The role of sport in Basque rural development policies. Opportunities, risks and an evaluative inquiry proposal

Aunque las investigaciones que combinan deporte y desarrollo rural no son muy profusas a nivel estatal, la preeminencia que ha ido adquiriendo la práctica deportiva, y su vinculación con las zonas rurales como espacio de «uso» lo convierten en objeto de estudio novedoso y muy interesante desde la perspectiva de la gestión de políticas públicas. En efecto, la deportividad de la sociedad se ha convertido en objeto de estudio emergente en el ámbito sociológico derivado su elevado impacto socioeconómico y las motivaciones que subyacen a dicha práctica entre otros aspectos principales. Al mismo tiempo, las zonas rurales, promovidas por una intensa política de desarrollo rural, asisten a su transformación en escenario privilegiado para la práctica deportiva, aumentando de manera significativa el desarrollo de actividades deportivas que utilizan estos espacios. El objetivo de esta investigación es delimitar las oportunidades y riesgos para el desarrollo de las zonas rurales desde una visión rigurosa, sostenible y evaluable

Control Loop for a Pulse Generator of a Fast Septum Magnet using DSP and Fuzzy Logic

A prototype of a fast pulsed eddy current septum magnet for one of thebeam extraction's from the SPS towards LHC is under development. The precision of the magnetic field must be better than ±1.0 10-4 during a flat top of 30 µs. The current pulse is generated by discharging the capacitors of a LC circuit that resonates on the 1st and on the 3rd harmonic of a sine wave with a repetition rate of 15 s. The parameters of the circuit and the voltage on the capacitors must be carefully adjusted to meet the specifications. Drifts during operation must be corrected between two pulses by mechanically adjusting the inductance of the coil in the generator as well as the primary capacitor voltage. This adjustment process is automated by acquiring the current pulse waveform with sufficient time and amplitude resolution, calculating the corrections needed and applying these corrections to the hardware for the next pulse. A very cost-effective and practical solution for this adjustment process is the integration of off-the-shelf commercially available boards into an active digital control loop. A 16-bit fixed point, 33 MIPS, DSP together with a 12-bit, 500 kSPS, ADC (total cost of under 250 $) has been used for this control process. The correction algorithm developed for the DSP uses Fuzzy Logic reasoning

El papel del deporte en las politicas de desarrollo rural de euskadi. Oportunidades, riesgos y una propuesta de investigación evaluativa

Though research that combines sport and rural development is no vey profuse at Spanish level, the preeminence that sport practice is getting at social level, together with its connection to rural spaces as a scenario for its practice, has transform this topic in an innovative and very interesting issue from public policy perspective. Firstly, social «sportification» has become an influent research at sociological level due to the high social and economic impact on population, together with the motivations below this practice. At the same time, rural areas are influenced by an intensive rural development policy that has favored the conversion of rural areas into a preeminent place for sport practice, increasing significantly the activities gaining from these areas.The objective of this research is to define the opportunities and risks for the development of rural areas from a rigorous, sustainable and measurable vision.Aunque las investigaciones que combinan deporte y desarrollo rural no son muy profusas a nivel estatal, la preeminencia que ha ido adquiriendo la práctica deportiva, y su vinculación con las zonas rurales como espacio de «uso» lo convierten en objeto de estudio novedoso y muy interesante desde la perspectiva de la gestión de políticas públicas. En efecto, la deportividad de la sociedad se ha convertido en objeto de estudio emergente en el ámbito sociológico derivado su elevado impacto socioeconómico y las motivaciones que subyacen a dicha práctica entre otros aspectos principales. Al mismo tiempo, las zonas rurales, promovidas por una intensa política de desarrollo rural, asisten a su transformación en escenario privilegiado para la práctica deportiva, aumentando de manera significativa el desarrollo de actividades deportivas que utilizan estos espacios.

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOX lo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Multimorbidity patterns in hospitalized older patients: Associations among chronic diseases and geriatric syndromes

Background/Objectives The clinical status of older individuals with multimorbidity can be further complicated by concomitant geriatric syndromes. This study explores multimorbidity patterns, encompassing both chronic diseases and geriatric syndromes, in geriatric patients attended in an acute hospital setting. Design Retrospective observational study. Setting Unit of Social and Clinical Assessment (UVSS), Miguel Servet University Hospital (HUMS), Zaragoza (Spain). Year, 2011. Participants A total of 924 hospitalized patients aged 65 years or older. Measurements Data on patients'' clinical, functional, cognitive and social statuses were gathered through comprehensive geriatric assessments. To identify diseases and/or geriatric syndromes that cluster into patterns, an exploratory factor analysis was applied, stratifying by sex. The factors can be interpreted as multimorbidity patterns, i.e., diseases non-randomly associated with each other within the study population. The resulting patterns were clinically assessed by several physicians. Results The mean age of the study population was 82.1 years (SD 7.2). Multimorbidity burden was lower in men under 80 years, but increased in those over 80. Immobility, urinary incontinence, hypertension, falls, dementia, cognitive decline, diabetes and arrhythmia were among the 10 most frequent health problems in both sexes, with prevalence rates above 20%. Four multimorbidity patterns were identified that were present in both sexes: Cardiovascular, Induced Dependency, Falls and Osteoarticular. The number of conditions comprising these patterns was similar in men and women. Conclusion The existence of specific multimorbidity patterns in geriatric patients, such as the Induced Dependency and Falls patterns, may facilitate the early detection of vulnerability to stressors, thus helping to avoid negative health outcomes such as functional disability

Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae

Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations. In contrast, P450/ABC transporter induction with rifampicin markedly impaired ivermectin absorption. The same ketoconazole-mediated cytochrome/ABC transporter inhibition also occurs outside the mammal host and enhances the mortality of Anopheles gambiae. This was proven by using the samples from the mini-pig experiments to conduct an ex-vivo synergistic bioassay by membrane-feeding Anopheles mosquitoes. Inhibiting the same cytochrome/xenobiotic pump complex in two different organisms to simultaneously boost the pharmacokinetic and pharmacodynamic activity of a drug is a novel concept that could be applied to other systems. Although the lack of a dose-response effect in the synergistic bioassay warrants further exploration, our study may have broad implications for the control of parasitic and vector-borne diseases

Información de medicamentos a la población desde el Servicio de Farmacia a través de Internet

Objectives: To describe and discuss the work of a Pharmacy Department for the health-care portal www.viatusalud.com. Methods: Using a web portal, a Pharmacy Department develops and updates a vademecum on drugs, and answers enquiries by end-users. Results: On December 31, 2002 more than 750 records on drugs were available, and 3030 enquiries had been answered. Conclusions: With this drug information and online enquiry service, our Pharmacy Department helps meet the demand of health-care information posed by the community and by patients previously seen at Clínica Universitaria. In addition, it allows areas of improvement to be detected in the information to be offered to patients fron a Pharmacy Department, and represents a tertiary source of information for health-care professionals

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOX lo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Wwox Deletion in Mouse B Cells Leads to Genomic Instability, Neoplastic Transformation, and Monoclonal Gammopathies

WWOX (WW domain containing oxidoreductase) expression loss is common in various cancers and characteristic of poor prognosis. Deletions, translocations, and loss of expression affecting the WWOX gene are a common feature of various B cell neoplasms such as certain B cell lymphomas and multiple myeloma. However, the role of this common abnormality in B cell tumor initiation and/or progression has not been defined. In this study, we conditionally deleted Wwox early in B cell development by means of breeding Cd19-Cre transgenic mice crossed to Wwox floxed mice (Cd19 Wwox KO). We observed a significant reduced survival in Cd19 Wwox KO mice and the development of B cell neoplasms including B cell lymphomas, plasma cell neoplasias characterized by increased numbers of CD138+ populations as well as monoclonal gammopathies detected by serum protein electrophoresis. To investigate whether Wwox loss could play a role in genomic instability, we analyzed DNA repair functions during immunoglobulin class switch joining between DNA segments in antibody genes. While class switch recombination (CSR) was only slightly impaired, Wwox deficiency resulted in a dramatic shift of double strand break (DSB) repair from normal classical-NHEJ toward the microhomology-mediated alternative-NHEJ pathway, a pathway associated with chromosome translocations and genome instability. Consistent with this, Wwox deficiency resulted in a marked increase of spontaneous translocations during CSR. This work defines for the first time a role for Wwox for maintaining B cell genome stability during a process that can promote neoplastic transformation and monoclonal gammopathies.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada