Estudio anatomopatológico de los tumores de las glándulas salivares

Hemos estudiado, de forma retrospectiva, las características epidemiológicas, morfológicas e inmunohistoquímicas de 400 tumores de las glándulas salivares. La clasificación diagnóstica utilizada ha sido la de Ellis y Auclair (AFIP 1995). Los tumores de las glándulas salivares de nuestras serie son neoplasias que afectan con mayor frecuencia a pacientes entre 30 y 60 años de edad; en los pacientes con tumores benignos, la edad es significativamente menor que los que presentan turmores malignos. La glándula parótida ha sido la localización más frecuente, tanto para los tumores benignos como para los malignos; en segundo lugar se encuentran en las glándulas salivares menores del paladar. El adenoma pleomorfo ha sido el tumor más frecuente en términos absolutos y, por supuesto, entre los tumores benignos; el carinoma epidermoide lo ha sido de los tumores malignos. La estructura histológica más comúnmente descrita ha sido la de tipo mixto, con tendencia a la formacion de glándulas y nidos tumorales. La celularidad mioepitelial y la inflamatoria han estado presentes en una elevada proporción de neoplasias. La relación cuantitativa entre parénquima y estoma está a favor del componente parenquimatoso en los tumores malignos y de foma inversa en los benignos. Las atipias celulars se han presentado tanto en los tumores benignos como en los malignos, pero las figuras de mitosis han resultado características de malignidad. La secreción de moco, el infiltrado inflamatorio y la fibrosis se relacionan de forma significativa con los tumores malignos: por el contrario, la presencia de mucoplisacáridos y de cápsulas tumoral lo han hecho con los de tipo benigno. El adenoma pleomorfo, presenta un gran contenido estromal de mucoplliscáridos, pero han sido poco relevantes los elementos osteocondroides y los escamosos. Los mioepiteliomas se han localizado en las glándulas salivares menores del paladar en la mitad de los casos, han sido de predominio plasmocitoide y carentes de cäpsula. Los tumores de Warthin y los cistadenomas, en ocasiones, pueden desarrollarse a partir de restos epiteliales incluidos en los ganglios linfáticos intraparotídeos. El carcinoma mucoepidermoide ha sido el tercer tumor en frecuencia de los tumores malignos y su localización preferente han sido las glándulas salivares menores del paladar. Los adenocarcinomas"sin otras especificaciones" de nuestra serie han mostrado un importante componente inflamatorio y un claro patrón infiltrativo, junto a un alto índice mitótico y nivel de pleomorfismo celular, con tendencia a la invasión vascular y perineural, criterios no muy frecuentemente encontrados en la literatura. El carcinoma adenoide quístico ha mostrado una considerable proporción de mucopolisacáridos. El carcinoma epidermoide ha supuesto un porcentaje de casos muy superior al reflejado por otros investigadores. No es posible separarlo del que afecta de una forma secundaria a las glándulas salivares si la evidencia clínica del tumor de origen en negativa. En dos de nuestros casos encontramos una patrón pseudoglandular con imágenes de acantolisis celular, un hallazgo escasamente aportado por otros grupos. El carcinoma epitelial-mioepitelial es el origen del adenocarcinoma de células claras, representando este último una fase muy evolucionada del primero. Desde el punto de vista histogenético y, en base a los resultados inmunohistoquímicos obtenidos en nuestra serie, las células clara proliferantes en este tumor, son de origen mioepitelial. El adenocarcinoma de células claras debe distinguirse de las variantes de células claras de otras neoplasias. La aportación de las técnicas de inmunohistoquímica ha resultado esencial en su diferenciación. El carcinoma ductal ha mostrado un importante pleomorfismo celular y un estroma denso y rico en células inflamatorias en los tumores de nuestra serie. En base a los resultados obtenidos y desde el punto de vista semántico, se debe cambiar la denominación de algunas entidades tumorales: El adenocarcinoma de células basales y el adenocarcinoma de células claras que en su crecimiento no forman glándulas, deben denominarse "carcinoma de células basales" y "carcinoma de células claras", respectivament

Accessibility instruments for planning practice: bridging the gap between academic research and decision-making.

One of the core objectives of urban planning practice is to provide spatial equity in terms of opportunities and use of public space and facilities. Accessibility is the element that serves this purpose as a concept linking the reciprocal relationship between transport and land use, thus shaping individual potential mobility to reach the desired destinations. Accessibility concepts are increasingly acknowledged as fundamental to understand the functioning of cities and urban regions. Indeed, by introducing them in planning practice, better solutions can be achieved in terms of spatial equity. The COST Action TU1002 "Accessibility instruments for planning practice" was specifically designed to address the gap between scientific research in measuring and modelling accessibility, and the current use of indicators of accessibility in urban planning practice. This paper shows the full process of introducing an easily understandable measure of accessibility to planning practitioners in Madrid, which is one of the case studies of the above-mentioned COST action. Changes in accessibility after the opening of a new metro line using contour measures were analyzed and then presented to a selection of urban planners and practitioners in Madrid as part of a workshop to evaluate the usefulness of this tool for planning practice. Isochrone maps were confirmed as an effective tool, as their utility can be supplemented by other indicators, and being GIS-based, it can be easily computed (when compared with transport models) and integrated with other datasets

Glomerulonefritis colapsante con marcadores de desdiferenciación podocitaria en síndrome hemofagocítico secundario a linfoma hepatoesplénico de células T

El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento

INSTrumento de Apoyo infoGRAFico (InstaGRAF)

El "INSTrumento de Apoyo infoGRAFico (InstaGRAF)" es una actividad docente basada en la creación de un recurso educativo innovador en abierto y virtual que utiliza infografías y redes sociales para motivar, apoyar e incentivar el aprendizaje activo de los estudiantes aplicando de forma integradora los diferentes conocimientos teóricos impartidos en clases teóricas de los Grados de Farmacia y Nutrición Humana y Dietética durante el curso academico 2020/2021. Los resultados de la implantación de InstaGRAF durante el curso académico ponen de manifiesto que La elaboración de infografías y su difusión a través de redes sociales constituyen un método didáctico original y creativo bien aceptado y valorado por los estudiantes que les ha permitido comprender mejor los conceptos explicados en clase y ha contribuido a obtener un mejor rendimiento académico de los estudiantes participantes. La plataforma InstaGRAF podría ser una herramienta útil y sencilla con gran versatilidad que podría ser utilizada en cualquier asignatura y grado académico

West Nile Virus Survey of Birds, Horses, and Mosquitoes of the Pacific Coast, Southern Mexico

Abstract. Serology of West Nile virus vectors and non-human reservoirs was surveyed at Acapulco, Jose Azueta, and Ometepec, three Pacific Coast localities of Guerrero State, Mexico. The objectives of this study were to use enzyme-linked immnosorbent assay (ELISA) to assess West Nile virus antibodies of bird and equine serum samples and use reverse transcription of polymerase chain reaction (RT-PCR) to detect the virus in field-collected resting mosquitoes. Forty birds trapped using mist nets yielded 10% seroprevalence. Similarly, 18.6% of 102 equine blood samples had West Nile virus. In addition, 4,854 mosquitoes were caught using motorized backpack aspirators and grouped into 116 pools. Of the 16 species and seven genera, no mosquito was positive for West Nile virus. Our study demonstrated West Nile virus seroprevalence on resident birds and equines in Guerrero State, Mexico

Mediterranean diet and invasive breast cancer risk in the predimed trial

Trabajo presentado en el X Congreso Internacional de la Dieta Mediterránea, celebrado en Barcelona (España) del 02 al 03 de abril de 2014.[Introduction]: Rates of breast cancer incidence have been rising over the past 3 decades. Dietary factors may play a role in the risk of breast cancer. Some observational cohort studies have suggested that the Mediterranean diet may reduce the risk of breast cancer but no randomized controlled trial had investigated this issue. We aimed to evaluate the effect of two interventions with Mediterranean diet on the primary prevention of breast cancer in a randomized controlled trial. [Methods]: The PREDIMED study (Prevención con Dieta Mediterránea) is a randomized, singleblind, and controlled trial conducted in Spanish primary healthcare centres. Out of 4,282 women recruited (aged 60 to 80 years), 1,478 were assigned to a Mediterranean diet supplemented with extra-virgin olive oil, 1,288 to a Mediterranean diet supplemented with mixed nuts and 1,393 to a control diet (advice to reduce dietary fat). Primary analyses were performed on an intention-to-treat basis. Poisson regression analyses were used to assess the relationship between the nutritional intervention and the incidence of confirmed invasive breast cancer. [Results]: After a median of 4.3 years after randomization, participants in both Mediterranean diet groups (extra-virgin olive oil or nuts) had a 55% relative reduction (95%CI: 9% to 78%) in the risk of invasive breast cancer compared with participants assigned to a control group (with the recommendation to follow a low-fat diet). Observed rates (per 1000 person-years) were 1.14, 1.82 and 2.90 for the Mediterranean diet with extra-virgin olive oil group, the Mediterranean diet supplemented with nuts group and the control group, respectively. The multivariable-adjusted rate ratios versus the control group were 0.34 (95% CI: 0.14 to 0.83) for the Mediterranean diet with extra-virgin olive oil group, and 0.60 (95% CI: 0.26 to 1.35) for the Mediterranean diet supplemented with nuts group. [Conclusions]: This is the first large randomized trial assessing the role of a dietary pattern on breast cancer incidence. Our results suggest that an intervention promoting adherence to the Mediterranean dietary pattern, specially when it is supplemented with extra-virgin olive oil, may contribute to a substantial reduction in the incidence of invasive breast cancer risk in women 60 years and older. However, a longer follow-up of our participants is needed to obtain more precise estimates

Papel fisiológico de los nucleótidos extracelulares en el sistema nervioso central: señalización vía receptores P2X y P2Y

In the last few years nucleotide receptors, the ionotropic P2X1-7 subunits and the metabotropic P2Y1, 2, 4, 6, 11, 12, 13, 14, have acquired an excepcional importance due to their strategic location in organs and tissues, their great variety along with the complexity of the associated signalling pathways and the first evidence of the serious alterations entailed in their dysfunctions. Our group has been pioneer in the characterization of these receptors in the nervous system, where we defined their location and functionality. The abundant presence, at a presynaptic level, of P2X3 and P2X7 should be emphasized, where by means of calcium intake they induce neurotransmitter exocytosis, such as glutamate, GABA, catecholamines and acetylcholine among others, as described in previous works by our group. In addition, they induce an extensive remodeling of the terminal’s cytoskeleton and exocytotic mechanisms through CaMKII and they can interact widely with other ionotropic and metabotropic receptors co-existing in nearby areas. Neural cells also exhibit the presence of most P2Y receptors signalling through a large variety of intracellular cascades. Recently we have demostrated that P2Y metabotropic receptors of the sub-family activated by ADP, especially P2Y13, are connected with the signalling towards GSK3 and â-catenin, opening new ways of understading the nucleotide function in survival and maintenance of neural cells. In addition both P2X and P2Y receptors play a role in early developmental stages and neural maturation where their function has to be fully understanded. Nucleotide receptors are also very abundant in glial cells, and our group has shown that most P2Y receptors are present and fully functional in cultured astrocytes, where, depending on the subtype receptor they activate a large variety of signalling cascades.En los ultimos anos los receptores de nucleotidos, receptores ionotropicos P2X1-7 y metabotropicos P2Y1, 2, 4, 6, 11, 12, 13, 14, han adquirido una importancia excepcional debido a su localizacion estrategica en organos y tejidos, a su gran variedad junto con la complejidad de vias de senalizacion a las que estan asociados y a las primeras evidencias de importantes alteraciones debidas a su mal funcionamiento. Nuestro grupo ha sido pionero en la caracterizacion estos receptores en el sistema nervioso, donde definimos su localizacion y su funcionalidad. La abundante presencia, a nivel presinaptico, de las subunidades P2X3 y P2X7 debe ser resaltada, donde gracias a la entrada de calcio inducen la exocitosis de varios neurotransmisores, como glutamato, GABA, catecolaminas y acetilcolina entre otros, como ha sido descrito por nuestro grupo en trabajos previos. Ademas, estos receptores inducen una profunda remodelacion del citoesqueleto de las terminales nerviosas y de los mecanismos exocitoticos a traves de la CaMKII y pueden interactuar con otros receptores ionotropicos y metabotropicos co-existentes en sus cercanias. La mayoria de los receptores P2Y tambien estan presentes en las celulas nerviosas, activando vias de senalizacion a traves de una gran variedad de cascadas intracelulares. Recientemente hemos demostrado que los receptores metabotropicos P2Y pertenecientes a la sub-familia de receptores activados por ADP, especialmente el P2Y13, estan conectados con la senalizacion hacia GSK3 y ƒÀ-catenina, lo que abre nuevas vias para la comprension de la funcion de los nucleotidos en la supervivencia y el mantenimiento de las celulas nerviosas. Ademas, tanto los receptores P2X como los P2Y juegan un papel en los estadios iniciales del desarrollo y en la maduracion neuronal donde su funcion aun ha de ser plenamente comprendida. Los receptores de nucleotidos son tambien muy abundantes en las celulas gliales, y nuestro grupo ha demostrado que la mayoría de los receptores P2Y están presentes y son plenamente funcionales en astrocitos en cultivo, donde, dependiendo del subtipo de receptor, activan una gran variedad de cascadas de señalización

Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

Background Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. Results FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001). Conclusion Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI

A Somatostatin Receptor Subtype-3 (SST3) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors

[Purpose] Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST2 and SST5. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST2. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST3 and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST3-agonists and characterize their effects on experimental NFPT models.[Experimental Design] Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST3-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST3-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST3-agonist. [Results] We successfully identified the first SST3-agonist peptides. SST3-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis in vitro, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST3-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST3 than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST3-agonist treatments. Concurrently, SSTR3 silencing increased cell viability in a subset of NFPTs. [Conclusions] This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.This work has been funded by the following grants: Junta de Andalucía [CTS-1406 (R.M. Luque), BIO-0139 (J.P. Castaño)]; Ministerio de Ciencia, Innovación y Universidades [BFU2016-80360-R (J.P. Castaño)] and Instituto de Salud Carlos III, co-funded by European Union [ERDF/ESF, “Investing in your future”: PI16/00264 (R.M. Luque), CP15/00156 (M.D. Gahete) and CIBERobn]. CIBER is an initiative of Instituto de Salud Carlos III

The Effect of Physical Activity and High Body Mass Index on Health-Related Quality of Life in Individuals with Metabolic Syndrome

[EN] The main objective of this study was to examine the relationship between the level of physical activity (PA) and the degree of obesity with health-related quality of life (HRQoL) in individuals with metabolic syndrome (MetS) who participated in the Predimed-Plus study. A total of 6875 subjects between 55 and 75 years of age with MetS were selected and randomized in 23 Spanish centers. Subjects were classified according to categories of body mass index (BMI). PA was measured with the validated Registre Gironi del Cor (REGICOR) questionnaire and subjects were classified according to their PA level (light, moderate, vigorous) and the HRQoL was measured with the validated short-form 36 (SF-36) questionnaire. By using the ANOVA model, we found a positive and statistically significant association between the level of PA and the HRQoL (aggregated physical and mental dimensions p < 0.001), but a negative association with higher BMI in aggregated physical dimensions p < 0.001. Furthermore, women obtained lower scores compared with men, more five points in all fields of SF-36. Therefore, it is essential to promote PA and body weight control from primary care consultations to improve HRQoL, paying special attention to the differences that sex incurs.SIThe Predimed-Plus trial was supported by the Spanish government’s official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (three coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/0147, PI14/00636, PI14/00972, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01,332), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-PLUS grant to Jordi Salas-Salvadó, the European Research Council (Advanced Research Grant 2013–2018; 340918) grant to Miguel Ángel Martínez-Gonzalez, the Recercaixa grant to Jordi Salas-Salvadó (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant and FEDER funds (CB06/03 and CB12/03), Olga Castaner is funded by the JR17/00,022 grant, ISCIII. Christopher Papandreou is supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016–2020 Incorporació de Científics i Tecnòlegs, SLT002/0016/00,428). María Rosa Bernal-Lopez was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER, Ignacio M.Giménez-Alba is supported by a FPU predoctoral contract (reference FPU18/01703) from the Ministerio de Ciencia, Innovación y Universidades, Spain