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A partir de la importancia que ha tomado la Delincuencia Organizada Transnacional actualmente, que se favorece por el proceso de globalización internacional, este libro busca abordar aquellas amenazas que en el marco de la seguridad multidimensional se categorizan en esta tipología criminal. En este sentido, el objetivo de esta investigación es analizar la incidencia de la Delincuencia Organizada Transnacional, tanto en la región como en Colombia. Esta investigación es un avance en la exploración de las amenazas a la seguridad que enfrentan las fronteras colombianas y trata temas de la coyuntura nacional e internacional, esperándose que sea un insumo de futuras investigaciones y proyecciones estatales en el abordaje de las amenazas de la Delincuencia Organizada Transnacional.

[Context] Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse., [Objectives] This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas., [Methods] A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years’ follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery., [Results] Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P, [Conclusion] This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas., This work was supported by the Junta de Andalucía (Nos. P20_00442, PEER-0048-2020, A-0006-2017, A-0055-2018, C-0015-2014, RC-0006-2018; postdoctoral grant DOC_01584, and BIO-0139); Ministry of Science and Innovation (Nos. PID2019-105564RB-I00 and PID2019-105201RB-I00); Instituto de Salud Carlos III, cofunded by the European Union (ERDF/ESF, “Investing in your future”; Nos. PI13/02043; PI16/00175, PI21/01012, and Sara Borrell programme CD19/00255); Spanish Ministry of Universities (predoctoral contract FPU16-05059); a GETNE2019 research grant; and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.

Intracellular signaling involved in the effects observed in response to SST3- agonists.

This supplementary file contains supplementary methods (library screening and statistical analysis) and table S1 (Pharmacological characterization of SST3-selective compounds), table S2 (Relation of functional experiments performed in responsive (RP) and unresponsive (URP) NFPTs), table S3 (Percentage of responsive and unresponsive NFPTs regarding SST3-specific agonists in terms of cell viability), table S4 (Results from Chi-square test of clinical parameters between responsive and unresponsive NFPTs), and table S5 (Clinical data and SST3 mRNA expression levels of individual NFPTs).

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.

EnglishThis article aims to unfold the definition of the concept of “migrant literature” in French, through the study of Laura Alcobas’s case and her novel Le Bleu des abeilles. A comparative analysis of identity search, enabled us to determine the extent to which the writer’s status as a political refugee, in a certain way, entails an original reformulation of issues, such as integration, acculturation, relation between “here” and “there” and the perspective of “in-between”. francaisNous proposons de nuancer la definition du concept de “litterature migrante” en langue francaise, en etudiant le cas de l’ecrivaine Laura Alcoba et de son roman Le Bleu des abeilles. Une analyse comparative sur sa quete identitaire nous permet de determiner a quel point sa condition de refugiee politique suppose, en quelque sorte, une reformulation originale des questions telles que l’integration, l’acculturation, les rapports “ici-la” et la perspective de l’entre-deux.

Purpose To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. Methods Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. Results Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. Conclusion An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP (n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, β-catenin accumulation was not related to tumor recurrence. View Full-Text, This work was supported by grants from the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI16/00175 to A.S-M. and D.A.C.) and the Sistema Andaluz de Salud (A-0006-2017 and A-0055-2018 to A.S-M, RC-0006-2018 to D.A.C.).

There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently, there is no cure for this disease. The transplantation of pancreatic islets that contain insulin-producing cells is a promising therapeutic alternative, particularly for type 1 diabetes. However, the shortage of organ donors constitutes a major limitation for this approach; thus, developing alternative sources of insulin-producing cells is of critical importance. In the last decade, our knowledge of the molecular mechanisms controlling embryonic pancreas development has significantly advanced. More importantly, this knowledge has provided the basis for the in vitro generation of insulin-producing cells from stem cells. Recent studies have revealed that GATA transcription factors are involved in various stages of pancreas formation and in the adult ß cell function. Here, we review the fundamental role of GATA transcription factors in pancreas morphogenesis and their association with congenital diseases associated with pancreas., L.V. was supported by a contract from Spanish Ministry of Economy and Competitiveness (RYC‐2013‐14533). This work was supported by the Spanish Ministry of Economy and Competitiveness (BFU2017‐82497‐P and RYC‐2013‐14533 to A. R). ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación cofunded with Fondos FEDER (PI16/00175 to D.A.C) and the Andalusian Ministry of Science and Innovation (CTS‐7478 to D.A.C).

[ES] La interoperabilidad semántica de la información sanitaria es un requisito imprescindible para la sostenibilidad de la atención sanitaria, y es fundamental para afrontar los nuevos retos sanitarios de un mundo globalizado. Esta tesis aporta nuevas metodologías para abordar algunos de los aspectos fundamentales de la interoperabilidad semántica, específicamente aquellos relacionados con la definición y gobernanza de modelos de información clínica expresados en forma de arquetipo. Las aportaciones de la tesis son: - Estudio de las metodologías de modelado existentes de componentes de interoperabilidad semántica que influirán en la definición de una metodología de modelado de arquetipos. - Análisis comparativo de los sistemas e iniciativas existentes para la gobernanza de modelos de información clínica. - Una propuesta de Metodología de Modelado de Arquetipos unificada que formalice las fases de desarrollo del arquetipo, los participantes requeridos y las buenas prácticas a seguir. - Identificación y definición de principios y características de gobernanza de arquetipos. - Diseño y desarrollo de herramientas que brinden soporte al modelado y la gobernanza de arquetipos. Las aportaciones de esta tesis se han puesto en práctica en múltiples proyectos y experiencias de desarrollo. Estas experiencias varían desde un proyecto local dentro de una sola organización que requirió la reutilización de datos clínicos basados en principios de interoperabilidad semántica, hasta el desarrollo de proyectos de historia clínica electrónica de alcance nacional., [CA] La interoperabilitat semàntica de la informació sanitària és un requisit imprescindible per a la sostenibilitat de l'atenció sanitària, i és fonamental per a afrontar els nous reptes sanitaris d'un món globalitzat. Aquesta tesi aporta noves metodologies per a abordar alguns dels aspectes fonamentals de la interoperabilitat semàntica, específicament aquells relacionats amb la definició i govern de models d'informació clínica expressats en forma d'arquetip. Les aportacions de la tesi són: - Estudi de les metodologies de modelatge existents de components d'interoperabilitat semàntica que influiran en la definició d'una metodologia de modelatge d'arquetips. - Anàlisi comparativa dels sistemes i iniciatives existents per al govern de models d'informació clínica. - Una proposta de Metodologia de Modelatge d'Arquetips unificada que formalitza les fases de desenvolupament de l'arquetip, els participants requerits i les bones pràctiques a seguir. - Identificació i definició de principis i característiques de govern d'arquetips. - Disseny i desenvolupament d'eines que brinden suport al modelatge i al govern d'arquetips. Les aportacions d'aquesta tesi s'han posat en pràctica en múltiples projectes i experiències de desenvolupament. Aquestes experiències varien des d'un projecte local dins d'una sola organització que va requerir la reutilització de dades clíniques basades en principis d'interoperabilitat semàntica, fins al desenvolupament de projectes d'història clínica electrònica d'abast nacional., [EN] Semantic interoperability of health information is an essential requirement for the sustainability of healthcare, and it is essential to face the new health challenges of a globalized world. This thesis provides new methodologies to tackle some of the fundamental aspects of semantic interoperability, specifically those aspects related to the definition and governance of clinical information models expressed in the form of archetypes. The contributions of the thesis are: - Study of existing modeling methodologies of semantic interoperability components that will influence in the definition of an archetype modeling methodology. - Comparative analysis of existing clinical information model governance systems and initiatives. - A proposal of a unified Archetype Modeling Methodology that formalizes the phases of archetype development, the required participants, and the good practices to be followed. - Identification and definition of archetype governance principles and characteristics. - Design and development of tools that provide support to archetype modeling and governance. The contributions of this thesis have been put into practice in multiple projects and development experiences. These experiences vary from a local project inside a single organization that required a reuse on clinical data based on semantic interoperability principles, to the development of national electronic health record projects., This thesis was partially funded by the Ministerio de Economía y Competitividad, ayudas para contratos para la formación de doctores en empresas “Doctorados Industriales”, grant DI-14-06564 and by the Agencia Valenciana de la Innovación, ayudas del Programa de Promoción del Talento – Doctorados empresariales (INNODOCTO), grant INNTA3/2020/12.

[EN] Introduction: Giant prolactinomas (tumor size larger than 40 mm) are a rare entity of benign nature. Prolactinomas larger than 60 mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. Patients and methods: We retrospective collected data from patients with prolactinomas larger than 60 mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200 μIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60 mm. Results: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594–514,984] μIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. Conclusions: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60 mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations., [ES] Introducción: Los prolactinomas gigantes (de tamaño superior a 40 mm) son una entidad rara de naturaleza benigna. Los prolactinomas mayores de 60 mm suelen estar infrarrepresentados en los estudios publicados, y su presentación clínica, resultados y tratamiento podrían ser diferentes de los de prolactinomas gigantes más pequeños. Pacientes y métodos: Recogimos retrospectivamente datos de pacientes con prolactinomas de más de 60 mm de diámetro máximo y con concentraciones séricas de prolactina (PRL) superiores a 21.200 μIU/ml de nuestra serie de prolactinomas (283). Los datos se recogieron entre enero de 2012 y diciembre de 2017. Se incluyeron 3 pacientes con prolactinomas mayores de 60 mm. Resultados: En el momento del diagnóstico, 2 pacientes presentaban síntomas neurológicos, y uno protrusión nasal. Todos los pacientes recibieron tratamiento médico con agonistas dopaminérgicos. No se realizó ninguna intervención quirúrgica. La mediana de las concentraciones de PRL al diagnóstico fue de 108.180 (52.594-514.984) μIU/ml. El tratamiento médico logró una reducción notable (> 99%) de los valores de prolactina en todos los casos. En todos los casos se observó una reducción del tamaño del tumor (superior al 33%). En un paciente se observó una fuga de líquido cefalorraquídeo (LCR) tras la reducción del tumor. Conclusión: Los agonistas dopaminérgicos parecen ser un tratamiento de primera línea eficaz y seguro en los prolactinomas mayores de 60 mm incluso en situaciones peligrosas para la vida. Se necesitan más estudios con un mayor número de pacientes para obtener datos suficientes para hacer recomendaciones importantes.

In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis. However, our knowledge of the master regulators involved in the deactivation and/or activation of fibrotic hepatic stellate cells is still limited. The transcription factor GATA4 has been previously shown to play an important role in embryonic hepatic stellate cell quiescence. In this work, we show that lack of GATA4 in adult mice caused hepatic stellate cell activation and, consequently, liver fibrosis. During regression of liver fibrosis, Gata4 was reexpressed in deactivated hepatic stellate cells. Overexpression of Gata4 in hepatic stellate cells promoted liver fibrosis regression in CCl4-treated mice. GATA4 induced changes in the expression of fibrogenic and antifibrogenic genes, promoting hepatic stellate cell deactivation. Finally, we show that GATA4 directly repressed EPAS1 transcription in hepatic stellate cells and that stabilization of the HIF2α protein in hepatic stellate cells leads to liver fibrosis., This work was supported by grants from the Spanish Ministry of Economy and Innovation (MICIN/AEI/10.13039/501100011033/ FEDER) (BFU2017-82497-P-to AR and BFU2017-83907-P to RMC and RC); from Spanish Ministry of Science and Innovation (MICIN/AEI/10.13039/501100011033) (PID2020-114656RB-I00 to AR); from Agencia Andaluza del Conocimiento, Consejería de Transformación Económica, Industria, Conocimiento y Universidades (PY20_00850 to AR); and from ISCIII-Subdirección General de Evaluación y Fomento de la Investigación cofunded with Fondos FEDER (PI16/00175 to DAC).

Sea turtle populations around the world face rapid decline due to the effect of anthropogenic and environmental factors. Among the affected populations are those of hawksbill turtles (Eretmochelys imbricata) and loggerhead turtles (Caretta caretta), which is why a greater effort is currently being made in their monitoring and tracing. The intragenic degree of heteroplasmic mutations, commonly associated with diseases of variable symptoms, has not been analyzed in these species. In this study, heteroplasmy in the complete mitogenome (mtDNA) of three loggerhead turtles and one hawksbill turtle was identified from data obtained by RNAseq. Individuals Cc3, Ei1, Cc1 and Cc2 presented 0.3, 1.7, 1.8 and 7.1% of heteroplasmic mutations in all their mtDNA, respectively. The protein-coding genes that presented the highest percentage of heteroplasmy were ND4 and ND5 in individual Cc2 with 16 and 38.6%, respectively. Of the tRNA genes, only tRNATyr was heteroplasmic in the four individuals with 5.63% (Cc1), 25.35% (Ei1 and Cc2) and 49.3% (Cc3). In this study, we identified the critical sites of heteroplasmy in each individual and the genetic variability of their mitogenomes. The data obtained represents the baseline for future projects that evaluate the population status of these species.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER PI16/00175 to A.S.-M. and D.A.C; PI16/00264 to R.M.L. Sistema Andaluz de Salud A-0006-2017 and A-0055-2018 to A.S.-M, C-0015-2014 and RC-0006-2018 to D.A.C. Ministerio de Ciencia, Innovación BFU2016-80360-R to J.P.C.; PID2019-105564RB-I00 to R.M.L. Junta de Andalucía BIO-0139 to J.P.C. and R.M.L. Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox; Pdx1‐Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4‐deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples., ER‐S. was supported by a ‘Juan de la Cierva’ postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness (IJCI‐2014‐19251). LV was supported by a contract from Spanish Ministry of Economy and Competitiveness (RYC‐2013‐14533). This work was supported by grants from the Spanish Ministry of Economy and Competitiveness BFU2017‐82497‐P to AR, ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación co‐funded with Fondos FEDER, PI16/00175 to DAC, the Andalusian Ministry of Science and Innovation CTS‐7478 to DAC, and grant SAF2015‐70553‐R to FXR. CNIO is supported by the “Ministerio de Ciencia, Innovación y Universidades” as a Centro de Excelencia Severo Ochoa (SEV‐2015‐0510).

Este trabajo tiene como objeto, estudiar la influencia de las adiciones de alúmina microestructurada en recubrimientos autofundentes base Níquel (NiCrBSi) sobre la microestructura, (difracción de rayos X (DRX) y microscopía electrónica de barrido (SEM y EDX)), propiedades mecánicas (perfil de microdurezas Vickers y desgaste abrasivo) como tribológicas en medios lubricados (Curva de Stribeck). Estos recubrimientos son depositados mediante proyección térmica (OF) y refundidos por llama oxiacetilénica. El par rozante empleado en estos estudios están comprendidos entre los siguientes recubrimientos comerciales sin modificar de base Níquel : (NíCrBSi,10,1%Cr, NiCrBSi, 15,25%Cr , NiCrBSi/WC 60/40% con un contenido en cromo del 15,25% y un disco de acero F-5220 templado en aceite y revenido.

[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.

El río Mira nace en Ecuador y desemboca en el Océano Pacífico en territorio colombiano. Su ictiofauna había sido muy poco estudiada y los registros disponibles indicaban una muy baja riqueza de especies. El aumento en el esfuerzo de muestreo a nivel temporal y espacial a lo largo de la cuenca del Mira en comparación con inventarios pasados, permitió incrementar el conocimiento de las especies de este río. Se reporta aquí la diversidad íctica regional encontrada en seis expediciones de campo realizadas entre 2009 y 2016, se documentan 39 especies, 29 dulceacuícolas nativas, una introducida y nueve de origen marino que remontan la cuenca baja; el material recolectado se encuentra depositado en la Colección de Peces del Instituto de Ciencias Naturales de la Universidad Nacional de Colombia (ICN-MHN). Las actividades antrópicas que se desarrollan en la cuenca, principalmente la tala de bosques nativos y los monocultivos (lícitos e ilícitos), implican a una severa alteración del hábitat, que pone en riesgo esta diversidad biológica.

Acromegaly is a hormonal disorder resulting from excessive growth hormone (GH) secretion frequently produced by pituitary adenomas and consequent increase in insulin‐like growth factor 1 (IGF‐I). Elevated GH and IGF‐I levels result in a wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Somatostatin analogues (SSAs) form the basis of medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy in patients undergoing unsuccessful surgery. However, a considerable percentage of patients do not respond to SSAs treatment. Somatostatin receptors (SSTR1‐5) and dopamine receptors (DRD1‐5) subtypes play critical roles in the regulation of hormone secretion. These receptors are considered important pharmacological targets to inhibit hormone oversecretion. It has been proposed that decreased expression of SSTRs may be associated with poor response to SSAs. Here, we systematically examine SSTRs and DRDs expression in human somatotroph adenomas by quantitative PCR. We observed an association between the response to SSAs treatment and DRD4, DRD5, SSTR1 and SSTR2 expression. We also examined SSTR expression by immunohistochemistry and found that the immunohistochemical detection of SSTR2 in particular might be a good predictor of response to SSAs.

Travelers in search of the “Orient” around 1900 in Southern Spain were willingly served by photographers such as Rafael Garzon. In his studio in Granada, they were able to have their portrait taken...

Introducción: En el mundo más de mil millones de personas en el mundo presentan algún tipo de diversidad funcional, por lo que para la generación de programas de inclusión es importante la realización de la caracterización de esta población. Objetivo: Caracterizar la funcionalidad de personas con alteraciones neurológicas que asisten a un centro de neurorehabilitación de Cali-Colombia Métodos: Se recolectó información relacionada con funcionalidad de 84 personas con alteraciones de tipo neurológico que asistieron a un centro de neurorehabilitación de entre los meses de abril a mayo de 2018. Resultados: 43 participantes presentaban diversidad múltiple. El 33,33% de los pacientes con hipertonía y el 51,85% de los pacientes con hemiplejía evidenciaron una dependencia moderada. Conclusiones: la mayoría de los pacientes incluidos en el estudio se encontraban una dependencia moderada, característica que debe ser tenida en cuenta en el diseño de programas de inclusión deportiva desde centros terapéuticos

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 SSTBinding to SSTs and cAMP level determinations were used to screen a peptide library and identify SSTWe successfully identified the first SSTThis study demonstrates that SST

Objective Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing’s disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. Design We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. Methods We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. Results We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P P Conclusions By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

INTRODUCTION Non-functioning pituitary adenomas (NFPAs) are usually benign. However, a substantial proportion of pituitary adenomas show an aggressive behavior with local invasion and increased risk of regrowth or recurrence after surgery. The treatment of choice for these adenomas is transsphenoidal resection but it is not always successful. NFPAs express somastostatin receptors (SSTRs) thus providing a theoretical rationale for the pharmacological treatment with somatostatin analogues. However, a consistent method for evaluating SSTR expression needs to be implemented. AIM The aim of the study was to systematically evaluate the expression of SSTRs in NFPAs by quantitative PCR and by immunohistochemistry with reliable commercial antibodies and analyze their potential association with aggressive features. METHODS. In this retrospective descriptive study, 114 patients that underwent transsphenoidal surgery were evaluated. Clinical variables, histological subtype (including classification of agressive histological subtypes) and need for radiotherapy were collected to analyze potential associations between these variables and SSTR expression. Tumor size and cavernous sinus invasion data were obtained from magnetic resonance images. Cavernous sinus invasion was evaluated using the Knosp classification. Knosp grade 3 and 4 were defined as invasive. The expression of SSTRs (SSTR2. SSTR3 and SSTR5) was evaluated using a score system previously described [Venegas-Moreno et al. J Cell Mol Med. 2018;22(3):1640-1649]. RESULTS Quantitative PCR analysis revealed that SSTR3 was the predominant SSTR subtype detected, followed by SSTR2, SSTR5, and SSTR1. Immunohistochemistry data showed a similar expression pattern. However, The expression of the different SSTRs displayed a notable variability among NFPAs. Thus, 28,9% of NFPAs showed substantial SSTR2 expression, as indicated by high immunohistochemistry scores. Also, 12,3% of NFPAs displayed high SSTR5 expression while 86,8% of NFPAs displayed high SSTR3 levels. No significant associations between SSTR expression and sex, tumor size, invasion and surgical cure. Patients with elevated SSTR2 expression were younger but this association was not observed with SSTR3 and SSTR5. CONCLUSIONS No major association between SSTR expression and aggressive features was observed in NFPAs. A proportion of NFPAs displayed marked expression of SSTR2 and SSTR5 and thus, they might be considered potential candidates for therapy with somatostatin analogues. Sources of Research Support: Spanish Ministry of Health, ISCIII co-funded with Fondos FEDER (PI16/00175) and Novartis Oncology Spain.

The populations of loggerhead (Caretta caretta) and hawksbill (Eretmochelys imbricata) sea turtles are suffering an exponential decline due to anthropic and environmental actions that threaten their survival. In these turtle populations, the degree of heteroplasmic mutations commonly related with pathologies, has not been studied. In this data report, the specifications of each heteroplasmic site (region, mutation, length) and the percentage of heteroplasmy of each gene for four mitochondrial genomes of turtles (loggerhead: Cc1, Cc2, Cc3 and hawksbill: Ei1) are presented. The highest value of heteroplasmy in tRNA was of 83.33% for the Cc2 turtle (tRNASer gene), in protein coding genes was 38.62% for Cc2 (ND5), and in rRNA genes of 0.74% for Ei1 turtle (rRNA-16S). The variability data obtained will be useful for further conservation projects, evolution studies and population health of these species. This is the first study of heteroplasmy in complete mitogenomes of loggerhead and hawksbill turtles.

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs., This work was supported by grants from the ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación co‐funded with Fondos FEDER (PI13/02043 to A.S‐M. and PI16/00175 to A.S‐M. and D.A.C), Junta de Andalucía (A‐0023‐2015, A‐0003‐2016 to A.S‐M, CTS‐1406, BIO‐0139 to J.P.C. and R.M.L.) and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. D.A.C. was supported by a research contract from the “Nicolás Monardes” program of the Andalusian Ministry of Health (C‐0015‐2014). Part of the analyses included in this study was carried out within the REMAH (“Spanish molecular registry of pituitary adenomas”) project, supported by Novartis Oncology as well as by the Andalusian and Spanish Societies of Endocrinology and Nutrition (SAEDYN and SEEN, respectively).

[Background] Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy., [Aims] We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center., [Methods] Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response., [Results] Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P = 0.002) and were more frequently sparsely granulated (P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen., [Conclusions] Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIP screening criteria could be significantly refined to focus on large, aggressive tumors in young patients., This research was supported by a grant from the Fonds d’Investissement pour la Recherche (FIRS) of the CHU de Liège, the JABBS Foundation, United Kingdom (to A B) and the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI13/02043 to A S-M and PI16/00175 to A S-M and D A C). A S-M and D A C were also supported by grants from the Andalusian Ministry of Health (A-0003-2016, A-0006-2015, C-0015-2014 and RC-0006-2018).

Background: The degree of histopathological response after neoadjuvant therapy in locally advanced gastric cancer (GC) is a key determinant of patients' long-term outcome. We aimed to assess the pattern of histopathological regression after two neoadjuvant approaches and its impact on survival times. Methods: Regression grade of the primary tumour (Becker criteria) and the degree of nodal response by a 4-point scale (grades A–D) were assessed. Grade A—true negative lymph nodes (LNs); grade B and C—infiltrated LNs with any or little evidence of nodal response; and grade D—complete pathological response in a previously infiltrated LN. A favourable pathological response was defined as Becker Ia–b and grade D. Results: From 2004 to 2014, 80 patients with GC (cT3–4/N+ by CT-scan/EUS) were treated with either preoperative chemotherapy (ChT, n=34) or chemoradiation (CRT, n=46). Patients in the CRT group had a higher likelihood of achieving a Becker Ia–b response (58 vs 32%, P=0.001), a grade D nodal regression (30 vs 6%, P=0.009) and a favourable pathological response (23 vs 3% P=0.019). Patients with a grade D nodal response had a longer 5-year PFS and OS compared with those with a grade B or C response. Patients with a baseline negative LN status had similar outcomes irrespective of the preoperative therapy received (5-year OS; ChT vs CRT, 58 vs 51%, P=0.92). Conclusions: Preoperative chemoradiation increases the likelihood of achieving favourable histopathological features that correlate with a 5-year OS>70% in GC patients.

There is a growing awareness that prevention and early diagnosis may reduce the high mortality associated with cancer, cardiovascular and other diseases. The role of whole-body computed tomography (WB-CT) in self-referred and asymptomatic patients has been debated. To determine frequency and spectrum of WB-CT findings in average-risk subjects derived from a Medical-Check-Up-Unit, to evaluate recommendations reported and distribution according to sex and age-groups. We retrospectively reviewed 6516 subjects who underwent WB-CT (June 2004/February 2015). All were > 40 years and referred by Medical-Check-Up-Unit of our hospital. The main findings were categorized and classified as normal or not. Its distribution according to sex and age-groups was evaluated using Chi-square test and linear-by-linear association test, respectively. Number of recommendations, type and interval of follow-up were recorded. Descriptive statistics were used. WB-CT performed in 6516 patients (69% men, 31% women, mean age = 58.4 years) revealed chest (81.4%), abdominal (93.06%) and spine (65.39%) abnormalities. Only 1.60% had completely normal exploration. Abnormal WB-CT in men was significantly higher than women (98.64% vs. 97.87%; p = 0.021), with significant increase as age was higher (40–49 years: 95.65%; 50–59 years: 98.33%; 60–69 years: 99.47%; > 69 years: 99.89%) (p

BackgroundPerioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharmacodynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients.MethodsPatients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks.ResultsA low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage ≥3 and linitis plastica absence, were correlated to a higher risk of death.ConclusionOur model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.

Hypoxia inducible factors (HIFs) are critical regulators of the response to oxygen deficiency by activating target genes involved in a variety of biological functions. HIFs have been implicated in the pathophysiology of numerous pathologies including cancer. Patients with mutations in the von Hippel-Lindau (VHL) gene, an essential regulator of HIF activity, develop tumors in several organs including the pancreas. Previous functional studies of HIF activation in the pancreas have used Vhlh (the murine homolog of VHL) deficient mice. However, the role of each specific HIF transcription factors in the pancreas has not been thoroughly examined. We derived mice that constitutively express a normoxia-stable form of HIF2α in the pancreas. Activation of HIF2α in the pancreas severely impairs postnatal exocrine pancreas. Mice with pancreas-specific activation of HIF2α develop histological features reminiscent of pancreatitis including loss of acinar cells, ductal dilation and fibrosis. Moreover, we provide evidence that signaling pathways important for acinar cell homeostasis are altered in HIF2α-overexpressing pancreata., D.A.C. was supported by the “Nicolás Monardes” program of the Andalusian Ministry of Health (C-0015- 2014) and by grants from the Andalusian Ministry of Science and Innovation (CTS-7478), Spanish Ministry of Science and Innovation (SAF2011-26805) and the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI16/00175). A.R. was supported by grants from ISCIII cofunded by Fondos FEDER (PI14/0804), Ministry of Economy and Competitiveness (BFU2017-82479-P) and the “Ramón y Cajal” program from the Spanish Ministry of Economy and Competitiveness (RYC-2013-14533). A.G.-N. was supported by a fellowship from the Andalusian Regional Government (P08-CVI-3727).

Purpose To evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE. Materials and Methods Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy. Tumor growth in mice was monitored using a digital caliper and by computed tomography in rabbits. Results Intratumoral administration of poly-ICLC immediately before IRE elicited shrinkage of Hepa.129 cell-derived tumors in 70% of mice, compared to 30% and 26% by poly-ICLC or IRE alone, respectively (P = .0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular carcinoma tumors in 40% of rabbits, whereas no response was achieved by either individual treatment (P = .045). The combined therapy activated a systemic antitumor response able to inhibit the growth of other untreated tumors. Conclusions IRE treatment, immediately preceded by the intratumoral administration of an immunogenic adjuvant such as poly-ICLC, might enhance the antitumor effect of the IRE procedure. This combination might facilitate the induction of a long-term systemic response to prevent tumor relapses and the appearance of metastases.

Con el fin de formular con más precisión los criterios que caracterizan a la literatura francófona antillana y relacionarlos con la producción literaria y crítica de la escritora guadalupeña Maryse Condé, debemos tener en cuenta todo un complejo conjunto de factores de diversa naturaleza. Dadas las obsoletas definiciones de la realidad insular y la dificultad que entraña actualmente su descripción exacta, hemos decidido tomar como punto de referencia la idea de complejidad introducida por Deborah M. Hess en su estudio Maryse Condé. Mythe, parabole et complexité (2011), con el fin de procurarnos una visión idónea en nuestro planteamiento de las cuestiones fundamentales de esta tesis. Centrar entonces nuestro interés en la obra de una autora como Maryse Condé requiere el desarrollo, a priori, de un marco teórico que nos proporcione los elementos clave para fundamentar este estudio. Por esta razón, hemos dedicado la primera parte a analizar la problemática que gira en torno al contexto de su obra y al de su personalidad. Iniciamos nuestro análisis a partir de la denominación, del origen y del desarrollo de una especificidad antillana, nociones fundamentales que van estrechamente relacionadas. Esta contextualización nos permite definir, desde un primer momento, los conceptos y concretar la metodología que vamos a utilizar a lo largo de todo el trabajo para, finalmente, exponer con más claridad nuestros objetivos, así como concretar nuestra perspectiva personal sin dar lugar a ambigüedades. A partir de este momento, somos conscientes de la envergadura de tales cuestiones, por lo que se impone la lógica necesidad de acotar nuestra investigación. En consecuencia, los siguientes capítulos de este trabajo han versado sobre un análisis textual concebido bajo este triple punto de vista: oralidad, feminidad y naturaleza, elementos esenciales en la búsqueda de identidad antillana, que Maryse Condé ha ido forjando particularmente a través de toda su obra. Así concluimos por adoptar esta perspectiva temática, sin obviar a los eruditos consagrados al estudio de esta literatura francófona, con el fin de profundizar con verosimilitud en el análisis propuesto. Nos hemos centrado no sólo en su obra literaria y en su trabajo teórico, sino también en el de aquellos intelectuales de su entorno. De esta forma, hemos introducido y contrastado los resultados con el pensamiento y el imaginario de otras escritoras francófonas, lo que nos ayuda a contextualizar y después a enriquecer la problemática de nuestra discusión. En definitiva, la presencia de la oralidad, el desarrollo del punto de vista femenino y la función específica que desempeña la naturaleza se superponen y se complementan en la obra de Maryse Condé. En efecto, estos elementos representan una triple vertiente que confluye en un único objetivo: analizar su obra y exponer diferentes argumentos en torno a una sensibilidad tan especial y, al a vez, tan compleja como es la de esta autora, no sujeta a formulismos y de difícil clasificación. La evolución de su escritura, puente de unión entre pasado y presente, traza un camino similar al del desarrollo de la propia literatura antillana y al de la creación de otras formas de expresión artística que comparten, junto con una historia colectiva, una identidad común. Su extensa obra literaria y su aportación intelectual no sólo consolidan la especificidad antillana, sino que también proponen nuevas vías de expansión. Nos permitimos asociar entonces el término “redefinición” a la trayectoria de esta autora, motivados por las conclusiones y las constataciones de este estudio: una peculiar participación en la reescritura de la Historia y en la reconstrucción de un espacio de identidad, impulsando, a su vez, un renacimiento literario insular por medio de su prolífico trabajo intelectual, máximo exponente de la feminidad francófona antillana., Orality and female identity in the narrative work of Maryse Condé In order to formulate the criteria characterizing francophone Caribbean literature more precisely and relate them to the literary production and criticism by Guadeloupian writer Maryse Condé, a complex set of diverse factors must be taken into account. Given the obsolescence of the existing definitions of insular reality and the prevailing difficulty to describe it in exact terms, the idea of complexity presented by Deborah M. Hess in her study Maryse Condé. Mythe, parabole et complexité (2011) has been taken as a referent so as to provide an appropriate perspective in the approach to the fundamental issues in this thesis. Hence, placing our interest in the work by an author such as Maryse Condé requires, initially, a development of a theoretical framework that should provide the key elements to support the present research. For this reason, the first part is devoted to the analysis of issues related to the context of her work as well as her personality. The analysis begins with a set of closely related fundamental notions: the name, the origin and the evolution of a Caribbean specificity. From the very start, this contextualization allows to define the concepts and to determine the methodology to be used in the research for the purpose of presenting the objectives with more clarity and specifying a personal perspective devoid of ambiguities. At this point, the scope of such questions becomes obvious; therefore, a logical need to narrow down the research prevails. Consequently, the subsequent chapters in this paper deal with a textual analysis from the following threefold point of view: oral tradition, femininity and nature. All of them are essential elements in the search for the Caribbean identity that Maryse Condé has especially forged in all her work. This thematic perspective has been adopted without disregarding the scholars devoted to the study of this francophone literature in order to delve into the proposed analysis with authenticity. Not only her literary work and theoretical writing, but also that by the intellectuals of her surroundings is brought into focus. Thus, the results have been presented and compared to other francophone female writers’ thought and collective imaginary, which helps to contextualize and, consequently, to enrich the points of the present discussion. Definitely, the presence of oral tradition, the development of the female perspective and the particular function of nature overlap and complement each other in Maryse Condé’s work. In fact, these elements constitute a threefold focus that converges in a sole objective: to analyze her work and to present different arguments on such a special and convoluted sensitivity belonging to an author unattached by formalisms and difficult to classify. The evolution of her writing, a bridge between the past and the present, traces a similar path to that of the evolution of the Caribbean literature itself and to the creation of other forms of artistic expression that share a common identity as well as a collective history. Not only does her extensive literary endeavour and intellectual contribution consolidate the Caribbean specificity, but also propose further developments. Thus, in sight of the conclusions and verifications of this research, the term “redefinition” can be associated to this author’s work: a peculiar participation in the rewriting of History and in the reconstruction of the space for identity, launching, at the same time, a literary rebirth on the islands by means of her prolific intellectual work – the finest portrayal of Caribbean francophone femininity.