niryuu/sni-each-converted huggingface dataset:
The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors-proven safe and successful in veterinary vaccine applications-are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).
Output: Multivalent and Multipathogen Viral Vector Vaccines
Aims: We undertook this study to define the incidence of toxigenic Clostridium difficile in our hospital and to characterise the isolates. Methods: All unformed stool was tested for the presence of Toxin A (TcdA) and Toxin B (TcdB), and cultured for C. difficile. Culture filtrates were also tested for TcdA and TcdB. Detection of tcdA and tcdB genes was carried out for A 2 B + strains by polymerase chain reaction (PCR).The minimum inhibitory concentrations (MICs) of metronidazole, vancomycin and clindamycin for all isolates were tested using the Etest. PCR ribotyping was carried out on all isolates. Results: The incidence of Clostridium difficile associated disease (CDAD) was 3.2 cases per 1000 admissions or discharges and 53.8 cases per 100 000 patient days. Most cases occurred in renal and haematology patients. CDAD was more common in patients aged over 50 years and of male gender. The Indian population was under-represented. Fourteen (11.8%) isolates were A 2 B + . All strains were susceptible to metronidazole but one strain showed intermediate resistance to vancomycin. Only 12.8% of the isolates were susceptible to clindamycin. Thirty-five isolates had PCR ribotype A, of which 29 (83%) had a clindamycin MIC .256 mg/L. Thirty-three had PCR ribotype B, of which only one (3%) had a clindamycin MIC .256 mg/L. The 14 A 2 B + strains were all PCR ribotype C, and had a range of MICs for clindamycin from 2 to .256 mg/L. Conclusions: The incidence of CDAD in our hospital is relatively low. Isolates remain susceptible to metronidazole and vancomycin.
Output: Epidemiology of Clostridium difficile infection in a large teaching hospital in Singapore
Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.
Output: Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus
Bronchiolitis; Human bocavirus; Human metapneumovirus; Respiratory syncytial virus; Taiwan Purpose: Viral etiology of bronchiolitis in children in Taiwan has been fragmentary. We conducted a prospective study to figure out the viral epidemiology of bronchiolitis in Taiwan. Materials and methods: From January 2009 to March 2011, a total of 113 children with bronchiolitis, aged <2 years, hospitalized in Chang Gung Children's Hospital were randomly selected for viral etiology investigation. Nasopharyngeal aspirates were obtained from each case and sent for viral detection by tissue culture, antigen test, and polymerase chain reaction. Results: A total of 120 viruses were detected from 113 children. Positive viral etiology was identified in 86 (76%) children. Mixed viral pathogens were found in 28 cases (25%). Respiratory syncytial virus (RSV) was the most common pathogen and was identified in 43.4% of the cases. Human bocavirus (hBoV) was the second most common identified virus (in 19.5%), followed by human metapneumovirus (hMPV), rhinovirus, influenza viruses, and coronavirus OC43. In terms of clinical characteristics, no significant difference was found among the children with bronchiolitis either caused by different single or mixed viral infection. Conclusion: RSV was the most common etiologic agent for children with bronchiolitis in Taiwan. Newly identified viruses, including hMPV and hBoV, were also among the common causative agents. Clinical characteristics were not significantly different among the children with bronchiolitis caused by different viruses.
Output: Viral etiology of bronchiolitis among pediatric inpatients in northern Taiwan with emphasis on newly identified respiratory viruses
In the USA, infectious diseases continue to exact a substantial toll on health and health-care resources. Endemic diseases such as chronic hepatitis, HIV, and other sexually transmitted infections aff ect millions of individuals and widen health disparities. Additional concerns include health-care-associated and foodborne infections-both of which have been targets of broad prevention eff orts, with success in some areas, yet major challenges remain. Although substantial progress in reduction of the burden of vaccine-preventable diseases has been made, continued cases and outbreaks of these diseases persist, driven by various contributing factors. Worldwide, emerging and reemerging infections continue to challenge prevention and control strategies while the growing problem of antimicrobial resistance needs urgent action. An important priority for control of infectious disease is to ensure that scientifi c and technological advances in molecular diagnostics and bioinformatics are well integrated into public health. Broad and diverse partnerships across governments, health care, academia, and industry, and with the public, are essential to eff ectively reduce the burden of infectious diseases.
Output: The Health of Americans 2 Challenges of infectious diseases in the USA
We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.
Output: Kawasaki syndrome and concurrent Coxsackie virus B3 infection
Transmission electron microscopy has had a profound impact on our knowledge and understanding of viruses and bacteria. The 1000-fold improvement in resolution provided by electron microscopy (EM) has allowed visualization of viruses, the existence of which had previously only been suspected as the causative agents of transmissible infectious disease. Viruses are grouped into families based on their morphology. Viruses from different families look different and these morphological variances are the basis for identification of viruses by EM. Electron microscopy initially came to prominence in diagnostic microbiology in the late 1960s when it was used in the rapid diagnosis of smallpox, by differentiating, on a morphological basis, poxviruses from the less problematic herpesviruses in skin lesions. Subsequently, the technique was employed in the diagnosis of other viral infections, such as hepatitis B and parvovirus B19. Electron microscopy has led to the discovery of many new viruses, most notably the various viruses associated with gastroenteritis, for which it remained the principal diagnostic method until fairly recent times. Development of molecular techniques, which offer greater sensitivity and often the capacity to easily process large numbers of samples, has replaced EM in many areas of diagnostic virology. Hence the role of EM in clinical virology is evolving with less emphasis on diagnosis and more on research, although this is likely only to be undertaken in specialist centres. However, EM still offers tremendous advantages to the microbiologist, both in the speed of diagnosis and the potential for detecting, by a single test, any viral pathogen or even multiple pathogens present within a sample. There is continuing use of EM for the investigation of new and emerging agents, such as SARS and human monkeypox virus. Furthermore, EM forms a vital part of the national emergency response programme of many countries and will provide a frontline diagnostic service in the event of a bioterrorism incident, particularly in the scenario of a deliberate release of smallpox virus. In the field of bacteriology, EM is of little use diagnostically, although some bacterial pathogens can be identified in biopsy material processed for EM examination. Electron microscopy has been used, however, to elucidate the structure and function of many bacterial features, such as flagellae, fimbriae and spores and in the study of bacteriophages. The combined use of EM and gold-labelled antibodies provides a powerful tool for the ultrastructural localisation of bacterial and viral antigens. q
Output: Application of transmission electron microscopy to the clinical study of viral and bacterial infections: Present and future
Objective: Healthcare providers in emergency departments should wear respirators for infection protection. However, the wearer's vigorous movements during cardiopulmonary resuscitation may affect the protective performance of the respirator. Herein, we aimed to assess the effects of chest compressions (CCs) on the protective performance of respirators. Methods: This crossover study evaluated 30 healthcare providers from 1 emergency department who performed CC with real-time feedback. The first, second, and third groups started with a cup-type, fold-type, and valve-type respirator, respectively, after which the respirators were randomized for each group. The fit factors were measured using a quantitative fit testing device before and during the CC in each experiment. The protection rate was defined as the proportion of respirators achieving a fit factor ≥100. Results: The fold-type respirator had a significantly greater protection rate at baseline (100.0% ± 0.0%) compared to the cup-type (73.6% ± 39.6%, P = .003) and valve-type respirators (87.5% ± 30.3%, P = .012). During the CC, the fit factor values significantly decreased for the cup-type (44.9% ± 42.8%, P < .001) and valve-type respirators (59.5% ± 41.7%, P = .002), but not for the fold-type respirator (93.2% ± 21.7%, P = .095). Conclusions: The protective performances of respirators may be influenced by CC. Healthcare providers should identify the respirator that provides the best fit for their intended tasks. Abbreviations: CC = Chest compression, CPR = Cardiopulmonary resuscitation, MERS = Middle East Respiratory Syndrome, NIOSH = National Institute for Occupational Safety and Health.
Output: Comparing the protective performances of 3 types of N95 filtering facepiece respirators during chest compressions A randomized simulation study
Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission. Despite the notoriety of ebolaviruses, particularly Ebola virus (EBOV), as prominent viral hemorrhagic fever agents, and the international concern regarding Ebola virus disease (EVD) outbreaks, very little is known about the pathophysiology of EVD in humans and, in particular, about the human immune correlates of survival and immune memory. This lack of basic knowledge about physiological characteristics of EVD is probably attributable to the dearth of clinical and laboratory data gathered from past outbreaks. The unprecedented magnitude of the EVD epidemic that occurred in West Africa from 2013 to 2016 has allowed, for the first time, evaluation of clinical, epidemiological, and immunological parameters in a significant number of patients using state-of-the-art laboratory equipment. This review will summarize the data from the literature regarding human pathophysiologic and immunologic responses to filoviral infection.
Output: Ebola Virus Disease in Humans: Pathophysiology and Immunity
This paper describes the isolation of porcine epidemic diarrhea (PED) virus in Vero and porcine cell cultures, and the in¯uence of age on disease in experimental infection. PED virus was isolated from the small intestine of piglets inoculated with PED samples and cultured in Vero, porcine bladder and kidney cells propagated in collagen-coated tissue culture plates in maintenance medium (MM) containing trypsin. In porcine bladder and kidney cell cultures inoculated with isolated PED virus, cytopathic effects (CPE) including cell fusion were detected. Speci®c brilliant¯uorescence was observed in the cytoplasm of these cells. Two-and 7-day old, and 2-, 4-, 8-and 12-week old speci®c pathogen-free (SPF) pigs were orally inoculated with PED virus isolated from an outbreak. All 2-and 7-day old pigs inoculated developed severe watery diarrhea from post-inoculation day (PID) 1 and died between PID 3 and 4. Although three of ®ve 2-week old pigs developed diarrhea on PID 1±4, they eventually recovered. In the 4-week old group, three of ®ve pigs had mild diarrhea for 1±2 days. None of the 8-and 12-week old pigs showed any clinical signs. Antibodies against PED virus were detected in all surviving pigs by virus neutralization (VN) test and immuno¯uorescence assay (IFA). Therefore, there is an age-dependent resistance to pathogenic PED virus infection in pigs. #
Output: Isolation of porcine epidemic diarrhea virus in porcine cell cultures and experimental infection of pigs of different ages
In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV.
Output: Development of a Poliovirus Neutralization Test with Poliovirus Pseudovirus for Measurement of Neutralizing Antibody Titer in Human Serum ᰔ Downloaded from
Transcriptomics has the potential to discover new RNA virus genomes by sequencing total intracellular RNA pools. In this study, we have searched publicly available transcriptomes for sequences similar to viruses of the Nidovirales order. We report two potential nidovirus genomes, a highly divergent 35.9 kb likely complete genome from the California sea hare Aplysia californica, which we assign to a nidovirus named Aplysia abyssovirus 1 (AAbV), and a coronavirus-like 22.3 kb partial genome from the ornamented pygmy frog Microhyla fissipes, which we assign to a nidovirus named Microhyla alphaletovirus 1 (MLeV). AAbV was shown to encode a functional main proteinase, and a translational readthrough signal. Phylogenetic analysis suggested that AAbV represents a new family, proposed here as Abyssoviridae. MLeV represents a sister group to the other known coronaviruses. The importance of MLeV and AAbV for understanding nidovirus evolution, and the origin of terrestrial nidoviruses are discussed.
Output: Description and initial characterization of metatranscriptomic nidovirus-like genomes from the proposed new family Abyssoviridae, and from a sister group to the Coronavirinae, the proposed genus Alphaletovirus
The concept of new and emerging diseases has captured the public interest and has revitalized the public health infectious disease research community. This interest has also resulted in competition for funding and turf wars between animal health and public health scientists and public officials and, in some cases, has delayed and hindered progress toward effective prevention, control and biodefense. There is a dynamic list of outbreaks causing substantial morbidity and mortality in humans and often in the reservoir animal species. Some agents have the potential to grow into major epidemics. There are many determinants that influence the emergence of diseases of concern that require the use of current understanding of the nature of agent persistence and spread. Additional factors that are global must be added to plans for prevention and control. To this complex mix has been added the potential for accidental or malicious release of agents. The nature of emerging infectious agents and their impact is largely unpredictable. Models that strive to predict the dynamics of agents may be useful but can also blind us to increasing disease risks if it does not match a specific model. Field investigations of early events will be critical and should drive prevention and control actions. Many disease agents have developed strategies to overcome extremes of reservoir qualities like population size and density. Every infectious agent spreads easier when its hosts are closer together. Zoonoses must be dealt with at the interface of human and animal health by all available information. Lessons learned from the emergence of and response to agents like West Nile virus, H5N1 avian influenza, SARS and bovine spongiform encephalopathy, the cause of new-variant Creutzfeldt-Jakob disease in humans, must be used to create better plans for response and meet the challenge for public health and biodefense. #
Output: Emerging zoonoses: The challenge for public health and biodefense §
Background: Cystic fibrosis is a degenerative disease characterized by progressive epithelial secretory gland dysfunction associated with repeated respiratory infections. Bacterial infections are very frequent in children with cystic fibrosis, but because rapid Methods: for screening for the wide variety of potentially involved viruses were unavailable until recently, the frequency of viral presence is unknown. Multiplex PCR enables screening for many viruses involved in respiratory infections. Objectives: This study aimed to evaluate the frequency of viruses and bacteria in respiratory specimens from children with cystic fibrosis and to clarify the incidence and characteristics (seasonality and age of patients) of different viruses detected in children with cystic fibrosis. Study design: In this 2-year prospective study, we obtained paired nasopharyngeal-swab and sputum specimens from children with cystic fibrosis during clinical respiratory examinations separated by at least 14 days. We analyzed viruses in nasopharyngeal-swab specimens with multiplex PCR and bacteria in sputum with standard methods. Results: We analyzed 368 paired specimens from 33 children. We detected viruses in 154 (41.8%) and bacteria in 132 (35.9%). Bacteria were commoner in spring and summer; viruses were commoner in autumn and winter. In every season, Staphylococcus aureus was the commonest bacteria and rhinovirus was the commonest virus. Nearly all infections with Haemophilus influenzae occurred in autumn and winter. Viruses were more prevalent in children <5 years old, and bacteria were more prevalent in children ≥12 years old. Conclusions: Multiplex PCR screening for respiratory viruses is feasible in children with cystic fibrosis; the clinical implications of screening warrant further study.
Output: Multiplex PCR reveals that viruses are more frequent than bacteria in children with cystic fibrosis
This work investigated the link between the type of treatment and the clinical evolution of lambs suffering from diarrhoea attributed to non-enterotoxigenic Escherichia coli. Two hundred and forty scouring lambs, and 25 healthy lambs selected as control, were used in this trial. The faecal samples from the scouring lambs were positive to non-enterotoxigenic E. coli. All the scouring lambs received supportive care and they were randomly allotted to two groups of 120 animals (treated group and untreated group). The lambs in the treated group were given two daily doses of 20 mg/kg live weight spectinomycin for 3 days, while the other group of lambs (untreated group) did not receive any antibiotic. Serum endotoxin was higher in the treated lambs. The combined infection of E. coli + Proteus mirabilis was the most frequent microbiological result in the deceased treated lambs, while the only enteric pathogen isolated in the untreated lambs submitted to necroscopy was E. coli. The pathological findings most commonly recorded in the untreated lambs were suggestive of a generalized inflammatory process attributed to colibacilosis, while the lesions in the treated lambs might correspond to an enterotoxoemic process. The overproduction of P. mirabilis might be consequence of the antibiotic treatment and it would be the most probable cause of the endotoxemia, the high mortality rate and the pathological findings in the treated lambs. Therefore, a supportive care without antibiotics does not lead to a poorer chance of survival in lambs with diarrhoea attributed to non-enterotoxigenic E. coli.
Output: Relationship between the treatment and the evolution of the clinical course in scouring Merino lambs from "La Serena" (Southwest Spain)
Background 3 In silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics 4 algorithms. Sequenced datasets include background organisms, creating ambiguity in the true 5 source organism for each read. Bacterial and viral datasets were created with even and staggered 6 coverage to evaluate organism identification, read mapping, and gene identification capabilities of 7 available algorithms. These truth datasets are provided as a resource for the development and 8 refinement of metagenomic algorithms. Algorithm performance on these truth datasets can inform 9 decision makers on strengths and weaknesses of available algorithms and how the results may be best 10 leveraged for bacterial and viral organism identification and characterization. 11 12 Source organisms were selected to mirror communities described in the Human Microbiome Project as 13 well as the emerging pathogens listed by the National Institute of Allergy and Infectious Diseases. The 14 six in silico datasets were used to evaluate the performance of six leading metagenomics algorithms: 15 MetaScope, Kraken, LMAT, MetaPhlAn, MetaCV, and MetaPhyler. 16 Results Algorithms were evaluated on runtime, true positive organisms identified to the genus and species 19 levels, false positive organisms identified to genus and species level, read mapping, relative abundance 20 estimation, and gene calling. No algorithm out performed the others in all categories, and the 21 algorithm or algorithms of choice strongly depends on analysis goals. MetaPhlAn excels for bacteria 22 and LMAT for viruses. The algorithms were ranked by overall performance using a normalized 23 weighted sum of the above metrics, and MetaScope emerged as the overall winner, followed by Kraken 24 and LMAT. 25 Conclusions 27 Simulated FASTQ datasets with well--characterized truth data about microbial community composition 28 reveal numerous insights about the relative strengths and weaknesses of the metagenomics algorithms 29 evaluated. The simulated datasets are available to download from the Sequence Read Archive 30 (SRP062063). 31 32
Output: Evaluating performance of metagenomic characterization algorithms using in silico datasets generated with FASTQSim
Sustainable development is forward-looking; it is a continuous mission for future developments of human society. A genuinely sustainable society is one that initiates developments in sustainable ways. The development of a genuinely sustainable society is supported by its citizens who think and act according to a recognized code of conduct -the sustainable culture. Similar to other forms of culture, sustainable culture of a society is not static, but changes over time. The changes found in a sustainable culture are reflections of the status of sustainability in a society and these changes should be measured from time to time. The resulting measurement gives very important information for decision-makers, in the government and in the private sector, to examine the magnitude of changes that have taken place in a given period of time. The results will also enable them to review and adjust policies in order to better accommodate changes according to the trends of society. This paper provides a method -the T-model, to investigate and measure the extent of change of sustainable culture through two extensive surveys among participants of the construction industry of Hong Kong. The change in sustainable culture is reflected by the change in attitude and practice among construction participants, this can be found in their performance in project development, design and construction operations. The data of these changes are collected and converted to numerical scores. The T-model synthesized these scores and revealed the change of sustainable culture within the specific study time frame.
Output: Cultural shift towards sustainability in the construction industry of Hong Kong
Introduction: Viruses are major aetiological agents of acute respiratory infection in young children. Although many studies have reported detection and analysis of respiratory viruses in sporadic cases, there have been few follow-up studies of individuals. The purpose of this study was to investigate the frequency of respiratory viral infections in a young child and to examine the duration of viral genome detection in clinical specimens. Case presentation: A total of 284 nasal swabs were collected during symptomatic (196 specimens) and asymptomatic (88 specimens) periods of respiratory symptoms from a young female child (from 4 months to 31 months of age, who was admitted to a nursery school at 9 months). Multiplex real-time PCR for 19 respiratory viruses or subtypes was performed. One hundred and ninety-eight of the tested specimens were virus positive (69.7 %) (symptomatic periods, 149/196, 76.0 %; asymptomatic periods, 49/88, 55.7 %). Rhinovirus was the most frequently detected (26 times). Long durations of detection were observed for human coronavirus NL63 (30 days), rhinovirus (28 days) and human bocavirus 1 (22 days). Conclusion: Young children living in a group context have a high risk of respiratory virus infections, especially rhinovirus. In some instances, viral genomes were detectable for about 1 month by PCR.
Output: Frequent respiratory viral infections in a young child in a 27-month follow-up study
To investigate the impact of inflammatory bowel disease (IBD) on α2-Heremans-Schmid Glycoprotein (AHSG/fetuin A) and potential associations with disease and patient characteristics. AHSG serum levels were determined in treatment-naïve newly-diagnosed patients, 96 with ulcerative colitis (UC), 84 with Crohn's disease (CD), 62 with diarrheapredominant or mixed irritable bowel syndrome (IBS, D-and M-types) and 180 healthy controls (HC), by an enzyme linked immunosorbent assay (ELISA). All patients were followed for a minimum period of 3 years at the Gastroenterology Department of the University Hospital of Larissa, Greece. C-reactive protein (CRP), anti-glycan antibodies, anti-Saccharomyces cerevisiae mannan antibodies IgG, anti-mannobioside carbohydrate antibodies IgG, anti-laminariobioside carbohydrate antibodies IgG and anti-chitobioside carbohydrate antibodies IgA were also determined via immunonephelometry and ELISA, respectively. The mean ± SE of serum AHSG, following adjustment for confounders, was 0.32 ± 0.02 g/L in IBD, 0.32 ± 0.03 g/L in CD and 0.34 ± 0.03 g/L in UC patients, significantly lower than in IBS patients (0.7 ± 0.018 g/L) and HC (0.71 ± 0.02 g/L) (P < 0.0001, in all cases). AHSG levels were comparable between the CD and UC groups. Based on AHSG levels IBD patients could be distinguished from HC with about 90% sensitivity and specificity. Further adjusted analysis verified the inverse association between AHSG and penetrating, as well as stricturing CD (partial correlation coefficient: -0.45 and -0.33, respectively) (P < 0.05). After adjusting for confounding factors, inverse correlations between AHSG and CRP and the need for anti-TNFα therapy or surgery, were found (partial correlation coefficients: -0.31, -0.33, -0.41, respectively, P < 0.05, in all cases). Finally, IBD individuals who were seropositive, for at least one marker, had AHSG levels falling within the two lower quartiles (OR = 2.86, 95%CI: 1.5-5.44, P < 0.001) while those with at least two serological markers positive exhibited AHSG concentrations within the lowest quartile (OR = 5.03, 95%CI: 2.07-12.21, P < 0.001), after adjusting for age, sex and smoking. AHSG can be used to distinguish between IBD and IBS patients or HC while at the same time "predicting" complicated disease behavior, need for therapy escalation and surgery. Moreover, AHSG may offer new insights into the pathogenesis of IBD, since it is involved in key processes.
Output: α2-Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease Basic Study
Loperamide is an antidiarrheal drug that targets μ-opioid receptors and calcium channels. A previous report demonstrated that loperamide induces autophagy and enhances antimicrobial activity towards M. tuberculosis in murine and human alveolar macrophages. The aim of this study was to evaluate the immunomodulatory effects of loperamide on macrophages with respect to cytokine and antimicrobial peptide production during mycobacterial infection. We infected monocyte-derived macrophages (macrophages) with M. tuberculosis H37Rv at a multiplicity of infection (MOI) of 5 and treated the cells with 3 μM loperamide. Cytokine production in the supernatants of 24-h cultures and gene expression of the cytokines TNFα, IL1β and IL10 and the antimicrobial peptides LL37 and bactericidal/permeability increasing protein (BPI) in the cell lysates was measured. Intracellular bacterial loads were evaluated by enumerating colony-forming units 3 days posttreatment for M. tuberculosis and 24 h posttreatment for M. smegmatis. We observed that loperamide exerted an immunomodulatory effect on TNFα production in human macrophages infected with M. tuberculosis and that these responses were independent of the bacteria, as they also occurred when macrophages were infected with M. smegmatis and to a lesser extent with M. bovis. In addition, antibacterial mechanisms triggered by loperamide induced a significant reduction in bacterial load and an upregulation of BPI and LL37 gene expression. Thus, our results show that loperamide exerts immunomodulatory effects, which supports its use for additional medical conditions other than diarrhea.
Output: Antimicrobial and immunomodulatory activity induced by loperamide in mycobacterial infections
16S rRNA gene is one of the preferred targets for resolving species phylogenesis issues in microbiological-related contexts. However, the identification of single-nucleotide variations capable of distinguishing a sequence among a set of homologous ones can be problematic. Here we present ORMA (Oligonucleotide Retrieving for Molecular Applications), a set of scripts for discriminating positions search and for performing the selection of high-quality oligonucleotide probes to be used in molecular applications. Two assays based on Ligase Detection Reaction (LDR) are presented. First, a new set of probe pairs on cyanobacteria 16S rRNA sequences of 18 different species was compared to that of a previous study. Then, a set of LDR probe pairs for the discrimination of 13 pathogens contaminating bovine milk was evaluated. The software determined more than 100 candidate probe pairs per dataset, from more than 300 16S rRNA sequences, in less than 5 min. Results demonstrated how ORMA improved the performance of the LDR assay on cyanobacteria, correctly identifying 12 out of 14 samples, and allowed the perfect discrimination among the 13 milk pathogenic-related species. ORMA represents a significant improvement from other contexts where enzyme-based techniques have been employed on already known mutations of a single base or on entire subsequences.
Output: ORMA: a tool for identification of species-specific variations in 16S rRNA gene and oligonucleotides design
Middle East Respiratory Syndrome (MERS), a pandemic threat to human beings, has aroused huge concern worldwide, but no bibliometric studies have been conducted on MERS research. The aim of this study was to map research productivity on the disease based on the articles indexed in PubMed. The articles related to MERS dated from 2012 to 2015 were retrieved from PubMed. The articles were classified into three categories according to their focus. Publication outputs were assessed and frequently used terms were mapped using the VOS viewer software. A total of 443 articles were included for analysis. They were published in 162 journals, with Journal of Virology being the most productive (44 articles; 9.9%) and by six types of organizations, with universities being the most productive (276 articles; 62.4%).The largest proportion of the articles focused on basic medical sciences and clinical studies (47.2%) and those on prevention and control ranked third (26.2%), with those on other focuses coming in between (26.6%). The articles on prevention and control had the highest mean rank for impact factor (IF) (226.34), followed by those on basic medical sciences and clinical studies (180.23) and those on other focuses (168.03). The mean rank differences were statistically significant (p = 0.000). Besides, "conronavirus", "case", "transmission" and "detection" were found to be the most frequently used terms. The findings of this first bibliometric study on MERS suggest that the prevention and control of the disease has become a big concern and related research should be strengthened.
Output: A Bibliometric Analysis of PubMed Literature on Middle East Respiratory Syndrome
The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.
Output: SARS -BEGINNING TO UNDERSTAND A NEW VIRUS
OBJECTIVE: To determine the frequency, etiology and impact of respiratory viral infection (RVI) on infants evaluated for late-onset sepsis (LOS), defined as sepsis occurring 472 h of life, in the neonatal intensive care unit. STUDY DESIGN: Prospective observational study conducted from 6 March 2014 to 3 May 2016 on infants evaluated for LOS. PCR viral panel performed on nasopharyngeal specimens among infants with clinical suspicion for RVI. Sequence analysis was performed to determine viral subtypes. Fisher's exact or χ 2 tests were done to determine the impact of RVI. RESULTS: During the 26-month study, there were 357 blood cultures obtained for LOS evaluations, 29 (8%) had a respiratory virus detected. Only 88 (25%) of infants evaluated for LOS also had clinical suspicion for a respiratory viral infection. RSV (14 of 29; 48%) was the predominant virus detected. Almost all infants (13 of 14; 93%) with RSV required increased respiratory support. Antimicrobial therapy was withheld or discontinued on most infants with a virus detected (18 of 29; 62%) and in the majority where there was no confirmed bacterial co-infection (18 of 20; 90%). CONCLUSION: The incidence of RVI in infants being evaluated for LOS is about 8%. RVI should be considered in LOS evaluation to prevent unnecessary antibiotic therapy.
Output: Incidence of respiratory viral infection in infants with respiratory symptoms evaluated for late-onset sepsis
Viruses of wild and domestic animals can infect humans in a process called zoonosis, and these events can give rise to explosive epidemics such as those caused by the HIV and Ebola viruses. While humans are constantly exposed to animal viruses, those that can successfully infect and transmit between humans are exceedingly rare. The key event in zoonosis is when an animal virus begins to replicate (one virion making many) in the first human subject. Only at this point will the animal virus first experience the selective environment of the human body, rendering possible viral adaptation and refinement for humans. In addition, appreciable viral titers in this first human may enable infection of a second, thus initiating selection for viral variants with increased capacity for spread. We assert that host genetics plays a critical role in defining which animal viruses in nature will achieve this key event of replication in a first human host. This is because animal viruses that pose the greatest risk to humans will have few (or no) genetic barriers to replicating themselves in human cells, thus requiring minimal mutations to make this jump. Only experimental virology provides a path to identifying animal viruses with the potential to replicate themselves in humans because this information will not be evident from viral sequencing data alone. Citation: Warren CJ, Sawyer SL (2019) How host genetics dictates successful viral zoonosis. PLoS Biol 17(4): e3000217. https://doi.
Output: How host genetics dictates successful viral zoonosis
G quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermo dynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conforma tional features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4 specific small molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweez ers, original chemical approaches, G4 detection in situ, in cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G quadruplexes.
Output: Structure, Properties, and Biological Relevance of the DNA and RNA G Quadruplexes: Overview 50 Years after Their Discovery
The current research presents the protein changes in plasma from healthy dairy cows and clinical mastitic cows using twodimensional gel electrophoresis (2-DE). After staining with silver nitrate and Coomassie Blue, differential expression proteins were detected by PDQuest 7.4 software, and then subjected to ion trap mass spectrometer equipped with a Surveyor HPLC System, differential spots of protein were identified. Three protein spots that originated from preparation gels were identified to be two proteins. Overall, haptoglobin precursor was up-regulated in cows infected with clinical mastitis and could be a mastitis-associated diagnostic marker, whereas SCGB 2A1 (secretoglobin, family 2A, member 1) was down-regulated protein. Plasma protein expression patterns were changed when cows were infected with mammary gland inflammation; it suggests that analysis of differential expression protein might be useful to clarify the mechanisms involved in the pathophysiology, and find new diagnostic markers of mastitis and potential protein targets for treatment.
Output: Comparative Proteomic Analysis of Plasma from Clinical Healthy Cows and Mastitic Cows
Background: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. Results: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of nonessential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries.
Output: Systematic Review of Economic Evaluations of Preparedness Strategies and Interventions against Influenza Pandemics
Background-Recently, several new human coronaviruses have been identified. Study design-A recombinant protein enzyme linked immunosorbent assay (ELISA) based on portions of the nucleocapsid protein of group I human coronaviruses was developed and was used to screen serum from 243 children and young adults. HCoV-229E, the percentages of seropositive individuals were 57.1% for infants < 2 months old; 38.9% for infants 2-3 months old; 4.7% for infants 4-5 months old; 42.9-50.0% for infants 6-12 months old; and 34.8-62.5% for individuals 1-20 years old. For HCoV-NL63, the percentages of seropositive individuals were 45.2% for infants < 2 months old; 11.1% for infants 2-3 months old; 4.7% for infants 4-5 months old; 28.6-40.0% for infants 6-12 months old; and 25.0-70.3% for individuals 1-20 years old. Conclusions-Infection with these viruses is common in childhood though the prevalence of these viruses may vary from year to year.
Output: Seroepidemiology of group I human coronaviruses in children
Undiagnosed cases of respiratory tract disease suspected of an infectious aetiology peak during the winter months. Since studies applying molecular diagnostic assays usually report reductions in the number of undiagnosed cases of infectious disease compared to traditional techniques, we applied PCR assays to investigate the role of two recently described viruses, namely human coronavirus (HCoV) HKU1 and human bocavirus (HBoV), in a hospital-based paediatric population. Both viruses were found among Australia children with upper or lower respiratory tract disease during the autumn and winter of 2004, contributing to 21.1% of all microbial diagnoses, with individual incidences of 3.1% (HCoV-HKU1) and 5.6% (HBoV) among 324 specimens. HBoV was found to coincide with another virus in more than half of all instances and displayed a single genetic lineage, whilst HCoV-HKU1 was more likely to occur in the absence of another microbe and strains could be divided into two genetic lineages which we propose be termed HCoV-HKU1 type A and type B. Children under the age of 2 years were most at risk of infection by these viruses which contribute significantly to the microbial burden among patients with respiratory tract disease during the colder months.
Output: Evidence of human coronavirus HKU1 and human bocavirus in Australian children