New potential pharmacological options for endometriosis associated pain

© 2024 by the author. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https://doi.org/10.3390/ ijms25137068Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited ef fectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurpos ing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometri osis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, im proving patients’ overall wellbeing

Visualisation of Perception of Experiential Activities in Business and Administration and Economy

This paper explores how to incorporate information visualization tools into qualitative studies to represent the underlying structure of knowledge. Information visualization plays a key role in many areas such as decision-making, data mining, market studies, or knowledge management. A case of experiential learning was developed for Quantitative Techniques in Business and Administration and Economy Degrees at the University of Granada, Spain. The goal is to analyze the opinion of students (n = 227) on the development of the activity through information visualization techniques. The gathered information was subjected to a categorization process to unify and homogenize the responses. After a term-clumping process, a co-word analysis using the VosViewer software is used to analyze the relationships among terms and provide the network maps. Results display the main associations and clusters of terms used when assessing the experiential activity, using qualitative techniques. In conclusion, the strengths of data visualization enabling a better understanding of data for qualitative studies are established

Optimization of peritoneal fluid and leukocyte collection in patients with endometriosis

© 2018. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the MP4 version of a published work that appeared in Fertility and Sterility To access the final work, see DOI: https://doi.org/10.1016/j.fertnstert.2023.06.030Objective: To propose a standardized protocol for peritoneal free fluid and leukocyte sample collection in women with endometriosis suitable for biomedical research on the basis of the surgical procedure, the clinical and technical conditions, and the quality of the samples obtained. Design: Video showing the step-by-step collection procedure and the suitability of samples obtained for biomedical research. Subjects: This study included 103 women with confirmed endometriosis by pathology analysis, who signed informed consent and were recruited from the Hospital ‘‘Virgen de la Arrixaca’’, Murcia, Spain. The study was approved by the Ethics Committee of University of Murcia (CEI 3156/2020). Main Outcome Measures: We analyzed the presence of free fluid in the peritoneal cavity and its relationship with hormonal treatment intake. In addition, the presence of blood contamination, the number of viable leukocytes and macrophages in free peritoneal fluid and lavages as well as their relationship with the lavage volume used, the body mass index, and the age of patients were analyzed. Results: The presence of free peritoneal fluid, in which cells and molecules could be quantified, was scarce in the patients (21%), and it was not significantly related to hormonal treatment intake. The cell viability was higher than 98% in all collected samples; although 54% showed good quality and enough cellularity to be used in biomedical research, 40% were contaminated with blood and 6% had low cellularity. The number of leukocytes and macrophages recovered from the peritoneal lavages correlated positively with the lavage volume used and negatively with the body mass index and was independent of the age of the patients. Conclusion: We describe a standardized step-by-step procedure for peritoneal fluid and leukocyte collection in women with endometriosis, suitable for biomedical research, taking into account that not all women present free fluid in the peritoneal cavity. We propose to increase the lavage volume recommended by the World Endometriosis Research Foundation from 10 mL to at least 40 mL of sterile saline solution and its mobilization for at least 30 seconds within the peritoneal cavity, especially in patients with higher body mass index, to improve the efficiency of the procedure

The role of peritoneal macrophages in Endometriosis.

© 2021 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https://doi.org/10.3390/ijms221910792Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology

El portafolio digital como recurso didáctico en las aulas universitarias

En el Espacio Europeo de Educación Superior la formación se centra en el desarrollo de competencias. Esto supone un nuevo planteamiento en torno a las metodologías desarrolladas en las aulas universitarias. El presente capítulo versa sobre el portafolio digital como herramienta didáctica facilitadora de la competencia básica de “aprender a aprender”, entre otras, y del protagonismo del estudiante en el proceso de enseñanza-aprendizaje

Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression

Although FoxP3+ regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3+CD69+ Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69+ and CD69−FoxP3+ Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFβ and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3+CD69+ Tregs restores the homeostasis in Cd69−/− mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3+CD69+ Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunityThis work was supported by funding from the Spanish Ministry of Economy and Competitiveness: SAF2011-27330 to P.M., SAF2010-15106 to M.L.T and SAF2011-25834 to F.S-M.; grant INDISNET (S2010/BMD-2332) from Comunidad de Madrid and RETICS Enfermedades Cardiovasculares (RD12/0042/0056) from Instituto de Salud Carlos III to P.M and F. S-M; and ERC-2011-AdG294340-GENTRIS to F.S-M. J.R.C. was supported by a CNIC post-doctoral fellowship, R. S-D is funded with a pre-doctoral fellowship from Comunidad de Madrid and E.R.B. and A.M-M. were supported by a FPI pre-doctoral fellowship from the Spanish Ministry of Economy and Competitiveness. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro CNIC Foundatio

Expression Patterns of Irx Genes in the Developing Chick Inner Ear

© 2016 Springer-Verlag Berlin Heidelberg.This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Brain Structure and Function. To access the final edited and published work see https://doi.org/10.1007/s00429-016-1326-6The vertebrate inner ear is a complex three-dimensional sensorial structure with auditory and vestibular functions. The molecular patterning of the developing otic epithelium creates various positional identities, consequently leading to the stereotyped specification of each neurosensory and non-sensory element of the membranous labyrinth. The Iroquois (Iro/Irx) genes, clustered in two groups (A: Irx1, Irx2, and Irx4; and B: Irx3, Irx5, and Irx6), encode for transcriptional factors involved directly in numerous patterning processes of embryonic tissues in many phyla. This work presents a detailed study of the expression patterns of these six Irx genes during chick inner ear development, paying particular attention to the axial specification of the otic anlagen. The Irx genes seem to play different roles at different embryonic periods. At the otic vesicle stage (HH18), all the genes of each cluster are expressed identically. Both clusters A and B seem involved in the specification of the lateral and posterior portions of the otic anlagen. Cluster B seems to regulate a larger area than cluster A, including the presumptive territory of the endolymphatic apparatus. Both clusters seem also to be involved in neurogenic events. At stages HH24/25-HH27, combinations of IrxA and IrxB genes participate in the specification of most sensory patches and some non-sensory components of the otic epithelium. At stage HH34, the six Irx genes show divergent patterns of expression, leading to the final specification of the membranous labyrinth, as well as to cell differentiation

Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression

Although FoxP3+ regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3+CD69+ Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69+ and CD69-FoxP3+ Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFβand have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3+CD69+ Tregs restores the homeostasis in Cd69-/- mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3+CD69+ Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunity.This work was supported by funding from the Spanish Ministry of Economy and Competitiveness: SAF2011-27330 to P.M., SAF2010-15106 to M.L.T and SAF2011-25834 to F.S-M.; grant INDISNET (S2010/BMD-2332) from Comunidad de Madrid and RETICS Enfermedades Cardiovasculares (RD12/0042/0056) from Instituto de Salud Carlos III to P.M and F. S-M; and ERC-2011-AdG294340-GENTRIS to F.S-M. J.R.C. was supported by a CNIC post-doctoral fellowship, R. S-D is funded with a pre-doctoral fellowship from Comunidad de Madrid and E.R.B. and A.M-M. were supported by a FPI pre-doctoral fellowship from the Spanish Ministry of Economy and Competitiveness. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro CNIC Foundation.Peer Reviewe

Preconcepciones de estudiantes de la Pontificia Universidad Javeriana Cali sobre el curso de estadística

One the most important difficulties that teachers of statistics face in teaching statistics in undergraduate courses are the student ́s equivocal preconceived ideas regarding the course. A 16 items-questionnaire aimed to find out the student’ s experience in the courses of statistics and mathematics, their preconceived ideas regarding the statistic courses and their previous knowledge on statistics was answered by 239 students from different schools. The students have agreement about the importance of make at least one statistics course in his/her professional training. Results showed that the courses of statistics must be thought and planned so as to promote a cultural environment dominated by the statistical thought, rather than being considered a course of calculus or mathematics in which students usually operate and do calculations without having clear ideas about the problem that give rise to such operationsUna de las dificultades más importantes a que se enfrentan los profesores que enseñan estadística en cursos de pre-grado, son las ideas preconcebidas equivocadas respecto al curso. Un cuestionario de 16 puntos dirigido a averiguar la experiencia de los estudiantes en cursos de estadística y matemáticas, sus ideas preconcebidas respecto a los cursos de estadística y su conocimiento previo de la estadística fue respondido por 239 estudiantes de diferentes escuelas. Los estudiantes estuvieron de acuerdo en la importancia de realizar por lo menos un curso de estadística en su entrenamiento personal. Los resultados mostraron que los cursos de estadística deben pensarse y planearse de tal manera que se promueva un medio ambiente dominado por el pensamiento estadístico, en lugar de ser considerado un curso de cálculo o de matemáticas en el que los estudiantes actúan y hacen cálculos sin tener ideas claras sobre el problema que da pie a tales cálculosUma das mais importantes dificuldades que os professores afrontam no ensino da estatística em cursos de grado são as ideias equivocadas e preconcebidas dos alunos em quanto ao curso. Um questionário de 16 itens foi construído para descobrir no estudante a sua experiência nos cursos de matemática e estatística, suas ideias preconcebidas em relação a cursos de estatística e os seus conhecimentos prévios sobre as estadísticas, e fora respondido por 239 alunos de diferentes escolas. Os estudantes mostraram acordo sobre a importância de fazer pelo menos um curso estatístico na sua formação profissional. Os resultados mostraram que os cursos de estatísticas devem ser pensados e planejados de modo a promover um ambiente cultural dominado pelo pensamento estatístico, em vez de ser considerado um curso de cálculo ou matemática no qual os alunos costumam operar e fazer cálculos sem ter ideias claras sobre o problema que da origem a tais operações

Síndrome de hipersensibilidad a medicamentos con exantema, eosinofilia y síntomas sistémicos inducido por carbamazepina

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient’s condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.El síndrome de hipersensibilidad a medicamentos, con exantema, eosinofilia y síntomas sistémicos (Drug Rash Eosinophylia with Systemic Symptoms, DRESS) es una reacción a diferentes medicamentos, principalmente anticonvulsivos, el cual cursa con compromiso sistémico y lesiones eritematosas, al igual que ocurre en diversas dermatosis por reacción a medicamentos. Este síndrome es una condición clínica poco frecuente, cuyo diagnóstico requiere un alto grado de sospecha por parte del personal clínico. Si no se hace un diagnóstico oportuno y se suministra el tratamiento adecuado, puede confundirse con otros tipos de alergias a medicamentos que implican riesgo de muerte.Se presenta el caso de un paciente de 22 años de edad con alteración del neurodesarrollo a quien se le inició tratamiento con carbamazepina. Dos meses después consultó debido a la aparición de síntomas generales y lesiones eritematosas en la piel, inicialmente en el tronco. En la atención ambulatoria se le prescribieron antihistamínicos y antipiréticos, con los cuales no mejoró adecuadamente; su condición empeoró, con la aparición de lesiones en la piel y síntomas sistémicos propios del síndrome DRESS.Al cabo del tratamiento farmacológico administrado durante su hospitalización según los lineamientos recomendados, las manifestaciones y complicaciones asociadas con el síndrome remitieron, la administración de esteroides pudo reducirse gradualmente y, finalmente, el paciente fue dado de alta