Randomized control trial to assess the efficacy of metacognitive training compared with a psycho-educational group in people with a recent-onset psychosis.

BACKGROUND: Aims were to assess the efficacy of metacognitive training (MCT) in people with a recent onset of psychosis in terms of symptoms as a primary outcome and metacognitive variables as a secondary outcome. METHOD: A multicenter, randomized, controlled clinical trial was performed. A total of 126 patients were randomized to an MCT or a psycho-educational intervention with cognitive-behavioral elements. The sample was composed of people with a recent onset of psychosis, recruited from nine public centers in Spain. The treatment consisted of eight weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at 6 months follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and metacognition was assessed with a battery of questionnaires of cognitive biases and social cognition. RESULTS: Both MCT and psycho-educational groups had improved symptoms post-treatment and at follow-up, with greater improvements in the MCT group. The MCT group was superior to the psycho-educational group on the Beck Cognitive Insight Scale (BCIS) total (p = 0.026) and self-certainty (p = 0.035) and dependence self-subscale of irrational beliefs, comparing baseline and post-treatment. Moreover, comparing baseline and follow-up, the MCT group was better than the psycho-educational group in self-reflectiveness on the BCIS (p = 0.047), total BCIS (p = 0.045), and intolerance to frustration (p = 0.014). Jumping to Conclusions (JTC) improved more in the MCT group than the psycho-educational group (p = 0.021). Regarding the comparison within each group, Theory of Mind (ToM), Personalizing Bias, and other subscales of irrational beliefs improved in the MCT group but not the psycho-educational group (p < 0.001-0.032). CONCLUSIONS: MCT could be an effective psychological intervention for people with recent onset of psychosis in order to improve cognitive insight, JTC, and tolerance to frustration. It seems that MCT could be useful to improve symptoms, ToM, and personalizing bias.

1-42 ß-amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death.

1-42 ß-Amyloid (Aß(1-42)) peptide is a key molecule involved in the development of Alzheimer's disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of Aß(1-42) peptide activation of the neurodegenerative program is still poorly understood. Here, Aß(1-42) peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of Aß(1-42) peptide in neurons.

Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is the first synthetic retinoid X receptor-selective retinoid (rexinoid) approved for the treatment of cutaneous T-cell lymphoma (CTCL). However, little is known about the signalling pathways by which it exerts its anticarcinogenic effect. OBJECTIVES: To characterize the effects of bexarotene in CTCL cell lines and elucidate the underlying molecular pathways of its antineoplastic effect. METHODS: The cell lines Hut-78, HH and MJ were used. Cell viability was assessed with the XTT assay. The self-renewal potential of cells after bexarotene treatment was studied with the methylcellulose clonogenic assay. Flow cytometry was used to analyse the effects on cell cycle, Ki-67 expression and apoptosis induction. Cell cycle and apoptosis-related protein expression were determined by Western blot and immunofluorescence. RESULTS: Bexarotene induced a loss of viability and more pronounced inhibition of clonogenic proliferation in HH and Hut-78 cells, whereas the MJ line exhibited resistance. Bexarotene upregulated and activated Bax in sensitive lines, although not enough to signal significant apoptosis. Instead, all data point to the inhibition of proliferation, rather than apoptosis, as the main mechanistic action of the rexinoid. Bexarotene signals both G(1) and G(2)/M arrest by the modulation of critical checkpoint proteins. We further found that bexarotene activates p53 by phosphorylation at Ser15, which influences the binding of p53 to promoters for cell cycle arrest, induces p73 upregulation, and, in concordance, also modulates some p53/p73 downstream target genes, such as p21, Bax, survivin and cdc2. Bexarotene-mediated ataxia telangiectasia mutated protein (ATM) activation in all studied lines suggests that ATM is likely to be the p53/p73 upstream activator. CONCLUSIONS: Our data indicate for the first time that bexarotene exerts its effect in CTCL mainly by triggering the p53/p73-dependent cell cycle inhibition pathway, probably by upstream ATM activation. Therefore, bexarotene-modulated genes represent potential biomarkers to assess the response to treatment of patients with CTCL.

Somatotypes of 14 to 19 years old urban boys and girls from Bilbao (Basque Country).

Following the anthropometric method of Heath-Carter (1967) individual somatotypes of a sample of 1260 school children (605 boys and 655 girls) living in Bilbao and aged between 14-19 years have been investigated. Age differences of the somatotype components and sexual dimorphism of the physique were also analyzed. In both sexes, somatotype varies with age. The main factor for these variations of the somatotype is in the boys the endomorphy, and in the girls the mesomorphy. The mean somatotypes of the total sample are in boys central (3.9-3.9-2.7) and in girls mesomorphic-endomorphic (5.3-3.1-2.3).

Menarcheal age in a sample of Basque schoolgirls: a comparative study with other Spanish populations.

Reported data on age at menarche in a sample of Biscayan schoolgirls are compared with data from several Spanish populations. Though the mean age falls in the range of variation of the Spanish means, the analysis of variance shows significant differences among the series. With regard to the possible secular trend of this event in the Biscay province, both a stability of menarcheal age and a diminution of the process of variability are observed.

Skin colour variability in Basque boys aged 8-19 years.

Skin colour variation with increasing age was analysed using a cross-sectional sample of 796 Basque boys aged from 8 to 19 years. Measurements were taken at the upper inner arm and forehead by means of an EEL DS29 Digital Unigalvo reflectance spectrophotometer with a nine-filter head. Ontogenic changes of skin pigmentation were found to be statistically significant. The influence of the month in which measurements were taken on reflectance values has been studied. Comparisons with another similar study (Pembrokeshire, Wales population) were carried out.

Age at menarche from a Biscayan coastal population (Basque Country).

Data on menarcheal age were collected by the status quo method on a sample of 894 schoolgirls (9-19 years of age), from the Biscay province coast (Basque Country, Spain). Logit analysis provided a mean age at menarche of 12.75 +/- 0.04 years with a standard deviation of 0.93. The result was compared with data from another previous Basque study.