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Cyclooxygenase 2 (COX-2) is a key enzyme of the tumorigenesis-inflammation interface and can be induced by hypoxia. A pseudohypoxic transcriptional signature characterizes pheochromocytomas and paragangliomas (PPGLs) of the cluster I, mainly represented by tumors with mutations in von Hippel&ndash, Lindau (VHL), endothelial PAS domain-containing protein 1 (EPAS1), or succinate dehydrogenase (SDH) subunit genes. The aim of this study was to investigate a possible association between underlying tumor driver mutations and COX-2 in PPGLs. COX-2 gene expression and immunoreactivity were examined in clinical specimens with documented mutations, as well as in spheroids and allografts derived from mouse pheochromocytoma (MPC) cells. COX-2 in vivo imaging was performed in allograft mice. We observed significantly higher COX-2 expression in cluster I, especially in VHL-mutant PPGLs, however, no specific association between COX-2 mRNA levels and a hypoxia-related transcriptional signature was found. COX-2 immunoreactivity was present in about 60% of clinical specimens as well as in MPC spheroids and allografts. A selective COX-2 tracer specifically accumulated in MPC allografts. This study demonstrates that, although pseudohypoxia is not the major determinant for high COX-2 levels in PPGLs, COX-2 is a relevant molecular target. This potentially allows for employing selective COX-2 inhibitors as targeted chemotherapeutic agents and radiosensitizers. Moreover, available models are suitable for preclinical testing of these treatments.

Pheochromocytomas and paragangliomas (PPGLs) with activated pseudohypoxic pathways are associated with an immature catecholamine phenotype and carry a higher risk for metastasis. For improved understanding of the underlying mechanisms we investigated the impact of hypoxia and pseudohypoxia on catecholamine biosynthesis in pheochromocytoma cells naturally lacking Hif2&alpha, (MPC and MTT) or expressing both Hif1&alpha, and Hif2&alpha, (PC12). Cultivation under extrinsic hypoxia or in spheroid culture (intrinsic hypoxia) increased cellular dopamine and norepinephrine contents in all cell lines. To distinguish further between Hif1&alpha, driven effects we expressed Hif2&alpha, in MTT and MPC-mCherry cells (naturally lacking Hif2&alpha, ). Presence of Hif2&alpha, resulted in similarly increased cellular dopamine and norepinephrine under hypoxia as in the control cells. Furthermore, hypoxia resulted in enhanced phosphorylation of tyrosine hydroxylase (TH). A specific knockdown of Hif1&alpha, in PC12 diminished these effects. Pseudohypoxic conditions, simulated by expression of Hif2&alpha, under normoxia resulted in increased TH phosphorylation, further stimulated by extrinsic hypoxia. Correlations with PPGL tissue data led us to conclude that catecholamine biosynthesis under hypoxia is mainly mediated through increased phosphorylation of TH, regulated as a short-term response (24&ndash, 48 h) by HIF1&alpha, Continuous activation of hypoxia-related genes under pseudohypoxia leads to a HIF2&alpha, mediated phosphorylation of TH (permanent status).

Background: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. Methods and results: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 +/- 18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. Conclusion: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.

The Catedra UC3M-SENER was first initiated in January 2017, defining the following objectives: Planning algorithm testing. Control algorithm testing. Atmospheric prediction inclusion. Commercial Orbital Transportation Services (COTS) hardware trials. * 3 end-of-degree projects have already been produced under this brand. * Empirical data obtained by several balloon launching in Spain and Mexico (International Collaboration). * 3 new end-of-degree projects (ongoing) with the following objectives: Platform testing (cameras, tracking). Attitude control flight test (ADCS). Glider control system flight test (aerodynamic control). Limited by regulation Simulator test.

Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance. Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

Trabajo presentado al 8th International Advances in Applied Physics & Materials Science Congress and Exhibition (APMAS), celebrado en Mugla (Turquia) del 24 al 30 de abril de 2018.

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. (C) 2016 SEEN. Published by Elsevier Espana, S.L.U. All rights reserved.

Propósito. Conocer tipos y prevalencia de las variantes anatómicas de la segmentación bronquial, en pacientes a quienes se les realizó TC de Tórax Multidetector 64 (TCMD 64). Evaluar la capacidad de este método para el diagnóstico de las mismas. Material y métodos. Se estudiaron en forma retrospectiva los estudios tomográficos que incluyeron el tórax, en 156 pacientes adultos, con tomógrafo Toshiba Aquilion 64, con adquisiciones volumétricas del tórax, cortes de 0.5 mm, obteniendo imágenes que permitieron reconstrucciones MPR, 3D y visualización endoscópica virtual traqueobronquial, en el período entre mayo de 2007 y mayo de 2011, independientemente del motivo por el cual fueron solicitados. Resultados. De los 156 estudios examinados, 89 (57%) fueron de sexo masculino y 67 (43%) femenino. En su análisis se encontraron 52 variantes, en 47 pacientes, ya que en cinco de ellos se observaron dos variantes. Entre las más frecuentes fueron: de número (28 variantes-53%), de las cuales: 15 (28%) con bronquio sub-superior; 6 (11%) bronquio accesorio en lóbulo inferior izquierdo; 5 (10%) isomerismo de lóbulos inferiores; y 2 (4%) bronquio accesorio en lóbulo superior derecho. Entre las variantes de origen (24 variantes-47%) encontramos 17 variantes (33%) con bifurcación del lóbulo superior derecho; 6 (12%) trifurcación del bronquio del lóbulo superior izquierdo; y 1 (2%) bronquio traqueal accesorio. Conclusión.Las variantes anatómicas en el árbol traqueobronquial presentaron una prevalencia en nuestra población de estudio del 33%, hallándose 52 en 47 pacientes, siendo las más frecuentes la bifurcación del lóbulo superior derecho y el bronquio subsuperior. Su estudio y el de la anatomía total del árbol traqueo-bronquial mediante TCMD 64, independientemente del protocolo de estudio empleado, puede aportar información de utilidad previo a la realización de procedimientos más invasivos como la broncoscopía convencional.

A collaboration network involving 6 countries in Europe, Latin-America and the Caribbean has embarked on a project (Network of Collaboration Between Europe and Latin American Caribbean Countries-NECOBELAC; www.necobelac.eu) aimed at improving scientific writing open access and scholarly communication to spread know-how regarding current and future issues and information related to health. The NECOBELAC project is sponsored by the European Community (7th Framework Programme) and will last for 3 years. The project recognises the challenge arising from socio-cultural differences between the participating countries and will deal with generating networks involving institutions working in close collaboration for carrying out training and know-how exchange programmes aimed at producing open access information and spreading it (including technical and ethical aspects). The NECOBELAC project currently involves the Istituto Superiore di Sanita - ISS from Italy (coordinating the project), the Consejo Superior de Investigaciones Cientificas (CSIC) from Spain, the University of Nottingham (SHERPA) from the United Kingdom, BIREME from Brazil, the Instituto de Salud Publica (ISP) from Colombia and the Universidade de Minho from Portugal.

Browning development is the most important factor limiting the quality of fresh-cut cherimoya (Annona cherimola Mill.). However, there is little information available about its causes and methods of control. The effectiveness of L-cysteine (0.125, 0.25 and 0.5%) in fresh-cut cherimoya harvested on two occasions (October and November) and stored for 6 and 12 days at 0 °C was studied. In order to understand the biological basis of browning, polyphenol oxidase (PPO) enzyme activity and total phenolic content in fresh-cut pieces were measured. Quality measurements and sensory analysis indicated that 0.5% L-cysteine was somewhat effective in reducing browning development, without affecting other quality attributes. In terms of physiological parameters, PPO activity did not show differences between mature (at harvest) and ripe fruit (at processing) in both harvest times, but cherimoya fruits picked in November presented lower PPO activity than fruit from October. In general, PPO activity and total phenolic content of L-cysteine treated fruits did not show consistent differences with untreated fruit at 6 or 12 days at 0 °C. PPO activity analyses demonstrated that PPO activity was higher in the outer part of cherimoya flesh compared to the middle or inner sector. These results would support the possibility of using L-cysteine as a postharvest treatment to reduce browning development in fresh-cut cherimoya.El desarrollo de pardeamiento es uno de los factores limitantes en la calidad de chirimoya (Annona cherimola Mill.) precortada (fresh-cut). No obstante, existe poca información disponible en relación a sus causas y métodos de control en esta fruta. Se estudió la efectividad de L-cisteína (0,125; 0,25 y 0,5%) en chirimoya precortada cosechada en dos oportunidades (octubre y noviembre) y almacenada por 6 y 12 días a 0 ºC. Con el objetivo de conocer las bases biológicas del pardeamiento, se estudió la actividad de polifenol oxidasa (PPO) y contenido de fenólicos totales en piezas resultantes del precortado. Las mediciones de calidad y análisis sensorial indicaron que el tratamiento 0,5% L-cisteína fue el más efectivo en reducir el desarrollo de pardeamiento sin afectar otros atributos de calidad. En términos de parámetros fisiológicos, la actividad de PPO no mostró diferencias entre frutos inmaduros (a la cosecha) y maduros (al procesamiento) en ambas cosechas. Sin embargo, chirimoyas cosechadas en noviembre presentaron niveles de actividad de PPO menores que en octubre. En general, la actividad de PPO y contenido total de fenoles de frutos tratados con L-cisteína no presentaron diferencias significativas con respecto a frutos no tratados después de 6 ó 12 días a 0 ºC. Los análisis de la actividad de PPO demostraron que ésta fue más alta en la parte externa de la pulpa que en el sector medio o interno. Estos resultados respaldarían la posibilidad de usar L-cisteína como un tratamiento de poscosecha para reducir el desarrollo de pardeamiento en chirimoya destinada a precortado.

Little is known about the natural course of patients with chronic stable illnesses colonized with methicillin-resistant Staphylococcus aureus (MRSA). The aim is to determine the impact of MRSA colonization in mortality among long-term health care facility (LTHCF) residents.A multicenter, prospective, observational study was designed. Residents in 4 LTHCFs were classified according to MRSA carriage status and followed for 12 months. Treatment consisted of 5 days of nasal mupirocin in MRSA carriers.Ninety-three MRSA-carriers among 413 residents were identified. Thirty-one MRSA-colonized patients died during the study period, 11 of whom from an infectious disease. Independent predictors of their higher mortality rates included heart failure, current neoplasm, MRSA carriage and COPD at 3 months and these same factors plus stroke, Bar-thel index40, pressure ulcers, and older age at 12 months. MRSA-persistence was 35% and 62.5% at 3 and 12 months, respectively.MRSA colonization among frail LTHCFs residents is highly prevalent, and is associated with higher mortality. Despite treatment of MRSA carriers, many remained colonized. Factors that promote persistence of MRSA colonization, and the impact of their modification on mortality rates in these patients, need further investigation.

Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome-wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well-defined Southern European case-control collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR = 1.64, p = 1.0 x 10(-22) , rs7037324: OR = 1.54, p = 1.2 x 10(-17) ). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123 and rs1254167) at 10q26.12 showed suggestive evidence of association with higher risk of the disease (OR = 1.35, p = 1.2 x 10(-04) , OR = 1.26, p = 5.2 x 10(-04) and OR = 1.38, p = 5.9 x 10(-05) , respectively). Finally, the rare allele of rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p = 2.0 x 10(-04) ). This study suggests that heterogeneity in genetic susceptibility between populations is a key feature to take into account when exploring genetic risk factors related to this disease.