Managing Adult-onset Still's disease: The effectiveness of high-dosage of corticosteroids as first-line treatment in inducing the clinical remission. Results from an observational study

To assess the effectiveness of the treatment with high dosage of corticosteroids (CCSs), as first-line therapy, in inducing remission in naïve Adult-onset Still's disease (AOSD) patients compared with low dosage of CCSs, after 6 months. To further evaluate the rate of patients maintaining the remission and the rate of CCSs discontinuation, after additional 12 months of follow-up.A retrospective evaluation of patients prospectively followed was designed to compare the rate of clinical remission in naïve AOSD patients treated with high dosages of CCSs (0.8-1 mg/kg/day of prednisone-equivalent) or low dosage of CCSs (0.2-0.3 mg/kg/day of prednisone-equivalent), after 6 months. An additional analysis was performed to compare the rate of monocyclic pattern between these groups, after further 12 months of follow-up.The clinical remission was achieved in a higher percentage of patients treated with the first-line treatment with high dosage of CCSs than treated the first-line treatment with low dosage of CCSs. At the end of 18 months of follow-up, a larger percentage of patients treated the first-line treatment with high dosage of CCSs was classified as monocyclic pattern and discontinued CCSs when compared with patients treated the first-line treatment with low dosage of CCSs. Patients defined as CCSs non-responder were treated with methotrexate (MTX)+CCSs or with combination therapy CCSs+MTX+biologic drug. The clinical remission was observed in a percentage of these patients.We showed the effectiveness of the first-line treatment with high dosage of CCSs in inducing clinical remission in naïve AOSD patients when compared with the first-line treatment with low dosage of CCSs. The first-line treatment with high dosage of CCSs was also associated with the achievement of monocyclic pattern and CCSs discontinuation, after 18 months of follow-up

On the ultraviolet behaviour of quantum fields over noncommutative manifolds

By exploiting the relation between Fredholm modules and the Segal-Shale-Stinespring version of canonical quantization, and taking as starting point the first-quantized fields described by Connes' axioms for noncommutative spin geometries, a Hamiltonian framework for fermion quantum fields over noncommutative manifolds is introduced. We analyze the ultraviolet behaviour of second-quantized fields over noncommutative 3-tori, and discuss what behaviour should be expected on other noncommutative spin manifolds.Comment: 10 pages, RevTeX version, a few references adde

Potencial de Mimosa acutistipula (MART.) BENTH. e Senegalia paraensis (DUCKE) Seigler & Ebinger para revegetação de áreas contaminadas por arsênio.

O presente trabalho teve como objetivo avaliar o crescimento de Mimosa acutistipula (Mart.) Benth. e Senegalia paraensis (Ducke) Seigler & Ebinger cultivadas em solo com diferentes concentrações de arsênio. Os ensaios foram conduzidos em casa de vegetação em blocos casualizados com quatro repetições

Biodisponibilidade de Arsênio em Dois Solos de Granulometrias Distintas sob Adição de Fosfato e Arsenato.

? Nos coloides do solo, o fosfato e o arsenato competem por sítios de adsorção, sendo que a adição de fosfato por meio de fertilizantes, por exemplo, pode elevar os teores de As em solução, tornando-o mais disponível para as plantas. Por outro lado, por competirem por sítios de absorção nas raízes, maiores teores de As em solução podem inibir a absorção de P e vice-versa. Dessa forma, este experimento teve como objetivo avaliar a biodisponibilidade de arsênio ao longo de 2 meses após a aplicação de doses de fosfato e arsenato em dois solos de granulometrias distintas. O experimento foi conduzido em casa de vegetação do Departamento de Solos da Universidade Federal de Viçosa utilizando-se um solo arenoso e um muito argiloso. O solos receberam cinco doses de P (0, 44, 150, 256, e 300 mg.kg -1 ) na forma de fosfato de sódio e cinco doses de As (0, 22, 75, 128 e 150 mg.kg -1 ) na forma de arsenato de sódio. A biodisponibilidade de arsênio foi analisada aos 15, 30 e 60 dias após a aplicação dos tratamentos, através do método de Neubauer e Schneider (1923). O delineamento utilizado foi o delineamento Central Composto Rotacional (DCCR), com cinco repetições no ponto central e valor alfa igual a 1,41. Os dados foram analisados por meio de superfície de respostas e demonstraram que a alta concentração de fósforo em solução compensa a maior disponibilidade de arsenato, causada por sua adição, podendo, assim, amenizar os efeitos fitotóxicos do arsênio

Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis

Objective To assess whether lithium has a specific preventive effect for suicide and self harm in people with unipolar and bipolar mood disorders. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, PsycINFO, CENTRAL, web based clinical trial registries, major textbooks, authors of important papers and other experts in the discipline, and websites of pharmaceutical companies that manufacture lithium or the comparator drugs (up to January 2013). Inclusion criteria Randomised controlled trials comparing lithium with placebo or active drugs in long term treatment for mood disorders. Review methods Two reviewers assessed studies for inclusion and risk of bias and extracted data. The main outcomes were the number of people who completed suicide, engaged in deliberate self harm, and died from any cause. Results 48 randomised controlled trials (6674 participants, 15 comparisons) were included. Lithium was more effective than placebo in reducing the number of suicides (odds ratio 0.13, 95% confidence interval 0.03 to 0.66) and deaths from any cause (0.38, 0.15 to 0.95). No clear benefits were observed for lithium compared with placebo in preventing deliberate self harm (0.60, 0.27 to 1.32). In unipolar depression, lithium was associated with a reduced risk of suicide (0.36, 0.13 to 0.98) and also the number of total deaths (0.13, 0.02 to 0.76) compared with placebo. When lithium was compared with each active individual treatment a statistically significant difference was found only with carbamazepine for deliberate self harm. Lithium tended to be generally better than the other active comparators, with small statistical variation between the results. Conclusions Lithium is an effective treatment for reducing the risk of suicide in people with mood disorders. Lithium may exert its antisuicidal effects by reducing relapse of mood disorder, but additional mechanisms should also be considered because there is some evidence that lithium decreases aggression and possibly impulsivity, which might be another mechanism mediating the antisuicidal effect

Fredholm Modules on P.C.F. Self-Similar Fractals and their Conformal Geometry

The aim of the present work is to show how, using the differential calculus associated to Dirichlet forms, it is possible to construct Fredholm modules on post critically finite fractals by regular harmonic structures. The modules are d-summable, the summability exponent d coinciding with the spectral dimension of the generalized laplacian operator associated with the regular harmonic structures. The characteristic tools of the noncommutative infinitesimal calculus allow to define a d-energy functional which is shown to be a self-similar conformal invariant.Comment: 16 page

Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: A new potential target for antifibrotic therapy

Background: Fibrosis may be considered the hallmark of systemic sclerosis (SSc), the end stage triggered by different pathological events. Transforming growth factor-β (TGF-β) and platelet-derived growth factor BB (PDGF-BB) are profibrotic molecules modulating myofibroblast differentiation and proliferation, respectively. There is evidence linking CD248 with these two molecules, both highly expressed in patients with SSc, and suggesting that CD248 may be a therapeutic target for several diseases. The aim of this work was to evaluate the expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process. Methods: After ethical approval was obtained, skin biopsies were collected from 20 patients with SSc and 10 healthy control subjects (HC). CD248 expression was investigated in the skin, as well as in bone marrow mesenchymal stem cells (MSCs) treated with TGF-β or PDGF-BB, by immunofluorescence, qRT-PCR, and Western blotting. Finally, in SSc-MSCs, the CD248 gene was silenced by siRNA. Results: Increased expression of CD248 was found in endothelial cells and perivascular stromal cells of SSc skin. In SSc-MSCs, the levels of CD248 and α-smooth muscle actin expression were significantly higher than in HC-MSCs. In both SSc- and HC-MSCs, PDGF-BB induced increased expression of Ki-67 when compared with untreated cells but was unable to modulate CD248 levels. After CD248 silencing, both TGF-β and PDGF-BB signaling were inhibited in SSc-MSCs. Conclusions: CD248 overexpression may play an important role in the fibrotic process by modulating the molecular target, leading to perivascular cells differentiation toward myofibroblasts and interfering with its expression, and thus might open a new therapeutic strategy to inhibit myofibroblast generation during SSc

Pyramiding resistance genes and widening the genetic base of the apple (Malus 7 domestica Borkh.) crop

Apple breeding is active worldwide and yet the apple crop is in a precarious state as it relies on few dominant cultivars and only the Rvi6 (formerly Vf) gene, that confers resistance to scab, has been extensively exploited in the cultivars entered the market in recent years. However, there are some 20 disease resistance genes described in apple and the apple germplasm includes thousands of accessions in the repositories. In this paper, a breeding programme is described, whereby 36 genotypes, including ancient and contemporary apple cultivars, were crossed to produce a new set of selections that combine extensive genetic resources with pyramided resistance genes to several apple diseases, such as scab and powdery mildew. The 110 cross combinations carried out successfully, of the 260 initially planned, produced 7,876 offsprings, reduced to 2,969 after screening with molecular markers associated with five resistance genes. Selections with three or two resistance genes and good agronomic characteristics were kept for further field observations with the aims of creating new cultivars for the market and new parents for future breeding projects

Adult-onset Still's disease: Evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

Background: Adult-onset Still's disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients. Methods: This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed. Results: One hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of 65 7.0 was reported. Conclusions: Our study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death