Thyroid hormone-mediated activation of the ERK/dual specificity phosphatase 1 pathway augments the apoptosis of GH4C1 cells by down-regulating nuclear factor-κB activity

14 pages, 5 figures.Thyroid hormone (T3) plays a crucial role in processes such as cell proliferation and differentiation, whereas its implication on cellular apoptosis has not been well documented. Here we examined the effect of T3 on the apoptosis of GH4C1 pituitary cells and the mechanisms underlying this effect. We show that T3 produced a significant increase in apoptosis in serum-depleted conditions. This effect was accompanied by a decrease in nuclear factor-kappaB (NF-kappaB)-dependent transcription, IkappaBalpha phosphorylation, translocation of p65/NF-kappaB to the nucleus, phosphorylation, and transactivation. Moreover, these effects were correlated with a T3-induced decrease in the expression of antiapoptotic gene products, such as members of the inhibitor of apoptosis protein and Bcl-2 families. On the other hand, ERK but not c-Jun N-terminal kinase or MAPK p38, was activated upon exposure to T3, and inhibition of ERK alone abrogated T3-mediated apoptosis. In addition, T3 increased the expression of the MAPK phosphatase, dual specificity phosphatase 1 (DUSP1), in an ERK-dependent manner. Interestingly, the suppression of DUSP1 expression abrogated T3-induced inhibition of NF-kappaB-dependent transcription and p65/NF-kappaB translocation to the nucleus, as well as T3-mediated apoptosis. Overall, our results indicate that T3 induces apoptosis in rat pituitary tumor cells by down-regulating NF-kappaB activity through a mechanism dependent on the ERK/DUSP1 pathway.This work was supported by grants from the Fundación Mutua Madrileña (2005X0615), from Fondo de Investigaciones Sanitarias (PI070832), from Ministerio de Educación y Ciencia (BFU2004 3465), from Fondo de Investigaciones Sanitarias (RD06/0020/0036), and the European grant CRESCENDO (FP-018652). A.S.-P. and M.L. are recipients of grants from the Spanish MEC (“Ramón y Cajal” Program).Peer reviewe

Visible Light Communication System Using an Organic Bulk Heterojunction Photodetector

A visible light communication (VLC) system using an organic bulk heterojunction photodetector (OPD) is presented. The system has been successfully proven indoors with an audio signal. The emitter consists of three commercial high-power white LEDs connected in parallel. The receiver is based on an organic photodetector having as active layer a blend of poly(3-hexylthiophene) (P3HT) and phenyl C61-butyric acid methyl ester (PCBM). The OPD is opto-electrically characterized, showing a responsivity of 0.18 A/W and a modulation response of 790 kHz at -6 V.This work has been supported by Comunidad Autónoma de Madrid under project S2009/ESP-1781.Publicad

Sensitive monitoring of enterobacterial contamination of food using self-propelled Janus microsensors

Food poisoning caused by bacteria is a major cause of disease and death worldwide. Herein we describe the use of Janus micromotors as mobile sensors for the detection of toxins released by enterobacteria as indicators of food contamination. The micromotors are prepared by a Pickering emulsion approach and rely on the simultaneous encapsulation of platinum nanoparticles for enhanced bubble-propulsion and receptor-functionalized quantum dots (QDs) for selective binding with the 3-deoxy-o-manno-oct-2-ulosonic acid target in the endotoxin molecule. Lipopolysaccharides (LPS) from Salmonella enterica were used as target endotoxins, which upon interaction with the QDs induce a rapid quenching of the native fluorescence of the micromotors in a concentration-dependent manner. The micromotor assay can readily detect concentrations as low as 0.07 ng mL(-1) of endotoxin, which is far below the level considered toxic to humans (275 mu g mL(-1)). Micromotors have been successfully applied for the detection of Salmonella toxin in food samples in 15 min compared with several hours required by the existing Gold Standard method. Such ultrafast and reliable approach holds considerable promise for food contamination screening while awaiting the results of bacterial cultures in a myriad of food safety and security defense applications.Ministerio de Economía y CompetitividadComunidad de Madri

Visible light driven Janus microvehicles in biological media

A light-driven multifunctional Janus micromotor for the removal of bacterial endotoxins and heavy metals is described. The micromotor was assembled by using the biocompatible polymer polycaprolactone for the encapsulation of CdTe or CdSe@ZnS quantum dots (QDs) as photoactive materials and an asymmetric Fe3O4 patch for propulsion. The micromotors can be activated with visible light (470-490 nm) to propel in peroxide or glucose media by a diffusiophoretic mechanism. Efficient propulsion was observed for the first time in complex samples such as human blood serum. These properties were exploited for efficient endotoxin removal using lipopolysaccharides from Escherichia coli O111:B4 as a model toxin. The micromotors were also used for mercury removal by cationic exchange with the CdSe@ZnS core-shell QDs. Cytotoxicity assays in HeLa cell lines demonstrated the high biocompatibility of the micromotors for future detoxification applications.Ministerio de Ciencia e InnovaciónEuropean CommissionComunidad de Madri

Responsiveness of the Spanish Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaires Short Forms (PFDI-20 and PFIQ-7) in women with pelvic floor disorders

6 p.Objective: To evaluate the responsiveness of the Spanish versions of Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire Short Forms (PFDI-20 and PFIQ-7), in order to assess symptoms and quality of life in Spanish women with pelvic floor disorders. Study design: Prospective observational study to assess the responsiveness in 85 women with pelvic floor disorders. PFDI-20 and PFIQ-7 were completed before and after Physiotherapy intervention. The responsiveness was assessed with the p values using the Wilcoxon signed-rank test, the standardized response means of the change (SRM) and the effect size (ES). Results: The Spanish PFDI-20 and PFIQ-7 and the subscales demonstrated small to good responsiveness. The responsiveness was higher for PFDI-20 than for PFIQ-7. The statistic for PFDI-20 was moderate to good (ES 0.68 and SRM 0.84; p<0.0001), and small to moderate for PFIQ-7 (ES 0.48 and SRM 0.57; p<0.0001). Regarding the subscales, the responsiveness was better for Pelvic Organ Prolapse Distress Inventory (POPDI) than Pelvic Organ Prolapse Impact Questionnaire (POPIQ) (ES 0.70 and SRM 0.78; ES 0.42 and SRM 0.47 respectively; p<0.0001). Moderate responsiveness was found for Urinary Distress Inventory (UDI) and Urinary Impact Questionnaire (UIQ) (ES 0.54 and SRM 0.67; ES 0.52 and SRM 0.61 respectively; p<0.0001). Colo-Rectal-Anal Distress Inventory (CRADI) and Colo-Rectal-Anal Impact Questionnaire (CRAIQ) showed poor responsiveness, small in both (ES 0.42, SRM 0.50 and p<0.0001; ES 0.34, SRM 0.39 respectively; p<0.001). All responsiveness was significant. Conclusions: PFDI-20 and PFIQ-7 Spanish versions showed good responsiveness to evaluate the symptoms and the quality of life in Spanish women with PFD undergoing Physiotherapy treatment.Instituto de Salud Carlos II

Spanish cultural adaptation and validation of the shoulder pain and disability index, and the oxford shoulder score after breast cancer surgery

11 p.Background: The Oxford Shoulder Score (OSS) and the Shoulder Pain and Disability Index (SPADI) are patient-based outcome scores with valid psychometric properties which are widely used for shoulder interventions. Objective: The purpose of the study is to adapt both questionnaires cross-culturally to Spanish, and to test their reliability, validity, responsiveness, and feasibility. Design: Cultural adaptation and psychometric validation study. Methods: Consecutive patients who had undergone breast cancer surgery referred to an outpatient clinic at the University of Alcalá de Henares, Spain. One hundred and twenty women who had undergone breast cancer surgery, with pain and shoulder dysfunction. Cross-cultural adaptation was performed according to the international guidelines. Reliability was analysed by test-retest reliability and internal consistency. Content and convergent construct validity were measured by the Expert Committee&apos;s and Spearman coefficient respectively. Responsiveness, feasibility, floor and ceiling effects were also tested. Results: One hundred and twenty women aged 54.2 (±11) years took part in the study. The reliability was excellent; test-retest reliability was 0.974 (p < 0.001) for OSS, and 0.992 (p < 0.001) for SPADI; and Cronbach&apos;s alpha value was 0.947 for OSS, and 0.965 for SPADI. High construct validity was found between the OSS and SPADI questionnaires (r = -0.674). The effect size (ES) and standardized response mean (SRM) was moderate in OSS (ES = 0.50 and SRM = 0.70 (p < 0.001)), and moderate to good in SPADI (ES = 0.59 and SRM = 0.82 (p < 0.001)). Limitations: This study has some limitations, such as the group of participants is composed only of women following breast cancer treatment; the measurement took place in a single centre; and all the questionnaires administered were always provided to the participants in the same order. Conclusions: The OSS and SPADI Spanish versions are applicable, reliable, valid, and responsive to assess shoulder symptoms and quality of life in Spanish women with shoulder pain and disability after breast cancer treatment

Cultural adaptation and validation of the pelvic floor distress inventory short form (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7) spanish versions

5 p.Objective: To develop a linguistically adapted and psychometrically validated Spanish version of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire Short Forms (PFDI-20 and PFIQ-7) to assess symptoms and quality of life in Spanish women with pelvic floor disorders. Study design: Cross-cultural linguistic adaptation was performed following the translation&-backtranslation method in 30 native Spanish-speaking women with pelvic floor disorders to obtain PFDI-20 and PFIQ-7 Spanish versions. The psychometric properties were evaluated in 114 women with pelvic floor disorders. We calculated the reliability with the intraclass correlation coefficient and Cronbach&apos;s alpha coefficient, the validity with Spearman coefficient, the feasibility with the response rate and the filling time, and the ceiling and floor effects. Results: Spanish versions of the PFDI-20 and PFIQ-7 achieved good semantic, conceptual, idiomatic and content equivalence. Concerning the psychometric validation, internal consistency was high with Cronbach&apos;s alpha coefficient of 0.837 (p < 0.001) for PFDI-20 and 0.967 (p < 0.001) for PFIQ-7. The test&- retest reliability was 0.644 (p < 0.001) for the PFDI-20 and 0.786 (p < 0.001) for the PFIQ-7. Good construct validity was found with questionnaires: SF-12, EPIQ and ICIQ-SF. The average administration time was 10.1 (5.8) min for the PFDI-20, and 7.5 (4.7) min for the PFIQ-7. A ceiling effect was detected in the PFIQ-7 (25.4%). Conclusions: The PFDI-20 and PFIQ-7 Spanish versions showed semantic, conceptual, idiomatic and content equivalence with the original versions. Both instruments are reliable, valid and feasible to evaluate symptoms and quality of life in Spanish women with pelvic floor disorders

D-chiro-inositol prevents memory deficits in the 3xTg mouse model of Alzheimer’s disease in a sex-dependent manner.

Subida por la tutora, a petición de Beatriz Pacheco Sánchez.Alzheimer’s disease (AD) is recognized as an age-related neurodegenerative disorder, characterized by the aggregation and deposition of amyloid-β (Aβ) in plaques and neurofibrillary tangles (NFTs) composed of aggregates of hyperphosphorylated tau, a microtubule-associated protein. Sporadic AD, the most prevalent form of the disease, has been proposed to be associated with alterations on insulin signaling. Insulin regulates a series of cognitive processes, such as learning and memory formation and emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of neurodegeneration, particularly in AD. The present study describes the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance, on the occurrence of the cognitive impairment of 3xTg-AD mice. This so called “triple‐ transgenic mice” model mimics many critical aspects of AD neuropathology. To this end, we analysed the effects of daily oral administration DCI 200 mg/Kg/day in male and female 3xTg and WT mice of 9 and 3 months of age. In addition to the evaluation of memory on the Novel Object Recognition, both the locomotion and time in the centre zone of an open field (OF), and the locomotion and anxiety-like behaviour in the elevated plus maze (EPM) test, were monitored. Our results showed that the exploration time of the new object was remarkably higher in the male 3xTg-DCI group when compared to those obtained from the 3xTg-vehicle and WT- vehicle groups at a middle and older age (3 and 9 months). When the center exploration time was analyzed in OPF test, three-way ANOVA showed an effect of the genotype in middle-aged animals. In the EPM test, only 9 months old 3xtg-DCI females were more prone to explore the open-arm, suggesting DCI decreases anxiety levels related to AD. In conclusion, our study suggest that DCI prevents and improves in a sex-dependent manner, the cognitive impairment associated to AD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Health related quality of life improvement in breast cancer patients: Secondary outcome from a simple blinded, randomised clinical trial

7 p.This clinical trial is registered in the International Standard Randomised Controlled Trial Number Register: number ISRCTN95870846Objective: To determine the effectiveness of an early physiotherapy intervention for the prevention of secondary lymphoedema on health-related quality of life in women who also received an education program after breast cancer surgery. Methods: One hundred and fifty three women diagnosed with unilateral breast cancer (stage I-II) treated with breast surgery, which included axillary lymph-node dissection, from Hospital Príncipe de Asturias, Alcalá de Henares, Madrid (Spain) were randomly assigned into two groups. Subjects in early physiotherapy group (n = 76) received a physiotherapy intervention combined with a therapeutic education program; women in the control group (n = 77) received only the therapeutic education program. Both interventions were delivered by two different physiotherapists of Physiotherapy in Women&apos;s Health Research Group at Physiotherapy Department of Alcala University. Health related quality of life was measured with EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires in 5 assessments: after surgery just before group interventions started (A1), after the 3-week group interventions finished (A2); and a follow-up period in 3 (A3), 6 (A4) and 12 (A5) months after surgical intervention. Results: Greater change in quality of life was observed for early physiotherapy group arm compared to control group, although no strong statistical evidence was found (p > .05) for most of the dimensions except for physical function and social function areas (p < .003). Conclusions: The control group with therapeutic education program reported a clear improvement in the perception of quality of life. Adding early physiotherapy to the therapeutic education program did not show statistically significant changes in the global score or in most of the dimensions, but showed an improvement in the physical and social dimensions.Instituto de Salud Carlos II

Spanish cultural adaptation and validation of the shoulder pain and disability index, and the oxford shoulder score after breast cancer surgery

BACKGROUND: The Oxford Shoulder Score (OSS) and the Shoulder Pain and Disability Index (SPADI) are patient-based outcome scores with valid psychometric properties which are widely used for shoulder interventions. OBJECTIVE: The purpose of the study is to adapt both questionnaires cross-culturally to Spanish, and to test their reliability, validity, responsiveness, and feasibility. DESIGN: Cultural adaptation and psychometric validation study. METHODS: Consecutive patients who had undergone breast cancer surgery referred to an outpatient clinic at the University of Alcalá de Henares, Spain. One hundred and twenty women who had undergone breast cancer surgery, with pain and shoulder dysfunction. Cross-cultural adaptation was performed according to the international guidelines. Reliability was analysed by test-retest reliability and internal consistency. Content and convergent construct validity were measured by the Expert Committee’s and Spearman coefficient respectively. Responsiveness, feasibility, floor and ceiling effects were also tested. RESULTS: One hundred and twenty women aged 54.2 (±11) years took part in the study. The reliability was excellent; test-retest reliability was 0.974 (p < 0.001) for OSS, and 0.992 (p < 0.001) for SPADI; and Cronbach’s alpha value was 0.947 for OSS, and 0.965 for SPADI. High construct validity was found between the OSS and SPADI questionnaires (r = −0.674). The effect size (ES) and standardized response mean (SRM) was moderate in OSS (ES = 0.50 and SRM = 0.70 (p < 0.001)), and moderate to good in SPADI (ES = 0.59 and SRM = 0.82 (p < 0.001)). LIMITATIONS: This study has some limitations, such as the group of participants is composed only of women following breast cancer treatment; the measurement took place in a single centre; and all the questionnaires administered were always provided to the participants in the same order. CONCLUSIONS: The OSS and SPADI Spanish versions are applicable, reliable, valid, and responsive to assess shoulder symptoms and quality of life in Spanish women with shoulder pain and disability after breast cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12955-015-0256-y) contains supplementary material, which is available to authorized users