niryuu/sni-each-converted huggingface dataset:
N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state. Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state. The same effects were also observed in NB cell lines with and without N-myc amplification. Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions. Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc. Such changes involved ISGs with various functions. Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFNstimulated antiviral state. Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses.
Output: N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
Even though coronavirus infection of humans is not normally associated with severe diseases, the identification of the coronavirus responsible for the outbreak of severe acute respiratory syndrome showed that highly pathogenic coronaviruses can enter the human population. Shortly thereafter, in Holland in 2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month old infant suffering from respiratory symptoms. This virus has subsequently been identified in various countries, indicating a worldwide distribution. HCoV-NL63 has been shown to infect mainly children and the immunocommpromised, who presented with either mild upper respiratory symptoms (cough, fever and rhinorrhoea) or more serious lower respiratory tract involvement such as bronchiolitis and croup, which was observed mainly in younger children. In fact, HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases. This review summarizes recent findings of human coronavirus HCoV-NL63 infections, including isolation and identification, phylogeny and taxonomy, genome structure and transcriptional regulation, transmission and pathogenesis, and detection and diagnosis.
Output: Understanding Human Coronavirus HCoV-NL63
In this paper we present Gryphon, a hybrid agent-based stochastic modeling and simulation platform developed for characterizing the geographic spread of infectious diseases and the effects of interventions. We study both local and non-local transmission dynamics of stochastic simulations based on the published parameters and data for SARS. The results suggest that the expected numbers of infections and the timeline of control strategies predicted by our stochastic model are in reasonably good agreement with previous studies. These preliminary results indicate that Gryphon is able to characterize other future infectious diseases and identify endangered regions in advance.
Output: Gryphon: A Hybrid Agent-Based Modeling and Simulation Platform for Infectious Diseases
Background: Detection of respiratory viruses by time-resolved fluoroimmunoassay based on monoclonal antibodies were developed in our laboratories in the late 1980s and they have been successfully used in daily diagnosis for more than seven years. Later, similar Biotin-EIAs were developed but the sensitivities were unsatisfactory. Objectives: Further optimization of monoclonal Biotin-EIAs and comparison of the optimized assays with TR-FIAs. Study design: Variations in test format, diluents, incubation times and temperatures, and different monoclonal antibodies were tested, and the final comparisons were made with TR-FIA using stored nasopharyngeal aspirates. Results: The improvements in Biotin-EIA featured four changes which increased sensitivity in the assay: (a) test diluent contained diethylenetriamino-pentaacetic acid; (b) antigen and biotinylated detector antibody were added simultaneously; (c) reaction time was extended from 1 h at 37°C to overnight at 4°C; (d) from the thirteen monoclonal antibodies used in TR-FIA, ten were optimal also in Biotin-EIA, but in the parainfluenza 1 and 2 assays other monoclonals proved more sensitive. Out of 257 originally positive specimens tested in the comparison studies, 192 (74.7%) were again positive and 54 (21.0%) were negative in both assays; nine were negative in TR-FIA but positive in Biotin-EIA, while two specimens were negative in Biotin-EIA but positive in TR-FIA. The overall agreement between the two assays was 95.7%.
Output: Clinical and Diagnostic Virology Comparison of monoclonal biotin-avidin enzyme immunoassay and monoclonal time-resolved fluoroimmunoassay in detection of respiratory virus antigens
Background: Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data, we demonstrate one such approach. Using an ecological niche model (ENM) algorithm, we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important factors in determining its transmission. Methods: A literature review was performed and the geospatial coordinates of 87 molecularly confirmed VACV outbreaks in Brazil were identified. An ENM was generated using MaxENT software by combining principal component analysis results of 19 bioclim spatial layers, and 25 randomly selected subsets of the original list of 87 outbreaks. The final ENM predicted all areas where Brazilian outbreaks occurred, one out of five of the Colombian outbreak regions and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range. The analyses here provide a means by which to study patterns of an emerging infectious disease and identify regions that are potentially suitable for its transmission, in spite of the paucity of high-quality critical data. Policy and methods for the control of infectious diseases often use a reactionary model, addressing diseases only after significant impact on human health has ensued. The methodology used in the present work allows the identification of areas where disease is likely to appear, which could be used for directed intervention.
Output: Ecological niche modeling to determine potential niche of Vaccinia virus: a case only study
Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15 year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7-94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 beddays compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r −0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking.
Output: Benchmarking of antibiotic usage: An adjustment to reflect antibiotic stewardship program outcome in a hospital in Saudi Arabia
Background-The data on human rhinovirus (HRV), coronavirus (hCoV), bocavirus (hBoV), metapneumovirus (hMPV), Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis infections in children with cancer is limited. Methods-We sought to determine prospectively the prevalence of respiratory pathogens in these children, using multiplexed-PCR. Results-We enrolled 253 children with upper, or lower respiratory tract infection (URTI/LRTI) during a one year period. A respiratory virus was detected in 193 (76%) patients; 156 (81%) patients had URTI. Human rhinovirus was the most common virus detected in 97 (62%) and 24 (65%) patients with URTI and LRTI, respectively. Leukemia or lymphoma (LL) was the most common underlying diagnosis in 95 (49%) patients followed by solid tumor 47 (24%), posthematopoietic stem cell transplant (HCT) 28 (15%), and brain tumor in 23 (12%) patients. By multiple logistic regression analysis hBoV was the most commonly detected respiratory virus in patients with LRTI (P = 0.008; odds ratio, 4.52; 95% confidence interval, 1.48-13.79). Coinfection with more than 1 virus was present in 47 (24%) patients, and did not increase the risk for LRTI. Two (0.7%) patients succumbed to LRTI from parainfluenza virus (PIV)-3 and respiratory syncytial virus/HRV infection, respectively. C.pneumoniae and M.pneumoniae were detected in 4 and 3 patients, respectively. Conclusions-HRV was the most common virus detected in children with cancer and post-HCT hospitalized with an acute respiratory illness, and was not associated with increased morbidity. Prospective studies with viral load determination and asymptomatic controls are needed to study the association of these emerging respiratory viruses with LRTI in children with cancer and post-HCT.
Output: Prospective Detection of Respiratory Pathogens in Symptomatic Children with Cancer
Biological weapons achieve their intended target effects through the infectivity of disease-causing infectious agents. The ability to use biological agents in warfare is prohibited by the Biological and Toxin Weapon Convention. Bioterrorism is defined as the deliberate release of viruses, bacteria or other agents used to cause illness or death in people, but also in animals or plants. It is aimed at creating casualties, terror, societal disruption, or economic loss, inspired by ideological, religious or political beliefs. The success of bioterroristic attempts is defined by the measure of societal disruption and panic, and not necessarily by the sheer number of casualties. Thus, making only a few individuals ill by the use of crude methods may be sufficient, as long as it creates the impact that is aimed for. The assessment of bioterrorism threats and motives have been described before. Biocrime implies the use of a biological agent to kill or make ill a single individual or small group of individuals, motivated by revenge or the desire for monetary gain by extortion, rather than by political, ideological, religious or other beliefs. The likelihood of a successful bioterrorist attack is not very large, given the technical difficulties and constraints. However, even if the number of casualties is likely to be limited, the impact of a bioterrorist attack can still be high. Measures aimed at enhancing diagnostic and therapeutic capabilities and capacities alongside training and education will improve the ability of society to combat 'regular' infectious diseases outbreaks, as well as mitigating the effects of bioterrorist attacks.
Output: Biological warfare, bioterrorism, and biocrime
Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.
Output: Health system capacity in Sydney, Australia in the event of a biological attack with smallpox
In trial 1, phase 1, 48 male Holstein calves initially 2 to 4 d of age were transported 3.5 h to the research facility. Calves were randomly selected to either receive a s.c. injection of Zuprevo (Merck Animal Health, Summit, NJ; 4 mg of tildipirosin/kg of BW; TIL) the day after arrival (d 0) and again at weaning (d 42) or receive no injections (CON). Calves were fed 0.66 kg of milk replacer DM daily for 39 d and then 0.33 kg daily for 3 d. A starter was fed free choice for the 56 d of phase 1. In trial 1, phase 2, the same calves from phase 1 grouped by CON and TIL were moved to group pens (4 pens per treatment, 4 calves per pen) for the next 56 d. The starter was blended with 5% chopped grass hay and fed free choice. Trial 2 was similar to trial 1, phase 2 and used 48 two-month-old male Holstein calves. Calves were randomly selected to receive either a s.c. injection of Zuprevo (4 mg of tildipirosin/kg of BW; TIL) on d 0 or no injections (CON). In trial 1, phase 1, preweaning ADG and BCS change; postweaning starter intake and hip width change; overall starter intake, ADG, and hip width change; final hip width; and final BCS were greater for TIL than CON. During phase 2 of trial 1 and trial 2, calf ADG and hip width change were greater for TIL than CON. Overall, in transported Holstein calves, TIL improved ADG and structural growth by approximately 13%.
Output: Case Study: Control of respiratory disease in male Holstein calves with tildipirosin and effect on health and growth from 0 to 4 months of age
Despite the wide use of Caenorhabditis elegans as a model organism, the first virus naturally infecting this organism was not discovered until six years ago. The Orsay virus and its related nematode viruses have a positive-sense RNA genome, encoding three proteins: CP, RdRP, and a novel δ protein that shares no homology with any other proteins. δ can be expressed either as a free δ or a CP-δ fusion protein by ribosomal frameshift, but the structure and function of both δ and CP-δ remain unknown. Using a combination of electron microscopy, X-ray crystallography, computational and biophysical analyses, here we show that the Orsay δ protein forms a~420-Å long, pentameric fiber with an N-terminal α-helical bundle, a β-stranded filament in the middle, and a C-terminal head domain. The pentameric nature of the δ fiber has been independently confirmed by both mass spectrometry and analytical ultracentrifugation. Recombinant Orsay capsid containing CP-δ shows protruding long fibers with globular heads at the distal end. Mutant viruses with disrupted CP-δ fibers were generated by organism-based reverse genetics. These viruses were found to be either non-viable or with poor infectivity according to phenotypic and qRT-PCR analyses. Furthermore, addition of purified δ proteins to worm culture greatly reduced Orsay infectivity in a sequence-specific manner. Based on the structure resemblance between the Orsay CP-δ fiber and the fibers from reovirus and adenovirus, we propose that CP-δ functions as a cell attachment protein to mediate Orsay entry into worm intestine cells. Orsay, the only virus known to naturally infect the nematode Caenorhabditis elegans, expresses a capsid-δ fusion protein. We have demonstrated that the Orsay fusion protein is incorporated into Orsay capsid and forms a~420-Å long fiber protruding from the PLOS Pathogens |
Output: Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells
respiratory symptoms in adults in general practice. Family Practice 2004; 21: 317-323. Background. Community studies have shown that ~30% of patients with acute respiratory tract symptoms have no identifiable infective aetiology. This may not be applicable in general practice. Objective. The purpose of this study was to determine the infective aetiology in patients who presented to primary care doctors with acute respiratory symptoms. Methods. A prospective study was carried out in all nine primary care clinics belonging to the National Healthcare Group Polyclinics (NHGPs) in Singapore. The subjects comprised 594 consecutive patients (318 males, 276 females) aged у21 years who presented with complaints of any one of cough, nasal or throat symptoms of Ͻ7 days duration. Data collection was through interview using structured questionnaire, physical examination, throat swabs for bacterial culture and nasal swabs for virus identification by immunofluorescence (IF) and polymerase chain reaction (PCR). Additional PCR was performed on a subsample of 100 patients. Patients were followed-up until resolution of symptoms. Results. The aetiological diagnosis by infective agent is as follows: 150 patients (25.2%) had virus infections, of which 90.7% (136/150) were by rhinovirus. Fourteen patients (2.4%) had bacterial infections, of which 10 were due to group G streptococcus. Group A streptococcus was not detected. Nineteen patients with new pathogens were identified by further PCR. These included parainfluenza 4, human coronavirus OC43, adenovirus, enterovirus and Chlamydia pneumoniae. No pathogen could be identified in 49% of patients. There were no differences in clinical presentation and socio-demographic variables between patients who had viral infections and those in whom no pathogen could be identified. In about half of patients who presented at NHGPs, no pathogens could be identified even after PCR. A non-infective aetiology could be considered in these patients.
Output: Acute respiratory symptoms in adults in general practice
Ge Gen Decoction (GGD), a Traditional Chinese Medicine prescription, is mainly used to treat infectious respiratory diseases and can relieve the symptoms of influenza A virus (IAV) infection. However, the underlying mechanism of GGD against IAV infection remains unclear. In this study, we found that GGD had moderate anti-IAV activity in vitro. GGD was more effective when given before the viral infection and targeted the viral attachment and replication stages rather than the internalization stage. In vivo, GGD treatment reduced the virus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes in H1N1-infected mice. We observed the changes in several key immuno-related indexes in GGD administrated H1N1-infected mice with anti-IAV drug oseltamivir phosphate as the control. GGD treatment decreased the expression of TNF-α and improved Th1/Th2 immune balance to reduce the excessive immune response in H1N1-infected mice. Besides, the expression of the toll-like receptor 7 signaling pathway in H1N1-infected mice decreased after GGD treatment. Our results showed that GGD has anti-IAV activity and can modulate the immune system to relieve lung inflammation.
Output: Chinese Journal of Natural Medicines Exploration of the mechanisms of Ge Gen Decoction against influenza A virus infection
Next year will mark the 100th anniversary of the Michaelis-Menten equation [1], one of the most important and well known models in enzymology. Remarkable progress in enzymology over the past hundred years has not only provided deep insight into biological processes, but also has dramatically changed our lives. However, because of limitations in available techniques, enzymologists primarily investigate the in vitro properties and catalytic mechanisms of individual enzymes. Thus, they often fail to address a fundamental scientific question: how are biological processes, most of which are chemical reactions catalyzed by enzymes, coordinated in space and time to produce a living organism [2]? Fortunately, applications of new techniques and, in particular, wide acceptance of the idea of systems have enabled enzymologists to begin studying enzymes in the context of dynamic, complicated biological systems in recent years. Many excellent reviews and research articles on enzymology have been published in the past few years. These articles highlight the latest developments in enzymology, and should prove helpful for understanding how to best integrate the idea of systems into enzymology research. In living organisms, protein post-translational modification (PTM) pathways are large and interconnected networks. Via reversible or irreversible covalent modifications, allo-steric regulations of PTM enzymes and cross-talk of PTM pathways, PTM networks enable organisms to respond to stimuli faster than is possible through gene transcription regulation. Therefore, PTM enzymes, as key nodes of biological networks, are a recent focus of attention.
Output: SCIENCE CHINA A glimpse of enzymology within the idea of systems
Acute lung injury (ALI) and its most severe extreme the acute respiratory distress syndrome (ARDS) refer to increased-permeability pulmonary edema caused by a variety of pulmonary or systemic insults. ALI and in particular ARDS, are usually accompanied by refractory hypoxemia and the need for mechanical ventilation. In most cases, an exaggerated inflammatory and pro-thrombotic reaction to an initial stimulus, such as systemic infection, elicits disruption of the alveolo-capillary membrane and vascular fluid leak. The pulmonary endothelium is a major metabolic organ promoting adequate pulmonary and systemic vascular homeostasis, and a main target of circulating cells and humoral mediators under injury; pulmonary endothelium is therefore critically involved in the pathogenesis of ALI. In this review we will discuss mechanisms of pulmonary endothelial dysfunction and edema generation in the lung with special emphasis on the interplay between the endothelium, the immune and hemostatic systems, and highlight how these principles apply in the context of defined disorders and specific insults implicated in ALI pathogenesis.
Output: Endothelial pathomechanisms in acute lung injury
Background. The diagnosis of severe acute respiratory syndrome (SARS) is difficult early in the illness, because its presentation resembles that of other nonspecific viral fevers, such as dengue. Dengue fever is endemic in many of the countries in which the large SARS outbreaks occurred in early 2003. Misdiagnosis may have serious public health consequences. We aimed to determine simple laboratory features to differentiate SARS from dengue. Methods. We compared the laboratory features of 55 adult patients with SARS at presentation (who were all admitted before radiological changes had occurred) and 147 patients with dengue. Features independently predictive of dengue were modeled by multivariate logistic regression to create a diagnostic tool with 100% specificity for dengue. Results. Multivariate analysis identified 3 laboratory features that together are highly predictive of a diagnosis of dengue and able to rule out the possibility of SARS: platelet count of ! platelets/L, white blood cell
Output: Use of Simple Laboratory Features to Distinguish the Early Stage of Severe Acute Respiratory Syndrome from Dengue Fever
Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the ''magic bullet'' has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1-2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use.
Output: Chapter 1 Therapeutic Antibodies: Current State and Future Trends -Is a Paradigm Change Coming Soon?
Acute Fibrinous and Organizing Pneumonitis (AFOP) is a disease with histopathological pattern characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia represented by inflammatory myofibroblastic polyps. Symptoms of this rare interstitial pulmonary disease can be either acute or sub-acute and it can rapidly progress to death. Diagnosis should be considered in the Intensive Care Unit (ICU) if patients' symptomatology and radiology correlates with non-responding or progressive pneumonia and when morphology, on biopsies, encompasses criteria of diffuse alveolar damage (DAD) and organizing pneumonia (OP) balancing in between. Three clinical cases of patients presenting severe lung disease requiring mechanical ventilation and prolonged intensive care fitted on the variable spectra of AFOP histopathology and had poor outcome: a 23 year-old women had AFOP in the context of antiphospholipid syndrome pulmonary compromise; a 35 year-old man developed a letal intensive care pneumonia with AFOP pattern registered in post-mortem biopsy; and a 79 year-old man died 21 days after intensive care unit treatment of a sub-pleural organizing pneumonia with intra-alveolar fibrin, seen in post-mortem biopsy. The predominance of acute fibrin alveolar deposition pattern is helpful in raising AFOP differential diagnosis while organizing pneumonia pattern establishes a wider range of diagnosis that can go till solitary pulmonary nodule, remaining indefinite to suggest diagnosis. The performance time of biopsy in a larger number of clinical cases may be helpful in establishing the evolutionary morphological pattern, taking in mind the poor outcome of the disease, deserving rapid diagnosis to define treatment.
Output: Pathophysiology of acute fibrinous and organizing pneumonia - Clinical and morphological spectra
Transportation amongst cities is found as one of the main factors which affect the outbreak of diseases. To understand the effect of transport-related infection on disease spread, an SEIRS (Susceptible, Exposed, Infectious, Recovered) epidemic model for two cities is formulated and analyzed. The epidemiological threshold, known as the basic reproduction number, of the model is derived. If the basic reproduction number is below unity, the disease-free equilibrium is locally asymptotically stable. Thus, the disease can be eradicated from the community. There exists an endemic equilibrium which is locally asymptotically stable if the reproduction number is larger than unity. This means that the disease will persist within the community. The results show that transportation among regions will change the disease dynamics and break infection out even if infectious diseases will go to extinction in each isolated region without transport-related infection. In addition, the result shows that transport-related infection intensifies the disease spread if infectious diseases break out to cause an endemic situation in each region, in the sense of that both the absolute and relative size of patients increase. Further, the formulated model is applied to the real data of SARS outbreak in 2003 to study the transmission of disease during the movement between two regions. The results show that the transport-related infection is effected to the number of infected individuals and the duration of outbreak in such the way that the disease becomes more endemic due to the movement between two cities. This study can be helpful in providing the information to public health authorities and policy maker to reduce spreading disease when its occurs.
Output: On the dynamics of SEIRS epidemic model with transport-related infection
Different strategies are being worked out for engineering the original baculovirus expression vector (BEV) system to produce cost-effective clinical biologics at commercial scale. To date, thousands of highly variable molecules in the form of heterologous proteins, virus-like particles, surface display proteins/antigen carriers, heterologous viral vectors and gene delivery vehicles have been produced using this system. These products are being used in vaccine production, tissue engineering, stem cell transduction, viral vector production, gene therapy, cancer treatment and development of biosensors. Recombinant proteins that are expressed and post-translationally modified using this system are also suitable for functional, crystallographic studies, microarray and drug discovery-based applications. Till now, four BEV-based commercial products (Cervarix ® , Provenge ® , Glybera ® and Flublok ® ) have been approved for humans, and myriad of others are in different stages of preclinical or clinical trials. Five products (Porcilis ® Pesti, BAYOVAC CSF E2 ® , Circumvent ® PCV, Ingelvac CircoFLEX ® and Porcilis ® PCV) got approval for veterinary use, and many more are in the pipeline. In the present chapter, we have emphasized on both approved and other baculovirus-based products produced in insect cells or larvae that are important from clinical perspective and are being developed as preventive, diagnostic or therapeutic agents. Further, the potential of recombinant adeno-associated virus (rAAV) as gene delivery vector has been described. This system, due to its relatively extended gene expression, lack of pathogenicity and the ability to transduce
Output: Preventive, Diagnostic and Therapeutic Applications of Baculovirus Expression Vector System
A TaqMan probe-based real-time RT-PCR assay was developed for simultaneous detection of RNA of transmissible gastroenteritis virus (TGEV) in pig fecal samples and RNA of enhanced green fluorescent protein (EGFP) added exogenously as an internal amplification control. The TGEV primers and probe were designed to be specific to a portion of the S gene sequence conserved in all TGEV isolates, but absent in the closely related porcine respiratory coronaviruses. The optimized TaqMan assay detected a minimum of 2.8 copies of in vitro transcribed RNA of the target S gene and RNA extracted from 1 TCID 50 /ml of TGEV. Using 113 clinical samples received at our diagnostic laboratory over a 4-year period, the performance of the assay was tested and compared with that of a previously described nested RT-PCR assay. All the fecal samples which tested positive for TGEV by the nested RT-PCR assay also tested positive by the TaqMan assay. However, approximately 9% of the samples that tested negative by the nested RT-PCR assay tested positive by the TaqMan assay. These results indicate that the developed TaqMan assay is a highly sensitive diagnostic test for rapid detection of TGEV in pig fecal samples.
Output: A real-time TaqMan ® RT-PCR assay with an internal amplification control for rapid detection of transmissible gastroenteritis virus in swine fecal samples
Objectives: To analyse the evidence suggesting a possible infectious origin of Kawasaki syndrome (KS). Methods: PubMed was searched for all of the studies published over the last 15 years using the key words "Kawasaki syndrome" or "mucocutaneous lymph node syndrome" and "infectious disease" or "genetics" or "vasculitis" or "pathogenesis". Results: Various levels of evidence support the hypothesis that KS is a complex disease triggered by an infection due to one or more pathogens. Viruses or bacteria may be the primum movens, although no specific infectious agent can be considered definitely etiological. A number of genetic polymorphisms have been identified in subjects with KS, but none of them can currently be considered a real marker of susceptibility. Conclusions: Various data suggest that KS is intimately related to infectious diseases and that its clinical expression is influenced by predisposing genetic backgrounds, but our knowledge of the infectious agent(s) involved and the genetic characteristics of susceptible children remains only partial. Further studies are needed to address the many still open questions concerning the disease.
Output: The role of infection in Kawasaki syndrome
We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56-1258 pg/mL vs. median 58 pg/mL, range 11-241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284-1875 pmol/ L vs. median 249 pmol/L, range 118-556 pmol/L, P < 0.001; D-dimer median 2.8 mg/L, range 0.6-34.0 mg/L vs. median 0.4 mg/L, range 0.2-1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs' procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients. Abbreviations: AKI = acute kidney injury, ALT = alanine aminotransferase, CRP = C-reactive protein, HCPS = hantavirus cardiopulmonary syndrome, HFRS = hemorrhagic fever with renal syndrome, HIV = human immunodeficiency virus, IL-6 = interleukin 6, IPF% = immature platelet fraction %, MP = microparticle, MPV = mean platelet volume, PFA-100 = platelet factor analyzer 100, PUUV = Puumala virus, STAT = signal transducers and activators of transcription, TF = tissue factor, TGFb = transforming growth factor b, TPO = thrombopoietin.
Output: Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection
In this paper we describe a molecular beacon format assay in which encoded nanowire particles are used to achieve multiplexing. We demonstrate this principle with the detection of five viral pathogens; Hepatitis A virus, Hepatitis C virus, West Nile Virus, Human Immune Deficiency virus and Severe Acute Respiratory Syndrome virus. Oligonucleotides are designed complementary to a target sequence of interest containing a 3′ universal fluorescence dye. A 5′ thiol causes the oligonucleotides to self-assemble onto the metal nanowire. The single-stranded oligonucleotide contains a self-complementary hairpin stem sequence of 10 bases that forces the 3′ fluorophore to come into contact with the metallic nanowire surface, thereby quenching the fluorescence. Upon addition of target DNA, there is hybridization with the complementary oligonucleotides. The resulting DNA hybrid is rigid, unfolds the hairpin structure, and causes the fluorophore to be moved away from the surface such that it is no longer quenched. By using differently encoded nanowires, each conjugated with a different oligonucleotide sequence, multiplexed DNA assays are possible using a single fluorophore, from a multiplexed RT-PCR reaction. (Nanobiotechnology
Output: Encoded Metal Nanoparticle-Based Molecular Beacons for Multiplexed Detection of DNA
Infectious bronchitis virus (IBV) is a highly contagious respiratory coronavirus of domestic chickens. Although mortality is low, infection with IBV results in substantial losses for the egg and meat chicken industries. Despite the economic importance of IBV and decades of research into the pathogenesis of infection, significant gaps in our knowledge exist. The aim of this study was to compare the early progression of air sac lesions in birds receiving a vaccine strain of the virus or a more virulent field strain. The air sacs are lined by different types of epithelia and are relatively isolated from the environment, so they represent a unique tissue in which to study virus-induced lesions. Both the pathogenic and vaccine strains of the virus produced significant lesions; however, the lesions progressed more rapidly in the birds receiving the pathogenic strain. Immunohistochemistry demonstrated that in birds infected with the pathogenic strain of virus, IBV spike protein is detected first in the ciliated cells lining the air sac. These preliminary data provide important clues regarding potential mechanisms for IBV tissue tropism and spread and show that the nature of the virus isolate influences the early progression of IBV infection.
Output: Histopathological and Immunohistochemical Study of Air Sac Lesions Induced by Two Strains of Infectious Bronchitis Virus
Objective: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. Design: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008-2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. Setting: Nonfederal acute care hospitals in the United States. Measurements and Main Results: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. Conclusions: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.
Output: Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States
Are pathogens in outdoor air a health issue at present or will they become a problem in the future? A working group called AirPath -Outdoor Environments and Human Pathogens in Air was set up in 2007 at University College London, UK with the aim of opening new discussion and creating a research network to investigate the science and impacts of outdoor pathogens. Our objective in this paper is to review and discuss the following areas: What is the source of human pathogens in outdoor air? What current, developing and future techniques do we need? Can we identify at-risk groups in relation to their activities and environments? How do we prepare for the anticipated challenges of environmental change and new and emerging diseases? And how can we control for and prevent pathogens in outdoor environments? We think that this work can benefit the wider research community and policy makers by providing a concise overview of various research aspects and considerations which may be important to their work.
Output: Environmental Health Outdoor environments and human pathogens in air
Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013-May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities.
Output: Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi
Using ultrathin cryosections and immunogold labelling, aminopeptidase N (CD 13) and dipeptidyl peptidase IV (CD 26) were localized on the luminal side of the brush border membrane of proximal tubular cells in human kidney as well as of enterocytes from rat small intestine. Furthermore, both enzymes could be detected on the cell surface of human T lymphocytes and especially aminopeptidase N on human synovial fibroblasts. Gold labelled vesicular structures were also found in the cytoplasm in the apical part of renal proximal tubular cells and synovial fibroblasts. In human kidney the colocalization of the two membrane antigens was possible by using several double labelling methods.
Output: Ada hislo~helRi~a Immunoelectron microscopic single and double labelling of aminopep- tidase N (CD 13) and dipeptidyl peptidase IV (CD 26)