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PURPOSETo better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin.PATIENTS AND METHODSWe selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison.RESULTSSeventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%).CONCLUSIONAlthough there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

Objetivos: la adecuación a la normativa y la garantía de la calidad del servicio son las principales preocupaciones de los responsables municipales encargados de las licitaciones de servicios de atención a las personas. Sin embargo, la combinación de ambos criterios requiere un importante esfuerzo de innovación pública. Este estudio tiene como objetivo identificar los desafíos a las Administraciones municipales, tanto endógenos como exógenos, en la redacción de pliegos de licitaciones. Metodología: se han analizado de los contratos licitados en estos servicios y se han realizado entrevistas a los equipos municipales responsables de la contratación y gestión en siete municipios de Catalunya (las capitales de provincia y tres de los municipios más poblados). Resultados: tanto los órganos de contratación como las entidades del tercer sector coinciden en la importancia de garantizar la calidad de estos servicios. Sin embargo, el marco normativo actual no permite priorizar a las entidades no lucrativas (excepto en el caso de la contratación reservada) ni considerar la proximidad geográfica de los licitadores, lo que limita la adecuación de la contratación a los servicios de atención a las personas. Conclusiones: se sugiere explorar otras opciones de gestión y contratación de estos servicios, tanto dentro como fuera del marco de la contratación pública.

Abstract The design of devices based on acoustic or optical fields requires the fabrication of cavities and structures capable of efficiently trapping these waves. A special type of cavity can be designed to support resonances with a theoretically infinite quality factor, named bound states in the continuum or BICs. The experimental measurement of such modes is still a challenging problem, as they are, by definition, not accessible from external perturbations. Here we report on the theoretical design and experimental realization of a two-dimensional, fully open acoustic resonator supporting BICs. This accidental BIC, whose symmetry is chosen during design by properly tailoring the geometrical properties of the system, is completely accessible and allows for the direct measurement of the whole pressure field and properties. We experimentally demonstrate its existence with high quality factor and field enhancement properties.

The COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021.Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.

Multiple scattering theory is applied to the study of clusters of point-like scatterers attached to a thin elastic plate and arranged in quasi-periodic distributions. Two types of structures are specifically considered: the twisted bilayer and the quasi-periodic line. The former consists in a couple of two-dimensional lattices rotated a relative angle, so that the cluster forms a moiré pattern. The latter can be seen as a periodic one-dimensional lattice where an incommensurate modulation is superimposed. Multiple scattering theory allows for the fast and efficient calculation of the resonant modes of these structures as well as for their quality factor, which is thoroughly analyzed in this work. The results show that quasi-periodic structures present a large density of states with high quality factors, being therefore a promising way for the design of high quality wave-localization devices.

In this work we study the localization of flexural waves in highly symmetric clusters of scatterers. It is shown that when the scatterers are placed regularly in the perimeter of a circumference, the quality factor of the resonances strongly increases with the number of scatterers in the cluster. It is also found that in the continuous limit, that is to say, when the number of scatterers tends to infinite, the quality factor is infinite so that the modes belong to the class of the so-called bound states in the continuum or BICs, and an analytical expression for the resonant frequency is found. These modes have different multipolar symmetries, and we show that for high multipolar orders the modes tend to localize at the border of the circumference, therefore forming a whispering gallery mode with an extraordinarily high quality factor. Numerical experiments are performed to check the robustness of these modes under different types of disorder and also to study their excitation from the far field. Although we have focused our study on flexural waves, the methodology presented in this work can be applied to other classical waves, like electromagnetic or acoustic waves, being a promising approach for the design of high-quality resonators based on finite clusters of scatterers.

Este artículo presenta la evolución en la contratación pública local en el ámbito de los servicios de atención a las personas en Barcelona, a partir de los cambios introducidos en la legislación y códigos de buenas prácticas que pretenden acciones positivas hacia los licitadores que demuestren conciencia social y buenas prácticas para aumentar la eficiencia social, económica e innovadora de la inversión pública municipal. A partir de estos cambios, se describe la evolución de la naturaleza jurídica de los licitantes y los adjudicatarios, diferenciando entre empresas mercantiles y entidades del tercer sector social, para examinar el posible vínculo entre los cambios mencionados y el tipo de licitador y adjudicatario. Para ello, se analizan los contratos en el ámbito de los servicios de atención a las personas realizados por el ayuntamiento de Barcelona, y otros siete municipios de Catalunya, entre 2017 y 2019. Los resultados identifican factores e innovaciones introducidas que suponen una acción positiva hacia las entidades del tercer sector social. Sin embargo, en general, se evidencia un mayor grado de competitividad de las empresas mercantiles en los contratos de este tipo de servicios, tanto en número de casos como en volumen presupuestario, a pesar de los cambios introducidos.

We present a multiple scattering analysis of robust interface states for flexural waves in thin elastic plates. We show that finite clusters of linear arrays of scatterers built on a quasi-periodic arrangement support bounded modes in the two-dimensional space of the plate. The spectrum of these modes plotted against the modulation defining the quasi-periodicity has the shape of a Hofstadter butterfly, which as suggested by previous works might support topologically protected modes. Some interface states appear inside the gaps of the butterfly, which are enhanced when one linear cluster is merged with its mirror reflected version. The robustness of these modes is verified by numerical experiments in which different degrees of disorder are introduced in the scatterers, showing that neither the frequency nor the shape of the modes is altered. Since the modes are at the interface between two one-dimensional arrays of scatterers deposited on a two-dimensional space, these modes are not fully surrounded by bulk gaped materials so that they are more suitable for their excitation by propagating waves. The generality of these results goes beyond flexural waves since similar results are expected for acoustic or electromagnetic waves.

Abstract Background The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population. Methods A representative sample (N = 7554) from the Catalan Health Interview Survey 2011–2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean. Results A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤ 30% in half of the 28 chronic conditions). Conclusion Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

Crohn's disease (CD) is characterized by the expansion of mesenteric fat, also known as “creeping fat.” We explored the plasticity and immune properties of adipose-derived stem cells (ASCs) in the context of CD as potential key players in the development of creeping fat. Mesenteric CD-derived ASCs presented a more proliferative, inflammatory, invasive, and phagocytic phenotype than equivalent cells from healthy donors, irrespective of the clinical stage. Remarkably, ASCs from the subcutaneous depot of patients with CD also showed an activated immune response that was associated with a reduction in their immunosuppressive properties. The invasive phenotype of mesenteric CD ASCs was governed by an inflammasome-mediated inflammatory state since blocking inflammasome signaling, mainly the secretion of interleukin-1β, reversed this characteristic. Thus, CD alters the biological functions of ASCs as adipocyte precursors, but also their immune properties. Selection of ASCs with the best immunomodulatory properties is advocated for the success of cell-based therapies.

Background: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. Methods: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. Findings: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. Interpretation: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. Funding: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen). Keywords: Intestinal microbiome, Crohn's disease, FMT, Recipient stratification, Microbial load, Anti-inflammatory cytokines

El Sistema de Información Sanitaria (SIS) español recoge información sobre la salud. Las personas trans tienen peor estado de salud. El objetivo de este trabajo ha sido valorar la adecuación del SIS para recoger las necesidades de salud de las personas trans. Se revisaron las fuentes de información del SIS disponibles en el Portal Estadístico del Sistema Nacional de Salud con datos sobre la población. Se buscaron las variables «sexo» e «identidad de género». Se incluyeron 19 fuentes. En todas estaba la variable «sexo» y en ninguna la variable «identidad de género». En dos, la variable «sexo» permitía valores de «transexual». El SIS contiene escasa información respecto a la identidad de género. Esto conduce a la invisibilidad de las personas trans en las estadísticas de salud. La obtención de esta información permitiría conocer las barreras de acceso y las necesidades de salud de uno de los colectivos más discriminados de nuestra sociedad.

En este artículo abordamos el debate sobre el vínculo entre cambios en la estratificación social y los procesos de gentrificación, el cual ha sido intenso en el mundo anglosajón a fin de interpretar la gentrificación como reflejo de la evolución “natural” de la estructura socio-ocupacional en las sociedades post-industriales del Norte Global o bien como un revanchismo de clase para colonizar las centralidades obreras de las ciudades. No parece casual que el auge de los estudios sobre gentrificación durante la última década en América Latina haya ido de la mano de una ampliación de la clase media en la región. Teniendo en cuenta la diferente configuración histórica de las clases sociales en América Latina, asumimos la tesis que es principalmente la aparición de nuevos grupos sociales atraídos por la centralidad urbana lo que explica la disputa y el desplazamiento de otros grupos de bajos ingresos. Sin embargo, nuestro análisis de la ciudad de Quito muestra que en el periodo analizado (2000-2010) no se detecta, por ahora, una “vuelta al centro”, sino fundamentalmente procesos de colonización de nuevas áreas periféricas, complejizando los procesos de segregación iniciados décadas atrás así como posibles procesos de reemplazamiento en los bordes de la ciudad consolidada.

This paper seeks a qualitative approach to the urban periphery of Quito with the purpose of investigating, in the context of the expansion process of the city, the possible effects of real-estate actions in the socio-spatial transformations of the traditional inhabitants of those areas where the urbanizing process intensified. Through the ethnographic method, sample contextualization techniques, passive observation processes and key actor interviews were used. From identifying the transformations in the urban landscapes and the characterization of the most relevant processes and actors within these transformations, it was possible to build empirical evidence on displacement processes and generation of conflicts as a result of urban development in the periphery in Quito.

Existe un creciente interés y una emergente literatura académica en los estudios urbanos sobre los comunes y su aplicación. Por un lado, destacan aquellas aportaciones que aplican al ámbito urbano, los estudios de Elinor Ostrom sobre las formas de autogestión de los recursos naturales de uso común. Por el otro, la literatura crítica sobre el neoliberalismo, las nuevas formas de acumulación por desposesión y las resistencias a ellas en forma de movimientos sociales también han abordado los comunes en la ciudad desde diferentes perspectivas de origen marxista. En este trabajo se ordenan y se analizan las contribuciones de ambas aproximaciones, sus puntos críticos, así como sus posibles complementariedades, para avanzar hacia una mejor conceptualización y una futura agenda de investigación sobre los comunes urbanos.

Objetivo: Describir la salud percibida, la salud mental y algunas conductas relacionadas con la salud según la atracción y la conducta sexual en los residentes en Barcelona en 2011. Métodos: Se analizó la salud percibida y mental, los trastornos crónicos y las conductas relacionadas con la salud, en 2675 personas de 15 a 64 años de edad teniendo en cuenta la atracción y la conducta sexual en el marco de la Encuesta de Salud de Barcelona 2011. Se ajustaron modelos multivariados de regresión de Poisson robusta para obtener razones de prevalencia. Resultados: Las personas atraídas por el mismo sexo presentaron mayor prevalencia de mala salud percibida y mental. Estas personas y las que habían tenido relaciones con personas del mismo sexo declararon más frecuentemente conductas perjudiciales para la salud. Conclusiones: La población lesbiana, gay, transexual y bisexual puede presentar problemas de salud que deben ser explorados en profundidad, prevenidos y atendidos.

BACKGROUND:The aim was to evaluate the impact of asthma on patients' Health-Related Quality of Life (HRQoL) by comparing asthmatic women and men with reference norms, to examine the factors which contributed to an impaired HRQoL, and to identify groups at higher risk. METHODS:Cross-sectional evaluation of 222 primary care patients with persistent asthma (18-40 years old). HRQoL impact was estimated with the EuroQol-5 Dimensions (EQ-5D), which allows calculating Quality-Adjusted Life-Years (QALYs) by applying society preferences. Participants self-completed the EQ-5D questionnaire online. Telephonic interviews collected information on medication and adherence, and administered the Asthma Control Questionnaire. Severity markers included asthma-related comorbidity, previous oral corticosteroids course prescription, and inhaled corticosteroids daily dose. After bivariate analyses, multiple linear regression models were constructed to examine the relations between HRQoL asthma impact and socio-demographic and clinical variables, using as dependent variable the deviation from general population-based EQ-5D reference norms. RESULTS:Deviation from the EQ-5D index norms was moderate in most age/gender groups (-0.1, which corresponds to 0.6 standard deviations), while it was large in women aged 18-24 years (-0.18, corresponding to 1.1 standard deviations). In regression models, a poor asthma control was the only factor independently associated to HRQoL impact in both women and men: β -0.18 (p

El artículo analiza la participación ciudadana en los Planes de Ordenación Urbanística Municipal (POUM) aprobados en Cataluña. Los resultados constatan, a pesar de los avances en esta materia de la legislación urbanística de Cataluña, una gran diversidad de situaciones entre municipios. En concreto, se detectan debilidades importantes en los municipios de menos de 10.000 habitantes por lo que se refiere a la planificación de la participación y a la realización de acciones informativas y talleres deliberativos. En términos generales, se pone de manifiesto una participación de mínimos, mientras que los municipios que apuestan por una plantificación más colaborativa y deliberativa en el proceso de elaboración de los POUM son aún una minoría.

El artículo que sigue presenta un nuevo enfoque sobre las sociedades económicas de amigos del país. Mas allá de los trabajos históricos clásicos, aunque figura un breve resumen cronológico del movimiento de creación de esas nuevas instituciones, se trata de considerar las sociedades económicas en su dimensión cultural. Con este propósito analizaremos los emblemas y lemas de esas asociaciones en relación con el contexto económico y social de la época. En los resultados emergen cuatro elementos esenciales: - la presencia de un código cultural clásico de referencia, el de la cultura grecolatina - un segundo código cultural, nuevo, el de la ilustración con la fe de la educación, el progreso y la razón - una perspectiva urbana sobre la actividad económica, considerada a partir del punto de vista de la clase propietaria - una actitud conservadora a pesar de la reivindicación de la idea de progreso.

Abstract Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD’s beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

Abstract Leriglitazone is a unique peroxisome proliferator‐activated receptor‐gamma (PPARγ) agonist that crosses the blood–brain barrier in humans and clinical trials have shown evidence of efficacy in neurodegenerative diseases. At clinical doses which are well‐tolerated, leriglitazone reaches the target central nervous system (CNS) concentrations that are needed for PPARγ engagement and efficacy; PPARγ engagement is also supported by clinical and anti‐inflammatory biomarker changes in the Cerebrospinal fluid in the CNS. Plasma pharmacokinetics (PK) of leriglitazone were determined in a phase 1 study in male healthy volunteers comprising a single ascending dose (SAD) and a multiple ascending dose (MAD) at oral doses of 30, 90, and 270 mg and 135 and 270 mg, respectively. Leriglitazone was rapidly absorbed with no food effect on overall exposure and showed a linear PK profile with dose‐exposure correlation. A physiologically based pharmacokinetic (PBPK) model was developed for leriglitazone based on phase 1 data (SAD part) and incorporated CYP3A4 (fmCYP3A4 = 24%) and CYP2C8‐mediated (fmCYP2C8 = 45%) metabolism, as well as biliary clearance (feBIL = 19.5%) derived from in vitro data, and was verified by comparing the observed versus predicted concentration‐time profiles from the MAD part. The PBPK model was prospectively applied to predict the starting pediatric doses and was preliminarily verified with data from five pediatric patients.

Background The extent of resection in colonic Crohn's disease [cCD] is still a topic of debate, depending on the number of locations, the risk of recurrence and permanent stoma, and the role of medical therapy. Methods The Segmental COlecTomy for CroHn's disease [SCOTCH] international study is a retrospective analysis on six tertiary centre prospective databases, comprising all consecutive, unselected patients operated on between 2000 and 2019 with segmental colectomy [SC] or total colectomy [TC] for cCD. The primary aim was long-term surgical recurrence. Secondary aims were perioperative complications, stoma formation and predictors of recurrence. Results Among 687 patients, SC was performed in 285 [41.5%] and TC in 402 [58.5%]. Mean age at diagnosis and surgery, disease duration, and follow-up were 30 ± 15.8, 40.4 ± 15.4, 10.4 ± 8.6 and 7.1 ± 5.2 years respectively. Isolated cCD, inflammatory pattern, perianal CD, younger age, longer disease duration and preoperative maximal therapy were more frequent in TC, while SC presented more small bowel locations and perforating disease, required fewer 90-day re-admissions, and fewer temporary and definitive stomas. Morbidity and mortality were similar. The 15-year surgical recurrence was 44% in TC and 27% in SC [ p  = 0.006]. In patients with one to three diseased segments, recurrence risk was related to the omission of biological therapy (hazard ratio [HR] 5.6), the number of segments [HR 2.5], perianal disease [HR 1.9] and paediatric diagnosis [HR 2.8]. Conclusion When technically feasible, SC is safe and reduces temporary and permanent stoma. Young age, number of locations and perianal disease adversely affect, but postoperative biological therapy significantly reduces, the long-term surgical recurrence. [ABSTRACT FROM AUTHOR]

El modelo instituto-escuela (CINE 0-2) se expande en Cataluña desde 2010 para prevenir el fracaso y el abandono escolar y facilitar la continuidad educativa en diversos contextos educativos. Mediante el uso de las evaluaciones externas de sistema de final de etapa (6º de Educación Primaria y 4º de Educación Secundaria), elaboradas por el Consell Superior d’Avaluació del Sistema Educatiu de Cataluña, se diseña una investigación comparativa que combina el análisis transversal y longitudinal de los resultados con el objetivo de analizar la capacidad de los institutos-escuela de alta complejidad para mejorar los resultados académicos frente al modelo público no integrado (alumnado que transiciona de escuela pública a instituto público). Aunque el alumnado de institutos-escuela obtiene puntuaciones más bajas que el del modelo público no integrado, longitudinalmente, el alumnado de institutos-escuela mejora significativamente los resultados en lengua castellana y competencia científico-tecnológica al final de la Educación Secundaria Obligatoria respecto a la Educación Primaria. Se evidencia un efecto positivo en la disminución del porcentaje de alumnado que no adquiere las competencias básicas al final de la Educación Secundaria Obligatoria.

We propose a twofold question applied to contemporary digital fiction: how do they recall the past and why do they recall it? The aim is not only to put cultural representations of history into historical perspective, but also to raise the question of the aesthetic construction of fiction and its development, from novels to video games and cinema. The historical nature of fictional creation will lead us to propose an aesthetic that takes this factor into account, using the example of video games.

The aim of the conference was to examine several categories at once in order to rethink the evaluation of fiction, particularly in contemporary creations. We return to some of the key points in order to propose a postface that outlines several possible directions, looking in particular at the relationship between creation and reception of digital material, which must undoubtedly be seen as the keystone of the emergence of new practices, those of 'digital cultures'. We will first attempt to define the notion of aesthetic categories, starting with a retrospective look at the classical era and the emergence and use of the concept of fiction. We will then assess the transformation that digital technology has brought to fiction. We will need to identify both the material and the new methods of production and distribution that it has engendered, but also to consider what its potential is and how it has been used in the creation of fiction.

Abstract Background Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment. Methods We have thoroughly described mitochondrial performance in two Rett models, patients’ primary fibroblasts and female Mecp2tm1.1Bird−/+ mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel. Results We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity. Conclusions Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial.