La educación y la cultura urbana: aprender a participar en procesos de mejora urbana. Proyecto educativo: Canillejas imagina un parque.

Presentamos una reflexión sobre el papel de la Educación a partir de las lecciones de la experiencia ' Canillejas imagina un Parque' , un proyecto educativo dirigido por Otro Hábitat en colaboración con el Colegio La Alameda , que busca animar a los alumnos a participar en un proceso de diseño e intervención colectiva para transformar un solar enfrente del colegio. Fa vorecer la participación de los niños en la mejora de su entorno urbano puede ser una estrategia clave para hacer frente a las desigualdades urbanas y generar un entendimiento común sobre la responsabilidad de todos en el desarrollo sostenible de nuestras ciudade

HER2 isoforms co-expression differently tunes mammary tumor phenotypes affecting onset, vasculature and therapeutic response

Full-length HER2 oncoprotein and splice variant Delta16 are co-expressed in human breast cancer. We studied their interaction in hybrid transgenic mice bearing human full-length HER2 and Delta16 (F1 HER2/Delta16) in comparison to parental HER2 and Delta16 transgenic mice. Mammary carcinomas onset was faster in F1 HER2/Delta16 and Delta16 than in HER2 mice, however tumor growth was slower, and metastatic spread was comparable in all transgenic mice. Full-length HER2 tumors contained few large vessels or vascular lacunae, whereas Delta16 tumors presented a more regular vascularization with numerous endothelium-lined small vessels. Delta16-expressing tumors showed a higher accumulation of i.v. injected doxorubicin than tumors expressing full-length HER2. F1 HER2/Delta16 tumors with high full-length HER2 expression made few large vessels, whereas tumors with low full-length HER2 and high Delta16 contained numerous small vessels and expressed higher levels of VEGF and VEGFR2. Trastuzumab strongly inhibited tumor onset in F1 HER2/Delta16 and Delta16 mice, but not in full-length HER2 mice. Addiction of F1 tumors to Delta16 was also shown by long-term stability of Delta16 levels during serial transplants, in contrast full-length HER2 levels underwent wide fluctuations. In conclusion, full-length HER2 leads to a faster tumor growth and to an irregular vascularization, whereas Delta16 leads to a faster tumor onset, with more regular vessels, which in turn could better transport cytotoxic drugs within the tumor, and to a higher sensitivity to targeted therapeutic agents. F1 HER2/Delta16 mice are a new immunocompetent mouse model, complementary to patient-derived xenografts, for studies of mammary carcinoma onset, prevention and therapy

The baseline comorbidity burden affects survival in elderly patients with acute myeloid leukemia receiving hypomethylating agents: Results from a multicentric clinical study

Background: In older patients with acute myeloid leukemia (AML), the definition of fitness, prognosis, and risk of death represents an open question. Methods: In the present study, we tested the impact on survival of disease- and patient-related parameters in a large cohort of elderly AML patients homogeneously assigned to treatment with hypomethylating agents (HMAs). Results: In 131 patients with a median age of 76 years, we confirmed that early response (<0.001) and biology-based risk classification (p = 0.003) can select patients with better-predicted survival. However, a full disease-oriented model had limitations in stratifying our patients, prompting us to investigate the impact of baseline comorbidities on overall survival basing on a comorbidity score. The albumin level (p = 0.001) and the presence of lung disease (p = 0.013) had a single-variable impact on prognosis. The baseline comorbidity burden was a powerful predictor of patients' frailty, correlating with increased incidence of adverse events, especially infections, and predicted overall survival (p < 0.001). Conclusion: The comorbidity burden may contribute to impact prognosis in addition to disease biology. While the therapeutic armamentarium of elderly AML is improving, a comprehensive approach that combines AML biology with tailored interventions to patients' frailty is likely to fully exploit the anti-leukemia potential of novel drugs

Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4 years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches

The behavioral immune system in action: Psychological correlates of pathogen disgust sensitivity in healthcare professionals working in a COVID-19 hospital

The behavioral immune system includes a set of proactive mechanisms that inhibit contact with pathogens in the first place. These mechanisms offer a sort of psychological and behavioral prophylaxis against infection. The aim of this study was to assess the functionality of the behavioral immune system under conditions of strong ecological validity. Our hypothesis was that the emotional and more primitive component of the behavioral immune system (i.e. pathogen disgust sensitivity) acts as a powerful predictor of fear of infection. The sample was made up of 101 healthcare professionals working in a COVID-19 hospital when vaccination was not yet available. We conducted a hierarchical regression analysis to assess the role of germ-related disgust in modulating levels of fear. After controlling for the significant effects of depressive symptoms and exposure to people with a confirmed diagnosis of COVID-19, we found that fear of infection was more intense in those healthcare workers who reported higher levels of germ-related disgust. Fear of infection was not related to perceived infectability, an individual variable informed by more rational cognitive appraisals. These findings show that, even in healthcare workers who can take advantage of their professional knowledge and acquired skills for rational appraisals, the most primitive component of the behavioral immune system still plays a major role in eliciting fear of COVID-19. It is likely that the psychological reactions elicited by the behavioral immune system promote preventive health behaviors in modern environments as well

Fear of COVID-19 among Healthcare Workers: The Role of Neuroticism and Fearful Attachment

Fear of becoming infected is an important factor of the complex suite of emotional reactions triggered by the COVID-19 pandemic. Among healthcare workers (HWs), fear of infection can put at risk their psychological well-being and occupational efficiency. The aim of this study was to analyze the role of personality (i.e., the big five traits) and adult attachment in predicting levels of fear (as measured by the FCV-19S) in 101 HWs employed in a COVID-19 university hospital. The three significant predictors retained by the stepwise regression model were age (beta = 0.26, t = 2.89, p < 0.01), emotional stability (i.e., the inverse of neuroticism) (beta = −0.26, t = −2.89, p < 0.01), and fearful attachment (beta = 0.25, t = 2.75, p < 0.01). Older HWs with higher levels of neuroticism and fearful attachment reported more intense fear of COVID-19. Our results can be useful to identify vulnerable subgroups of HWs and to implement selective programs of prevention based on counseling and psychological support

Biodegradable Mulch Films and Bioformulations Based on <i>Trichoderma</i> sp. and Seaweed Extract Differentially Affect the Metabolome of Industrial Tomato Plants

The use of biostimulants and biofilms in agriculture is constantly increasing, as they may support plant growth and productivity by improving nutrient absorption, increasing stress resilience and providing sustainable alternatives to chemical management practices. In this work, two commercial products based on Trichoderma afroharzianum strain T22 (Trianum P®) and a seaweed extract from Ascophyllum nodosum (Phylgreen®) were tested on industrial tomato plants (Solanum lycopersicum var. Heinz 5108F1) in a field experiment. The effects of single and combined applications of microbial and plant biostimulants on plants grown on two different biodegradable mulch films were evaluated in terms of changes in the metabolic profiles of leaves and berries. Untargeted metabolomics analysis by LC-MS Q-TOF revealed the presence of several significantly accumulated compounds, depending on the biostimulant treatment, the mulch biofilm and the tissue examined. Among the differential compounds identified, some metabolites, belonging to alkaloids, flavonoids and their derivatives, were more abundant in tomato berries and leaves upon application of Trichoderma-based product. Interestingly, the biostimulants, when applied alone, similarly affected the plant metabolome compared to control or combined treatments, while significant differences were observed according to the mulch biofilm applied