181 research outputs found

    Citizen participation in the Plan for the Recovery of the Gomera Giant Lizard

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    [Resumo] Este programa forma parte do Proxecto Life denominado “Plano de Recuperación do Lagarto Xigante da Gomera”, cofinanciado pola Unión Europea, Ministerio de Medio Ambiente, Goberno de Canarias e Cabido Insular da Gomera.[Abstract] This programme forms a part of the Life Project entitled “Plan for the Recovery of the Gomera Giant Lizard” which is co-financed by the European Union, the Ministry of the Environment and the Government of the Canary Islands and the Island Council of La Gomera

    Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats

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    Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levelsThis work was supported by Ministerio de Economía y Competitividad (SAF2015-71026R) and Fondo de Investigación Sanitaria-FEDER (PI19/00785 and PI19/00990). CIBEROBN is an initiative of the Instituto de Salud Carlos III, SpainS

    Crystalline silicon solar cells beyond 20% efficiency

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    —This paper describes a fabrication process to obtain high efficiency c-Si cells (> 20%) based on the Laser Fired Contact Passivated Emitter Rear Cell (LFC-PERC) concept. Photovoltaic efficiencies beyond 20% have been achieved using thermal SiO2 as a rear passivation layer on 2 cm x 2 cm solar cells with 0.45 cm Fz c-Si substrates. Efficiencies up to 22% are expected for material resistivities in the 0.4–5 cm using an optimized rear contact gridPostprint (published version

    Factores de riesgo de mortalidad en pacientes hospitalizados con COVID-19 aplicando un algoritmo de aprendizaje automático

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    Introduction Risk stratification of patients with COVID-19 can be fundamental to support clinical decision-making and optimize resources. The objective of our study is to identify among the routinely tested clinical and analytical parameters those that would allow us to determine patients with the highest risk of dying from COVID-19. Material and methods We carried out a retrospective cohort multicentric study by consecutively, including hospitalized patients with COVID-19 admitted in any of the 11 hospitals in the healthcare network of HM Hospitals-Spain. We collected the clinical, demographic, analytical, and radiological data from the patient's medical records. To assess each of the biomarkers’ predictive impact and measure the statistical significance of the variables involved in the analysis, we applied a random forest with a permutation method. We used the similarity measure induced by a previously classification model and adjusted the k-groups clustering algorithm based on the energy distance to stratify patients into a high and low-risk group. Finally, we adjusted two optimal classification trees to have a schematic representation of the cut-off points. Results We included 1246 patients (average age of 65.36 years, 62% males). During the study one hundred sixty-eight patients (13%) died. High values of age, D-Dimer, White Blood Cell, Na, CRP, and creatinine represent the factors that identify high-risk patients who would die. Conclusions Age seems to be the primary predictor of mortality in patients with SARS-CoV-2 infection, while the impact of acute phase reactants and blood cellularity is also highly relevant.S

    Declared experiences of risky sexual behaviors in relation to alcohol consumption in the first year of college

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    Fundamentos: En universitarios, el consumo de alcohol de mayor riesgo (borracheras y binge drinking (BD), tiene consecuencias negativas sobre su desarrollo y probablemente facilita conductas sexuales de riesgo. El objetivo de este trabajo fue estudiar si las conductas sexuales de riesgo al consumir alcohol (CSRA) se asocian a los consumos de mayor riesgo. Métodos: Estudio multicéntrico transversal con datos del Proyecto uniHcos, de universitarios de 1er año de 11 universidades españolas, entre los cursos 2011-2012 y 2017- 2018. Datos recogidos mediante cuestionario autoadministrado. Se realizó un análisis uni y bivariable, evaluando la significación estadística de las diferencias de prevalencia con chi-cuadrado. Se utilizó media y desviación típica para variables cuantitativas y como estadístico de contraste t de Student. Resultados: 9.862 participantes (72,2% mujeres). El 90,3% consumió alcohol y el 60,9% tuvo borracheras en último año; el 49% tuvo BD en el último mes. El consumo en el último mes y las borracheras fueron mayores en hombres y < 21 años. Las CSRA fueron superiores entre los que se emborracharon (15,7% sexo sin protección, 1,9% abuso sexual y 0,7% aprovecharse sexualmente) y consumieron en BD (17,1%, 1,9% y 0,7%). Las mujeres con ambos consumos de riesgo presentaron más abusos sexuales (2,2%), y los hombres fueron quienes más se aprovecharon sexualmente de otros (borracheras:1,2%; BD: 1,3%). Conclusiones: El consumo de alcohol está por encima de grupos similares. El BD tiene un patrón similar por género y edad. Las CSRA se asocian a los consumos de mayor riesgo, no detectándose en este grupo diferencias por género en sexo sin protección, sí en otras CSRA.Objective: In college students, higher risk alcohol consumption (drunkenness and binge drinking-BD) has negative consequences on their development and and probably facilitates risk sexual behaviors. The objective was to study if risky sexual behaviors when consuming alcohol (RSBA) are associated with higher risk consumption. Methods: Cross-sectional multicenter study with UniHcos Project, 1st year university students from 11 universities in Spain, academic years 2011-2012 to 2017-2018 data. This data were collected by self-administered questionnaire. A uni and bivariate analysis was performed, evaluated the statistical significance of the differences in prevalence with chi-square. Mean and standard deviation were used for quantitative variables and Student's t test statistic was used. Results: 9,862 subjects (72.2% women). 90.3% reported having consumed alcohol and 60.9% had drunk the last year, 49% BD in last month. It was deteded in men, significantly higher consumption in the last month and drunkenness. Last month consumption and drunkenness were significantly higher in men and in <21 years. The RSBA were significantly higher among who were drunk (15.7% unprotected sex, 1.9% sexual abuse and 0.7% taking sexual advantage) and had BD (17.1%, 1.9% and 0.7 %). Women with both risk consumptions had more sexual abuse (2.2%), and men had greater behaviors of taking sexual advantage of someone (drunk: 1.2%; BD: 1.3%). Conclusions: Alcohol consumption was above similar groups. BD consumption was similar by gender and age. Risk sexual behaviors appear mainly in problematic consumption. Gender differences are not detected in alcohol consumers in unprotected sex but deteded in the rest.Financiación: El estudio ha sido financiado por el Plan Nacional Sobre Drogas del Ministerio de Salud, Servicios Sociales e Igualdad. Convocatoria de 2010 y de 2013. (Códigos: 2010/145 and 2013/034) y por el Instituto de Salud Carlos III a través de la convocatoria del FIS (Fondo de Investigación Sanitaria) de 2016 (PI16/01947)

    Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

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    Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

    Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

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    Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3-h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty-two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose-limiting toxicities (DLTs) occurred during dose escalation. The highest dose level evaluated (plitidepsin 5.0 mg/m2 , BTZ 1.3 mg/m2 , DXM 40.0 mg) was the RD for phase II studies. Results shown herein are focused on this RD. Two patients had DLTs (grade 3 diarrhea, and grade 3 nausea/vomiting refractory to antiemetic therapy). Grade ? 3 hematological toxicity (thrombocytopenia 46%, anemia 33%, and neutropenia 17%) was manageable and did not result in treatment discontinuation. Transient and manageable grade 3 ALT increase (26%) was the most common biochemical abnormality. At the RD cohort, overall response rate was 22.2% (95%CI, 6.4%-47.6%), including one stringent complete response, one very good partial response, and two partial responses in r/r patients to BTZ and/or lenalidomide. The clinical benefit rate was 77.8% (95%CI, 52.4-93.6%). No major pharmacokinetic drug-drug interaction was found. In conclusion, the triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM.FUNDING: The study was funded by Pharma Mar, S.A. ACKNOWLEDGMENTS: The authors thank the patients, their families, and investigators teams for their participation in this phase I clinical trial

    Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19

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    We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.C.d.F., J.G.-P., and J.A. are supported by Instituto de Salud Carlos III (ISCII). We thank JM Ligos and Cytek Biosciences for their technical support. Research in E.L.-C.’s lab was supported by Fundación Familia Alonso, Santander Bank, Real Seguros, Fundación Mutua Madrileña, Fundación Uria, Fundación La Caixa, and Ayuntamiento de Madrid.S
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