Teoría e Historia de la Arquitectura 2005-2013

La enseñanza de la teoría y la historia de la arquitectura, para ser efectivas, requieren de un objeto, una finalidad y un método. El objeto ya no serán sólo las obras, los textos, sino también las experiencias de la arquitectura, producidos en cierto momento y en determinado contexto, que se pretenden elucidar, comprender y explicar: en una palabra, interpretar. La finalidad estribará en tener un conocimiento suficiente de la creación y producción de la arquitectura contemporánea, entendiendo ésta como una actividad que depende de su propia evolución histórica y que a su vez se manifiesta de forma múltiple según diversas singularidades. La metodología no puede ser otra que la actitud crítica desarrollada para encontrar el sentido, entendiendo simultáneamente los contenidos de esta arquitectura como posible objeto de proyecto, ponerse “en lugar de” los creadores de la arquitectura, los arquitectos, e intentar comprender su propia sistemática, y su capacidad simbólica derivada., que nos ampliará dicho sentido. Será pues importante la reflexión sobre determinados códigos arquitectónicos y sus mecanismos de comunicación, estableciendo a ser posible una serie de distinciones propias de lo que la arquitectura puede aportar para una mejor metodología de su interpretación y de los límites pertinentes impuestos a ésta. Pero lo realmente interesante será la dialéctica de los acontecimientos, elevarse al procedimiento general, ver cómo un arquitecto llegó a formular su pensamiento por medio de un determinado sistema: esto es mucho más rico en consecuencias. Al enfrentarnos a las obras complejas de la Historia lo que debemos analizar no es esencialmente la manera en que el arquitecto llegó a determinados sistemas formales, edificios concretos, sino mucho más, esforzarnos en analizar la relación misma de estos edificios y estructuras con otros, la relación entre la expresión y el contenido del pensamiento de un arquitecto con el de otros arquitectos. En cualquier caso, lo que sí parece claro es que la enseñanza de la arquitectura en la mayoría de las actuales escuelas es todavía insatisfactoria en grado sumo, por cuanto está basada bien en criterios académicos tipo Beaux-Arts más o menos corregidos y actualizados, o bien sobre una falta de método escondida dentro de actitudes empíricas inconsistentes. Esta situación es una consecuencia, y al mismo tiempo una causa, del actual desinterés y desintegración de la cultura arquitectónica; se puede construir “cualquier cosa” porque nada es verdaderamente significativo y, en realidad, no importa a nadie. Confusión, escepticismo, vitalismo sin verdadera vitalidad e interés, son los resultados espontáneos de una cultura desintegrada que se refleja y se auto - reproduce en las escuelas. La razón clave de la desintegración cultural es, por tanto, la enseñanza nsatisfactoria de la arquitectura, que es individualizada en la dicotomía existente entre la “historia” y el “proyecto”. La primera es enseñada, en el mejor de los casos, como una disciplina no funcional, útil para la educación general del estudiante arquitecto, paro carente de importancia como documento instrumental para la producción arquitectónica. El segundo es enseñado de forma >, usando por lo general un vocabulario crítico anticuado, que resulta casi grotesco en una época científica como la nuestra. No debemos ni podemos exigir que se sepa toda la historia que nos ha traído de la arquitectura primitiva hasta el empleo de la tecnología actual. Es útil enseñar, ante todo, la gramática en el punto al que se ha llegado, en su morfología y en su sintaxis. Pero no es vano saber exactamente de dónde viene esta gramática, cómo ha evolucionado, y en qué es susceptible de transformarse. Este problema nos encamina hacia una cuestión particularmente importante: la de la herencia. Se suele decir de un arquitecto que ha heredado las cualidades de algún otro. ¿Qué es esa herencia? Y en la medida en que pudiera existir, ¿qué es lo transmisible, qué no lo es, tanto desde el punto de vista individual como del punto de vista colectivo? Es decir: desde el punto de vista individual… ¿qué puede transmitir uno de la herencia que ha recibido? Y desde el punto de vista colectivo… ¿qué es lo transmisible directamente o no con respecto a la historia? No hay don, por brillante que sea, que pueda prescindir de la historia. La enseñanza moderna de la arquitectura debería enseñar los modos de componer. Las nuevas escuelas podrían plantear los hechos históricos con precisión, de tal forma que permitieran a los alumnos revivir el proceso creador como si trabajaran en el estudio de los arquitectos. La crítica del profesor podría ejercitarse con el mismo rigor que era norma en la academia del pasado, impidiendo al alumno caer en el eclecticismo, e imponiéndole una coherencia en el ámbito de un lenguaje determinado. Según Zevi, este tipo de didáctica historizada es, todavía una “hipótesis de trabajo", y en la actualidad se podría superar deduciendo de la historia los fundamentos disciplinares de la arquitectura

Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treatment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provides limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory disorders and experimental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs could regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model resembling human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, restoring podocyte numbers. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by modulation of NOTCH pathway. JQ1 inhibited the gene expression of the NOTCH effectors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis

Breast cancer patient’s outcomes after neoadjuvant chemotherapy and surgery at 5 and 10 years for stage II–III disease

Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan-Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1-1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

La garantía de calidad en el ámbito universitario puede considerarse como la atención sistemática, estructurada y continua a las titulaciones ofertadas. La garantía de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y así cumplir con la obligación que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfacción de los colectivos implicados en el proceso de enseñanza-aprendizaje (Profesorado, Estudiantes y PAS)

Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension