Kinetic study of the interaction of gold nanoparticles with thiol compounds: determination of n-acetylcysteine using light scattering detection

II Encuentro sobre nanociencia y nanotecnología de investigadores y tecnólogos de la Universidad de Córdoba. NANOUC

Photometric determination of thioglycolic acid in cosmetics by using a stopped-flow reverse flow-injection system and the formation of gold nanoparticles

III Encuentro sobre Nanociencia y Nanotecnología de Investigadores y Tecnólogos Andaluce

EXPLORING THE IMPACT OF APOE POLYMORPHISM ON THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S PATIENTS

Comunicación presentada a FENS Forum 2022Alzheimer¿s disease (AD) is pathologically characterised by the presence of amyloid-beta plaques, neurofibrillary tangles containing hyperphosphorylated Tau protein, neuroinflammation and neuronal death leading to progressive cognitive impairment. The ¿4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte differentiation, maturation and function is not yet fully understood. To go in depth on these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ¿3 and ¿4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated by establishing a differentiation protocol through the consecutive addition of small molecules and growth factors, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) and APOE was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves production. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual¿s genetic background in favouring or perhaps preventing AD pathology

ANALYSING THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S DISEASE PATIENTS

Comunicación presentada en Global Summit on Neurodegenerative Diseases NEURO 2020/22The ε4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte maturation and function as well as their inflammatory profile is not yet fully understood. To answer these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ε3 and ε4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated through the consecutive addition of small molecules and growth factors to the culture medium, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual's genetic background in favouring or perhaps preventing AD pathology

Todo está en el mapa: Atlas Integrales de Salud Mental para la planificación de servicios. Informe SESPAS 2020

nObjetivo: Este artículo revisa y evalúa el uso de los Atlas Integrales de Salud Mental como herramientasde apoyo a la planificación de servicios dentro del modelo de investigación de ecosistemas de atenciónde salud.Método: Se describen los tipos de atlas y el procedimiento para su elaboración. Se presentan los realizadosen Espa˜na y se evalúa su impacto en la planificación de servicios de salud mental. Los atlas agreganinformación sobre las características locales del sistema de atención, la disponibilidad geográfica derecursos recogida mediante el instrumento DESDE-LTC, y su uso. Utilizan un sistema de informacióngeográfica y otras herramientas visuales. Siguen una metodología de abajo arriba con colaboración depersonas decisoras de agencias de planificación para su elaboración y validación externa.Resultados: Desde 2005 se han realizado Atlas Integrales de Salud Mental en nueve comunidades autó-nomas que comprenden alrededor del 65% de la población de Espa˜na. Los atlas han tenido un impactodesigual en la planificación de servicios, con un mayor impacto en Catalu˜na, Vizcaya y Guipúzcoa, yAndalucía, donde responsables sociales han participado activamente en su codise˜no y su aplicación a laplanificación de servicios sociosanitarios.Conclusiones: Los atlas permiten detectar carencias o duplicidades en la atención, monitorizar cambiosa lo largo del tiempo, realizar comparaciones nacionales e internacionales, modelar la eficiencia y haceranálisis benchmark. Este conocimiento puede incorporarse a los sistemas de apoyo a la decisión para unamás eficaz planificación de los servicios de salud mental basada en evidencia informada.© 2020 SESPAS. Publicado por Elsevier Espa˜na, S.L.U

KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor

Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. Materials and methods: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. Results: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. Conclusions: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical featureThis work was supported by CLARIFY project (https://www.clarify2020.eu/). ES-H was supported by the Consejería de Ciencia, Universidades e Innovación of the Comunidad de Madrid (Doctorados Industriales of the Comunidad de Madrid) [grant number IND2019/BMD-17258]. EG-V was supported by AECC (Asociación española Contra el Cáncer) grant ‘Programa de Prácticas de Laboratorio de curso académico AECC 2020’ (no grant number)

Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Bristol-Myers Squibb (BMS); Grupo Español de Cáncer de Pulmón (GECP); European Social Fund (ESF) i Comunidad de Madrid (PEJD-2019-PRE/BMD-17006, PEJ16/MED/AI-1972, PEJD-2018-PRE/SAL-8641).Background Pneumonitis (Pn) is one of the main immune-related adverse effects, having a special importance in lung cancer, since they share affected tissue. Despite its clinical relevance, Pn development remains an unpredictable treatment adverse effect, whose mechanisms are mainly unknown, being even more obscure when it is associated to chemoimmunotherapy. Methods In order to identify parameters associated to treatment related Pn, we analyzed clinical variables and molecular parameters from 46 patients with potentially resectable stage IIIA non-small-cell lung cancer treated with neoadjuvant chemoimmunotherapy included in the NADIM clinical trial (NCT03081689). Pn was defined as clinical or radiographic evidence of lung inflammation without alternative diagnoses, from treatment initiation to 180 days. Results Among 46 patients, 12 developed Pn (26.1%). Sex, age, smoking status, packs-year, histological subtype, clinical or pathological response, progression-free survival, overall survival and number of nivolumab cycles, were not associated to Pn development. Regarding molecular parameters at diagnosis, Pn development was not associated to programmed death ligand 1, TPS, T cell receptor repertoire parameters, or tumor mutational burden. However, patients who developed Pn had statistically significant lower blood median levels of platelet to monocyte ratio (p=0.012) and teratocarcinoma-derived growth factor 1 (p=0.013; area under the curve (AUC) 0.801), but higher median percentages of natural killers (NKs) (p=0.019; AUC 0.786), monocytes (p=0.017; AUC 0.791), MSP (p=0.006; AUC 0.838), PARN (p=0.017; AUC 0.790), and E-Cadherin (p=0.022; AUC 0.788). In addition, the immune scenario of Pn after neoadjuvant treatment involves: high levels of neutrophils and NK cells, but low levels of B and T cells in peripheral blood; increased clonality of intratumoral T cells; and elevated plasma levels of several growth factors (EGF, HGF, VEGF, ANG-1, PDGF, NGF, and NT4) and inflammatory cytokines (MIF, CCL16, neutrophil gelatinase-associated lipocalin, BMP-4, and u-PAR). Conclusions Although statistically underpowered, our results shed light on the possible mechanisms behind Pn development, involving innate and adaptative immunity, and open the possibility to predict patients at high risk. If confirmed, this may allow the personalization of both, the surveillance strategy and the therapeutic approaches to manage Pn in patients receiving chemoimmunotherapy