Líneas de investigación en ADICI : diseño de procesos de producción social del hábitat

La ciudad contemporánea se caracteriza por la interrelación de dos dinámicas negativas que se interrelacionan: la creciente huella ecológica que generan los modelos de desarrollo vigentes (por incrementar el consumo de recursos y la producción de residuos) y la creciente segregación social, funcional y espacial que estos modelos producen. Estas dinámicas son generadas por el modelo de desarrollo dominante y a ella contribuyen los paradigmas de conocimiento positivistas que reducen la realidad a una sumatoria de objetos aislados en áreas de especialidad, sobre los que se desarrollan acciones sectoriales inconexas. El desarrollo se limita a su acepción economicista, que acentúa la mercantilización de la ciudad, y esta dinámica obvia las relaciones entre el objeto (ciudad) y su contexto (naturaleza), entre los sujetos y la ciudad que habitan y transforman, reduciendo al ciudadano a la condición de consumidor de ciudad (planificada y desarrollada por los técnicos, los políticos y el mercado). Es preciso por tanto construir herramientas de conocimiento y estrategias de acción que permitan comprender y actuar ante problemáticas típicamente complejas, como las urbanas, que escapan a la fragmentación del conocimiento en disciplinas estancas. Y herramientas que inserten el conocimiento técnico en procesos transformadores que recuperen la POLIS, los espacios de participación de los ciudadanos en la toma de decisiones. Es decir que amplíen y modifiquen la relación de fuerzas que se produce en el triángulo de actores de la ciudad (técnicos-políticos-sociedad), para recuperar la sociedad de ciudadanos, hoy reducida a sociedad de mercado. El marco teórico y metodológico que estamos construyendo se apoya en: 1. La teoría de la complejidad, que aporta una visión transdisciplinar para la comprensión de los fenómenos complejos, aquellos que pierden, en la fragmentación del saber propia del paradigma positivista, la relación entre disciplinas y entre sujetos y objetos de la investigación. La visión compleja de la ciudad nos permitirá comprenderla desde la interacción entre URBS, CIVITAS y POLIS. 2. El paradigma de investigación acción participativa, que permite construir el conocimiento colectivamente y diseñar entre técnicos, políticos y ciudadanos las estrategias de intervención. Ello exige trabajar tres dimensiones básicas de la participación: QUERER, SABER y PODER. Los pasos del proceso se realizan en procesos cíclicos: i. desde la observación-descripción de los problemas y potencialidades (toma de datos), ii. la interpretación de datos- comprensión del problema iii. el diseño de estrategias de intervención. iv. la comunicación de los resultados / retroalimentación del proceso Esta doble aproximación a la Arquitectura nos conduce a redefinir sus límites para situar la investigación en el marco de la Producción Social del Hábitat, cuyo eje metodológico recae sobre la participación del usuario en la producción del urbanismo y la arquitectura. En este escenario debemos revisar el papel que el arquitecto está llamado a desempeñar. Es preciso pasar del arquitecto-autor al arquitecto-actor para transitar del diseño de objetos al diseño de procesos de transformación urbana y social. Pero no un diseño entendido como planificación rígida y calculada, sino como orientación situacional abierta a una revisión constante y en permanente interacción con los actores implicados, lo cual equivale a reconocer la naturaleza intuitiva de todo proceso creativo. Desarrollamos este marco teórico en proyectos de: . Planeamiento urbano participativo (Palomares del Río, Sanlúcar la Mayor). . Procesos de transformación social del hábitat en áreas vulnerables, mediante la creación de grupos de apoyo técnico. (Taller de los Barrios en Sevilla y Larache en Marruecos). En esta comunicación presentamos los casos, en distintos momentos del proceso, desde la perspectiva de la interacción entre las dimensiones URBS-CIVITAS-POLIS, por un lado, y la interrelación entre la gente, los técnicos y las administraciones públicas por otro

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage neurodegenerative disease highly prevalent in children. CLN7/MFSD8 gene encodes a lysosomal membrane glycoprotein, but the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found, in the Cln7∆ex2 mouse model of CLN7 disease, that failure in autophagy causes accumulation of structurally and bioenergetically impaired neuronal mitochondria. In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. Mechanistically, mROS sustains a signaling cascade leading to protein stabilization of PFKFB3, normally unstable in healthy neurons. Administration of the highly selective PFKFB3 inhibitor AZ67 in Cln7∆ex2 mouse brain in vivo and in CLN7 patients-derived cells rectifies key disease hallmarks. Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases.This work was funded by the European Regional Development Fund, European Union’s Horizon 2020 Research and Innovation Programme (BATCure grant No. 666918 to J.P.B., S.E.M., D.L.M., S.S., and T.R.M.; PANA grant No. 686009 to A.A.), Agencia Estatal de Investigación (PID2019-105699RB-I00/AEI/10.13039/501100011033 and RED2018‐102576‐T to J.P.B.; SAF2017-90794-REDT to A.A.), Instituto de Salud Carlos III (CB16/10/00282 to J.P.B.; PI18/00285; RD16/0019/0018 to A.A.), Junta de Castilla y León (CS/151P20 and Escalera de Excelencia CLU-2017-03 to J.P.B. and A.A.), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA (to J.P.B.), and Fundación Ramón Areces (to J.P.B. and A.A.). SM benefits from MRC funding to the MRC Laboratory for Molecular Cell Biology University Unit at UCL (award code MC_U12266B) towards lab and office space. Part of this work was funded by Gero Discovery L.L.C. M.G.M. is an ISCIII-Sara Borrel contract recipient (CD18/00203)

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Pla estratègic d’atenció pal·liativa especialitzada de Catalunya: bases del model de futur

Pla estratègic; Atenció pal·liativa; Atenció centrada en la personaPlan estratégico; Atención paliativa; Atención centrada en la personaStrategic plan; Palliative care; Person centered careAquest Pla estratègic aborda la planificació estratègica de l’atenció a les persones amb necessitats pal·liatives per part dels equips i dispositius de cures pal·liatives específics (a partir d’ara, atenció pal·liativa especialitzada), mentre que de forma conjunta amb la direcció estratègica d’atenció primària i comunitària serà necessari el replantejament de l’atenció al final de vida de forma transversal

Pla estratègic d'atenció geriàtrica i pal·liativa especialitzada de Catalunya: línies estratègiques, projectes i actuacions

Pla estratègic; Atenció pal·liativa; Atenció centrada en la personaPlan estratégico; Atención paliativa; Atención centrada en la personaStrategic plan; Palliative care; Person centered careAquest document conté les línies estratègiques, projectes i actuacions del Pla estratègic d'atenció geriàtrica i pal·liativa especialitzada de Catalunya

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

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