El problema de la muerte: Jacques Derrida y las figuras de Artemisa, Antígona y Sócrates

El problema que hay que desanudar es aquel que surge de la necesidad de incorporar la muerte a la vida; se lo ha hecho siempre y sin más pero encierra mucho en la atadura. Lo subjetivo es el contenido y lo objetivo la forma; por eso parecería ser el mismo lazo: dos puntas que se abrazan y se confunden, la vida, la muerte. Vale intentar señalar que la vida está plagada de muerte; la primera halla en este hecho su significado y, la segunda intenta definirse en el mismo acto; en el planteamiento de este problema se abre la escritura que partirá de tres reflexiones sobre tres figuras cuya característica última será la atemporalidad anudada en lo subjetivo que aparece en los textos de Derrida, constituidos al mismo tiempo en pretextos de este trabajo. Por esto, el trabajo sobre ‘la muerte’ es, hasta cierto punto, imposible de delimitar en un sentido riguroso. El término ‘la muerte’ encierra, en su enunciación, tal imposibilidad. De tal manera, la única forma de escribir lo que a continuación se presenta, es hacerlo desde la marginalidad de tres figuras cuya relación con ‘la muerte’ es por demás necesaria. Estas figuras, Artemisa, Antígona y Sócrates comparten, un mismo espacio de significación que se ha construido en lo que llamamos la Grecia antigua, más aun, en la forma en que se vivió y pensó el evento de la mortalidad..

Genealogía del paradigma onto-teo-político

In 2016 the research was focused on analyzing some contemporary perspectives that contribute critically to the understanding of the onto-theo-political paradigm. On the one hand, following some contemporary conceptions of Spinoza’s work we can show that a thought of subjectivity is still possible if we release it from the framework of the onto-theological conception of metaphysics, and we can examine it as a non-substantial subject, discarded its position of principle and foundation, to become secondary, witness and, therefore, militant. Nietzsche and Kierkegaard operate an existential shift in philosophy, giving primacy to ethics, driven by the question of “how to live.” From this existential turning, the human challenge lies in finding meaning. From this point on, they differ, both in the basis of the question on meaning and in the formulation of answers. Thus, both invite to a search after the great stories, from a problematized individuality, autonomy and freedom. In Adorno’s thinking we can also see how the main foundations of the paradigm are put into question. Adorno maintains that it is no longer possible to grasp the totality of the real with the force of thought, since reason no longer agrees with a chaotic and fragmentary reality, after the catastrophes of the twentieth century. Hence his attempt is to pose a negative dialectic, since philosophy, otherwise, would only serve to veil reality and perpetuate its current situation. Lacoue-Labarthe allows us to think of a subject that is constituted from the reflection on politics and art, and that has its main reference point in Heidegger. He manages to distance himself from Heidegger’s metaphysics and, by doing so, to condition the subject from his ethical condition summarized in responsibility. Finally, we study the conception of geoculture by philosopher R. Kusch, who proposes an integrative worldview between the sacred and the profane, interpreting cultures of the Puna region and doing fieldwork, as well as reading the culture from the political point of view. In the same way, we continue to work phenomenologically with the Encyclical “Laudato si´” which, from the point of view of philosophical anthropology, deepens Heidegger’s criticism to the era of the technique essence. Caring for the common house is an appeal to privilege the place of man in the cosmos as a guarantor of all life, rather than to financial greed.En 2016 la investigación se abocó a relevar algunas perspectivas contemporáneas que aportan críticamente a la comprensión del paradigma onto-teo-político. Por un lado, siguiendo algunas concepciones contemporáneas de la obra de Spinoza, podemos mostrar que un pensamiento de la subjetividad sigue siendo posible si lo liberamos del marco de la concepción ontoteológica de la metafísica, y podemos examinarlo como un sujeto no sustancial, descartada su posición de principio y fundamento, para hacerse secundario, testigo y por lo tanto militante. Nietzsche y Kierkegaard operan un giro existencial en la filosofía, dando primacía a la ética, conducidos por la pregunta “cómo vivir”. Desde este giro existencial, el desafío humano radica en encontrar sentido. A partir de este punto divergen tanto en el fundamento de la pregunta por el sentido como en la formulación de las respuestas. Así, ambos invitan a una búsqueda después de los grandes relatos, a partir de una individualidad, una autonomía y una libertad problematizada. En el pensamiento de Adorno también podemos ver cómo los principales fundamentos del paradigma son puestos en cuestión. Sostiene Adorno que ya no es posible apresar con la fuerza del pensamiento la totalidad de lo real, dado que la razón ya no concuerda con una realidad caótica y fragmentaria, luego de las catástrofes del siglo XX. De ahí su intento de plantear una dialéctica negativa, en tanto que la filosofía, de otro modo, solo serviría para velar la realidad y eternizar su situación actual. Lacoue-Labarthe nos permite pensar en un sujeto que se constituye a partir de la reflexión sobre la política y el arte y que tiene como referente fundamental a Heidegger. Logra marcar una distancia con la metafísica heideggeriana y, al hacerlo, condicionar al sujeto desde su condición ética resumida en la responsabilidad. Por último, estudiamos la concepción de geocultura del filósofo R. Kusch, que plantea una cosmovisión integradora entre lo sagrado y lo profano, interpretando culturas de nuestra Puna y realizando trabajos de campo, como así también leyendo la cultura desde el campo de lo político. Del mismo modo, continuamos trabajando fenomenológicamente con la Encíclica Laudato Si’ que profundiza, desde la antropología filosófica, la crítica de Heidegger a la época de la esencia de la técnica. Cuidar la casa común es una apelación a privilegiar el puesto del hombre en el cosmos, como garante de la vida toda, antes que la avaricia financiera

La técnica y la política. Perspectivas desde América Latina

Este nuevo libro colectivo recoge los trabajos del grupo de investigación de Filosofía de la PUCE, elaborados entre 2019 y 2020. El tema elegido, Tecnología y política, define una de las problemáticas contemporáneas más relevantes dentro del trabajo académico. Como en ocasiones anteriores, cada autor plantea contextos de lectura diversos; los aportes recorren un escenario complejo, resultado de los caminos que cada uno ha elegido para consolidar su propia reflexión a partir de los proyectos de escritura de tesis de posgrado y de investigaciones desarrolladas tanto en universidades europeas como americanas. Sin embargo, el punto de encuentro está dado en la perspectiva y en las condiciones que determinan la posibilidad de proponer un pensamiento crítico y propositivo desde América Latina

La técnica y la política. Perspectivas desde América Latina

Este nuevo libro colectivo recoge los trabajos del grupo de investigación de Filosofía de la PUCE, elaborados entre 2019 y 2020. El tema elegido, Tecnología y política, define una de las problemáticas contemporáneas más relevantes dentro del trabajo académico. Como en ocasiones anteriores, cada autor plantea contextos de lectura diversos; los aportes recorren un escenario complejo, resultado de los caminos que cada uno ha elegido para consolidar su propia reflexión a partir de los proyectos de escritura de tesis de posgrado y de investigaciones desarrolladas tanto en universidades europeas como americanas. Sin embargo, el punto de encuentro está dado en la perspectiva y en las condiciones que determinan la posibilidad de proponer un pensamiento crítico y propositivo desde América Latina

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D

Adipocyte mesenchymal transition contributes to mammary tumor progression

Obesity is associated with increased cancer incidence and progression. However, the relationship between adiposity and cancer remains poorly understood at the mechanistic level. Here, we report that adipocytes from tumor-invasive mammary fat undergo de-differentiation to fibroblast-like precursor cells during tumor progression and integrate into the tumor microenvironment. Single-cell sequencing reveals that these de-differentiated adipocytes lose their original identities and transform into multiple cell types, including myofibroblast- and macrophage-like cells, with their characteristic features involved in immune response, inflammation, and extracellular matrix remodeling. The de-differentiated cells are metabolically distinct from tumor-associated fibroblasts but exhibit comparable effects on tumor cell proliferation. Inducing de-differentiation by Xbp1s overexpression promotes tumor progression despite lower adiposity. In contrast, promoting lipid-storage capacity in adipocytes through MitoNEET overexpression curbs tumor growth despite greater adiposity. Collectively, the metabolic interplay between tumor cells and adipocytes induces adipocyte mesenchymal transition and contributes to reconfigure the stroma into a more tumor-friendly microenvironment

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission