Showing papers by "University of Perugia published in 2007"
TL;DR: The estimated total number of symptomatic VTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715; almost three-quarters of all VTE-related deaths were from hospital-acquired VTE.
Abstract: Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.
1,287 citations
TL;DR: In this article, the authors present a detailed analysis of the performance of the Large Hadron Collider (CMS) at 14 TeV and compare it with the state-of-the-art analytical tools.
Abstract: CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking--through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb−1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb−1 to 30 fb−1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing ET, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model
973 citations
TL;DR: In the framework of computer-aided diagnosis of eye diseases, retinal vessel segmentation based on line operators is proposed and two segmentation methods are considered.
Abstract: In the framework of computer-aided diagnosis of eye diseases, retinal vessel segmentation based on line operators is proposed. A line detector, previously used in mammography, is applied to the green channel of the retinal image. It is based on the evaluation of the average grey level along lines of fixed length passing through the target pixel at different orientations. Two segmentation methods are considered. The first uses the basic line detector whose response is thresholded to obtain unsupervised pixel classification. As a further development, we employ two orthogonal line detectors along with the grey level of the target pixel to construct a feature vector for supervised classification using a support vector machine. The effectiveness of both methods is demonstrated through receiver operating characteristic analysis on two publicly available databases of color fundus images.
819 citations
TL;DR: A model in which the spontaneous membrane oscillations of neurons projecting from the striatum, in addition to the pattern of release of endogenous dopamine, bias the synapse towards preferential induction of LTP or LTD is proposed.
764 citations
TL;DR: A meta-analysis of studies in patients with acute pulmonary embolism to assess the prognostic value of elevated troponin levels for short-term death and adverse outcome events found that these levels were associated with a high mortality in the subgroup of hemodynamically stable patients.
Abstract: Background— Whether elevated serum troponin levels identify patients with acute pulmonary embolism at high risk of short-term mortality or adverse outcome is undefined. Methods and Results— We perf...
653 citations
TL;DR: This work provides all the instructions for downloading the R statistical software from internet and illustrates how to use it for analysis of a sample dataset of patients who underwent haematopoietic stem cell transplantation for acute leukaemia.
Abstract: In the last decade with widespread use of quantitative analyses in medical research, close co-operation between statisticians and physicians has become essential from the experimental design through all phases of complex statistical analysis. On the other hand, easy-to-use statistical packages allow clinicians to perform basic statistical analyses themselves. Since the software they most commonly use does not perform in depth competing risk analysis, we recommend an add-on package for the R statistical software. We provide all the instructions for downloading it from internet and illustrate how to use it for analysis of a sample dataset of patients who underwent haematopoietic stem cell transplantation for acute leukaemia.
595 citations
TL;DR: The present report expands the spectrum of knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.
Abstract: Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bone-marrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.
556 citations
TL;DR: The data are the first demonstrating that the IL‐23/IL‐17 pathway promotes inflammation and susceptibility in an infectious disease model and modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi.
Abstract: Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi.
534 citations
TL;DR: NPMc+ AML shows increased frequency in adults and females, wide morphologic spectrum, multilineage involvement, high frequency of FLT3-ITD, CD34 negativity, and a distinct gene-expression profile.
525 citations
TL;DR: The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens.
Abstract: The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens. We report that, unexpectedly, PTX3 is stored in specific granules and undergoes release in response to microbial recognition and inflammatory signals. Released PTX3 can partially localize in neutrophil extracellular traps formed by extruded DNA. Eosinophils and basophils do not contain preformed PTX3. PTX3-deficient neutrophils have defective microbial recognition and phagocytosis, and PTX3 is nonredundant for neutrophil-mediated resistance against Aspergillus fumigatus. Thus, neutrophils serve as a reservoir, ready for rapid release, of the long PTX3, a key component of humoral innate immunity with opsonic activity.
488 citations
TL;DR: These studies indicate that monocytopoiesis is controlled by a circuitry involving sequentially miRNA 17-5p–20a–106a, AML1 and M-CSFR, whereby miRNAs function as a master gene complex interlinked withAML1 in a mutual negative feedback loop.
Abstract: We investigated the role of microRNAs (miRNA) 17-5p, 20a and 106a in monocytic differentiation and maturation. In unilineage monocytic culture generated by haematopoietic progenitor cells these miRNAs are downregulated, whereas the transcription factor acute myeloid leukaemia-1 (AML1; also known as Runt-related transcription factor 1, Runx1) is upregulated at protein but not mRNA level. As miRNAs 17-5p, 20a and 106a bind the AML1 mRNA 3'UTR, their decline may unblock AML1 translation. Accordingly, transfection with miRNA 17-5p-20a-106a suppresses AML1 protein expression, leading to M-CSF receptor (M-CSFR) downregulation, enhanced blast proliferation and inhibition of monocytic differentiation and maturation. Treatment with anti-miRNA 17-5p, 20a and 106a causes opposite effects. Knockdown of AML1 or M-CSFR by short interfering RNA (siRNA) mimics the action of the miRNA 17-5p-20a-106a, confirming that these miRNAs target AML1, which promotes M-CSFR transcription. In addition, AML1 binds the miRNA 17-5p-92 and 106a-92 cluster promoters and transcriptionally inhibits the expression of miRNA 17-5p-20a-106a. These studies indicate that monocytopoiesis is controlled by a circuitry involving sequentially miRNA 17-5p-20a-106a, AML1 and M-CSFR, whereby miRNA 17-5p-20a-106a function as a master gene complex interlinked with AML1 in a mutual negative feedback loop.
TL;DR: It is proposed that IDO acts as a bridge between dendritic cells and CD4+ regulatory T cells, and that Regulatory T cells use reverse signalling and non-canonical NF-κB activation for effector function and self-propagation.
Abstract: The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in mammalian pregnancy, tumour resistance, chronic infection, autoimmunity and allergic inflammation. 'Reverse signalling' and 'non-canonical activation' of the transcription factor nuclear factor-kappaB (NF-kappaB) characterize the peculiar events that occur in dendritic cells when T-cell-engaged ligands work as signalling receptors and culminate in the induction of IDO expression by dendritic cells in an inhibitor of NF-kappaB (IkappaB) kinase-alpha (IKKalpha)-dependent manner. In this Opinion article, we propose that IDO acts as a bridge between dendritic cells and CD4+ regulatory T cells, and that regulatory T cells use reverse signalling and non-canonical NF-kappaB activation for effector function and self-propagation. This mechanism may also underlie the protective function of glucocorticoids in pathological conditions.
TL;DR: This paper proposes novel channel estimators to combat both the noise and the out-of-band interference in orthogonal frequency-division multiplexing (OFDM) systems.
Abstract: In this paper, we deal with channel estimation for orthogonal frequency-division multiplexing (OFDM) systems. The channels are assumed to be time-varying (TV) and approximated by a basis expansion model (BEM). Due to the time-variation, the resulting channel matrix in the frequency domain is no longer diagonal, but approximately banded. Based on this observation, we propose novel channel estimators to combat both the noise and the out-of-band interference. In addition, the effect of a receiver window on channel estimation is also studied. Our claims are supported by simulation results, which are obtained considering Jakes' channels with fairly high Doppler spreads
TL;DR: Fractionation of the water-extractable organic carbon showed that the ratio of hydrophobic to hydrophilic carbon increased to values greater than unity for stabilized compost, and confirmed the influence of solubilization, mineralization and organic matter transformation on the quality of the final compost.
TL;DR: The data suggest that lymphocytes are essential stabilizers of basal bone turnover and critical regulators of peak bone mass in vivo.
TL;DR: Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period, particularly after preterm birth, while male sex is an independent risk factor for adverse pregnancy outcome.
TL;DR: The background to the new procedure is presented and case studies illustrating several relevant applications of the new approach are presented, which can be used effectively for ligand-based virtual screening and structure-basedvirtual screening, with the pharmacophore molecular recognition.
Abstract: A fast new algorithm (Fingerprints for Ligands And Proteins or FLAP) able to describe small molecules and protein structures using a common reference framework of four-point pharmacophore fingerprints and a molecular-cavity shape is described in detail. The procedure starts by using the GRID force field to calculate molecular interaction fields, which are then used to identify particular target locations where an energetic interaction with small molecular features would be very favorable. The target points thus calculated are then used by FLAP to build all possible four-point pharmacophores present in the given target site. A related approach can be applied to small molecules, using directly the GRID atom types to identify pharmacophoric features, and this complementary description of the target and ligand then leads to several novel applications. FLAP can be used for selectivity studies or similarity analyses in order to compare macromolecules without superposing them. Protein families can be compared an...
TL;DR: Female gender, corrected QT (QTc) interval, LQT2 genotype, and frequency of cardiac events before age 18 years were associated with increased risk of having any cardiac events between the ages of 18 and 40 years.
TL;DR: It is shown that miR-223 is a direct transcriptional target of AML1/ETO, and an additional action for a leukemia fusion protein linking the epigenetic silencing of a microRNA locus to the differentiation block of leukemia is identified.
TL;DR: Aspergillus species is the most frequently detected agent in patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers, and aspergillosis is characterized by a high mortality rate.
Abstract: Background. The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. Methods. This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). Results. Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). Conclusions. IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.
TL;DR: In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS.
TL;DR: The present review discusses the potential use of solid lipid nanoparticles for brain drug targeting purposes and the state of the art on surfactant-coated poly(alkylcyanoacrylate) nanoparticles specifically designed for brain targeting is given by emphasizing the transfer of this technology to solid lipid matrices.
TL;DR: In this paper, the capabilities of the CERN Large Hadron Collider (LHC) experiment to explore the rich heavy-ion physics program offered by the LHC are presented, and the potential of the CMS experiment to carry out a series of representative Pb-Pb measurements.
Abstract: This report presents the capabilities of the CMS experiment to explore the rich heavy-ion physics programme offered by the CERN Large Hadron Collider (LHC). The collisions of lead nuclei at energies , will probe quark and gluon matter at unprecedented values of energy density. The prime goal of this research is to study the fundamental theory of the strong interaction ? Quantum Chromodynamics (QCD) ? in extreme conditions of temperature, density and parton momentum fraction (low-x).This report covers in detail the potential of CMS to carry out a series of representative Pb-Pb measurements. These include bulk observables, (charged hadron multiplicity, low pT inclusive hadron identified spectra and elliptic flow) which provide information on the collective properties of the system, as well as perturbative probes such as quarkonia, heavy-quarks, jets and high pT hadrons which yield tomographic information of the hottest and densest phases of the reaction.
TL;DR: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism, which may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut P TCs.
Abstract: Context: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. Objective: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. Design/Setting and Patients: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. Results: mRNA levels for all thyroid-specific genes were reduced in ...
TL;DR: Vitamin D status was inversely associated with poor physical performance and additional studies examining the association between vitamin D status and physical function are needed.
Abstract: With a growing older population, there is an increasing need to identify potentially modifiable risk factors for the onset of disability. In the past two decades, it has become evident that the role of vitamin D extends beyond calcium homeostasis and includes modulation of skeletal and cardiac muscle function, immune cell function, and anticancer activity (1). Within the muscle cell, vitamin D plays an important role in the regulation of calcium transport and protein synthesis (2,3). In older adults, low serum vitamin D (serum 25OHD) levels have been associated with muscle weakness, poor physical performance, balance problems, and falls, although findings from different studies are somewhat inconsistent (4–11). Thus, vitamin D deficiency may not only affect the onset of chronic conditions, which are frequent causes of disability, but may also directly affect functional status through vitamin D’s role in muscle function.
Consensus to define a cut-point for vitamin D insufficiency based on serum 25OHD levels is lacking. Various cut-points have been proposed based on population-based reference limits or biological indices, such as parathyroid hormone (PTH), calcium absorption, or bone mineral density, with cut-points for serum 25OHD insufficiency ranging from 50 to 80 nmol/L (12–14). Regardless, low levels of serum 25OHD are common in older populations with wide variability in prevalence depending on geographic location, season, and the cut-points used to define insufficiency and/or deficiency (15–19). Older adults are at risk for low serum 25OHD because of reduced exposure to ultraviolet B (UVB) radiation and reduced efficiency of previtamin D synthesis in the skin (20). Dietary intake of vitamin D is also often inadequate, as there are few natural food sources of vitamin D (16).
Low serum 25OHD may also indirectly affect muscle function via hyperparathyroidism secondary to vitamin D deficiency (17). Primary hyperparathyroidism is characterized by muscle weakness that is improved by treatment (21,22). It has been demonstrated that administration of PTH negatively affects skeletal muscle function in animal models (2,3,17). PTH has also been shown to induce the production of serum interleukin-6 (IL-6) (23). Observational studies have shown that elevated IL-6 levels are associated with lower muscle strength and poor physical performance (24,25). However, few studies have examined the joint effect of vitamin D and PTH on physical performance (9,10).
The objective of this study was to examine the associations between vitamin D status and physical performance using data from the InCHIANTI study. Comparisons between different serum 25OHD cut-points and physical performance were examined. Additionally, the association between PTH and physical performance and the role of PTH as a potential mediator in the association between serum 25OHD and physical performance was examined.
TL;DR: This paper identified the major determinants that seem to affect the incidence, and/or emergence, of coordination failure in the lab and reviewed the existing experimental studies on coordination games with Pareto-ranked equilibria.
Abstract: Coordination games with Pareto-ranked equilibria have attracted major attention over the past two decades. Two early path-breaking sets of experimental studies were widely interpreted as suggesting that coordination failure is a common phenomenon in the laboratory. We identify the major determinants that seem to affect the incidence, and/or emergence, of coordination failure in the lab and review critically the existing experimental studies on coordination games with Pareto-ranked equilibria since that early evidence emerged. We conclude that there are many ways to engineer coordination successes.
TL;DR: Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban, because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing.
Abstract: Background— An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation. Rivaroxaban (BAY 59-7939) is an oral direct factor Xa inhibitor currently under clinical development. Methods and Results— This randomized, parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist. Each treatment was administered for 12 weeks. The primary efficacy end point was an improvement in thrombotic burden at day 21 (assessed by quantitative compression ultrasonography; ≥4-point improvement in thrombus score) without recurrent symptomatic venous thromboembolism or venous thromboembolism-related death. The primary safety end point was major bleeding during 12 weeks of treatment. Outcomes were adjudicated centrally without knowledge of treat...
TL;DR: It is shown that reverse signaling through GITRL after engagement by soluble GITR initiates the immunoregulatory pathway of tryptophan catabolism in mouse plasmacytoid dendritic cells, by means of noncanonical NF-κB–dependent induction of indoleamine 2,3-dioxygenase (IDO).
Abstract: Glucocorticoid-induced tumor necrosis factor receptor (GITR) on T cells and its natural ligand, GITRL, on accessory cells contribute to the control of immune homeostasis. Here we show that reverse signaling through GITRL after engagement by soluble GITR initiates the immunoregulatory pathway of tryptophan catabolism in mouse plasmacytoid dendritic cells, by means of noncanonical NF-κB–dependent induction of indoleamine 2,3-dioxygenase (IDO). The synthetic glucocorticoid dexamethasone administered in vivo activated IDO through the symmetric induction of GITR in CD4+ T cells and GITRL in plasmacytoid dendritic cells. The drug exerted IDO-dependent protection in a model of allergic airway inflammation. Modulation of tryptophan catabolism via the GITR-GITRL coreceptor system might represent an effective therapeutic target in immune regulation. Induction of IDO could be an important mechanism underlying the anti-inflammatory action of corticosteroids.
TL;DR: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.
Abstract: Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.
TL;DR: In this article, a measurement of the cosmic ray positron fraction in the energy range of 1 −30 GeV was presented, based on data taken by the AMS-01 experiment during its 10-day Space Shuttle flight in June 1998.