A large comparison of integrated SAR/QSAR models of the Ames test for mutagenicity$.

Results from the Ames test are the first outcome considered to assess the possible mutagenicity of substances. Many QSAR models and structural alerts are available to predict this endpoint. From a regulatory point of view, the recommendation from international authorities is to consider the predictions of more than one model and to combine results in order to develop conclusions about the mutagenicity risk posed by chemicals. However, the results of those models are often conflicting, and the existing inconsistency in the predictions requires intelligent strategies to integrate them. In our study, we evaluated different strategies for combining results of models for Ames mutagenicity, starting from a set of 10 diverse individual models, each built on a dataset of around 6000 compounds. The novelty of our study is that we collected a much larger set of about 18,000 compounds and used the new data to build a family of integrated models. These integrations used probabilistic approaches, decision theory, machine learning, and voting strategies in the integration scheme. Results are discussed considering balanced or conservative perspectives, regarding the possible uses for different purposes, including screening of large collection of substances for prioritization.

A Self-determination theory based intervention to promote healthy eating and physical activity in school-aged children / Una intervención basada en la teoría de la autodeterminación para promover la alimentación saludable y la actividad física en los niños en edad escolar / Uma intervenção baseada na teoria de auto-determinação para promover a alimentação saudável e atividade física em crianças em idade escolar

Childhood overweight and obesity in both girls and boys is reaching epidemic proportions over the world, Italy included. Childhood obesity has been linked to deleterious health consequences. There is a need to develop theory based and cost-effective interventions to promote healthy eating and physical activity with the aim to reduce obesity. The purpose of this study was to evaluate a long-term theory-based intervention to promote healthy lifestyles in underserved school-aged children. A quasi experimental design was adopted, in order to evaluate the effectiveness of the intervention, considering information from their parents. Parents were asked to rate their children attitude, motivation and behaviour regarding two energy balance-related behaviours. Results indicate that pupils involved in the intervention were more likely to do physical activity in leisure time and have more positive attitudes toward exercise compared to the control group. About eating habits, children involved in the intervention were more likely to choose healthy foods and less likely to choose fat foods compare to the control group. Changes in attitude and motivation between the baseline and the follow up and the two groups are also shown, even if not significant. Despite several limitations in the design, this study provided further support to the argument that Self-determination theory-based interventions could result in meaningful health-behavior changes (AU)

Niñez sobrepeso y obesidad en niños y niñas está alcanzando proporciones epidémicas en el mundo entero, Italia incluida. La obesidad infantil se ha relacionado con consecuencias perjudiciales para la salud. Hay una necesidad de desarrollar intervenciones teoría basada y rentables para promover la alimentación saludable y la actividad física con el objetivo de reducir la obesidad. El propósito de este estudio fue evaluar una intervención basada en la teoría de largo plazo para promover estilos de vida saludables en niños en edad escolar de escasos recursos. Se adoptó un diseño cuasi experimental, con el fin de evaluar la eficacia de la intervención, teniendo en cuenta la información de sus padres. Se pide a los padres para evaluar a sus hijos la actitud, la motivación y el comportamiento con respecto a los comportamientos relacionados con saldo de dos energías. Los resultados indican que los alumnos que participan en la intervención tenían más probabilidades de hacer actividad física en el tiempo libre y tienen actitudes más positivas hacia el ejercicio en comparación con el grupo control. Acerca de los hábitos alimenticios, los niños que participaron en la intervención eran más propensos a elegir alimentos saludables y menos propensos a elegir alimentos ricos en grasas en comparación con el grupo control. Los cambios en la actitud y la motivación entre el inicio y el seguimiento y los dos grupos se muestran también, aunque no significativamente. A pesar de varias limitaciones en el diseño, este estudio proporcionan más apoyo al argumento de que las intervenciones basadas en teoría de la autodeterminación podrían resultar en cambios significativos que afectan a su salud significativamente (AU)

Infância sobrepeso e obesidade em meninas e meninos Ambas está atingindo proporções epidêmicas no mundo inteiro, Itália incluído. Infância a obesidade tem-se ligado a consequências para a saúde deletérios. ere a necessidade de desenvolver a teoria com base e de custou-se intervenções estive para promover saudável comer e atividade física Com o objetivo de reduzir a obesidade. e efeitos de estudo ESTA foi avaliar uma intervenção baseada na teoria de longo prazo para promover estilos de vida saudáveis em crianças em idade escolar carentes. Um projeto quase-experimental foi adotado, a fim de avaliar o estiveres da intervenção, considerando as informações de seus pais. Os pais foram convidados a avaliar sua atitude infantil, motivação e comportamento em relação dois comportamentos relacionados com o balanço de dois energia. Os resultados indicam que alunos envolvidos na intervenção eram mais propensos a fazer atividade física no tempo livre e têm atitudes mais positivas em relação ao exercício comparado ao grupo controle. Sobre os hábitos alimentares, as crianças na intervenção envolvidos eram mais propensos a escolher alimentos saudáveis e menos propensos a escolher alimentos ricos em gordura comparar com o grupo de controle. Mudanças de atitude e motivação Entre a linha de base e o acompanhamento e os dois grupos são mostrados Além disso, mesmo que não seja significante. Apesar das limitações na concepção Vários, Este estudo forneceu ainda apoio ao argumento de que intervenções baseadas em teoria da autodeterminação poderia resultar em mudanças de comportamento de saúde significativos (AU)

Running away from stress: How regulatory modes prospectively affect athletes' stress through passion.

A prospective field study conducted with runners training for an upcoming marathon (Marathon of Rome 2013) examined the relation between regulatory modes, locomotion and assessment, and stress. Integrating regulatory mode theory and the dualistic model of passion, we hypothesized that the relation between regulatory modes (evaluated 3 months before the race) and the experience of stress approaching the marathon, is mediated by the type of passion (harmonious vs obsessive) athletes experience with regard to marathoning. Results revealed that (a) locomotion positively predicted harmonious passion, which in turn reduced athletes' experience of stress; and (b) assessment positively predicted obsessive passion, which in turn enhanced athletes' experience of stress. Overall, the present results suggest that proximal psychological mechanisms such as basic regulatory mode orientations can predict distal outcomes such as stress indirectly through their relation with motivational phenomena such as passion.

Comparison of in silico tools for evaluating rat oral acute toxicity.

Different in silico models have been developed and implemented for the evaluation of mammalian acute toxicity, exploring acute oral toxicity data expressed as median lethal dose (LD(50)). We compared five software programs (TOPKAT, ACD/ToxSuite, TerraQSAR, ADMET Predictor and T.E.S.T.) using a dataset of 7417 chemicals. We tested the models' performance using the quantitative results and, in classification, the toxicity threshold defined within the Classifying, Labelling and Packaging (CLP) regulation. ACD gave the best results with r(2) of 0.79 and 0.66 accuracy. However, its performance dropped when considering the molecules not present in its training set, and the other models behaved similarly. We also considered the information on the applicability domain (AD), which improved the models' performance, but not enough for the molecules external to the models' training set. We also considered the chemical classes and found that all models gave high performance for certain classes (e.g. hydrazones and sulphides) while other classes were always badly predicted (e.g. aromatic secondary amides).

Efficacy and safety of anti-TNF-alpha therapy combined with cyclosporine A in patients with rheumatoid arthritis and concomitant hepatitis C virus infection.

This study further expands our previous observation demonstrating the usefulness of combination therapy of anti-TNF-alpha and cyclosporine A in the treatment of rheumatoid arthritis and concurrent hepatitis C virus infection, as well its efficacy and safety in controlling HCV viremia and liver toxicity. Seven patients were included in the study; transaminase levels remained unchanged, HCV RNA serum levels decreased significantly and DAS 28 significantly improved after twelve month follow-up. No side effects were registered.

Cytokine secretion in nasal mucus of normal subjects and patients with allergic rhinitis.

Allergic rhinitis is regulated by the local production and release of several cytokines. The levels of Th2 cytokines IL-4, IL-6, IL-10 and the Th1 cytokine IFN-gamma were studied in nasal mucus from 30 subjects with allergic rhinitis and 45 non-atopic healthy controls. In this study a sampling technique for collecting nasal mucus, well tolerated by the subjects and with a minimal stimulation of the mucosa, was performed. The cytokine concentrations in nasal mucus samples were detected and quantitated by a new paramagnetic particle-based immunofluorescent assay system more sensitive than the conventional ELISA techniques. The new technique showed reliable values of the measured parameters. The nasal mucus from allergic patients contained significantly higher concentrations of IL-4 (25.5 +/- 3.6 pg/ml; P < 0.001) and IL-10 (1300 +/- 190 pg/ml; P < 0.05) compared to the nasal mucus from control subjects (15.2 +/- 2.3 and 532 +/- 28 pg/ml, respectively, for IL-4 and IL-10). No significant modification in IFN-gamma levels of allergic patients was found when compared to control group (respectively, 19.9 +/- 3.3 vs. 25.7 +/- 5.1 pg/ml; P > 0.05). Moreover, the allergic patients showed lower levels of IL-6 concentrations in the nasal mucus compared to control subjects (64.8 +/- 9.1 vs. 129.0 +/- 18.1 pg/ml; P = 0.0099). These data can be interpreted by the hypothesis that in response to environmental allergens there is a preferential Th2 polarity by activated CD4+ T cells and that the cytokines IL-6 and IL-10 have, respectively, an important anti-inflammatory and counterregulatory action in the pathogenesis of allergic rhinitis.

Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis.

OBJECTIVE: To evaluate whether, in patients with the diffuse form of systemic sclerosis (dSSc), macrophage migration inhibitory factor (MIF) production is dysregulated. METHODS: 10 patients with dSSc and 10 healthy controls, matched for age and sex, were studied. MIF expression was evaluated by immunohistochemistry on formalin fixed skin biopsies of patients with dSSc and controls. MIF levels were assayed in the sera and in the supernatants of skin cultured fibroblasts by a colorimetric sandwich enzyme linked immunosorbent assay (ELISA). MIF concentrations in culture medium samples and in serum samples were compared by Student's two tailed t test for unpaired data. RESULTS: Anti-MIF antibody immunostained the basal and mainly suprabasal keratinocytes. Small perivascular clusters of infiltrating mononuclear cells were positive; scattered spindle fibroblast-like cells were immunostained in superficial and deep dermal layers. The serum concentrations of MIF in patients with dSSc (mean (SD) 10705.6 (9311) pg/ml) were significantly higher than in controls (2157.5 (1288.6) pg/ml; p=0.011); MIF levels from dSSc fibroblast cultures (mean (SD) 1.74 (0.16) ng/2 x 10(5) cells) were also significantly higher than in controls (0.6 (0.2) ng/2 x 10(5) cells; p=0.008). CONCLUSION: These results suggest that MIF may be involved in the amplifying proinflammatory loop leading to scleroderma tissue remodelling.

Diff Quik staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids.

OBJECTIVE: To evaluate whether the Diff Quik (DQ) staining method might prove useful in identifying monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals on permanent mounted stained slides. METHODS: 27 synovial fluid (SF) samples obtained from the knees of 21 patients with acute CPPD disease and 6 with acute gout were studied. Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, 16 inflammatory synovial effusions obtained from patients with knee arthritis induced by non-crystalline inflammatory diseases were studied. For each SF, a DQ stained slide was analysed by two of the authors trained in SF analysis. The observers were blinded to the type of crystals present in the SF. Each slide was analysed by compensated polarised as well as transmitted light microscopy. An SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observer was asked to identify the type of the crystals using compensated polarised light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the DQ staining method were determined. RESULTS: 51 true positive and 28 true negative cases were correctly classified (39 CPPD samples, 12 MSU samples, 28 samples of crystal unrelated arthropathies). Overall, four false positive and three false negative cases were reported. In all the false positive cases, extracellular CPPD crystals were erroneously identified, whereas CPPD crystals present in the SF were not identified in the three false negative cases. All MSU specimens were correctly diagnosed. The overall specificity, sensitivity, and accuracy using DQ stained slides for crystal confirmation were respectively 87.5%, 94.4%, and 91.9%. The PPV was 92.7% and the NPV 90.3%. In particular, the specificity, sensitivity, and accuracy for CPPD detection were 90.9%, 92.9%, and 91.9%, with a PPV of 90.7 and an NPV of 93.0%. All the MSU specimens were correctly identified, providing 100% sensitivity, specificity, accuracy, PPV, and NPV. CONCLUSIONS: Stained preparations of SF, including DQ stained smears, could provide a useful tool for delayed SF analysis suitable for quality controls, including cytological examination and crystals detection and identification.

[Diff-Quik(R) staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids] / La colorazione con Diff-Quik(R) per l'identificazione di cristalli di urato monosodico e pirofosfato di calcio diidrato nel liquido sinoviale.

The aim of this study was to evaluate whether DQ could prove useful to identify monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals on permanent mounted stained slides. To this end, we studied 27 synovial fluid (SF) samples obtained from the knees of patients with the pseudogout (n=21) and acute gouty arthritis (n=6). Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, we studied 16 inflammatory synovial effusions obtained from patients with knee arthritis not induced by crystals. For each SF, DQ stained slides were analyzed by 2 experienced doctors in SF analysis. The observers were blinded to the type of crystal present in the SF. Each slide was analyzed by compensated polarized and transmitted light microscopy. SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observers were asked to identify the type of the crystals using compensated polarized light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the DQ staining method were determined. 51 true positive and 28 true negative specimens were correctly classified (39 CPPD samples, 12 MSU samples, and 28 samples of crystals-unrelated arthropathies). All MSU specimens were correctly diagnosed.

Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome.

OBJECTIVE: Substance P (SP), a neurotransmitter stored within the afferent nociceptive fibers, is likely to be involved in the pathogenesis of musculoskeletal pain. We investigated SP immunoreactive (SP-ir) nerve fibers in the upper trapezius of patients with fibromyalgia (FM) and myofascial pain syndrome (MPS) by immunochemistry. METHODS: Trapezius muscle obtained from tender points of 9 women with primary FM, from trigger points of 9 women with regional myofascial pain, and from 9 control women were immunostained with anti-SP sera. Quantitative evaluation was performed by computerized image analysis. RESULTS: No significant differences in the number of SP-ir areas were detected between groups (one way ANOVA: p = 0.2); in contrast, mean optical density (OD) of SP-ir showed a significant difference comparing the groups (one way ANOVA: p < 0.0001). Mean OD of the immunostaining for SP was statistically greater in trapezius muscle of patients with MPS (0.594 +/- 0.096) compared to specimens from patients with FM (0.436 +/- 0.140) (p < 0.05) and controls (0.314 +/- 0.105) (p < 0.05); mean OD of immunostaining for SP was greater in FM specimens than in controls (p < 0.05). CONCLUSION: Our results point to a peripheral hyperactivity of the peptidergic nervous system in FM as well as in MPS. These findings support the notion of pathogenetic involvement of the afferent nervous system in the development and perception of myofascial pain.

Rotator cuff tear associated with an acromioclavicular cyst in rheumatoid arthritis.

We report two cases of a full-thickness rotator cuff tear followed by acromioclavicular cyst formation in patients with longstanding erosive polyarticular rheumatoid arthritis. One of the consequences of a rotator cuff tear is articular instability with upward migration of the humeral head. The ensuing chronic friction against the undersurface of the acromioclavicular joint caused by arm movements can lead to a non-inflammatory effusion of the acromioclavicular joint with cyst formation. Clinical and ultrasonographic features and a pathogenetic hypothesis are discussed.

Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo.

This study assessed the analgesic action of tramadol compared with placebo in patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one male) were treated according to a double-blind crossover experimental design. Each patient, after signing informed consent, was randomly allocated to either tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo for a single dose treatment. At the second visit, patients crossed over to the other drug for a further single dose treatment. There was a wash-out period of 1 week. Nine patients completed the study, while in three cases (two tramadol, one placebo) the study was discontinued due to the onset of side effects. The assessment of efficacy, carried out at the baseline and 15 min and 2 hours after administration of each dose, involved the use of a visual analog scale (VAS 100 mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic" tender points and nine "control" tender points for fibromyalgic pain. During the first treatment cycle effective control of spontaneous pain was achieved with tramadol, which determined a reduction of 20.6% while with the placebo spontaneous pain increased by 19.8%. With pressure dolorimetry there were no clinically important differences observed after either active treatment or placebo. The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.