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ObjectivesThe aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy.Materials and methodsThis retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness.ResultsA total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4–6.6). With a median follow-up of 8.7 months (95% CI: 7.7–10.2), median PFS and OS were 4.5 months (95% CI: 3.9–5.0) and 8.9 months (95% CI: 7.8–10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia.ConclusionThis study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias.

BackgroundCART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations.MethodEleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death.ResultsAfter a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression.ConclusionThis is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.

Transpiration (T), the component of evapotranspiration (ET) controlled by the vegetation, dominates terrestrial ET in many ecosystems; however, estimating it accurately, especially at the global scale, remains a considerable challenge. Existing approaches mostly rely on the relationship between T and photosynthesis, but untangling this relationship is difficult and leads to diverging T estimates. Limited in-situ measurements and the inability to directly measure transpiration from space further complicate the reliable assessment of this crucial process in the terrestrial water cycle. Here, we developed a new hybrid Priestley–Taylor (PT) model combined with an Artificial Neural Network (ANN) using globally available remote sensing and reanalysis data of soil moisture, vapor pressure deficit and windspeed. We also take advantage of the newly released global sap flow measurement network SAPFLUXNET. In the proposed approach, we avoid the parameterization of stomatal conductance by training the ANN on the PT-Coefficient α , obtained by inverting the PT equation. The results showed that our model framework can estimate T in different forest ecosystems based on few predictors. By utilizing forcings from independent datasets, we eliminate the reliance on in-situ measurements for predicting T. Through upscaling actual observations to a larger scale, this model framework helps alleviate the scarcity of T products. Intercomparison of T with ET partitioning methods based on eddy covariance data, shows high performances (KGE of 0.69 in Europe and 0.60 in North America), slightly improving estimates compared to other models. Analysis of contribution of T to ET across 100 FLUXNET sites result in a global mean of 55.2%. We believe that modelling T independent from the carbon cycle can support our understanding of land-atmosphere feedbacks and climate extremes in future research.

Se exponen cómo se han ido articulando espacios de violencia machista “manosferas” y en particular Forocoches, uno de los foros más conocidos por sus contenidos misóginos y machistas, y como estos fenómenos se vinculan con eficacias y sinergias propias de la neurocomunicación. Se ha analizado el grado de estos, y clasificando los tipos de masculinidades virtuales que interaccionan en el mismo, identificando las identidades incel (célibes involuntarios: que se consideran sexualmente discriminados por su físico), volcel (célibes voluntarios: que “renuncian” al sexo por despecho) y PUA (autodenominados “artistas del ligue”). Se han tomado como referentes trabajos que emanan del conocido movimiento Men going their own way (MGTOW) fomentador de masculinidades y feminidades, normativas y binarias; hostil a la denominada “hegemonía feminista”; buscador de una hegemonía masculina y la puesta en valor de una masculinidad “orgullosa, independiente y autosuficiente”. Principios que enfatizan actitudes misóginas y machistas.

Abstract CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA− T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM.

Despite the impressive results of autologous CAR-T cell therapy in refractory B lymphoproliferative diseases, CAR-NK immunotherapy emerges as a safer, faster, and cost-effective approach with no signs of severe toxicities as described for CAR-T cells. Permanently scrutinized for its efficacy, recent promising data in CAR-NK clinical trials point out the achievement of deep, high-quality responses, thus confirming its potential clinical use. Although CAR-NK cell therapy is not significantly affected by the loss or downregulation of its CAR tumor target, as in the case of CAR-T cell, a plethora of common additional tumor intrinsic or extrinsic mechanisms that could also disable NK cell function have been described. Therefore, considering lessons learned from CAR-T cell therapy, the emergence of CAR-NK cell therapy resistance can also be envisioned. In this review we highlight the processes that could be involved in its development, focusing on cytokine addiction and potential fratricide during manufacturing, poor tumor trafficking, exhaustion within the tumor microenvironment (TME), and NK cell short in vivo persistence on account of the limited expansion, replicative senescence, and rejection by patient’s immune system after lymphodepletion recovery. Finally, we outline new actively explored alternatives to overcome these resistance mechanisms, with a special emphasis on CRISPR/Cas9 mediated genetic engineering approaches, a promising platform to optimize CAR-NK cell function to eradicate refractory cancers.

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/−) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/− mice exhibited incipient renal fibrosis with epithelial–mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/− mice. Kidneys of Tgfb3+/− mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1. This article has an associated First Person interview with the first author of the paper.

Abstract Background Intensity of drought stress and pest attacks is forecasted to increase in the near future posing a serious threat to natural and agricultural ecosystems. Knowledge on potential effects of a combined abiotic-biotic stress on whole-plant physiology is lacking. We monitored the water status and carbon metabolism of a vine rootstock with or without scion subjected to water shortening and/or infestation with the sucking insect phylloxera (Daktulosphaira vitifoliae Fitch). We measured non-structural carbohydrates and biomass of different plant organs to assess the stress-induced responses at the root, stem, and leaf level. Effects of watering on root infestation were also addressed. Results Higher root infestation was observed in drought-stressed plants compared to well-watered. The drought had a significant impact on most of the measured functional traits. Phylloxera further influenced vines water and carbon metabolism and enforced the sink strength of the roots by stimulating photosynthates translocation. The insect induced carbon depletion, reprogramed vine development, while preventing biomass compensation. A synergic effect of biotic-abiotic stress could be detected in several physiological and morphological traits. Conclusions Our results indicate that events of water shortage favour insects’ feeding damage and increase the abundance of root nodosities. Root phylloxera infestation imposes a considerable stress to the plants which might exacerbate the negative effects of drought.

Este estudio analiza la publicidad de juguetes emitida en España durante el periodo de Navidad 2014/15 con la finalidad de iniciar una revisión cuantitativa de la representación de la familia en los anuncios. En su primera parte revisa los conceptos de infancia y niñez, los relaciona con el concepto de socialización y presenta un breve análisis del fenómeno publicitario. Los resultados evalúan la presencia de los tipos de emociones, valores y acciones asociados al género de los personajes y cuantifica la frecuencia de aparición de padres y abuelos en los anuncios de juguetes dirigidos a niños. La baja presencia de estos establece una discusión acerca del rol de dichos personajes como figuras de referencia y autoridad necesarias en el desarrollo infantil. También se plantea una reflexión final sobre la homogeneidad de las representaciones de los géneros asociadas a los roles de los personajes, tanto de adultos como niños. Finalmente se justifica el interés por ampliar el estudio hacia un escenario internacional, que permita comprobar los grados de similitud y contraste en dichas representaciones como forma de contribuir a la comprensión y visualización de la familia en los discursos publicitarios.

La idea de Cyborg de Haraway trata de romper, en cierta medida, con el cuerpo como algo simplemente natural, y consecuentemente discutirá con autoras como Fireston o Plant la idea de un mundo dual e inequívoco. Lo más interesante y lo que aquí queremos poner de relieve, no es tanto regresar a una descripción de los Cyborgs, sino por el contrario observar cómo el concepto ha sido clave para entender el cuerpo contemporáneo y post-capitalista, donde el imaginario de la carne monstruosa se trastoca bajo el principio de la ciencia. Haraway abrió el camino para pensar de manera performativa el cuerpo y un buen número de autoras, desde Butler a Preciado, son en cierta medida deudoras de esta tradición, la cual al final permite pensar incluso los nuevos anti-humanismos, los cuerpos en transición o simplemente el lugar de las interpretaciones sobre el sentido de la carne. Partiendo de aquí, nos preguntamos cuáles son las condiciones de estos cuerpos y qué relación tienen con el bien común, la monstruosidad, las miradas a la individualidad, al género y a los procesos científicos.

Desde hace varios años, la figura de Antonio Enríquez Gómez ha despertado el interés de quienes trabajan en teatro áureo en España y sus obras están siendo recuperadas y editadas para poder profundizar en el conocimiento de la obra dramática de este autor. Este trabajo pretende colaborar en el estudio de su teatro al analizar los puntos más relevantes de una comedia clave de su producción, Engañar para reinar, probablemente la primera de las comedias que Enríquez Gómez escribió.

Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency.Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain).Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm.Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52.Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction.Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route.Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Trial registration numbers NCT 01476007; EUDRACT (2010-024129-20).

El repertorio de teatro infantil y juvenil en la escena actual es realmente diverso. Y entre todas las obras que podemos ver encontramos un número considerable de montajes que son adaptaciones de obras clásicas. Sin embargo, en muchas ocasiones no son textos dramáticos de los que parten, sino textos narrativos como El Quijote o los cuentos de Perrault. Y en el caso de ser una pieza dramática, Shakespeare y su tragedia Romeo y Julieta son el autor y la obra que más vemos representados. Este trabajo analiza esta situación y trata de mostrar, a través de montajes innovadores llevados a cabo por compañías como Pie Izquierdo o Tropos Teatro de títeres, que el teatro de los dramaturgos barrocos españoles como Lope de Vega y Calderón, también puede ser una apuesta excelente para divertir y enseñar valores universales al público más joven.

The aim of this work was to study the effect of pre-treatments on drying of ‘mortiño’, on the drying rate and total content of soluble polyphenols and anthocyanins. It was applied to fresh fruit pre-treatment of immersion bath of aqueous solution of ethyl oleate and potassium carbonate. It was used a 22 factorial design with axial points, to evaluate its effect on the drying rate and content of phenolic compounds. It was performed a second pre-treatment with SO2, it was used a 22 factorial design to study its effect on the content of phenolic compounds. Stability assays were performed with dried fruits stored in a laminated multilayer film and metalized for 2 months under refrigeration (4 °C), freezing (-17 °C) and 25 °C at 90 % RH. It was evaluated the moisture content, color, soluble polyphenols and anthocyanins. It was conducted a sensory analysis of the product. The best conditions to dry ‘mortiño’ are 40 ºC, airflow of 0.24 m3/s, immersion bath concentration of 1.55 % K2CO3 (w/w) - 1.25 % of ethyl oleate (V/V), concentration of SO2 2 000 ppm and sulfidation 2 h. The product was dried to 5 % moisture in the oven in 40 % less time required to dry without pretreatments. The dried ‘mortiño’ retained 98.2 % of anthocyanins and 99.7 % of soluble polyphenols in relation to freeze-dried ‘mortiño’. Meanwhile the ‘mortiño’ dried by solar dryer hybrid retained 88.5 % of anthocyanins and 99.7 % of soluble polyphenols. The product stored at 18 °C in a multilayer film laminated and metalized, retains 50 % of anthocyanins in relation to its initial content in 4 months and 11 days

Este trabajo esconde en su título lo que realmente se pretende analizar y verificar: la validez de la etnografía digital. Para ello hemos procedido primero en realizar un breve marco teórico, explicando la metodología y las técnicas, y su adecuación al espacio social en estudio: la cibersociedad. Una vez explicado el espacio social, procedemos a explicar qué es el machismo en internet y las micro violencias machistas, así como las diferentes teorías que nos han servido para, posteriormente, diseñar una ficha de control. Tras esa incursión teórica, una vez diseñada la ficha de control que nos servirá como base para poder llevar a cabo la etnografía digital, se procede a diseñar la aproximación exploratoria y a llevarla a cabo, utilizando la metodología de la etnografía virtual y las técnicas de investigación, observación de los textos de las interacciones comunicativas de los usuarios y entrevistas en profundidad a usuarios de internet, relacionados con los espacios virtuales a análisis: foros temáticos, Foros generalistas de diarios digitales y conversaciones/comentarios a un youtuber.

Entre el año 2008 y 2013 se desarrolló el proyecto de exhumación e identificación de víctimas de la represión franquista en el Cementerio Viejo de Palencia, hoy parque de La Carcavilla. Se trataba de un caso complejo debido al tiempo transcurrido desde que ocurrieron los hechos, al elevado número de víctimas buscadas y a la falta de referencias espaciales tras la conversión del Cementerio Viejo en parque de recreo. El resultado fue la exhumación de 108 represaliados de los cuales 57 fueron identificados. La identificación de los restos, objetivo de la intervención, fue posible debido a un enfoque multidisciplinar basado en el cruce de información procedente de fuentes documentales, arqueológicas, osteológicas y genéticas. La reconstrucción de los eventos alrededor de la muerte durante la búsqueda y recuperación de los restos óseos, basada en la interpretación arqueológica y los datos de archivo, el análisis in situ de los mismos en el contexto en el que se encontraron y su posterior estudio en laboratorio, y finalmente el estudio genético, constituye un ejemplo práctico del crecimiento e intersección de la antropología forense con otras disciplinas.

Dogs have been under strong artificial selection as a consequence of their relationship with man. Differences between breeds are evident that could be reflected in seminal characteristics. The present study was to evaluate differences in sperm head morphometry between seven well-defined breeds of dog: the British Bulldog, Chihuahua, German Shepherd, Labrador Retriever, Spanish Mastiff, Staffordshire Terrier, and Valencian Rat Hunting dog. Semen samples were obtained by masturbation and smears stained with Diff-Quik. Morphometric analysis (CASA-Morph) produced four size and four shape parameters. Length, Ellipticity, and Elongation showed higher differences between breeds. MANOVA revealed differences among all breeds. Considering the whole dataset, principal component analysis (PCA) showed that PC1 was related to head shape and PC2 to size. Procluster analysis showed the British Bulldog to be the most isolated breed, followed by the German Shepherd. The PCA breed by breed showed the Chihuahua, Labrador Retriever, Spanish Mastiff, and Staffordshire Terrier to have PC1 related to shape and PC2 to size, whereas the British Bulldog, Valencia Rat Hunting dog, and German Shepherd had PC1 related to size and PC2 to shape. The dendrogram for cluster groupings and the distance between them showed the British Bulldog to be separated from the rest of the breeds. Future work on dog semen must take into account the large differences in the breeds′ sperm characteristics. The results provide a base for future work on phylogenetic and evolutionary studies of dogs, based on their seminal characteristics.

This work provides information on the blue fox ejaculated sperm quality needed for seminal dose calculations. Twenty semen samples, obtained by masturbation, were analyzed for kinematic and morphometric parameters by using CASA-Mot and CASA-Morph system and principal component (PC) analysis. For motility, eight kinematic parameters were evaluated, which were reduced to PC1, related to linear variables, and PC2, related to oscillatory movement. The whole population was divided into three independent subpopulations: SP1, fast cells with linear movement; SP2, slow cells and nonoscillatory motility; and SP3, medium speed cells and oscillatory movement. In almost all cases, the subpopulation distribution by animal was significantly different. Head morphology analysis generated four size and four shape parameters, which were reduced to PC1, related to size, and PC2, related to shape of the cells. Three morphometric subpopulations existed: SP1: large oval cells; SP2: medium size elongated cells; and SP3: small and short cells. The subpopulation distribution differed between animals. Combining the kinematic and morphometric datasets produced PC1, related to morphometric parameters, and PC2, related to kinematics, which generated four sperm subpopulations - SP1: high oscillatory motility, large and short heads; SP2: medium velocity with small and short heads; SP3: slow motion small and elongated cells; and SP4: high linear speed and large elongated cells. Subpopulation distribution was different in all animals. The establishment of sperm subpopulations from kinematic, morphometric, and combined variables not only improves the well-defined fox semen characteristics and offers a good conceptual basis for fertility and sperm preservation techniques in this species, but also opens the door to use this approach in other species, included humans.

Gold glyconanoparticles loaded with the listeriolysin O peptide 91–99 (GNP-LLO91-99), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO91-99 nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO91-99 nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO91-99 nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO91-99 nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO91-99 nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.

This work evaluates sperm head morphometric characteristics in adolescents from 12 to 18 years of age, and the effect of varicocele. Volunteers between 150 and 224 months of age (mean 191, n = 87), who had reached oigarche by 12 years old, were recruited in the area of Barranquilla, Colombia. Morphometric analysis of sperm heads was performed with principal component (PC) and discriminant analysis. Combining seminal fluid and sperm parameters provided five PCs: two related to sperm morphometry, one to sperm motility, and two to seminal fluid components. Discriminant analysis on the morphometric results of varicocele and nonvaricocele groups did not provide a useful classification matrix. Of the semen-related PCs, the most explanatory (40%) was related to sperm motility. Two PCs, including sperm head elongation and size, were sufficient to evaluate sperm morphometric characteristics. Most of the morphometric variables were correlated with age, with an increase in size and decrease in the elongation of the sperm head. For head size, the entire sperm population could be divided into two morphometric subpopulations, SP1 and SP2, which did not change during adolescence. In general, for varicocele individuals, SP1 had larger and more elongated sperm heads than SP2, which had smaller and more elongated heads than in nonvaricocele men. In summary, sperm head morphometry assessed by CASA-Morph and multivariate cluster analysis provides a better comprehension of the ejaculate structure and possibly sperm function. Morphometric analysis provides much more information than data obtained from conventional semen analysis.

DNA fragmentation has been shown to be one of the causes of male infertility, particularly related to repeated abortions, and different methods have been developed to analyze it. In the present study, two commercial kits based on the SCD technique (Halosperm ® and SDFA) were evaluated by the use of the DNA fragmentation module of the ISAS ® v1 CASA system. Seven semen samples from volunteers were analyzed. To compare the results between techniques, the Kruskal-Wallis test was used. Data were used for calculation of Principal Components (two PCs were obtained), and subsequent subpopulations were identified using the Halo, Halo/Core Ratio, and PC data. Results from both kits were significantly different (P < 0.001). In each case, four subpopulations were obtained, independently of the classification method used. The distribution of subpopulations differed depending on the kit used. From the PC data, a discriminant analysis matrix was obtained and a good a posteriori classification was obtained (97.1% for Halosperm and 96.6% for SDFA). The present results are the first approach on morphometric evaluation of DNA fragmentation from the SCD technique. This approach could be used for the future definition of a classification matrix surpassing the current subjective evaluation of this important sperm factor.

The aim of this study was to evaluate Andean blueberries (Vaccinium floribundum Kunth) from Ecuador as a potential functional ingredient for the food and pharmaceutical industries. The analysis of bioactive compounds by HPLC–DAD–MSn determined a high content of (poly)phenols, mainly anthocyanins, and the presence of the carotenoid lutein. Regarding its biological properties, Andean blueberry did not show toxicity by the zebrafish embryogenesis test, showing also a lack of the antinutrients lectins. Moreover, the results of in vitro and in vivo antioxidant capacity evaluation suggested its possibility to be used as natural antioxidant. This fruit also exhibited antimicrobial activity toward Staphylococcus aureus and Escherichia coli in low doses. Finally, in vitro gastrointestinal (GI) digestion showed a partial bioaccessibility of (poly) phenols (~50% at the final step), showing high antioxidant capacity in the different GI phases. These results revealed Andean blueberry as an interesting candidate for being used as a functional ingredient and the development of further in vivo and clinical assays.

El presente trabajo tiene dos objetivos principales. El primero es comprobar cómo la cibersociedad, al igual que la sociedad ofline, perpetúa los estereotipos de género tradicionales. El segundo objetivo trata de mostrar cómo la cibersociedad, desde los ciberfeminismos, puede convertirse en un espacio social contragenérico que crea un código-lenguaje que elimine la categoría género. El contragénero que se plantea en este trabajo es fruto de una exposición teórica que abarca el ciberfeminismo, la figura política del ciborg (Haraway), la idea de contrasexualidad (Preciado) y la performatividad y parodia del género (Butler) junto con ciertas ideas de la teoría queer y la acción del Net.art como medio de producción. Tras la exposición teórica damos paso al análisis exploratorio de enfoque cualitativo basado en la técnica de análisis de contenidos y del discurso de 12 webs a las que podríamos denominar contragénero y el análisis de una obra Net.art explicando el uso de la performatividad paródica del género y la posibilidad del contragénero.

El surgimiento de planteamientos éticos, así como el retroceso actual hacia dogmatismos morales, en el campo de la investigación científica, se genera gracias a la crisis de la ética y la moral en el medio investigativo. En los últimos años, el discurso sobre la integridad científica ha sido prolífico, vinculándola con aspectos éticos del quehacer del investigador, relacionándola con las (buenas o malas) prácticas y (buenas o malas) conductas surgidas dentro de los procesos de investigación. Si se concibe la integridad científica así, es decir, como un elemento que evalúa, juzga, mide, coacciona y castiga las malas prácticas del investigador, el concepto está siendo limitado desde su naturaleza. Así, surge el siguiente interrogante: ¿Por qué integridad científica y no solamente integridad? ¿Por qué darle apellido cuando la integridad es holística en su esencia y principio? En este escrito se hará una invitación a vincular la formación en y para la integridad con sentido bioético. La disculpa será la paradigmática emergencia y crítico estado de la integridad científica.

The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-θ (PKC-θ) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of β-actin and PKC-θ from the lamellipodium-like distal (d)-SMAC, promoting PKC-θ activation. Furthermore, eNOS-derived NO S-nitrosylated β-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-θ was corroborated by overexpression of PFN1- and actin-binding defective mutants of β-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-θ at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS.

La Baltasara fue una célebre actriz entre finales del siglo XVI y principios del XVII, que dejó los escenarios para retirarse a vivir en una ermita hasta su muerte. Este suceso fue recuperado varios años más tarde por Luis Vélez de Guevara, Antonio Coello y Francisco de Rojas Zorrilla como argumento para una de las comedias que los tres dramaturgos escribieron en colaboración, titulada con el nombre de la actriz. A lo largo de este artículo, se presentan varios datos documentales con los que se pretende aportar información sobre la actriz y su retiro. Asimismo, se analizan los motivos y elementos dramáticos que configuran la pieza, tomados de uno de los géneros más exitosos en la época: las comedias de santos.

Western culture has been built on dualisms reference. Thus was born the cyborg, half machine, and half human, as a paradigm of anti-informatics of domination: The cyborg is a creature in a world postgenerator, machine /computer /network and women share similarities mimetic in terms of flexibility, fluidity and plenipotencialidad, which raises an alliance between women and machines. Understand and critically analyze cyberfeminism provides a theoretical base from which to reflect on the changes and continuities in the discourse articulated around the idea of female representation and their ability to generate a debate suggestive, multifunctional and educational educationally coherent.

El presente trabajo pretende explicar, desde diversas experiencias formativas universitarias utilizando herramientas Web 2.0, la posibilidad o no de avanzar hacia una formación más abierta, autónoma, así como una formación centrada en la autoformación de cara a un reciclaje formativo posterior, algo muy requerido en el presente mercado laboral y escenario social. Se pretende enfatizar el uso formativo de TICs colaborativas con criterios de calidad y uso responsable. El edupunk sería el punto de partida pero con ciertos matices. La formación DIY –do it yourself o “hágalo usted mismo”– ha de tener una supervisión, tutorización y guía para que pueda estar inmersa en los circuitos de la formación universitaria reglada, con unos criterios de calidad óptimos.

An accurate estimation of extreme claims is fundamental to assess solvency capital requirements (SCR) established by Solvency II. Basing on the Extreme Value Theory (EVT), this paper performs a parametric estimation to fit the motor liability insurance historical datasets of two significant and representative companies operating within the Spanish market to a Generalized Pareto Distribution. We illustrate how EVT improves classical adjustments, as it considers outliers apart from mass risks, what leads to optimize the pricing decision-making and fix a risk transfer position.

This document consists of a social movement, the cyberfeminism, based on its own reality: Internet. This movement tries to synthesize its feminist meaning, based on the Cyborg theory, and the meaning that this movement gives the reality, with the purpose of transforming it of artistic, ironic and political way.

Se pretende medir los cambios en el tiempo en la situación de Seguridad Alimentaria y Nutricional de las Familias participantes en los PESA (Programa Especial para la Seguridad Alimentaria) y, en segunda instancia, medir los cambios con relación a las inicios del 2009, el objetivo será medir los efectos e impacto ocurridos en las familias participantes de los Programas PESA como producto de los resultados y actividades realizadas y en comparación a los datos obtenidos en la primera medición. Además, se validará, a nivel centroamericano, el CAYSAN1, herramienta desarrollada durante el proceso, como instrumento para obtener información sobre los indicadores de impacto seleccionados para el Programa Especial para la Seguridad Alimentaria -PESA- de los países de Centroamérica.

This paper begins with a brief review of the current situation of violence against women in Brazilian context, focusing more in the Northeast and in the State of Maranhão. For this we will make a slight reference to studies and research on violence against women. Then we review the legislation on gender violence in particular No. 11,340 / 2006 and Law Maria da Penha Law, making a criticism of its use and failure to adapt to the realities of Brazilian society. In order to contrast the data analyzed in the reviewed studies and analysis of the scientific literature, we proceeded to perform, from a qualitative approach, an exploratory approach to the reality of violence against women in Maranhão. To that end, using qualitative techniques were carried out 12 in-depth interviews to women of different ages and socio-economic status. Two in-depth interviews with key informants –a Judge of the "Tercera Vara Especial de Combate à Violência Doméstica e Familiar Contra a Mulher" of the city of Sao Luis do Maranhão and prosecuted for domestic violence in rehabilitation man. A discussion group with 7 graduates and lawyers was also performed. In addition to participatory-indirect observation in the streets of the city of Sao Luis do Maranhão, recording the analysis in a field diary for a week.

La salud es un componente que ha estado presente en los procedimientos de tramitación administrativa de licencias, de forma general, hasta que España entró en la Unión Europea, en el año 1986, cuando el informe sanitario quedó diluido. El objetivo de este artículo es el de dar una visión general del marco normativo actual del tema de referencia y tratar de describir, brevemente, las prioridades sanitarias y los cauces para hacer viable la integración de la variable salud, en el proceso de la evaluación ambiental de planes, programas y proyectos públicos y privados. La existencia actual de dos leyes, una de Evaluación Ambiental y otra de Salud Pública, puede ayudar a este objetivo. En la elaboración del estudio ambiental estratégico y del estudio de impacto ambiental, la evaluación del impacto en salud debería ser considerada como un trámite esencial de estos procedimientos medioambientales y tener el tratamiento jurídico que tienen “los informes preceptivos y determinantes” de dichos procedimientos. Así pues, se concluye que es indispensable desarrollar normativamente los aspectos relativos a la evaluación de impacto en salud de planes, programas y proyectos contemplados en la ley de evaluación ambiental, utilizando la evaluación del impacto en salud como llave para hacerlo.

This essay provides data and insights to the current debate on prostitution in Spain which constitutes a fact not only economic and legal, but social and humanitarian.

Delirium is a functional disorder of the central nervous system, very common among oncological patients, consequence of the presence in the organism of “false neurotransmitters” that could be exogenous or endogenous and give place to alterations inside several aspects (cognitive, perceptive, behavior, attention). The restoration of the symptoms is acute and the course is fluctuating along the day. In an important percentage of the cases the situation is reversible. Nevertheless, in other occasions it is an indicator of a situation premortem of the patient (“terminal agitation”). Most of cases etiology is multifactorial and there can be implied both, the proper tumor and the treatments administered to fight it or to solve the symptoms that this one causes (chemotherapy, opioids, steroids). The managing of this entity implies several questions of psychological area (information to the family), of environmental hygiene (skills of reorientation) and pharmacologist (control the symptoms with neuroleptics, benzodiacepines). Nevertheless, the most important point is to eliminate the ethiologic factor, in case of this one exists.

Fundamento: La emergencia y re-emergencia de enfermedades infecciosas revisten una gran preocupación en Salud Pública. Las peculiaridades socio-demográficas de la Comunidad de Madrid hacen que deba prestarse una mayor atención a las zoonosis transmitidas por animales de compañía. Los objetivos del trabajo fueron mejorar el conocimiento de las zoonosis emergentes y re-emergentes transmitidas por animales de compañía y el diseño de un método para la priorización de éstas. Métodos: A partir de las enfermedades recogidas de fuentes oficiales, laboratorios y revisión bibliográfica se aplicó un método de cuantificación y ponderación diseñado por el grupo de trabajo y adaptado a la especificidad del estudio. Resultados: Del análisis de 137 enfermedades, 24 cumplieron los criterios de admisión. El método de ponderación se refleja en una tabla que recoge once criterios de puntuación, sus categorías y los coeficientes adoptados. La Salmonelosis fue la enfermedad que ocupó el primer lugar, seguida de Fiebre Q, Tularemia e Infección por Hantavirus. Conclusiones: Se ha diseñado un método de evaluación específico de enfermedades emergentes y re-emergentes que permite establecer prioridades en el campo de la planificación en Salud Pública. El presente estudio aporta una relación, por orden de importancia, de 24 zoonosis sobre las que se deberán plantear nuevas líneas estratégicas para su investigación y/o control.

Oncological treatment of cancer patients still requires in the majority of cases chemotherapy and/or radiotherapy. Due to their lack of specificity, they are aggressive treatments that can cause different toxicities. Nowadays, new more selective and, therefore, less aggressive treatments against healthy tissues are being developped. Meanwhile, it is essential to inform patients against the expected toxicity of each drug, to inform them about toxicity prevention and about the treatment required on each case. Moreover, it is very important to prepare them psychologically, to relieve them and to prepare them to face the treatment in the best possible way. In order to achieve so, it is extremely valuable to know that paradoxically the more common or potentially lethal toxicities from the doctor’s point of view might not match in some cases with those that distress the patient. Therefore, if this information is not taken into account in advance, all the help that might be given could result in fact worthless. The aim is to minimize cancer and chemotherapy consequences improving quality of life.

Passiflora mollissima (Kunth) L.H. Bailey is an exotic fruit native to South America, known as taxo in Ecuador. This paper characterizes its flavonoid and carotenoid composition and antioxidant capacity and evaluates the effect of the spray-drying process on its phytochemical composition and antioxidant capacity. A total of 18 flavonoid compounds, nine proanthocyanidins and nine flavan-3-ol monomers, were identified and quantified. Glycosides of (epi)-afzelechin stood out as the most abundant flavonoid. Three carotenoids were identified, with β-carotene having the highest concentration. The DPPH· and ORAC assay methods indicated a high antioxidant capacity. Furthermore, the bioactive content showed a positive and direct correlation with antioxidant capacity. On the other hand, the spray-drying process produced a stable phytochemical composition and antioxidant activity of taxo. These results demonstrate the potential applicability of microencapsulated taxo as a functional ingredient in the food industry.

La implantación del Espacio Europeo de Educación Superior (EEES) supone un reto para la universidad española. Supone la utilización de nuevas metodologías docentes por profesores y alumnos no habituados a las mismas. Este artículo muestra el resultado del uso de metodologías participativas y de las Tecnologías de la Información y las Comunicaciones (TIC) en algunas asignaturas de los nuevos títulos de grado. En concreto, se analiza el uso de blogs y wikis en la adquisición de competencias básicas y específicas, y en su posterior evaluación. El artículo concluye discutiendo las potencialidades y dificultades del uso de estas metodologías.