference through colostrum. The antibody titers declined to close to or below the ELISA cut-off value by the age of weaning (3 weeks of age). Development of a significant antibody response to PToV occurred before 7 weeks of age in about 50% of piglets, and the remaining animals developed the response by weeks 11 or 15. These results indicate that PToV infection occurred soon after weaning. Although the prevalence of infection in suckling piglets varied among the studied farms, PToV prevalences in 7 and 11-week-old pigs were between 50–67% and 58–75%, respectively, in all farms. Sequencing results indicated that more than one PToV strains were circulating in the studied farms. Present data suggest that PToV was endemic on the studied farms, and provide new insights on the epidemiology of PToV.


title: Development and evaluation of a rapid detection assay for severe fever with thrombocytopenia syndrome virus based on reverse-transcription recombinase polymerase amplification

text: Abstract Rapid detection of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for its control and surveillance. In this study, a rapid isothermal real-time reverse-transcription recombinase polymerase amplification (RT-RPA) assay was developed for the detection of SFTSV. The detection limit at 95% probability was 241 copies per reaction. A test of 120 serum samples of suspected severe fever with thrombocytopenia syndrome (SFTS) patients revealed that the sensitivity and specificity of the RT-RPA assay was approximately 96.00% (95%CI: 80.46%–99.79%) and 98.95% (95% CI: 94.28%–99.95%), respectively; the kappa value was 0.9495 (P＜0.001). The Bland-Altman analysis showed that 87.50% of the different data points were located within the 95% limits of agreement, indicating a good correlation between the results from RT-RPA assays and those of RT-qPCR assays. In conclusion, the rapid and efficient RT-RPA assay can be a promising candidate for point-of-care detection method of SFTSV.


title: What Solid Organ Transplant Healthcare Providers should know about Renin‐Angiotensin‐Aldosterone System Inhibitors and COVID‐19

text: The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID‐19) are still emerging. Kidney transplant recipients are commonly prescribed renin‐angiotensin‐aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin‐converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of Renin‐Angiotensin‐Aldosterone System (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS‐CoV‐2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID‐19 pandemic. At present there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID‐19 pandemic.


title: Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats

text: Abstract Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV). However, a recent study found that one-third of FIPV isolates have an intact 3c and suggested that it is not solely involved in FIP but is essential for intestinal replication. In order to confirm these assumptions, 27 fecal and 32 FIP coronavirus isolates were obtained from resident or adopted cats from a large metropolitan shelter during 2008–2009 and their 3a–c, E, and M genes sequenced. Forty percent of coronavirus isolates from FIP tissues had an intact 3c gene, while 60% had mutations that truncated the gene product. The 3c genes of fecal isolates from healthy cats were always intact. Coronavirus from FIP diseased tissues consistently induced FIP when given either oronasally or intraperitoneally (i.p.), regardless of the functional status of their 3c genes, thus confirming them to be FIPVs. In contrast, fecal isolates from healthy cats were infectious following oronasal infection and shed at high levels in feces without causing disease, as expected for FECVs. Only one in three cats shed FECV in the feces following i.p. infection, indicating that FECVs can replicate systemically, but with difficulty. FIPVs having a mutated 3c were not shed in the feces following either oronasal or i.p. inoculation, while FIPVs with intact 3c genes were shed in the feces following oronasal but not i.p. inoculation. Therefore, an intact 3c appears to be essential for intestinal replication. Although FIPVs with an intact 3c were shed in the feces following oronasal inoculation, fecal virus from these cats was not infectious for other cats. Attempts to identify potential FIP mutations in the 3a, 3b, E, and M were negative. However, the 3c gene of FIPVs, even though appearing intact, contained many more non-synonymous amino acid changes in the 3′ one-third of the 3c protein than FECVs. An attempt to trace FIPV isolates back to enteric strains existing in the shelter was only partially successful due to the large region over which shelter cats and kittens originated, housing conditions prior to acquisition, and rapid movement through the shelter. No evidence could be found to support a recent theory that FIPVs and FECVs are genetically distinct.


title: Identification of novel Bartonella spp. in bats and evidence of Asian gray shrew as a new potential reservoir of Bartonella

text: Abstract Many studies indicated that small mammals are important reservoirs for Bartonella species. Using molecular methods, several studies have documented that bats could harbor Bartonella. This study was conducted to investigate the relationship of Bartonella spp. identified in bats and small mammals living in the same ecological environment. During May 2009 and March 2010, a total of 102 blood specimens were collected. By whole blood culture and molecular identification, a total of 6 bats, 1 rodent and 9 shrews were shown to be infected by Bartonella species. After sequencing and phylogenetic analyses of the sequences of gltA, ftsZ, rpoB and ribC genes, these specific isolates from bats were not similar to the known Bartonella species (the similarity values were less than 91.2%, 90.5%, 88.8%, and 82.2%, respectively); these isolates formed an independent clade away from other known Bartonella type strains. The Bartonella spp. isolated from small mammals, which were closely related to Bartonella tribocorum, Bartonella elizabethae, Bartonella grahamii, Bartonella rattimassiliensis and Bartonella queenslandensis, were similar to the findings in previous studies worldwide. Therefore, the results implied that the species of Bartonella strains isolated from small mammals were different from those identified in bats. Our results strongly suggested that the bat isolate could be a new Bartonella species. This study is also the first one to isolate Bartonella organisms from Asian gray shrews, Crocidura attenuata tanakae.


title: Influenza and the Vocal Performer: Update on Prevention and Treatment

text: Summary Upper respiratory tract infections (URIs) are a major cause of morbidity among vocal arts professionals, both from their acute impairment of the vocal mechanism and their predisposing influence for the development of serious vocal sequelae. In this review, we present some of the salient features of currently available treatments effective against influenza, the virus family responsible for the most serious form of URI. At present, these include an inactivated vaccine and four antiviral drugs, each approved in the United States and many other countries for the prevention and treatment of influenza. A live attenuated vaccine is also available, and other vaccines and antiviral drugs are under development. This review details the current options available for treating both influenza and noninfluenza related URIs in the professional voice user.


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title: COVID‐19 and implications for thiopurine use


title: A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey

text: Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.


title: Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study

text: Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05–1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44–9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3–5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0–4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.


title: Plasminogen activator inhibitor-1 in sputum and nasal fluids increases in asthmatics during common colds

text: This study showed that sputum and nasal lavage levels of plasminogen activator inhibitor-1 (PAI-1) rise during a common cold in asthmatic patients. This rise may contribute to the progression of airway remodeling.


title: Concerns for low-resource countries, with under-prepared intensive care units, facing the COVID-19 pandemic

text: BACKGROUND: Low-resource countries with fragile healthcare systems lack trained healthcare professionals and specialized resources for COVID-19 patient hospitalization, including mechanical ventilators. Additional socio-economic complications such as civil war and financial crisis in Libya and other low-resource countries further complicate healthcare delivery. METHODS: A cross-sectional survey evaluating hospital and intensive care unit's capacity and readiness was performed from 16 leading Libyan hospitals in March 2020. In addition, a survey was conducted among 400 doctors who worked in these hospitals to evaluate the status of personal protective equipment. RESULTS: Out of 16 hospitals, the highest hospital capacity was 1000 in-patient beds, while the lowest was 25 beds with a median of 200 (IQR 52-417, range 25 – 1000) hospital beds. However, a median of only eight (IQR 6-14, range 3 – 37) available functioning ICU beds were reported in these hospitals. Only 9 (IQR 4.5-14, range 2 – 20) mechanical ventilators were reported and none of the hospitals had a reverse transcription-polymerase chain reaction machine for COVID-19 testing. Moreover, they relied on one of two central laboratories located in major cities. Our PPE survey revealed that 56.7% hospitals lacked PPE and 53% of healthcare workers reported that they did not receive proper PPE training. In addition, 70% reported that they were buying the PPE themselves as hospitals did not provide them. CONCLUSIONS: This study provides an alarming overview of the unpreparedness of Libyan hospitals for detecting and treating patients with COVID-19 and limiting the spread of the pandemic.


title: Severe acute respiratory syndrome (SARS) coronavirus: application of monoclonal antibodies and development of an effective vaccine

text: SARS‐CoV is a new type of human coronavirus identified as a causative agent of severe acute respiratory syndrome (SARS). On the occasion of the SARS outbreak, various monoclonal antibodies (mAbs) against SARS‐CoV have been developed and applied for diagnosis, clinical management and basic research. In this review, we overview the biochemical and functional properties and applications of these SARS‐CoV mAbs. We also focus on a variety of vaccines currently under development and discuss the immune response elicited by these vaccines in animal models, hopefully to better understand what we need to do next to fight against newly emerging pathogens in the future. Copyright © 2006 John Wiley & Sons, Ltd.


title: Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection

text: Abstract Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system of susceptible rodents. Astrocytes are the major target for MHV persistence. However, the mechanisms by which astrocytes survive MHV infection and permit viral persistence are not known. Here we performed DNA microarray analysis on differential gene expression in astrocyte DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3 was significantly decreased following MHV infection. This finding was further confirmed by quantitative reverse transcription–polymerase chain reaction, Western blot analysis, and BNip3-promoter-luciferase reporter system. Interestingly, infection with live and ultraviolet light-inactivated viruses equally repressed BNip3 expression, indicating that the down-regulation of BNip3 expression does not require virus replication and is mediated during cell entry. Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. Deletion analysis showed that the sequence between nucleotides 262 and 550 of the 588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3 expression and that it contains signals that are responsible for MHV-induced down-regulation of BNip3 expression in DBT cells. These results may provide insights into the mechanisms by which MHV evades host antiviral defense and promotes cell survival, thereby allowing its persistence in the host astrocytes.


title: Development and Application of a Framework for Maintenance of Medical Terminological Systems

text: OBJECTIVE: Terminological Systems (TSs) need to be maintained in order to sustain their utility. This paper describes a study aiming at the standardization of the maintenance processes of medical TSs by capturing the criteria for the management of the maintenance processes into a framework. Furthermore, this paper describes application of the framework, which sheds light on the current practice of TS maintenance. DESIGN: Observational study. MEASUREMENTS: By means of a literature study, criteria for the maintenance of TSs were obtained and categorized into a framework. The current practice of TS maintenance was explored by a survey among organizations that maintain a TS. Results were stratified by the size of the TS being maintained. RESULTS: From Sixty-three relevant articles, criteria for the maintenance processes of TSs were extracted and organized into four components. The primary component “Execution” concerns the core activities of the maintenance process. The other three components “Process management,” “Change specifications,” and “Editing tools” support the core activities of the component “Execution.” The survey had a response rate of 40% (37 of 93). The answers reflect the large variation in the number of criteria that are satisfied for the participating organizations. Overall, maintenance of larger TSs seems to satisfy more criteria. CONCLUSIONS: The framework is an important step towards standardization of the maintenance of medical TSs and can be used to eliminate shortcomings in this process. Surveying the current practice showed that there is ample room to improve the maintenance processes of medical TSs, especially for the smaller TSs.


title: A novel parainfluenza virus type 3 (PIV3) identified from goat herds with respiratory diseases in eastern China

text: Abstract Parainfluenza virus type 3 (PIV3) is one of the most important viral respiratory pathogens for humans and for many animals, but goat infection has been rarely reported. Starting in Aug 2013, goats in the Jiangsu and Anhui provinces of eastern China suffered severe respiratory diseases. In order to identify the causative agent, numerous related pathogens were tested with RT-PCR or PCR. A unique PIV3 strain was detected in most of the clinical nasal swabs or serum samples. The virus was isolated on MDBK cells and characterized by RT-PCR, nucleotide sequence analysis and hemagglutination test. The entire M and F gene coding regions, HN, 5′-UTR-N and L gene fragments were amplified using pairs of degenerate primers. Nucleotide, amino acid sequence alignments and phylogenetic analyses based on these genes indicated that the goat-derived PIV3 strain was distinct from previously reported BPIV3 genotypes and HPIV3 strains. The novel isolate, named JS2013, might be a potentially new member of the respirovirus genus. Goats were experimentally infected with JS2013 culture. The virus-inoculated goats displayed coughing and nasal discharges that were related to respiratory diseases. Viremia and virus shedding were detected during 4–10 days post-inoculation (dpi). Virus-specific HI antibodies became positive from 14dpi. This is the first report of the detection of PIV3 from Chinese goat herds and genetic and pathogenetic characterization of the novel goat-derived PIV3.


docid: fsmauidc

title: Coopetition and COVID-19: Collaborative business-to-business marketing strategies in a pandemic crisis

text: Abstract Although coopetition (simultaneous cooperation and competition) should positively affect company performance, it is unclear how implementation of these business-to-business marketing strategies can take place during large-scale emergencies. Therefore, guided by resource-based theory and the relational view, this investigation examines how organisations have used coopetition to cope with the Coronavirus (COVID-19) pandemic. Key examples include retailers sharing information about stock levels, pharmaceutical organisations working together to develop a vaccine, technological giants collaborating for the greater good, and charities forming alliances for a joint cause. This paper strengthens the extant literature by highlighting the heterogeneity of coopetition strategies that firms can use within a global crisis. Practitioners must balance the risks and rewards of coopetition activities. In turn, they should decide whether to continue to cooperate with their competitors once the pandemic has ended, or resume operating under individualistic business models. This article ends with some future research directions.


title: Factors affecting bilateral tourism flows

text: Abstract This paper examines the structure of bilateral tourism and identifies five broad categories of factors that may affect the overall size of tourism flows. Such analysis of tourism is important because diplomacy and trade continues to be conducted on a nation-to-nation basis despite a growing shift towards multilateralism in free trade blocks such as the European Union and the North American Free Trade Agreement. Further, Bilateralism is important because countries have reduced abilities to control tourism imports in an era of growing globalization. A framework that may be employed to analyze problems in bilateral tourism flows is also outlined.


title: Severe Acute Respiratory Syndrome Coronavirus Elicits a Weak Interferon Response Compared to Traditional Interferon-Inducing Viruses

text: The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-α, -β and -γ compared to VSV and NDV. Characterization of the profile of IFN-α subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-α2 and −6 subtypes were higher compared to other IFN-α subtypes namely, IFN-α5, −8, −10, −13/1, −17, and −21. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.


title: The Chemistry and Biology of Theta Defensins

text: Cyclic peptides are found in a diverse range of organisms and are characterized by their stability and role in defense. Why is only one class of cyclic peptides found in mammals? Possibly we have not looked hard enough for them, or the technologies needed to identify them are not fully developed. We also do not yet understand their intriguing biosynthesis from two separate gene products. Addressing these challenges will require the application of chemical tools and insights from other classes of cyclic peptides. Herein, we highlight recent developments in the characterization of theta defensins and describe the important role that chemistry has played in delineating their modes of action. Furthermore, we emphasize the potential of theta defensins as antimicrobial agents and scaffolds for peptide drug design.


title: Decomposition analysis of energy-related carbon emissions from the transportation sector in Beijing

text: Abstract In the process of rapid development and urbanization in Beijing, identifying the potential factors of carbon emissions in the transportation sector is an important prerequisite to controlling carbon emissions. Based on the expanded Kaya identity, we built a multivariate generalized Fisher index (GFI) decomposition model to measure the influence of the energy structure, energy intensity, output value of per unit traffic turnover, transportation intensity, economic growth and population size on carbon emissions from 1995 to 2012 in the transportation sector of Beijing. Compared to most methods used in previous studies, the GFI model possesses the advantage of eliminating decomposition residuals, which enables it to display better decomposition characteristics (Ang et al., 2004). The results show: (i) The primary positive drivers of carbon emissions in the transportation sector include the economic growth, energy intensity and population size. The cumulative contribution of economic growth to transportation carbon emissions reaches 334.5%. (ii) The negative drivers are the transportation intensity and energy structure, while the transportation intensity is the main factor that restrains transportation carbon emissions. The energy structure displays a certain inhibition effect, but its inhibition is not obvious. (iii) The contribution rate of the output value of per unit traffic turnover on transportation carbon emissions appears as a flat “M”. To suppress the growth of carbon emissions in transportation further, the government of Beijing should take the measures of promoting the development of new energy vehicles, limiting private vehicles’ increase and promoting public transportation, evacuating non-core functions of Beijing and continuingly controlling population size.


title: Interleukin-1β expression by a recombinant porcine reproductive and respiratory syndrome virus

text: Abstract The cytokine interleukin-1 beta (IL-1β) is a potent inflammatory mediator in response to infection, and can be used as an immunological adjuvant. In this study, we constructed a recombinant porcine reproductive and respiratory syndrome virus (vP129/swIL1β) expressing swine IL-1β from the separate subgenomic mRNA inserted between the ORF1b and ORF2 genome region. MARC-145 cells infected with vP129/swIL1β secreted 1947pg of IL-1β per 2×105 cells at 36h post-infection. In vitro growth kinetics analysis in MARC-145 cells showed that the vP129/swIL1β virus had a similar replication rate as that of parental virus. We further performed in vivo characterization of the vP129/swIL1β virus in a nursery pig disease model. The vP129/swIL1β infected pigs did not show visible clinical signs, while respiratory distress and lethargy were evident in pigs infected with the parental virus. The expression of various cytokines from peripheral blood mononuclear cells measured by fluorescent microsphere immunoassay showed that IL-1β, IL-4 and IFN-γ expression levels were up-regulated in pigs infected with vP129/swIL1β at 7 and 14 days post-infection. However, no detectable level of IL-1β was found in serum samples from pigs infected with either vP129/swIL1β or parental virus. In summary, this study demonstrated a recombinant PRRSV as a useful tool to study the role of different cytokines in disease progression and immune responses, which represents a new strategy for future therapeutic application and vaccine development.


title: Experimental infection of dogs with a novel strain of canine coronavirus causing systemic disease and lymphopenia

text: Abstract A pantropic canine coronavirus (CCoV) strain (CB/05) has been recently associated to a fatal outbreak of systemic disease in young dogs. We report the clinical, virological and serological findings in dogs experimentally infected with strain CB/05. The dogs, three 2.5-month-old and two 6-month-old pups, were successfully infected, shedding viral RNA with their faeces for the entire observation period (21 days) and displaying systemic clinical signs resembling those observed during the course of natural infection. Leucopenia (acute lymphopenia) occurred in all infected dogs, with values dropping below 60% of the initial counts. Considering the severity of the CB/05-induced disease, two of the youngest pups were euthanized for ethical reasons at days 8–9 postinfection, whereas the other pups underwent a slow but progressive improvement of their clinical status with complete recovery. At postmortem examination, remarkable lesions were observed in the internal organs of the euthanized pups, that tested positive for CCoV by real-time RT-PCR and virus isolation on cell cultures. All pups seroconverted for CCoV, as shown by the high optical density values and antibody titres detected by ELISA and virusneutralisation tests, respectively. The present study confirms that strain CB/05 is highly pathogenic for dogs, being able to induce a severe disease (and in some cases the death) even in experimental conditions.


COVID-19 and Older Adult


title: A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study

text: Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.


docid: zxganumj

title: New developments for the design, synthesis and biological evaluation of potent SARS-CoV 3CL(pro) inhibitors

text: A series of trifluoromethyl, benzothiazolyl or thiazolyl ketone-containing peptidic compounds as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Three candidates had encouraging results for the development of new anti-SARS compounds.


title: High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection

text: The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing (“meta-transcriptomics”) to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease.


title: Purpose by design or disaster: Preserving a sense of purpose amid environmental uncertainty

text: Abstract Psychological research suggests a sense of purpose in life is a coveted asset, with well-established linkages to well-being and healthy functioning. But how do individuals preserve this sense when previously reliable settings – and the opportunities they afford – are profoundly disrupted? The current moment provides a formidable test of this question, as widespread transmission of Covid-19 and intense efforts to slow it drastically transform our environment. Here, we consider how the experience of purpose may be impacted by disruptions in three key person-environment interactions: how we engage with work, how we engage in education, and how we manage physical proximity. We hope to motivate critical thinking about how this pandemic, and our collective responses to it, influence the experience of purpose and delineate a research agenda that may inform how individuals’ can preserve a sense of engagement and contribution.


title: The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases

text: Since its discovery in 2003, the type III interferon-λ (IFN-λ) family has been found to contribute significantly to the host response to infection. Whilst IFN-λ shares many features with type I IFN induction and signalling pathways, the tissue-specific restricted expression of its receptor, IL28RA, makes IFN-λ a major mediator of host innate immunity in tissues and organs with a high epithelial cell content. Host susceptibility and responses to infection are known to be heterogeneous, and the identification of common genetic variants linked to disease outcome by genome-wide association studies (GWAS) has underscored the significance of host polymorphisms in responses to infection. Several such GWAS have highlighted the IFN-λ locus on chromosome 19q13 as an area of genetic variation significantly associated with hepatitis C virus (HCV) infection, and the rs12979860 genotype can be used in clinical practice as a biomarker for predicting a successful response to treatment with pegylated IFN and ribavarin. Here, we discuss IFN-λ genetic polymorphisms and their role in HCV and other infectious diseases as well as their potential impact on clinical diagnostics, patient stratification and therapy. Finally, the broader role of IFN-λ in the immunopathogenesis of non-infectious inflammatory diseases is considered.


title: Mouse Hepatitis Virus Replicase Protein Complexes Are Translocated to Sites of M Protein Accumulation in the ERGIC at Late Times of Infection

text: Abstract The coronavirus mouse hepatitis virus (MHV) directs the synthesis of viral RNA on discrete membranous complexes that are distributed throughout the cell cytoplasm. These putative replication complexes are composed of intimately associated but biochemically distinct membrane populations, each of which contains proteins processed from the replicase (gene 1) polyprotein. Specifically, one membrane population contains the gene 1 proteins p65 and p1a-22, while the other contains the gene 1 proteins p28 and helicase, as well as the structural nucleocapsid (N) protein and newly synthesized viral RNA. In this study, immunofluorescence confocal microscopy was used to define the relationship of the membrane populations comprising the putative replication complexes at different times of infection in MHV-A59-infected delayed brain tumor cells. At 5.5 h postinfection (p.i.) the membranes containing N and helicase colocalized with the membranes containing p1a-22/p65 at foci distinct from sites of M accumulation. By 8 to 12 h p.i., however, the membranes containing helicase and N had a predominantly perinuclear distribution and colocalized with M. In contrast, the p1a-22/p65-containing membranes retained a peripheral, punctate distribution at all times of infection and did not colocalize with M. By late times of infection, helicase, N, and M each also colocalized with ERGIC p53, a specific marker for the endoplasmic reticulum–Golgi–intermediate compartment. These data demonstrated that the putative replication complexes separated into component membranes that relocalized during the course of infection. These results suggest that the membrane populations within the MHV replication complex serve distinct functions both in RNA synthesis and in delivery of replication products to sites of virus assembly.


title: Drugs supply and pharmaceutical care management practices at a designated hospital during the COVID-19 epidemic

text: Abstract The coronavirus disease-19 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus that was first detected at the end of December 2019. The epidemic has affected various regions of China in different degrees. As the situations evolve, the COVID-19 had been confirmed in many countries, and made a assessment that it can be characterized as a pandemic by the World Health Organization on March 11, 2020. Drugs are the main treatment of COVID-19 patients. Pharmaceutical service offers drug safety ensurance for COVID-19 patients. According to COVID-19 prevention and control policy and requirements, combined with series of diagnosis and treatment plans, pharmacists in the first provincial-level COVID-19 diagnosis and treatment unit in Jilin Province in Northeast China have established the management practices of drug supply and pharmaceutical care from four aspects: personnel, drugs supply management, off-label drug use management and pharmaceutical care. During the outbreak, the pharmaceutical department of THJU completed its assigned workload to ensure drug supply. So far, no nosocomial infections and medication errors have occurred, which has stabilized the mood of the staff and boosted the pharmacists' confidence in fighting the epidemic. For the treatment of COVID-19, pharmacists conducted adverse reaction monitoring and participated in the multidisciplinary consultation of COVID-19. Up to now, the COVID-19 patients admitted to THJU have not shown any new serious adverse reactions and been cured finally. The hospital pharmacy department timely adjusted the work mode, and the formed management practices is a powerful guarantee for the prevention and control of the COVID-19 epidemic. This paper summarized the details and practices of drug supply and pharmaceutical services management to provide experience for the people who involving in COVID-19 prevention and contain in other abroad epidemic areas.


title: Slowdown of urology residents’ learning curve during the COVID‐19 emergency

text: The coronavirus disease 2019 (COVID-19), has rapidly been spreading worldwide and Italy has been hit hard, forced the Italian Healthcare System to change and adapt to these extreme conditions. The Urology Department daily activities were drastically reduced and limited only to non-deferrable procedures and the entire organogram were reorganized following a rigorous flow-chart. It's evident that this unprecedent scenario is having an impact on residents training program, considering that it is very difficult to predict the duration of emergency. The urology residents do not have the opportunity to carry out clinical activities nor to be tutored, as the senior physicians are engaged in the emergency's management.


docid: idymxcdx

title: Segmenting communities as public health strategy: a view from the social sciences and humanities

text: On the 5th of May 2020, a group of modellers, epidemiologists and biomedical scientists from the University of Edinburgh proposed a “segmenting and shielding” approach to easing the lockdown in the UK over the coming months. Their proposal, which has been submitted to the government and since been discussed in the media, offers what appears to be a pragmatic solution out of the current lockdown. The approach identifies segments of the population as at-risk groups and outlines ways in which these remain shielded, while ‘healthy’ segments would be allowed to return to some kind of normality, gradually, over several weeks. This proposal highlights how narrowly conceived scientific responses may result in unintended consequences and repeat harmful public health practices. As an interdisciplinary group of researchers from the humanities and social sciences at the University of Edinburgh, we respond to this proposal and highlight how ethics, history, medical sociology and anthropology - as well as disability studies and decolonial approaches - offer critical engagement with such responses, and call for more creative and inclusive responses to public health crises.


title: Structural lability in stem-loop 1 drives a 5' UTR-3' UTR interaction in coronavirus replication

text: The leader RNA of the 5' untranslated region (UTR) of coronaviral genomes contains two stem-loop structures denoted SL1 and SL2. Herein, we show that SL1 is functionally and structurally bipartite. While the upper region of SL1 is required to be paired, we observe strong genetic selection against viruses that contain a deletion of A35, an extrahelical nucleotide that destabilizes SL1, in favor of genomes that contain a diverse panel of destabilizing second-site mutations, due to introduction of a non-canonical base pair near A35. Viruses containing destabilizing SL1-ΔA35 mutations also contain one of two specific mutations in the 3' UTR. Thermal denaturation and imino proton solvent exchange experiments reveal that the lower half of SL1 is unstable and that second-site SL1-ΔA35 substitutions are characterized by one or more features of the wild-type SL1. We propose a "dynamic SL1" model, in which the base of SL1 has an optimized lability required to mediate a physical interaction between the 5' and 3' UTRs that stimulates subgenomic RNA synthesis. Although not conserved at the nucleotide sequence level, these general structural characteristics of SL1 appear to be conserved in other coronaviral genomes.


title: Type I IFN family members: Similarity, differences and interaction

text: Abstract Interferons (IFN) are key cytokines with multifaceted antiviral and cell-modulatory properties. Three distinct types of IFN are recognized (I–III) based on structural features, receptor usage, cellular source and biological activities. The action of IFNs is mediated by a complex, partially overlapping, transcriptional program initiated by the interaction with specific receptors. Genetic diversity, with polymorphisms and mutations, can modulate the extent of IFN responses and the susceptibility to infections. Almost all viruses developed mechanisms to subvert the IFN response, involving both IFN induction and effector mechanisms. Interactions between IFN types may occur, for both antiviral and cell-modulatory effects, in a complex interplay, involving both synergistic and antagonistic effects. Interferon-associated diseases, not related to virus infections may occur, some of them frequently observed in IFN-treated patients. On the whole, IFNs are pleiotropic biologic response modifiers, that, upon activation of thousands genes, induce a broad spectrum of activities, regulating cell cycle, differentiation, plasma membrane molecules, release of mediators, etc., that can be relevant for cell proliferation, innate and adaptive immunity, hematopoiesis, angiogenesis and other body functions.


Positioning Epidemiology in a Changing Environment Over the Next 25 Years: Introduction


title: Correspondence: Angiotensin-converting enzyme 2 coated nanoparticles containing respiratory masks, chewing gums and nasal filters may be used for protection against COVID-19 infection

text: • World has encountered a novel pandemic called as COVID-19. • All people need protective items such as masks and gloves worldwide. • Preventing COVID-19 infection has become the most important issue. • ACE2 containing nanomaterials may be used in the respiratory masks, gloves and clothes. • Using nanotechnology to prevent this pandemic may be hope for fighting against COVID-19.


title: Antigenic variation among murine coronaviruses: Evidence for polymorphism on the peplomer glycoprotein, E2

text: Abstract A panel of 28 monoclonal antibodies (MAb) against the structural proteins of murine hepatitis virus-4, strain JHM (MHV-4) was used in three antigen binding assays to determine the extent of antigenic homology among six strains of murine coronaviruses. The antigenic determinants studied were highly conserved on the E1 glycoproteins and nucleocapsid (N) proteins of all strains tested. In contrast, antigenic polymorphism was observed among the E2 glycoproteins. Of three previously described antigenic determinants against which neutralizing antibodies are directed, only one, termed A(E2), was conserved on all strains. Antigenic site B(E2) was found only on the strongly neurotropic MHV-4 and site C(E2) was present on the virulent MHV-4 and MHV-3 (hepatotropic) strains, but absent on the weakly pathogenic MHV-A59, MHV-1 and MHV-S strains. Four non-neutralizing antibodies against at least one topographically distinct antigenic determinant, which we previously designated D(E2), gave binding patterns consistent with two distinct sites. One of these was present on all MHV strains tested and the other was present on all strains except MHV-S. These non-neutralizing antigenic sites were redesignated E(E2) and D(E2) respectively.


Staying Safe, Caring for Each Other, and Moving the Needle-Together.


title: Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival

text: PURPOSE OF THE REVIEW: The ongoing outbreak of novel coronavirus pneumonia (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) in China is lifting widespread concerns. Thus, therapeutic options are urgently needed, and will be discussed in this review. RECENT FINDINGS: Iron-containing enzymes are required for viruses most likely including coronaviruses (CoVs) to complete their replication process. Moreover, poor prognosis occurred in the conditions of iron overload for patients upon infections of viruses. Thus, limiting iron represents a promising adjuvant strategy in treating viral infection through oral uptake or venous injection of iron chelators, or through the manipulation of the key iron regulators. For example, treatment with iron chelator deferiprone has been shown to prolong the survival of acquired immunodeficiency syndrome (AIDS) patients. Increasing intracellular iron efflux via increasing iron exporter ferroportin expression also exhibits antiviral effect on human immunodeficiency virus (HIV). The implications of other metals besides iron are also briefly discussed. SUMMARY: For even though we know little about iron regulation in COVID-19 patients thus far, it could be deduced from other viral infections that iron chelation might be an alternative beneficial adjuvant in treating COVID-19.


title: The association between vitamin D status and infectious diseases of the respiratory system in infancy and childhood

text: PURPOSE: Respiratory tract infections (RTIs) are a major cause of illness worldwide and the most common cause of hospitalization for pneumonia and bronchiolitis. These two diseases are the leading causes of morbidity and mortality among children under 5 years of age. Vitamin D is believed to have immunomodulatory effects on the innate and adaptive immune systems by modulating the expression of antimicrobial peptides, like cathelicidin, in response to both viral and bacterial stimuli. The aim of this review is to summarize the more recently published data with regard to potential associations of 25-hydroxyvitamin D [25(OH)D] with infectious respiratory tract diseases of childhood and the possible health benefits from vitamin D supplementation. METHODS: The literature search was conducted by using the PubMed, Scopus, and Google Scholar databases, with the following keywords: vitamin D, respiratory tract infection, tuberculosis, influenza, infancy, and childhood. RESULTS: Several studies have identified links between inadequate 25(OH)D concentrations and the development of upper or lower respiratory tract infections in infants and young children. Some of them also suggest that intervention with vitamin D supplements could decrease both child morbidity and mortality from such causes. CONCLUSIONS: Most studies agree in that decreased vitamin D concentrations are prevalent among most infants and children with RTIs. Also, normal to high-serum 25(OH)D appears to have some beneficial influence on the incidence and severity of some, but not all, types of these infections. However, studies with vitamin D supplementation revealed conflicting results as to whether supplementation may be of benefit, and at what doses.


title: Chapter 4 Biology and Diseases of Rats

text: The laboratory rat, Rattus norvegicus, is within the order Rodentia and family Muridae. The genus Rattus contains at least 56 species (retrieved January 28, 2014, from the Integrated Taxonomic Information System online database http://www.itis.gov); however, the Norway rat, R. norvegicus, and the black rat, R. rattus, are the two species most commonly associated with the genus. Rattus rattus preceded R. norvegicus in migration from Asia to Europe and the Americas by several hundred years. The former species reached Europe in the 12th century, and the Americas in the 16th century; whereas, R. norvegicus emerged in the 18th century in Europe and in the 19th century in the Western Hemisphere. Globally, the Norway rat has largely displaced the black rat, probably because of the Norway rat’s larger size and aggressiveness. The domestication and introduction of the albino R. norvegicus is rooted by its use in Europe and America in the 1800s as prey for a sport (rat baiting) in which individuals would wager on which terrier dog would most swiftly kill the largest number of rats confined to a pit. Because of the large numbers of rats needed for this sport, wild rats were purpose-bred, and albinos were selected out by some people as a hobby (Robinson, 1965; Mayhew, 1851).


Mayo Clinic Proceedings 2004: A View of the Present, a Peek at the Future


From SARS to the stars


title: Estimating employment from energy-efficiency investments

text: We develop a methodology for estimating the number and types of jobs that would result from investments in energy efficiency in homes, businesses, and industry. The methodology involves the development of input-output (I-O) bills of goods that characterize how energy-efficiency funds would be spent across sectors of the economy. The methodology builds on and adds greater articulation to the research conducted in prior studies of U.S. energy-efficiency policies. • The first two steps involve estimating the magnitude of investments in energy-efficient technologies and systems required to produce a unit of energy consumption reduction, and then identifying how these investments are expensed across the broad investment categories, which creates the preliminary “bills of goods” for investments in energy efficiency in homes, businesses, and industry. • The third step involves soliciting feedback on the preliminary bills of goods from experts in delivering and evaluating energy-efficiency programs, and then making necessary modifications. • In the final step we apply the input-output coefficients representing the bills of goods to estimate the direct, indirect and induced employment per million dollars of investment in energy efficiency.


SARS during Pregnancy, United States


title: COVID-19 and Cardiac Arrhythmias

text: BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVE: To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50±18 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 – 13.18]) and NSVT (OR 8.92 [95% CI 1.73 – 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 – 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 – 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.


title: O030 Evasion of the OAS-RNase L pathway by murine coronavirus ns2 protein is required for viral replication and hepatitis

text: Introduction The 2′,5′-oligoadenylate synthetase-ribonuclease L (OAS-RNase L) system is a potent IFN induced antiviral pathway. Following infection, IFNs induce a group of OAS genes whose products are activated by viral double-stranded RNA. OAS uses ATP to generate 2′,5′-linked oligoadenylates (2-5A). 2-5A binds to and activates the ubiquitous cellular endoribonuclease RNase L causing cleavages of single stranded regions of both viral and cellular RNA thus inhibiting viral replication. In addition, detection of the newly generated short RNAs by cellular pattern recognition receptors, MDA5 and RIG-I, further enhances IFN production and the ensuing antiviral activities. The intracellular concentration of 2-5A is believed to be the primary factor controlling RNase L activation. The liver contains abundant innate immune cells, which provide the first line of defense against pathogens. However, the factors that determine whether a virus can bypass this defense to access and infect the liver parenchyma are not well understood. The murine coronavirus, mouse hepatitis virus (MHV), strain A59, infection of mice provides a model for virus induced hepatitis. The MHV accessory protein, ns2, antagonizes the type I IFN response in macrophages and promotes the induction of hepatitis. Here we will describe how the ns2 protein facilitates the development of viral hepatitis by blocking OAS-RNase L pathway. Methods Bone marrow macrophages (BMM) from wild type (wt) and RNase L−/− mice were infected with A59 and ns2 mutant MHV. Viral titers were determined by plaque assays. RNase L activity was monitored by rRNA integrity in RNA chips. Intracellular levels of 2-5A were measured using RNase L activation assays. Effects of ns2 on 2-5A levels in cells were determined by transfecting ns2 or mutant ns2 cDNAs into HEK-293T cells. Recombinant ns2 and mutant ns2H126R proteins were purified and incubated with 2-5A in vitro and the 2-5A breakdown products were measured by HPLC. Hepatitis was determined by histology following inoculation A59 or ns2 mutant MHV into wt and RNase L−/− mice. Results We found evidence for a new molecular mechanism of subversion of the RNase L pathway in macrophages that regulates acute hepatitis during MHV infection. Coronavirus ns2 belongs to the LigT-like protein family, within the 2H phosphoesterase superfamily, some of which possess cyclophosphodiesterase activity (CPD). We have found that ns2 is not a CPD, but instead is a 2′,5′-phosphodiesterase (PDE) that cleaves, and thus eliminates 2-5A, the activator of RNase L. We observed that ns2 blocks the IFN inducible OAS-RNase L pathway to facilitate hepatitis development. Ns2 prevents activation of RNase L and consequently limits viral RNA degradation. An ns2 mutant virus was unable to replicate in the liver or induce hepatitis in wt mice, but was highly pathogenic in RNase L−/− mice. Thus, RNase L is a critical cellular factor for protection against viral infection of the liver and the resulting hepatitis. Conclusion MHV accessory protein ns2 is a 2′,5′-PDE which degrades 2-5A and limits RNase L activation thus facilitating virus-induced hepatitis in mice.


title: Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L

text: Abstract RNase L is a cellular endoribonuclease that is activated by 2′,5′-linked oligoadenylates (2–5A), which are unique and specific ligands synthesized by a family of interferon-inducible, dsRNA-activated enzymes named oligoadenylate synthetases. In the typical antiviral pathway, activated RNase L degrades viral and cellular RNAs, thus limiting viral replication and spread. Although the antiviral activity of RNase L has been demonstrated for several RNA viruses, there is little evidence regarding its role against DNA viruses. In the present study, the potential antiviral activity of RNase L against hepatitis B virus (HBV) was explored utilizing the recently reported infection protocol based on human hepatoma HepG2 cells stably complemented with the virus entry factor NTCP. Viral replication and expression in this cell type was markedly inhibited by poly(I:C)- or 2–5A-mediated activation of RNase L; however, the inhibition was significantly reversed by RNase L knockdown. Further analysis in HBV1.2-transfected Huh-7 hepatoma cells indicated that the antiviral activity of RNase L depends on its ribonuclease function. We also provide evidence for the specific roles of OAS family members in this process. These results suggest that HBV replication can be regulated through interferon-mediated RNA decay pathways and that activation of these host antiviral factors may represent a novel therapeutic strategy for HBV infection.


title: Human Papillomavirus and carcinogenesis: Novel mechanisms of cell communication involving extracellular vesicles

text: Abstract A small group of mucosal Human Papillomaviruses are the causative agents of cervical cancer and are also associated with other types of cancers. Certain cutaneous Human Papillomaviruses seem to have a role as co-factors in the UV-induced carcinogenesis of the skin. The main mechanism of the tumorigenesis induced by Human Papillomaviruses is linked to the transforming activity of the viral E6 and E7 oncoproteins. However, other mechanisms, such as the gene expression control by specific microRNAs expression and deregulation of immune inflammatory mediators, may be important in the process of transformation. In this context, the release of Extracellular Vesicles with a specific cargo (microRNAs involved in tumorigenesis, mRNAs of viral oncoproteins, cytokines, chemokines) appears to play a key role.


docid: ijxsoohh

title: Fulminant Cerebral Edema as a Lethal Manifestation of COVID-19

text: The contribution of neurological symptomatology to morbidity and mortality after infection with Severe Acute Respiratory Syndrome-associated Coronavirus (SARS CoV II), is ill-defined. We hereby present a case of a 57-year old male patient, in excellent physical condition, who was admitted to the Intensive Care Unit (ICU), with respiratory distress duo to SARS CoV II-induced bilateral pneumonia. After two weeks at the ICU, with respiratory conditions improving, the patient developed lethal cerebral edema. This case advocates regular wake-up calls in Coronavirus disease 2019 (COVID-19) patients for neurological (radiological) evaluation, to provide rapid diagnosis and a therapeutic window for fulminant central nervous system complications.


title: Concept learning via granular computing: A cognitive viewpoint

text: Abstract Concepts are the most fundamental units of cognition in philosophy and how to learn concepts from various aspects in the real world is the main concern within the domain of conceptual knowledge presentation and processing. In order to improve efficiency and flexibility of concept learning, in this paper we discuss concept learning via granular computing from the point of view of cognitive computing. More precisely, cognitive mechanism of forming concepts is analyzed based on the principles from philosophy and cognitive psychology, including how to model concept-forming cognitive operators, define cognitive concepts and establish cognitive concept structure. Granular computing is then combined with the cognitive concept structure to improve efficiency of concept learning. Furthermore, we put forward a cognitive computing system which is the initial environment to learn composite concepts and can integrate past experiences into itself for enhancing flexibility of concept learning. Also, we investigate cognitive processes whose aims are to deal with the problem of learning one exact or two approximate cognitive concepts from a given object set, attribute set or pair of object and attribute sets.


title: Effects of pay-for-performance system on tuberculosis default cases control and treatment in Taiwan

text: Summary Objectives In order to make tuberculosis (TB) treatment more effective and to lower the default rate of the disease, the Bureau of National Health Insurance (BNHI) in Taiwan implemented the “pay-for-performance on Tuberculosis” program (P4P on TB) in 2004. The purpose of this study is to investigate the effectiveness of the P4P system in terms of default rate. Methods This is a retrospective study. National Health Insurance Research Datasets in Taiwan from 2002 to 2005 has been used for the study. The study compared the differences of TB default rate before and after the implementation of P4P program, between participating and non-participating hospitals, and between P4P hospitals with and without case managers. Furthermore, logistic regression analysis was conducted to explore the related factors influencing TB patients default treatment after TB detected. Results The treatment default rate after “P4P on TB” was 11.37% compared with the 15.56% before “P4P on TB” implementation. The treatment default rate in P4P hospitals was 10.67% compared to 12.7% in non-P4P hospitals. In addition, the default rate was 10.4% in hospitals with case managers compared with 12.68% in hospitals without case managers. Conclusions The results of the study showed that “P4P on TB” program improved the treatment default rate for TB patients. In addition, case managers improved the treatment outcome in controlling patients’ default rate.


title: Cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape codon usage bias in coronaviruses

text: Abstract Using the complete genome sequences of 19 coronavirus genomes, we analyzed the codon usage bias, dinucleotide relative abundance and cytosine deamination in coronavirus genomes. Of the eight codons that contain CpG, six were markedly suppressed. The mean NNU/NNC ratio of the six amino acids using either NNC or NNU as codon is 3.262, suggesting cytosine deamination. Among the 16 dinucleotides, CpG was most markedly suppressed (mean relative abundance 0.509). No correlation was observed between CpG abundance and mean NNU/NNC ratio. Among the 19 coronaviruses, CoV-HKU1 showed the most extreme codon usage bias and extremely high NNU/NNC ratio of 8.835. Cytosine deamination and selection of CpG suppressed clones by the immune system are the two major independent biochemical and biological selective forces that shape codon usage bias in coronavirus genomes. The underlying mechanism for the extreme codon usage bias, cytosine deamination and G+C content in CoV-HKU1 warrants further studies.


title: A marine-sourced fucoidan solution inhibits Toll-like-receptor-3-induced cytokine release by human bronchial epithelial cells

text: Abstract Fucoidans are sulfated polysaccharides from brown algae, known to have immunomodulatory activity. Their effects on the response of airway epithelial cells to Toll-like receptor 3 (TLR3) stimulation have not been characterized. Our objective was to evaluate the effects of a marine-sourced fucoidan solution (MFS) on the TLR3-induced expression and/or production of cytokines and prostaglandin by human primary bronchial epithelial cells as a model of the airway epithelium. The cells were incubated with MFS in the presence or absence of Poly(I:C) (a TLR3 agonist that mimics viral RNA). Cytokine expression and production were assessed using RT-qPCR and ELISA. The expression of cyclooxygenase-2 and the production of prostaglandin E2 were also measured. Relative to control, exposure to MFS was associated with lower Poly(I:C)-induced mRNA expression of various cytokines and chemokines, and lower COX-2 production. The MFS inhibited the production of some cytokines (IL-1α, IL-1β, TNFα, and IL-6), chemokines (CCL5, CCL22, CXCL1, CXCL5 and CXCL8) and prostaglandin E2 but did not alter the production of IL-12/25, CCL2 and CCL20. At clinically relevant concentrations, the MFS inhibited the TLR3-mediated production of inflammatory mediators by human primary bronchial epithelial cells - suggesting that locally applied MFS might help to reduce airway inflammation in viral infections.


title: Clinical and economical impact of multiplex respiratory virus assays

text: Abstract During the last decade, a variety of molecular assays targeting respiratory viruses have been developed and commercialized. Therefore, multiplex PCR are increasingly used in everyday clinical practice. This improves our understanding of respiratory virus epidemiology and enhances our concerns about their clinical impact in specific patient populations. However, questions remain regarding cost-effectiveness of performing these diagnostic tests in routine and their real impact on patient care. This article will review available data and highlight unresolved questions about cost-effectiveness, infection control, clinical utility and public health impact of multiplex respiratory virus assays.


title: Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27

text: The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.


docid: ymcqkofq

title: Nanopore sequencing: a rapid solution for infectious disease epidemics


title: The microarray technology: facts and controversies

text: Molecular diagnostic techniques for viral testing have undergone rapid development in recent years. They are becoming more widely used than the classical virological assays in the majority of clinical virology laboratories, and now represent a new method for the diagnosis of human viral infections. Recently, new techniques based on multiplex RT-PCR amplification followed by microarray analysis have been developed and evaluated. On the basis of amplification of viral genome-specific fragments by multiplex RT-PCR and their subsequent detection via hybridization with microorganism-specific binding probes on solid surfaces, they allow simultaneous detection and identification of multiple viruses in a single clinical sample. The management of viral central nervous system and respiratory tract infections currently represents the two main applications of the microarrays in routine virological practice. Microarrays have shown reliable results in comparison with those of referenced (RT)-PCR assays, and appear to be of major interest for the detection of a broad range of respiratory and neurotropic viruses, assessment of the pathogenicity of newly discovered or neglected viruses, and identification of multiple viral infections in clinical samples. Despite several limitations observed during the different studies performed, this new technology might improve the clinical management of patients by enlarging the range of the viruses detected, in particular in cases of severe infections leading to patient hospitalization in the intensive-care unit. They might also help in the prevention of nosocomial transmission in hospital departments by contributing to the development of new epidemiological surveillance systems for viral infections.


title: Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community

text: An encephalitis outbreak was investigated in Faridpur District, Bangladesh, in April–May 2004 to determine the cause of the outbreak and risk factors for disease. Biologic specimens were tested for Nipah virus. Surfaces were evaluated for Nipah virus contamination by using reverse transcription–PCR (RT-PCR). Thirty-six cases of Nipah virus illness were identified; 75% of case-patients died. Multiple peaks of illness occurred, and 33 case-patients had close contact with another Nipah virus patient before their illness. Results from a case-control study showed that contact with 1 patient carried the highest risk for infection (odds ratio 6.7, 95% confidence interval 2.9–16.8, p<0.001). RT-PCR testing of environmental samples confirmed Nipah virus contamination of hospital surfaces. This investigation provides evidence for person-to-person transmission of Nipah virus. Capacity for person-to-person transmission increases the potential for wider spread of this highly lethal pathogen and highlights the need for infection control strategies for resource-poor settings.