1,114 research outputs found

    Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

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    INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNÎł, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

    Insight into glucocorticoid receptor signalling through interactome model analysis

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    Glucocorticoid hormones (GCs) are used to treat a variety of diseases because of their potent anti-inflammatory effect and their ability to induce apoptosis in lymphoid malignancies through the glucocorticoid receptor (GR). Despite ongoing research, high glucocorticoid efficacy and widespread usage in medicine, resistance, disease relapse and toxicity remain factors that need addressing. Understanding the mechanisms of glucocorticoid signalling and how resistance may arise is highly important towards improving therapy. To gain insight into this we undertook a systems biology approach, aiming to generate a Boolean model of the glucocorticoid receptor protein interaction network that encapsulates functional relationships between the GR, its target genes or genes that target GR, and the interactions between the genes that interact with the GR. This model named GEB052 consists of 52 nodes representing genes or proteins, the model input (GC) and model outputs (cell death and inflammation), connected by 241 logical interactions of activation or inhibition. 323 changes in the relationships between model constituents following in silico knockouts were uncovered, and steady-state analysis followed by cell-based microarray genome-wide model validation led to an average of 57% correct predictions, which was taken further by assessment of model predictions against patient microarray data. Lastly, semi-quantitative model analysis via microarray data superimposed onto the model with a score flow algorithm has also been performed, which demonstrated significantly higher correct prediction ratios (average of 80%), and the model has been assessed as a predictive clinical tool using published patient microarray data. In summary we present an in silico simulation of the glucocorticoid receptor interaction network, linked to downstream biological processes that can be analysed to uncover relationships between GR and its interactants. Ultimately the model provides a platform for future development both by directing laboratory research and allowing for incorporation of further components, encapsulating more interactions/genes involved in glucocorticoid receptor signalling

    Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

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    This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}andcorrespondtoanintegratedluminosityof and correspond to an integrated luminosity of 4.6\;{\rm f}{{{\rm b}}^{-1}}.ThemeasurementisperformedbyreconstructingtheboostedWorZbosonsinsinglejets.ThereconstructedjetmassisusedtoidentifytheWandZbosons,andajetsubstructuremethodbasedonenergyclusterinformationinthejetcentre−of−massframeisusedtosuppressthelargemulti−jetbackground.Thecross−sectionforeventswithahadronicallydecayingWorZboson,withtransversemomentum. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum {{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}andpseudorapidity and pseudorapidity |\eta |\lt 1.9,ismeasuredtobe, is measured to be {{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

    Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

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    The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

    Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

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    The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Fuzzy obesity index (MAFOI) for obesity evaluation and bariatric surgery indication

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    Background: the Miyahira-Araujo Fuzzy Obesity Index (MAFOI) for being used as an alternative in bariatric surgery indication (BSI) is validated in this paper. the search for a more accurate method to evaluate obesity and to indicate a better treatment is important in the world health context. Body mass index (BMI) is considered the main criteria for obesity treatment and BSI. Nevertheless, the fat excess related to the percentage of Body Fat (%BF) is actually the principal harmful factor in obesity disease that is usually neglected. the aim of this research is to validate a previous fuzzy mechanism by associating BMI with %BF that yields the Miyahira-Araujo Fuzzy Obesity Index (MAFOI) for obesity evaluation, classification, analysis, treatment, as well for better indication of surgical treatment.Methods: Seventy-two patients were evaluated for both BMI and %BF. the BMI and %BF classes are aggregated yielding a new index (MAFOI). the input linguistic variables are the BMI and %BF, and the output linguistic variable is employed an obesity classification with entirely new types of obesity in the fuzzy context, being used for BSI, as well.Results: There is gradual and smooth obesity classification and BSI criteria when using the Miyahira-Araujo Fuzzy Obesity Index (MAFOI), mainly if compared to BMI or %BF alone for dealing with obesity assessment, analysis, and treatment.Conclusion: the resulting fuzzy decision support system (MAFOI) becomes a feasible alternative for obesity classification and bariatric surgery indication

    Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

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    Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported ñ from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio
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