Antinociceptive effects of tetrazole inhibitors of endocannabinoid inactivation: Cannabinoid and non-cannabinoid receptor-mediated mechanisms

Background and purpose: Tetrazoles were recently developed as inhibitors of the cellular uptake of the endocannabinoid anandamide or of its hydrolysis by fatty acid amide hydrolase (FAAH), but were proposed to act also on non-endocannabinoid-related serine hydrolases. Experimental approach: We tested, in a model of inflammatory pain induced in mice by formalin, five chemically similar inhibitors: (i) OMDM119 and OMDM122, two potent carbamoyl tetrazole FAAH inhibitors with no effect on anandamide uptake; (ii) LY2183240, a carbamoyl tetrazole with activity as both FAAH and uptake inhibitor; (iii) OMDM132, a non-carbamoyl tetrazole with activity only as uptake inhibitor and iv) OMDM133, a non-carbamoyl tetrazole with no activity at either FAAH or uptake. Results: All compounds (2.5-10 mg kg -1, i.p.) inhibited the second phase of the nocifensive response induced by intraplantar injection of formalin. The effects of OMDM119, OMDM122 and OMDM133 were not antagonized by pretreatment with cannabinoid CB 1 receptor antagonists, such as rimonabant or AM251 (1-3 mg kg -1, i.p.). The effects of LY2183240 and OMDM132 were fully or partially antagonized by rimonabant, respectively, and the latter compound was also partly antagonized by the CB 2 receptor antagonist, AM630. Conclusions and implications: (i) non-FAAH hydrolases might be entirely responsible for the antinociceptive activity of some, but not all, tetrazole FAAH inhibitors, (ii) the presence of a carbamoylating group is neither necessary nor sufficient for such compounds to act through targets other than FAAH and (iii) inhibition of anandamide uptake is responsible for part of this antinociceptive activity, independently of effects on FAAH. © 2008 Macmillan Publishers Limited All rights reserved

Association Between Endometriosis and Preterm Birth in Women With Spontaneous Conception or Using Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of Cohort Studies

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado.OBJECTIVE: To perform a systematic review and meta-analysis to estimate the effect of endometriosis on preterm birth (PB) risk. METHODS: Searches were conducted in PubMed-MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, Google Scholar, and SciELO for studies published in all languages from inception through April 2017. We included cohort studies evaluating pregnant women with and without endometriosis and conception either by spontaneous conception (SC) or with assisted reproductive technology (ART). Primary outcome was PB (<37 weeks), and secondary outcomes were intrauterine growth restriction (IUGR), low birthweight, small for gestational age (SGA), and birthweight. Pooled odds ratios (ORs) and its 95% confidence interval (CI) were calculated as effects, and random-effects models were used for meta-analyses. Risk of bias was assessed with the Newcastle-Ottawa Scale, and heterogeneity of effects among studies was described with the I2 statistic. RESULTS: We identified 9 cohort studies including a total of 1 496 715 pregnancies (13 798 with endometriosis diagnosis). In women with endometriosis, the PB risk was significantly increased in both SC (OR: 1.59; 95% CI: 1.32-1.90) and ART (OR: 1.43; 95% CI: 1.14-1.79). The SGA risk was increased in women with endometriosis (OR: 1.16; 95% CI: 1.05-1.28), while the IUGR and low birthweight risks and birthweight were not affected by endometriosis. CONCLUSION: Endometriosis is associated with increased PB risk in both SC and women who obtained pregnancy using ART. Prospective studies evaluating relevant outcomes are needed to confirm these results.Revisión por pare

Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p<0·0001). After adjustment, multivariable analysis showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine and valproate as well as for phenobarbital at doses of more than 80 mg/day than for lamotrigine at doses of 325 mg/day or less. Valproate at doses of 650 mg/day or less was also associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250?4000 mg/day (odds ratio [OR] 2·43, 95% CI 1·30?4·55; p=0·0069). Carbamazepine at doses of more than 700 mg/day was associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250?4000 mg/day (OR 2·41, 95% CI 1·33?4·38; p=0·0055) and oxcarbazepine at doses of 75?4500 mg/day (2·37, 1·17?4·80; p=0·0169). Interpretation: Different antiepileptic drugs and dosages have different teratogenic risks. Risks of major congenital malformation associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the literature for offspring unexposed to antiepileptic drugs. These findings facilitate rational selection of these drugs, taking into account comparative risks associated with treatment alternatives. Data for topiramate and phenytoin should be interpreted cautiously because of the small number of exposures in this study. Funding: Bial, Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, UCB, the Netherlands Epilepsy Foundation, and Stockholm County Council.Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Battino, Dina. Foundation Irccs Neurological Institute "c. Besta"; ItaliaFil: Bonizzoni, Erminio. Università degli Studi di Milano; ItaliaFil: Craig, John. Belfast Health And Social Care Trust; Reino UnidoFil: Lindhout, Dick. Stichting Epilepsie Instellingen Nederland; Países BajosFil: Perucca, Emilio. Universita Degli Studi Di Pavia; ItaliaFil: Sabers, Anne. Rigshospitalet; DinamarcaFil: Thomas, Sanjeev V. Sree Chitra Tirunal Institute For Medical Sciences And Technology; IndiaFil: Vajda, Frank. University of Melbourne; AustraliaFil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Bohorquez Morera, Natalia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentin

GC Insights: Lessons from participatory water quality research in the upper Santa River basin, Peru

Here we share four key lessons from an inter-disciplinary project (Nuestro Rio) that gathered community perspectives on local water quality in the Santa River basin (Peru) utilising a digital technological approach where we collected data via a novel photo elicitation app, supported by a field work campaign. The lessons explored in this article provide insights into challenges and opportunities for researchers considering developing technological tools for encouraging participation and engagement in marginalised communities

Estructura óptima de capital para Walmart México y Centroamérica

Trabajo final de Graduación (Maestría en Administración de Empresas) Instituto Tecnológico de Costa Rica, Escuela de Administración de Empresas, 2019.El principal objetivo del presente trabajo es determinar el costo promedio ponderado de capital y la estructura óptima de capital de Walmart México y Centroamérica que debería utilizar Walmart para maximizar el valor de su compañía. En el primer capítulo se plantea y sustenta el problema de estudio y se determina la base de la investigación, y de este se derivan el tema central y el enfoque. Actualmente Walmart se financia con más de 90% de capital propio. Al ser Walmart una empresa que realiza constantes inversiones es clave determinar el apalancamiento adecuado para maximizar los rendimientos de la compañía. En el segundo capítulo del trabajo de investigación se plantean la base y la fundamentación teórica. Se desarrolla una estructura conceptual relacionada con el problema y con los objetivos planteados; se establecen conceptos de términos y nociones que se aplican para el cálculo del costo promedio ponderado de capital y la estructura óptima de capital. En el tercer capítulo del documento se explican los procedimientos metodológicos seguidos en el desarrollo del estudio; de los estados financieros de Walmart publicados por la Bolsa Mexicana de Valores se extrae información requerida para el cálculo del costo promedio ponderado de capital para realizar un análisis de sensibilidad de los factores deuda y capital a fin de determinar la estructura óptima de capital. En el cuarto capítulo, una vez analizados los temas ya mencionados, se presentan los resultados de la investigación en cuanto a la presentación y el análisis de los resultados del cálculo del costo promedio ponderado de capital, y en cuanto al cálculo de la estructura IV óptima de capital. En este punto es clave el análisis de los resultados puesto que se obtuvo como resultados que el Walmex debería utilizar un apalancamiento por deuda de 25% y de 75% de patrimonio o capital propio con respecto a la estructura actual. Y, finalmente, se determinó un costo promedio ponderado de capital de 9,01%, el cual se utilizará para evaluar futuras inversiones. En el capítulo quinto del documento, se presentan, primeramente, las conclusiones obtenidas del estudio, ordenadas las ideas con base en los objetivos específicos planteados para la investigación, así como según la naturaleza general de cada tema. Seguidamente se plantean las recomendaciones pertinentes. En ellas se destacan los cursos de acción específicos y las opciones propuestas para mejorar o replantear aspectos importantes en términos de la estructura óptima. También se plantean las recomendaciones sobre la necesidad de efectuar evaluaciones de cálculo de valor económico agregado y valoración de la empresa utilizando flujos futuros de efectivo.The main objective of the present study is to determine the Weighted Average Capital Cost or WACC and the Optimal Capital Structure for Walmart Mexico and central America countries that Walmart should use to maximize enterprise value. First Chapter, the problem of the study is raised and sustained. It is determined as base of the investigation the central topic and the focus of the investigation. Currently, Walmart financed its operations and project with more that 90% of equity. Walmart is constantly investing in new project; therefore, it is critical to determine the rate of leveraging required to maximize company results. In the second chapter of the investigation the theoretical basis and foundation is presented. A conceptual structure related to the problem and the proposed objectives is developed. The concepts of terms and notions are established that apply to the calculation of the weighted average cost of capital and the optimal capital structure. For the third chapter of the document, the methodological procedures used in the development of the study are stipulated; Walmart's financial statements published on the Mexican stock exchange are taken to extract information required for the calculation of the weighted average cost of capital and to carry out a sensitization analysis of the debt and capital factors in order to determine the optimal capital structure VI For the fourth chapter, and once all the previous topics have been explained, the results of the study carried out, the presentation and analysis of the results of the Weighted Average Cost of Capital calculation and the calculation of the optimal capital structure are presented. At this point the analysis of the results is critical, it was obtained as results that Walmex should use a leverage of 25% debt and 75% equity or equity with respect to the current structure. And finally, a Weighted Average Cost of Capital of 9.01% was determined, which will be used for future investment evaluations. Finally, in the chapter five of the document, the conclusions obtained in the study are established, ordering the ideas based on the specific objectives set for the investigation, as well as the general nature of the subject. Next, the recommendations of the work are established, highlighting the specific courses of action, and proposed options focused on improving or rethinking important aspects in terms of optimal structure as well as the recommendations to make evaluations of calculation of Economic Value Added and valuation of the company using future cash flows

Isolation of Neisseria meningitidis strains with increase of penicillin minimal inhibitory concentrations

We report the isolation and characterization of ten strains showing an increase in the minimal inhibitory concentrations to penicillin (MICs > 0·1 μg/ml), and describe the epidemiological, clinical and microbiological features. The susceptibility of 3432 meningococcal strains isolated from patients in the recent epidemic wave (1978–86) in Spain, to several antimicrobial agents used in the treatment and chemoprophylaxis of meningococcal infection has been tested. Most were resistant to sulphadiazine but sensitive to other antibiotics. The possible existence of a new pattern of behaviour of meningococcal to penicillin is discussed

Representations of Utopian Urbanism and the Feminist Geopolitics of ‘New City’ Development

Increasingly over the past few years the building of new cities “from scratch” has become a key strategy to promote development across much of the Global South. While several projects are currently under construction, many others exist primarily as proposals awaiting adequate investment or government action. This paper builds on previous literature that considers representations of such projects – promotional materials, digitally-produced video simulations, and master plans – as key components in the production of imagined urban futures. Through an exploration of the proposed Zone for Economic Development and Employment (ZEDE) in Honduras, this article demonstrates a feminist geopolitical approach focused on how such representations of utopian urbanism circulate through the local communities slated for new city development. I examine how representations of future urban spaces and future urban governance regimes become appropriated by local residents in organizing opposition or otherwise making sense of the proposed project’s potential impact on their lives.12 month embargo; published online: 30 Dec 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The influence of technology on the mathematical modelling of physical phenomena

A study is presented in which students are asked to model two physical phenomena using applications on electronic tablets : a bounce of a ball and the extension of a spring. The analysis focusses on (a) the influence of characteristics of the applications on the tablets on the decisions that groups of 16-year-old students made during the modelling phases in which reality and mathematics are related, (b) mathematisation of the phenomena and (c) interpretation of the models. The phenomena were recorded using an app that requests users establish a set of references during the mathematisation process, which makes students focus on the way the references have been set to interpret the model properly. Our findings indicated inconsistences between student decisions made during mathematisation and their considerations during interpretation of the model. To conclude we suggest reasons students experience problems in working without a pre-defined reference syste