Mitochondrial peptide humanin facilitates chemoresistance in glioblastoma cells

Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells. We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies. An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation. Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4). These effects were observed in glioma cells with heterogeneous genetic backgrounds, i.e., glioma cells with wild-type (wtIDH) and mutated (mIDH) isocitrate dehydrogenase. HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells. Taken together, our findings suggest that HN boosts the hallmark characteristics of GBM, i.e., chemoresistance, migration and endothelial cell proliferation. Thus, strategies that inhibit the HN/FPR2 pathway may improve the response of GBM to standard therapyInstituto de Biotecnología y Biología Molecula

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Clavigero. Comunidad de saberes, núm 2: Educaciones alternativas

Este número se compone de textos que presentan una perspectiva política de la educación, podríamos decir que es una gran reflexión contrahegemónica. Participan autores que, desde su práctica y distintas trincheras, han impulsado nuevas estrategias de educar, pero que también son actores públicos con una postura crítica, que dialogan en este espacio con los clásicos pensadores de lo educativo

Melatonin decreases pulmonary vascular remodeling and oxygen sensitivity in pulmonary hypertensive newborn lambs

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg(-1) .d(-1)) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers alpha-actin (CN 1.28 +/- 0.18 vs. MN 0.77 +/- 0.04, p < 0.05) and smoothelin-B (CN 2.13 +/- 0.31 vs. MN 0.88 +/- 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 +/- 0.84 vs. MN 1.14 +/- 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs. These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia

Clavigero. Comunidad de saberes, núm 10: Antidoping para una sociedad adictiva

Desmitificar el tema de las adicciones y de la persona del adicto no es tarea sencilla, se requiere una nueva perspectiva que parta del diálogo de saberes y una lectura desde la complejidad, más allá del problema centrado en el consumo. La creación de puentes de conocimiento e intercambio de experiencias entre profesionales, miembros de la sociedad civil y los aquejados por las adicciones se vuelve hoy más que nunca pertinente, ya que de todas estas fuentes de saber se nutre la construcción del fenómeno adictivo en la comunidad. Esperamos que este número pueda ofrecer vísperas de soluciones y perspectivas que construyan una más amplia definición y alternativas de intervención

Derechos humanos en Paraguay 2003

Índice. Presentación. 1. Análisis socio-político y económico: Análisis de coyuntura sociopolítica / María Lis Rodríguez. Análisis Económico: El sistema económico heredado / Lila Molinier. 2. Derecho a la Vida: Violencia policial, fatales desenlaces / Hugo Valiente. 3. Derecho a la libertad, seguridad personal e integridad física: Tortura: impunidad garantizada / Hugo Valiente. La crisis del sistema penitenciario paraguayo no es nueva / Elizabeth Flores Negri, Hernán Mayor y Jorge Rolón Luna. 4. Derecho a la protección judicial: Estalla la crisis del sistema de justicia / Luis Emilio Escobar Faella. Derecho a las Garantías Judiciales y al Debido Proceso / Alfredo Enrique Kronawetter Zarza. Signo de esperanza de lograr la reparación: la Comisión Verdad y Justicia / Dionisio Gauto y Raquel Talavera. 5. Derecho a la igualdad y a la no discriminación: La igualdad de las mujeres y los desafíos ante el nuevo gobierno / Ofelia Martínez y Myrian González. Institucionalidad de género: El acceso a cargos en la administración de justicia / Carmen Vallejo. Buscando un espacio contra la intolerancia / Grupo de Acción Gay Lésbico (GAG-L). Situación de los migrantes en el país / Tomás Palau Viladesau. La situación de exclusión de las personas con discapacidad en las políticas sociales nacionales / Claudia Pacheco y Martha Horvath. 6. Derecho a la libertad ideológica, religiosa y de conciencia: La objeción de conciencia: 10 años de crecimiento constante / Orlando Castillo Caballero y Enrique Gauto Bozzano. 7. Derecho a la información y a la libertad de expresión: No disminuyen obstáculos para el acceso a información pública / Sindicato de Periodistas del Paraguay (SPP). Libertad de expresión a través de las radios comunitarias / Mirian Candia S. Derechos humanos, sociedad de la información y acceso informacional / Roberto L. Céspedes y Luis Ortiz Sandoval. 8. Derecho a la asociación, reunión y participación: Organizaciones campesinas / Quintin Riquelme. Movimiento sindical: aún mucho por resolver / Roberto Villalba. La participación para la defensa de los derechos / Laura Bareiro. 9. Derechos Políticos: Elecciones generales 2003: avances y retrocesos de la participación ciudadana / Rossana Gómez. 10. Derecho al Desarrollo Sostenible: Pobreza y desigualdad / Domingo M. Rivarola. Un año de intensa "descampesinización" por empobrecimiento / Gladys Fariña. 11. Derecho al Empleo: Un marco normativo global que atienda condiciones particulares / Verónica Serafini Geoghegan y Hugo Royg Aranda. 12. Derecho a la Seguridad Social: El estado del Derecho a la Seguridad Social en Paraguay / José María Amarilla. 13. Derecho a la Salud: Se aguardan medidas en el sector salud / Esperanza Martínez. La reestructuración de los servicios de atención en salud mental / Carlos Portillo. 14. Derecho a la Seguridad Alimentaria: Seguridad alimentaria: cada vez menos segura, cada vez menos alimentaria / Tomás Palau Viladesau. 15. Derecho a la Educación: Desafíos impostergables en Educación / Cristina Coronel y Marta Almada Denis. 16. Derechos Culturales: Cultura: el derecho postergado / Gabriel Lema. 17. Derecho a la Vivienda: El déficit de vivienda crece año a año / Cristina Vila y Ricardo Canese. 18. Derechos de la Infancia y la Adolescencia: Avances que se deben consolidar / Heve Otero. 19. Derechos de los Pueblos Indígenas: Pocos avances para los pueblos indígenas / Andrés Ramírez. 20. Derecho a la Paz y al Desarme: El riesgo de la militarización de los problemas sociales / Orlando Castillo. Víctimas de violencia institucional en las Fuerzas Armadas / María Noguera y Andrés Vázquez. 21. Derecho al Ambiente Sano: La falta de políticas públicas y de instituciones como contraste / Beatriz Silvero. 22. Cumplimiento de Compromisos Internacionales: Aumenta la conciencia ciudadana a favor de una política exterior en pro de los derechos humanos / Raquel Talavera. 23. Temas del Año: Oportunidad para la democracia del Paraguay: implementación y funcionamiento de la Comisión de Verdad y Justicia / Aldo Antonio Pelli. Significativo aumento de la criminalización de las luchas sociales / Marielle Palau y Raquel Talavera. Síntesis General de las recomendaciones. Directorio de organizaciones integrantes de la CODEHUPY

International Ignatian Reconciliation Conference: From crisis and confrontation to healing and forgiveness, how is reconciliation possible?

El compromiso de la Compañía de Jesús en el quehacer universitario se expresa en el deseo de contribuir efectivamente a hacer posible una vida digna, plena, para todos y cada uno de los seres humanos, en el presente y en el futuro. Para lograr una vida digna, una vida plena, se requiere la reconciliación. Por ello, la Universidad jesuita debe ser una fuente de vida, comprometida a fondo en los procesos de reconciliación. La Universidad Pontificia Comillas y la Pontificia Universidad Javeriana trabajaron bajo la orientación y el estímulo del padre Michael J. Garanzini, S. J. en la organización de la Conferencia Internacional de Reconciliación Ignaciana de la Crisis y el Enfrentamiento a la Sanación y el Perdón: ¿Cómo es Posible la Reconciliación?, que se realizó del 10 al 12 de mayo de 2021, en modalidad combinada (presencial y remota), desde Madrid. En esta, además de abordajes conceptuales sobre la reconciliación, se presentaron experiencias consolidadas en territorios o con comunidades específicas de construcción de paz y reconciliación de instituciones vinculadas a la Compañía de Jesús. Las memorias de la Conferencia que aquí presentamos tienen el fin de contribuir a que las conversaciones de perdón se den y se multipliquen, de modo que la reconstrucción del tejido social deje de ser una utopía para convertirse en una posibilidad palpable. Sin más, esta Conferencia fue el resultado de esa unión por la que tanto propende la reconciliación, pues no debemos olvidar que parte del proceso para llegar a ella nace del amor y de una meta por trascender todo aquello que nos divide y que, en este caso, se hace desde unas universidades comprometidas y de la mano del legado espiritual de san Ignacio.The commitment of the Society of Jesus in university work is expressed in the desire to effectively contribute to making possible a dignified, full life for each and every one of the human beings, in the present and in the future. To achieve a dignified life, a full life, reconciliation is required. For this reason, the Jesuit University must be a source of life, fully committed to reconciliation processes. Comillas Pontifical University and Javeriana Pontifical University worked under the guidance and encouragement of Father Michael J. Garanzini, S.J. in organizing the International Conference on Ignatian Reconciliation from Crisis and Confrontation to Healing and Forgiveness: How is Possible Reconciliation?, which took place from May 10 to 12, 2021, in a combined modality (face-to-face and remote), from Madrid. In this, in addition to conceptual approaches on reconciliation, consolidated experiences in territories or with specific communities of peacebuilding and reconciliation of institutions linked to the Society of Jesus were presented. The Conference proceedings that we present here have the purpose of contributing to the conversations of forgiveness occurring and multiplying, so that the reconstruction of the social fabric ceases to be a utopia and becomes a palpable possibility. Without further ado, this Conference was the result of that union for which reconciliation tends so much, because we must not forget that part of the process to reach it is born of love and of a goal to transcend everything that divides us and that, in this case, it is done from committed universities and hand in hand with the spiritual legacy of Saint Ignatius.Madri

The impact of stapling technique and surgeon specialism on anastomotic failure after right?sided colorectal resection: an international multicentre, prospective audit

Aim There is little evidence to support choice of technique and configuration for stapled anastomoses after right hemicolectomy and ileocaecal resection. This study aimed to determine the relationship between stapling technique and anastomotic failure. Method Any unit performing gastrointestinal surgery was invited to contribute data on consecutive adult patients undergoing right hemicolectomy or ileocolic resection to this prospective, observational, international, multicentre study. Patients undergoing stapled, side?to?side ileocolic anastomoses were identified and multilevel, multivariable logistic regression analyses were performed to explore factors associated with anastomotic leak. Results One thousand three hundred and forty?seven patients were included from 200 centres in 32 countries. The overall anastomotic leak rate was 8.3%. Upon multivariate analysis there was no difference in leak rate with use of a cutting stapler for apical closure compared with a noncutting stapler (8.4% vs 8.0%, OR 0.91, 95% CI 0.54–1.53, P = 0.72). Oversewing of the apical staple line, whether in the cutting group (7.9% vs 9.7%, OR 0.87, 95% CI 0.52–1.46, P = 0.60) or noncutting group (8.9% vs 5.7%, OR 1.40, 95% CI 0.46–4.23, P = 0.55) also conferred no benefit in terms of reducing leak rates. Surgeons reporting to be general surgeons had a significantly higher leak rate than those reporting to be colorectal surgeons (12.1% vs 7.3%, OR 1.65, 95% CI 1.04–2.64, P = 0.04). Conclusion This study did not identify any difference in anastomotic leak rates according to the type of stapling device used to close the apical aspect. In addition, oversewing of the anastomotic staple lines appears to confer no benefit in terms of reducing leak rates. Although general surgeons operated on patients with more high?risk characteristics than colorectal surgeons, a higher leak rate for general surgeons which remained after risk adjustment needs further exploration

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim: The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30\ua0days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results: This study included 3208 patients, of whom 78.4% (n\ua0=\ua02515) underwent surgery for malignancy and 11.7% (n\ua0=\ua0375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n\ua0=\ua03041) of patients, which was handsewn in 38.9% (n\ua0=\ua01183) and stapled in 61.1% (n\ua0=\ua01858). Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P\ua0=\ua00.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR\ua0=\ua01.43; 95% CI: 1.04\u20131.95; P\ua0=\ua00.03). Conclusion: Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe

The relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit.

BACKGROUND: Anastomosis technique following right sided colonic resection is widely variable and may affect patient outcomes. This study aimed to assess the association between leak and anastomosis technique (stapled versus handsewn) METHODS: This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a two-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, using a pre-specified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random effect variable. RESULTS: This study included 3208 patients, of whom 78.4% (n=2515) underwent surgery for malignancy and 11.7% (n=375) for Crohn's disease. An anastomosis was performed in 94.8% (n=3041) of patients, which was handsewn in 38.9% (n=1183) and stapled in 61.1% (n=1858) cases. Patients undergoing handsewn anastomosis were more likely to be emergency admissions (20.5% handsewn versus 12.9% stapled) and to undergo open surgery (54.7% versus 36.6%). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (p=0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted odds ratio 1.43, 95% confidence interval 1.04-1.95, p=0.03). DISCUSSION: Despite being used in lower risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe. This article is protected by copyright. All rights reserve