Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa

Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional (2D) models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA) - poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e., they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality

Improving quality of care and clinical outcomes for rectal cancer through clinical audits in a multicentre cancer care organisation

Introduction: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. Methods: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. Results: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p < 0.001). Conclusions: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time

Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice guidelines and Quality Certification Do Not Avert Variability in Clinical Practice

Background: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. Methods: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. Results: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. Conclusions: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process

Model d'atenció integrada al pacient crònic: insuficiència cardíaca (IC), malaltia pulmonar obstructiva crònica (MPOC)

Atenció al pacient crònic; Insuficiència cardíaca; Malaltia pulmonar obstructiva crònicaAtención al paciente crónico; Insuficiencia cardíaca; Enfermedad pulmonar obstructiva crónicaChronic patient care; Heart failure; Chronic obstructive pulmonary diseaseAquest document pretén establir un marc d’actuació per a la transformació a mitjà termini de l’atenció que es presta als i les pacients crònics des de l’Institut Català de la Salut (ICS), però tenint en compte que molts dels canvis necessaris només són possibles si s’estableixen els mecanismes de col·laboració adequats entre tots els actors del sistema, específicament, si s’estableixen els incentius per tal de garantir-ne la continuïtat, i si evolucionem cap a un model d’atenció que curi i tingui cura dels i les pacients, i alhora serveixi també per reduir les hospitalitzacions innecessàries. L’abordatge s’ha fet escollint la insuficiència cardíaca (IC) i la malaltia pulmonar obstructiva crònica (MPOC), perquè són dues de les malalties que tenen un major impacte en dependència, discapacitat, qualitat de vida i anys de vida perduts al nostre país, i també, perquè concentren una part molt important del cost de la cronicitat

Ensayo de una tipología de las cuencas mediterráneas del proyecto GUADALMED siguiendo las directrices de la Directiva Marco del Agua

RESUMEN Utilizando la propuesta de tipología de ríos de la Directiva Marco del Agua en su anexo 2 se realiza un ensayo tipológico de los puntos de muestreo del proyecto GUADALMED. Según el sistema A, se presentan 16 ecotipos, lo que se juzga poco adecuado para la gestión de los mismos y sin una base ecológica que lo justifique. De acuerdo con la selección previa hecha por los miembros del grupo GUADALMED para 5 de estos ecotipos no habría estaciones de referencia. Con algunas variables medidas en los puntos de muestreo y otras de tipo geológico e hidromorfológico, se realiza un ensayo tipológico usando el sistema B. El método implica un análisis de la correlación entre variables, un cluster de las estaciones utilizando el método K-means y un análisis discriminante de cuáles son las variables que distinguen estos grupos. El estudio da como resultado la caracterización de 6 ecotipos que sin embargo, a juicio de los miembros del proyecto GUADALMED, no recogen la variedad de tipos de ríos mediterráneos. Valorando cualitativamente parámetros no introducidos (por falta de datos) en el análisis K-means, se propone una tipología provisional en 9 grupos. Un análisis de las comunidades de macroinvertebrados (a nivel taxonómico de familia) revela un grado importante de coherencia entre las familias asociadas a cada tipo y sus preferencias ecológicas conocidas. ABSTRACT A preliminary analysis was conducted of the river types in the GUADALMED project using the river typology proposed in the Water Framework Directive (WFD) in its annex 2. Using System A, 16 different types were found, a number too high for water management purposes and such typology lacks a supportive ecological basis. For 5 of these 16 ecotypes, no reference stations exist. Reference stations were selected a priori in project GUADALMED for each of the 12 basins sampled. An ecotypological analysis was performed using System B of the WFD using several variables measured during the study, and other variables obtained from maps or data bases (e.g., geology). The method included the analysis of the calibration between variables, the clustering of stations by the K-means method and a discriminant analysis. The latter revealed which factors were distinctive of each group. Six ecotypes were established for the GUADALMED study sites. These, however, do not include all the mediterranean-type streams of the region. This is mainly due to the absence in the data base of some important features of streams in the data base such as temporality or the dependence of flow on the presence of karstic aquifers, attribute

The brazilian Amaryllidaceae as a source of acetylcholinesterase inhibitory alkaloids

Nine Brazilian Amaryllidaceae species were studied for their alkaloid composition and acetylcholinesterase (AChE) inhibitory activity via GC-MS and a modified Ellman assay, respectively. A total of thirty-six alkaloids were identified in these plants, of which Hippeastrum papilio and H. glau-cescens exhibited the highest galanthamine content and the best IC50 values against AChE. Furthermore, Hippeastrum vittatum and Rhodophiala bifida also showed notable AChE inhibitory effects. X-ray crys-tallographic data for four galanthamine-type com-pounds revealed significant differences in the orientation of theN-methyl group, which are shown to be related to AChE inhibition

Criterios para la selección de condiciones de referencia en los ríos mediterráneos. Resultados del proyecto GUADALMED

La Directiva Marco del Agua (DMA) establece la necesidad de definir las condiciones de referencia, que sirvan de patrón del estado ecológico del resto de estaciones del mismo ecotipo. Varios son los criterios que pueden ser utilizados para la selección de las condiciones de referencia. En el proyecto GUADALMED cinco localidades por cuenca muestreada, fueron escogidas a priori según la experiencia de los expertos en cada zona, uno de los criterios contemplados en la DMA. Los resultados mostraron en muchas de las estaciones seleccionadas (un 72%) una calidad biológica alterada (IBMWP <100 en todas las campañas muestreadas) y un bosque de ribera perturbado (QBR <75). A partir de estos resultados se analizó si era posible el establecimiento de una serie de criterios que ayudaran a establecer condiciones de referencia. Para ello se seleccionaron diferentes criterios como la conservación del bosque de ribera, los usos naturales de la cuenca, la naturalidad del canal fluvial, la ausencia de embalses que regularan el caudal, un hábitat del lecho adecuado y concentraciones bajas de parámetros físico-químicos, en cada uno de los puntos estudiados. Algunas estaciones cumplían todos los criterios, mientras que otras podrían fácilmente cumplirlos reubicando el punto de muestreo aguas arriba o abajo del río o mediante técnicas de restauración. Los resultados fueron comparados con la tipología mediante el Sistema B establecida en otro trabajo de este volumen. En algunos ecotipos, la falta de estaciones de referencia y la imposibilidad de encontrarlas dadas las características de la cuenca y el tramo, implica la imposibilidad de establecer condiciones de referencia y la necesidad de establecer el Máximo Potencial Ecológico. Al comparar los criterios establecidos para cada estación con los valores de los índices biológicos hallados en todas las campañas, se observa que los criterios establecidos son adecuados, ya que las estaciones que los cumplen tienen un IBMWP y QBR superior. Este trabajo pretende establecer unos criterios generales que serán utilizados como base para la selección y validación de condiciones de referencia en la segunda fase del proyecto GUADALMED. ABSTRACT The water Frame Directive (WFD) establishes the need to define reference conditions in order to determine the ecological status of all the test sites from each ecotype. Several criteria may be used to select reference conditions. In the GUADALMED project, five localities per basin were selected a priori according to the experience of experts, which is one of the criteria considered in the WFD. Results showed that in 72% of selected reference conditions, water quality was poor (IBMWP<100 in all sampled seasons) and the riparian vegetation, altered (QBR<75). Consequently, we established a set of new criteria for appropriate selection of reference conditions for natural riparian vegetation status, natural basin uses, unaltered fluvial channel, absence of reservoirs, diverse river habitat conditions and low nutrient concentrations. A few sites conform to all these criteria, whereas others may comply when a site upstream or downstream is considered instead, or after restoration techniques are applied. Results obtained were compared with the previously established System B typologies. For some ecotypes, no reference sites were found occasionally because of the difficulty in finding given basin or river reach characteristics. In these cases, a"Maximum Ecological Potential" was used instead of the reference condition. When the criteria established were compared with the biological indices across seasons for each site, a positive and significant relationship was found between all criteria and the IBMWP and QBR indices. Here, we present a set of criteria for use as a general framework to select and validate reference condition during the second phase of the project GUADALMED

Model d'atenció integrada al pacient crònic: insuficiència cardíaca (IC), malaltia pulmonar obstructiva crònica (MPOC)

Atenció al pacient crònic; Insuficiència cardíaca; Malaltia pulmonar obstructiva crònicaAtención al paciente crónico; Insuficiencia cardíaca; Enfermedad pulmonar obstructiva crónicaChronic patient care; Heart failure; Chronic obstructive pulmonary diseaseAquest document pretén establir un marc d’actuació per a la transformació a mitjà termini de l’atenció que es presta als i les pacients crònics des de l’Institut Català de la Salut (ICS), però tenint en compte que molts dels canvis necessaris només són possibles si s’estableixen els mecanismes de col·laboració adequats entre tots els actors del sistema, específicament, si s’estableixen els incentius per tal de garantir-ne la continuïtat, i si evolucionem cap a un model d’atenció que curi i tingui cura dels i les pacients, i alhora serveixi també per reduir les hospitalitzacions innecessàries. L’abordatge s’ha fet escollint la insuficiència cardíaca (IC) i la malaltia pulmonar obstructiva crònica (MPOC), perquè són dues de les malalties que tenen un major impacte en dependència, discapacitat, qualitat de vida i anys de vida perduts al nostre país, i també, perquè concentren una part molt important del cost de la cronicitat

Bodies in motion: spaces, emotions and representations that (de)construct realities

OBJETIVO Analizar las representaciones sociales del cuerpo entre personas transexuales brasileñas y costarricenses a través de sus historias de vida. MÉTODO Investigación cualitativa, multicéntrica y descriptiva. La población del estudio consistió en 70 participantes. Se contó con la colaboración de dos organizaciones en Florianópolis, SC, Brasil y San José, capital de Costa Rica para recopilar información. Los datos se analizaron mediante Análisis de Contenido. RESULTADOS A partir de los resultados, se dio a conocer una sola representación social asociada con la corporalidad, "Cuerpos modelados: la elasticidad de la corporalidad". Esta representación describió dos unidades de contexto elementales (matrices del discurso) claras. La primera asocia al cuerpo a un objeto sin terminar, transitorio, volátil, maleable, conformable y fluido, mientras que la segunda relaciona al cuerpo con una institución específica pero regulado y controlado por otros. CONCLUSIÓN Se llegó a la conclusión de que el cuerpo transexual es una institución voluble, efímera, transformable y atravesada por las marcas de un tiempo historizante e historizable, inscripto no sólo en lo que puede ser identificado en el uso de los signos lingüísticos, sino también lo que pertenece al registro de lo indecible en términos de percepciones y sensaciones socioculturales.OBJETIVO Analisar as representações sociais do corpo entre pessoas transexuais brasileiras e costa-riquenhas por meio das suas histórias de vida. MÉTODO Pesquisa qualitativa, multicêntrica e descritiva. A população do estudo foi composta por 70 participantes. Contou-se com a colaboração de duas organizações, em Florianópolis, SC-Brasil e em San José, capital da Costa Rica para coletar as informações. Os dados foram analisados segundo a Análise de Conteúdo. RESULTADOS A partir dos resultados, desvelou-se uma única representação social associada à corporeidade: “Corpos modelados: sobre a elasticidade da corporeidade”. Esta representação descreveu duas unidades de contexto elementar (matrizes do discurso) claras. A primeira delas associa o corpo a um objeto inconcluso, transitório, volátil, maleável, moldável e fluido, enquanto a segunda relaciona o corpo com uma instituição própria, mas regulada e controlada pelos outros. CONCLUSÃO Conclui-se que o corpo transexual é uma instituição volúvel, efêmera, transformável e atravessada pelas marcas de um tempo historizante e historizável, que se inscreve não só naquilo que pode ser nomeado diante do emprego de signos linguísticos, mas também naquilo que pertence ao registro do inominável em termos de percepções e sensações socioculturais.OBJECTIVE To analyze the social representations of the body among Brazilian and Costa Rican transsexual people through their life stories. METHOD Qualitative and descriptive multicenter research. The study population consisted of 70 participants. Two organizations cooperated to collect the information, one in Florianópolis, SC-Brazil and one in San José, the capital of Costa Rica. Content Analysis was used to analyze the data. RESULTS Based on the results, a single social representation of corporeality was unveiled: “Modeled bodies: about the elasticity of corporeality”. This representation described two clear elementary context units (discourse matrices). The first associates the body with an inconclusive, transitory, volatile, pliable, moldable and fluid object, while the second relates the body with a separate institution, but regulated and controlled by others. CONCLUSION In conclusion, the transsexual body is a volatile, transient, transformable institution, crossed by the marks of a historicizing and historicizable time, which comes within the scope not only of what can be named by means of linguistic signs, but also of what belongs to the unnamable in terms of sociocultural perceptions and feelings