Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes

Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.

Influence of quinidine, fluvoxamine, and ketoconazole on the enantioselective pharmacokinetics of citalopram in rats

Citalopram (CITA) is available as a racemic mixture or as (+)-(S)-CITA. In humans, CITA is metabolized to demethylcitalopram (DCITA) by CYP2C19, CYP2D6, and CYP3A and to didemethylcitalopram by CYP2D6. There are no data regarding the enzymes involved in CITA and DCITA metabolism in rats. The present study investigated the influence of CYP inhibitors on the enantioselective metabolism of CITA in rats. Male Wistar rats (n = 6) received a single dose of 20 mg.kg(-1) CITA after pretreatment with 80 mg.kg(-1) quinidine, 10 mg.kg(-1) fluvoxamine, 50 mg.kg(-1) ketoconazole, or vehicle (control). Blood samples were collected up to 20 h after CITA administration. The CITA and DCITA enantiomers were analyzed by LC-MS/MS using a Chiralcel OD-R column. The kinetic disposition of CITA was enantioselective in rats (AUC(S/R) ratio = 0.4). Coadministration with quinidine resulted in non-enantioselective inhibition of the metabolism of CITA. Coadministration with fluvoxamine or ketoconazole, however, inhibited only the metabolism of (+)-(S)-CITA, but not of (-)-(R)-CITA when the racemic drug was administered to rats.

Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

A critical view on biaxial and short-beam uniaxial flexural strength tests applied to resin composites using Weibull, fractographic and finite element analyses

Objective. To evaluate the biaxial and short-beam uniaxial strength tests applied to resin composites based upon their Weibull parameters, fractographic features and stress distribution. Methods. Disk- (15 mm x 1 mm) and beam-shaped specimens (10 mm x 2 mm x 1 mm) of three commercial composites (Concept/Vigodent, CA; Heliomolar/Ivoclar-Vivadent, HE; Z250/3M ESPE, FZ) were prepared. After 48h dry storage at 37 degrees C, disks and beams were submitted to piston-on-three-balls (BI) and three-point bending (UNI) tests, respectively. Data were analyzed by Weibull statistics. Fractured surfaces were observed under stereomicroscope and scanning electron microscope. Maximum principal stress (sigma(1)) distribution was determined by finite element analysis (FEA). Maximum sigma(1-BI) and sigma(1-UNI) were compared to FZ strengths calculated by applying the average failure loads to the analytical equations (sigma(a-BI) and sigma(a-UNI)). Results. For BI, characteristic strengths were: 169.9a (FZ), 122.4b (CA) and 104.8c (HE), and for UNI were: 160.3a (FZ), 98.2b (CA) and 91.6b (HE). Weibull moduli ( m) were similar within the same test. CA and HE presented statistically higher m for BI. Surface pores ( BI) and edge flaws ( UNI) were the most frequent fracture origins. sigma(1-BI) was 14% lower than sigma(a-BI.) sigma(1-UNI) was 43% higher than sigma(a-UNI). Significance. Compared to the short-beam uniaxial test, the biaxial test detected more differences among composites and displayed less data scattering for two of the tested materials. Also, biaxial strength was closer to the material`s strength estimated by FEA. (C) 2009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Cue competition between elementary trained stimuli: US miscuing, interference, and US omission

The present series of experiments was designed to assess whether rule-based accounts of Pavlovian learning can account for cue competition effects observed after elemental training. All experiments involved initial differential conditioning training with A-US and B alone presentations. Miscuing refers to the fact that responding to A is impaired after one B-US presentation whereas interference is the impairment of responding to A after presentation of C-US pairings. Omission refers to the effects on B of A alone presentations. Experiments 1-2a provided clear evidence for miscuing whereas interference was not found after 1, 5 or 10 C-US pairings. Moreover, Experiments 3 and 3a found only weak evidence for interference in an A-US, B I C-US, D I A design used previously to show the effect. Experiments 4 and 5 failed to find any effect of US omission after one or five omission trials. The present results indicate that miscuing is more robust than is the interference effect. Moreover, the asymmetrical effects of US miscuing and US omission are difficult to accommodate within rule-based accounts of Pavlovian conditioning. (C) 2002 Elsevier Science (USA). All rights reserved.

The synthesis and X-ray crystal structure of 9-carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one

9-Carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one (1) was prepared and examined by X-ray crystallography to probe its potential as a new peptide scaffold/template. The crystal structure of the anhydride precursor 7-(2-acetoxyethyl)-4-methoxy-3a,4,7,7a-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione (6) is also reported.

Boletim eletr??nico de bibliografias especializadas: meio ambiente e sustentabilidade

A 3a edi????o de 2013 do Boletim Eletr??nico de Bibliografias Especializadas re??ne publica????es do acervo da Biblioteca Graciliano Ramos com a tem??tica Meio Ambiente e Sustentabilidade, por ocasi??o do Dia Mundial do Meio Ambiente, comemorado anualmente em 5 de junho. A data busca chamar a aten????o e a a????o pol??tica de povos e pa??ses a fim de aumentar a conscientiza????o e a preserva????o ambiental. A divulga????o das publica????es a seguir - que tratam de ecologia, saneamento b??sico, polui????o, desenvolvimento sustent??vel, economia verde, gest??o ambiental, entre outros - tem como expectativa apoiar a forma????o e a capacita????o de servidores p??blicos, bem como a aplica????o desse conhecimento em pol??ticas p??blicas, em benef??cio da popula????o

Potencial cognitivo P300 realizado em campo livre: aplicabilidade do teste

Avaliar a função auditiva em usuários de dispositivos eletrônicos aplicados a surdez é muito importante para o processo de reabilitação. Entretanto, nestes indivíduos os procedimentos devem ser realizados em campo livre. OBJETIVO: Analisar a aplicabilidade do potencial cognitivo P300 pesquisado em campo livre. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Foram avaliados 33 indivíduos de ambos os sexos com idade entre 7 e 34 anos, com audição normal e sem fator de risco para problemas mentais. O potencial cognitivo P300 foi realizado por meio do equipamento Biologic's Evoked Potential System (EP), com fones de inserção (3A) e em campo livre (0º Azimute e 45º Azimute). RESULTADOS: Não houve diferença estatisticamente significante para a latência do N2 e P300 e amplitude do P300 quando analisado o sexo e o modo de realização do teste (fone e campo livre), assim como não houve diferença ao comparar as medidas em campo livre a 0º e 45º Azimute. CONCLUSÃO: A pesquisa do potencial cognitivo P300 em campo livre é um procedimento viável de ser realizado.

Response of a multi-domain continental margin to compression: Study from seismic reflection-refraction and numerical modelling in the Tagus Abyssal Plain

The effects of the Miocene through Present compression in the Tagus Abyssal Plain are mapped using the most up to date available to scientific community multi-channel seismic reflection and refraction data. Correlation of the rift basin fault pattern with the deep crustal structure is presented along seismic line IAM-5. Four structural domains were recognized. In the oceanic realm mild deformation concentrates in Domain I adjacent to the Tore-Madeira Rise. Domain 2 is characterized by the absence of shortening structures, except near the ocean-continent transition (OCT), implying that Miocene deformation did not propagate into the Abyssal Plain, In Domain 3 we distinguish three sub-domains: Sub-domain 3A which coincides with the OCT, Sub-domain 3B which is a highly deformed adjacent continental segment, and Sub-domain 3C. The Miocene tectonic inversion is mainly accommodated in Domain 3 by oceanwards directed thrusting at the ocean-continent transition and continentwards on the continental slope. Domain 4 corresponds to the non-rifted continental margin where only minor extensional and shortening deformation structures are observed. Finite element numerical models address the response of the various domains to the Miocene compression, emphasizing the long-wavelength differential vertical movements and the role of possible rheologic contrasts. The concentration of the Miocene deformation in the transitional zone (TC), which is the addition of Sub-domain 3A and part of 3B, is a result of two main factors: (1) focusing of compression in an already stressed region due to plate curvature and sediment loading; and (2) theological weakening. We estimate that the frictional strength in the TC is reduced in 30% relative to the surrounding regions. A model of compressive deformation propagation by means of horizontal impingement of the middle continental crust rift wedge and horizontal shearing on serpentinized mantle in the oceanic realm is presented. This model is consistent with both the geological interpretation of seismic data and the results of numerical modelling.

A construção de sentidos em política educativa: o caso da Escola a Tempo Inteiro

Com o presente texto pretendemos apresentar sucintamente as principais linhas de força dum projecto de investigação sobre as medidas políticas que configuram a ideia de Escola a Tempo Inteiro no âmbito do 1.º Ciclo do Ensino Básico optando por uma abordagem pela “análise das políticas públicas” centrado na formulação e implementação dessas medidas. Desta forma, procuramos assentar o estudo em dois “modos de abordagem” que se interligam: um centrado na análise do processo de decisão política, a partir do qual procuraremos compreender como nasceu e se transformou/transforma a política; outro na sua implementação focalizado no estudo da acção do Estado e no posicionamento dos seus actores em interacção com outros actores sociais. Como “ferramentas” teóricas optamos pela análise cognitiva das políticas públicas recorrendo, em particular, ao conceito de referencial e pela abordagem pelos instrumentos de acção pública.

Determination of airborne nanoparticles from welding operations

The aim of this study is to assess the levels of airborne ultrafine particles emitted in welding processes (tungsten inert gas [TIG], metal active gas [MAG] of carbon steel, and friction stir welding [FSW] of aluminum) in terms of deposited area in pulmonary alveolar tract using a nanoparticle surface area monitor (NSAM) analyzer. The obtained results showed the dependence of process parameters on emitted ultrafine particles and demonstrated the presence of ultrafine particles compared to background levels. Data indicated that the process that resulted in the lowest levels of alveolar deposited surface area (ADSA) was FSW, followed by TIG and MAG. However, all tested processes resulted in significant concentrations of ultrafine particles being deposited in humans lungs of exposed workers.

New syntheses of potential biologically active xanthones and benzoxanthones

10º Encontro Nacional de Química Orgânica e 1º Simpósio Luso-Brasileiro de Química Orgânica, Lisboa, 4-6 Setembro de 2013.

Basic dyestuffs removal from textile effluents using feathers: equilibrium, kinetic and column studies

This research work has been focused in the study of gallinaceous feathers, a waste that may be valorised as sorbent, to remove the Dark Blue Astrazon 2RN (DBA) from Dystar. This study was focused on the following aspects: optimization of experimental conditions through factorial design methodology, kinetic studies into a continuous stirred tank adsorber (at pH 7 and 20ºC), equilibrium isotherms (at pH 5, 7 and 9 at 20 and 45ºC) and column studies (at 20ºC, at pH 5, 7 and 9). In order to evaluate the influence of the presence of other components in the sorption of the dyestuff, all experiments were performed both for the dyestuff in aqueous solution and in real textile effluent. The pseudo-first and pseudo-second order kinetic models were fitted to the experimental data, being the latter the best fit for the aqueous solution of dyestuff. For the real effluent both models fit the experimental results and there is no statistical difference between them. The Central Composite Design (CCD) was used to evaluate the effects of temperature (15 - 45ºC) and pH (5 - 9) over the sorption in aqueous solution. The influence of pH was more significant than temperature. The optimal conditions selected were 45ºC and pH 9. Both Langmuir and Freundlich models could fit the equilibrium data. In the concentration range studied, the highest sorbent capacity was obtained for the optimal conditions in aqueous solution, which corresponds to a maximum capacity of 47± 4 mg g-1. The Yoon-Nelson, Thomas and Yan’s models fitted well the column experimental data. The highest breakthrough time for 50% removal, 170 min, was obtained at pH 9 in aqueous solution. The presence of the dyeing agents in the real wastewater decreased the sorption of the dyestuff mostly for pH 9, which is the optimal pH. The effect of pH is less pronounced in the real effluent than in aqueous solution. This work shows that feathers can be used as sorbent in the treatment of textile wastewaters containing DBA.

Chronic liver disease staging classification based on ultrasound, clinical and laboratorial data

In this work the identification and diagnosis of various stages of chronic liver disease is addressed. The classification results of a support vector machine, a decision tree and a k-nearest neighbor classifier are compared. Ultrasound image intensity and textural features are jointly used with clinical and laboratorial data in the staging process. The classifiers training is performed by using a population of 97 patients at six different stages of chronic liver disease and a leave-one-out cross-validation strategy. The best results are obtained using the support vector machine with a radial-basis kernel, with 73.20% of overall accuracy. The good performance of the method is a promising indicator that it can be used, in a non invasive way, to provide reliable information about the chronic liver disease staging.

Estrutura da boa vida em pessoas com doença crónica

Doenças crónicas (DC) são doenças que têm de ser geridas em vez de curadas. Giovannini, Bitti, Sarchielli e Speltini (1986) caracterizam as doenças crónicas como: a) doenças de longa duração, b) que tendem a prolongar-se por toda a vida do doente, c) que provocam invalidez em graus variáveis, d) são devidas a causas não reversíveis, e) que exigem formas particulares de reeducação, f) que obrigam o doente a seguir determinadas prescrições terapêuticas, g) que normalmente exigem a aprendizagem de um novo estilo de vida, h) que necessitam de controlo periódico, de observação e de tratamento regulares. As DC não se definem pela sua aparente ou real gravidade. As pessoas que têm DC podem fazer a vida do dia-a-dia como qualquer outro cidadão, e grande parte deles acaba por falecer de velhice ou de outras doenças, que não a DC que os acompanhou grande parte da vida. Para estas pessoas viverem uma boa vida o processo de ajustamento é decisivo. O ajustamento à DC torna-se então um objectivo fundamental para as pessoas e para a sociedade. O ajustamento pode definir-se como uma resposta a uma alteração do meio ambiente, que leva um organismo a adaptar-se a essa alteração. Esta definição, explicam as autoras, implica que ele ocorre ao longo do tempo e, também, que é um resultado desejável. Para Stanton, Revenson, e Tennen, (2007), o ajustamento engloba inúmeros componentes que cruzam domínios interpessoais, cognitivos, emocionais, físicos e comportamentais. Estes autores referem que da revisão da literatura se pode concluir que, grosso modo a DC requer, ajustamento em múltiplos domínios, que o ajustamento se desenrola ao longo do tempo, e que existe uma heterogeneidade acentuada no modo como os indivíduos se ajustam à DC. O ajustamento é um conceito do senso comum que tanto é verbo como substantivo.