Cognitive insight in first-episode psychosis : changes during Metacognitive Training

Altres ajuts: The project has been funded by the Instituto de Salud Carlos III (Spanish Government); by the Fondo Europeo de Desarrollo Regional (FEDER), Progress and Health Foundation of the Andalusian Regional Ministry of Health, grant PI-0634/2011; Obra Social La Caixa (RecerCaixa call 2013); and Obra Social Sant Joan de Déu (BML).Background: Metacognitive training (MCT) has demonstrated its efficacy in psychosis. However, the effect of each MCT session has not been studied. The aim of the study was to assess changes in cognitive insight after MCT: (a) between baseline, post-treatment, and follow-up; (b) after each session of the MCT controlled for intellectual quotient (IQ) and educational level. Method: A total of 65 patients with first-episode psychosis were included in the MCT group from nine centers of Spain. Patients were assessed at baseline, post-treatment, and 6 months follow-up, as well as after each session of MCT with the Beck Cognitive Insight Scale (BCIS). The BCIS contains two subscales: self-reflectiveness and self-certainty, and the Composite Index. Statistical analysis was performed using linear mixed models with repeated measures at different time points. Results: Self-certainty decreased significantly (p = 0.03) over time and the effect of IQ was negative and significant (p = 0.02). From session 4 to session 8, all sessions improved cognitive insight by significantly reducing self-certainty and the Composite Index. Conclusions: MCT intervention appears to have beneficial effects on cognitive insight by reducing self-certainty, especially after four sessions. Moreover, a minimum IQ is required to ensure benefits from MCT group intervention

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting

Pruritic nodular secondary syphilis in a 61-year-old man with HIV infection

The typical finding in secondary syphilis stage is a generalized non-pruritic maculopapular eruption. We report a case of secondary syphilis in an HIV-infected patient presenting with pruritic crusted nodules showing numerous eosinophils on the histopathological examinatio

Optimization of the sintering thermal treatment and the ceramic ink used in direct ink writing of a-Al2O3: Characterization and catalytic application

Unlike other engineered ceramic products, alumina (Al2O3) displays interesting mechanical and physical properties, which makes it an ideal candidate for a wide range of uses in different fields and in particular for catalytic applications. However, the manufacturing of ceramic components has still a major drawback in production of highly complex three-dimensional (3D) shapes, microfeatures or structures with tailored porosity. Direct Ink Writing (DIW), also known as robocasting, is a material extrusion Additive Manufacturing technology and is one of such versatile methods with unique flexibility in material and geometry. In this work, a-Al2O3 ceramic materials were designed and produced by DIW to determine the most suitable sintering treatment and ceramic ink composition to design new components for catalytic applications. Several thermal treatments varying sintering temperature and time were tested previously to the preparation of inks with different ceramic loadings, up to 75 wt%. A systematic study of the DIW specimens sintered at the optimal sintering temperature – time combination, in terms of microstructure (density and porosity) and mechanical properties (hardness and indentation fracture toughness), was performed to determine the optimize ceramic loading. Finally, finite element modeling and catalytic experiments conducted for the optimal ceramic ink showed that 3D printed parts with a rectilinear infill pattern and 40% infill density favored catalytic performance.Peer ReviewedPostprint (author's final draft

Cognitive insight in first-episode psychosis : changes during Metacognitive Training

Altres ajuts: The project has been funded by the Instituto de Salud Carlos III (Spanish Government); by the Fondo Europeo de Desarrollo Regional (FEDER), Progress and Health Foundation of the Andalusian Regional Ministry of Health, grant PI-0634/2011; Obra Social La Caixa (RecerCaixa call 2013); and Obra Social Sant Joan de Déu (BML).Background: Metacognitive training (MCT) has demonstrated its efficacy in psychosis. However, the effect of each MCT session has not been studied. The aim of the study was to assess changes in cognitive insight after MCT: (a) between baseline, post-treatment, and follow-up; (b) after each session of the MCT controlled for intellectual quotient (IQ) and educational level. Method: A total of 65 patients with first-episode psychosis were included in the MCT group from nine centers of Spain. Patients were assessed at baseline, post-treatment, and 6 months follow-up, as well as after each session of MCT with the Beck Cognitive Insight Scale (BCIS). The BCIS contains two subscales: self-reflectiveness and self-certainty, and the Composite Index. Statistical analysis was performed using linear mixed models with repeated measures at different time points. Results: Self-certainty decreased significantly (p = 0.03) over time and the effect of IQ was negative and significant (p = 0.02). From session 4 to session 8, all sessions improved cognitive insight by significantly reducing self-certainty and the Composite Index. Conclusions: MCT intervention appears to have beneficial effects on cognitive insight by reducing self-certainty, especially after four sessions. Moreover, a minimum IQ is required to ensure benefits from MCT group intervention

Optical control of pain in vivo with a photoactive mGlu receptor negative allosteric modulator

Altres ajuts: ICREA (ICREA Academia-2010), Fundació la Marató de TV3 (Grant 20152031) and IWT (SBO-140028).Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders

Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.This work was funded by ISCIII/FEDER-Subdirección General de Evaluación y Fomento de la Investigación (PI07/0778, PI10/01128, PS09/1296 and PS09/01285), AGAUR (2009SGR23 and 2009SGR321) and Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), iniciativa Ingenio 2010, Programa Consolider and Instituto de Salud Carlos III (ISCIII)/FEDER (RD06/0020/0098 and RD06/0020/0109). Financial support was provided to RRG by BBVA foundation and Asociación Española Contra el Cáncer. NLB acknowledges funding from the Spanish Ministry of Science and Technology (SAF2009-06954). AJ-S was funded by Science and Education Spanish Ministry (MEC) FPI predoctoral fellowship (BES-2008-001850). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders