Análisis de las estrategias de atención al paciente crónico pluripatológico en el territorio español

El progresivo envejecimiento de la población como consecuencia de la transición epidemiológica ha propiciado el crecimiento exponencial de los pacientes con enfermedades crónicas y pluripatología. Esto provoca un mayor consumo de recursos y un aumento de la dependencia. Las comunidades autónomas españolas, para afrontar estos desafíos y valiéndose de las recomendaciones internacionales y del documento “Estrategia para el abordaje de la cronicidad” del Sistema Nacional de Salud, han desarrollado diversas estrategias de atención al paciente crónico intentando evitar la variabilidad en la atención a los pacientes y fomentando la equidad. El objetivo de este trabajo es realizar una comparativa de la atención prestada al paciente crónico pluripatológico entre las distintas comunidades del territorio español. Se realizó una revisión bibliográfica utilizando las bases de datos COCHRANE PLUS, PUBMED, LILACS y CUIDEN, además de los diferentes portales de salud del territorio español. La revisión abarcó desde noviembre de 2015 hasta enero de 2016. Se utilizaron los tesauros DeCS y MeSH, combinándolos mediante el operador booleano AND, aplicando los criterios de inclusión y exclusión y realizando la lectura crítica mediante las parrillas CASPe y AGREE II. Se seleccionaron 26 artículos. Los resultados principales muestran que la mayoría de las comunidades autónomas estratifican a la población según la pirámide de Kaiser Permanente, estableciéndose en todo el territorio español la Atención Primaria como eje de asistencia al paciente crónico, siendo el domicilio el lugar idóneo para realizar los cuidados. La enfermera gestora de casos se convierte en el profesional idóneo para fomentar el empoderamiento y autocuidado del paciente. Se debe prestar especial atención a las personas cuidadoras del paciente, poniendo a su alcance programas de apoyo y de autocuidado. La progresiva instauración de la Historia Clínica Electrónica y la telemonitorización en todo el territorio español ha mejorado la continuidad asistencial de estos pacientes.Grado en Enfermerí

Molecular characterization of myelodysplastic syndromes with chromosome 7 abnormalities

Trabajo de fin de grado. Grado en Medicina. Curso académico 2021-2022Los síndromes mielodisplásicos son un conjunto de neoplasias hematológicas clonales, caracterizados por una hematopoyesis anómala, alteraciones morfológicas, funcionales y genéticas de las células madre hematopoyéticas mieloides, además de un sustancial riesgo de transformación a leucemia aguda. Para su diagnóstico es necesario llevar a cabo un estudio integrado de morfología, citogenética y, cada vez más aceptado, molecular. De hecho, la presencia de determinadas anomalías cromosómicas (del(5q), del(7q)/-7, cariotipo complejo) así como mutaciones en determinados genes (SF3B1, DNMT3A, ASXL1, TP53) se han asociado con la patogenia y el pronóstico de esta enfermedad. El objetivo principal de este trabajo es profundizar en el estudio de las características demográficas, diagnósticas, genéticas y pronósticas de aquellos pacientes con SMD que presentan alteraciones en el cromosoma 7. Se observó que un 6% de los pacientes presentaron alteraciones en el cromosoma 7, ya sea de forma aislada (monosomía o deleción) o combinada con otras anomalías (dobles, triples o cariotipo complejo). En cuanto a las mutaciones, identificadas mediante secuenciación masiva, se observó que aquellas en TP53 y U2AF1 eran estadísticamente más frecuentes en el subgrupo de pacientes con alteraciones del 7. En concreto, las mutaciones de TP53 aparecían en los pacientes con alteraciones del 7, sólo cuando éstas estaban en combinación con otras, asociándose también a la presencia de del(5q) como anomalía adicional, y relacionadas con una supervivencia global y tiempo hasta la progresión más cortos. Interesantemente, ninguno de los pacientes con anomalías del 7 aisladas tenían mutaciones de TP53, ni en TET2 ni SRSF2, donde otras mutaciones (DNMT3A, EZH2, GATA2, RUNX1) podrían tener implicación pronóstica. Sin embargo, es necesario profundizar en su estudio en series más amplias. Es de gran importancia la realización de estudios combinados de cariotipo/FISH y secuenciación masiva en los pacientes con SMD, para detectar cualquiera de estas anomalías, así como cualquier combinación de las mismas, pudiendo avanzar en el análisis de su impacto pronóstico y valor en la toma de decisiones

Pridopidine Reverses Phencyclidine-Induced Memory Impairment

Pridopidine is in clinical trials for Huntington's diseasetreatment. Originally developedas a dopamine D2receptor (D2R) ligand, pridopidine displays about 100-fold higheraffinity for the sigma-1 receptor (sigma-1R). Interestingly, pridopidine slows diseaseprogression and improves motor function in Huntington's disease model mice and,in preliminarily reports, Huntington's disease patients.The present study examinedthe anti-amnesic potential of pridopidine. Thus, memory impairment was produced inmice by administration of phencyclidine (PCP, 10 mg/kg/day) for 10 days, followedby 14 days' treatment with pridopidine (6 mg/kg/day), or saline. Finally, novel objectrecognition performance was assessed in the animals. Mice receiving PCP andsaline exhibited deficits in novel object recognition, as expected, while pridopidinetreatment counteracted PCP-induced memory impairment. The effect of pridopidine wasattenuated by co-administration of the sigma receptor antagonist, NE-100 (10 mg/kg).Our results suggest that pridopidine exerts anti-amnesic and potentially neuroprotectiveactions. These data provide new insights into the therapeutic potential of pridopidine asa pro-cognitive drug

Digitalización, monitorización y evaluación del impacto de la Economía Social. Análisis en el Tercer Sector de Acción Social español : el caso de Juntos por el Empleo

Durante los últimos años se han elaborado numerosos estudios sobre la necesidad de que las entidades del Tercer Sector de Acción Social (TSAS) desarrollen habilidades para comunicar y demostrar sus resultados y la eficiencia en el desempeño de su actividad. En este proceso, la monitorización y la evaluación se convierten en actividades claves para hacer partícipes a los distintos grupos de interés del impacto por ellas generado. Junto a esto, la sociedad ha vivido una evolución digital que ha generado cambios profundos en todos los ámbitos, grupos e individuos.Partiendo de un análisis realizado desde la teoría institucional y la teoría de la dependencia de recursos para poner en valor la importancia que adquiere este proceso dentro del contexto de los requerimientos de los financiadores y de los grupos de interés en general, planteamos la necesidad de identificar las nuevas herramientas digitales y formas de trabajo con las mismas que pueden apoyar la realización de la evaluación en las entidades del TSAS y que ésta sea de utilidad para el cumplimiento de la misión y los objetivos de las organizaciones. Analizamos el caso de Juntos por el Empleo, iniciativa promovida por la Fundacion Accenture junto a varias organizaciones sociales, empresas y administraciones públicas, cómo práctica de interés en la implementación de nuevas herramientas digitales que han facilitado el trabajo compartido de gestión y evaluación de sus proyectos sociales. El enfoque de impacto colectivo se descubre como una nueva forma, colaborativa y estructurada, necesaria para abordar los problemas a los que se enfrenta el TSAS

Exploring the symbol processing 'time interval' parametric constraint in a Belousov-Zhabotinsky operated chemical Turing machine

Chemical reactions are powerful molecular recognition machines. This power has been recently harnessed to build actual instances of each class of experimentally realizable computing automata, using exclusively small-molecule chemistry (i.e. without requiring biomolecules). The most powerful of them, a programmable Turing machine, uses the Belousov-Zhabotinsky oscillatory chemistry, and accepts/rejects input sequences through a dual oscillatory and thermodynamic output signature. The time interval between the aliquots representing each letter of the input is the parameter that determines the time it takes to run the computation. Here, we investigate this critical performance parameter, and its effect not only on the computation speed, but also on the robustness of the accept/reject oscillatory and thermodynamic criteria. Our work demonstrates that the time interval is a non-trivial design parameter, whose choice should be made with great care. The guidelines we provide can be used in the optimization of the speed, robustness, and energy efficiency of chemical automata computations

Revealing Adenosine A2A-Dopamine D2 Receptor Heteromers in Parkinson's Disease Post-Mortem Brain through a New AlphaScreen-Based Assay

Background: Several biophysical techniques have been successfully implemented to detect G protein-coupled receptors (GPCRs) heteromerization. Although these approaches have made it possible to ascertain the presence of GPCR heteromers in animal models of disease, no success has been accomplished in pathological human post-mortem brains. The AlphaScreen technology has been consistently used to quantify small analyte accumulation or depletion, bimolecular interactions, and post-translational modifications. The high signal-to-background, dynamic range and sensitivity exhibited by this technology support that it may be suitable to detect GPCR heteromers even under non-optimal conditions. Methods: Here, we describe the development of a new AlphaScreen assay to detect GPCR oligomers in human post-mortem brain. Results: Adenosine A2A-dopamine D2 receptor (A2AR/D2R) heteromer formation was monitored in caudate from healthy and Parkinson's disease (PD) subjects. The approach was first validated using striatal membranes from wild type and A2AR deficient mice. Secondly, we took advantage of the 6-hydroxydopamine hemiparkinsonian rat model to validate previous results. In addition, finally, A2AR/D2R heteromer formation was assessed in caudate membranes from human post-mortem brains. Importantly, our preliminary results revealed an increase in A2AR/D2R heteromer formation in PD brains. Conclusions: The new AlphaScreen assay allowed assessing GPCR heteromers in human post-mortem brains with high sensitivity

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration

Fosmetpantotenate; Randomized controlled trialFosmetpantotenato; Ensayo controlado aleatorizadoFosmetpantotenat; Assaig controlat aleatoritzatBackground Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. Results Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN.The FORT trial was supported by Retrophin, Inc

Inventory control of particulate processes

Abstract In this work we address the problem of designing model-based controllers for particulate processes described by population balance (PB) models. We focus on PB models that are solved by numerical discretization, for which many standard control methodologies are not suitable due to the high order of these models. We interpret discretized PB models as chemical reaction networks and suggest to combine inventory control with techniques of stability of chemical reaction networks to design the controller. Inventory control is based on the idea of manipulating process flows so that certain extensive variables defining the system, called inventories, follow their setpoints. The whole system is stabilized by controlling the dominant inventories. The discretized PB is exploited in all aspects of controller design, from determining the controlled inventories to the final implementation of the control law. The methodology is illustrated with an industrial leaching reactor, the Silgrain ® process. We show that the discretized PB model takes the form of a Feinberg-Horn-Jackson zero-deficiency network, allowing us to prove stabilization of the whole system. The performance of standard inventory control and robust inventory control are investigated by simulation, with satisfactory results even in the presence of modeling errors

Generation of three human iPSC lines from PLAN (PLA2G6-associated neurodegeneration) patients

Neurodegeneració; MutacióNeurodegeneración; MutaciónNeurodegeneration; MutationThe human iPSC cell lines, PLANFiPS1-Sv4F-1 (RCPFi004-A), PLANFiPS2-Sv4F-1 (RCPFi005-A), PLANFiPS3-Sv4F-1 RCPFi006-A), derived from dermal fibroblast from three patients suffering PLAN (PLA2G6-associated neurodegeneration; MIM 256600) caused by mutations in the PLA2G6 gene, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors. The pluripotency was assessed by immunocytochemistry and RT-PCR. Differentiation capacity was verified in vitro. This iPSC line can be further differentiated toward affected cells to better understand molecular mechanisms of disease and pathophysiology.This work was supported by the Instituto de Salud Carlos III (ISCIII) - Subdirección General de Evaluación y Fomento de la Investigación [PI18/00147to CE and PI18/01319 to BPD], and by the Generalitat Valenciana [PROMETEO/2018/135], within the framework of the National R + D + I Plan co-funded with ERDF funds. CM has a CIPF-PhD fellowship [P.I.06/2017]. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020)

The Spatial Extent of Pain Is Associated with Pain Intensity, Catastrophizing and Some Measures of Central Sensitization in People with Frozen Shoulder

The aim of this cross-sectional study was to explore the spatial extent of pain and its association with clinical symptoms, psychological features, and pain sensitization in people with frozen shoulder (FS). Forty-eight individuals with FS completed pain drawings (PDs) and reported their clinical symptoms including pain intensity (Visual Analogue Scale) and shoulder disability (Shoulder Pain and Disability Index). Moreover, pain sensitization measurements (pressure pain thresholds, temporal summation, conditioned pain modulation, and Central Sensitization Inventory (CSI)) were assessed. Psychological features were assessed by Pain Catastrophizing Scale (PCS) and Pain Vigilance and Awareness Questionnaire. Pain frequency maps were generated, Margolis rating scale was used for pain location, and Spearman correlation coefficients were computed. The mean (SD) pain extent was 12.5% (6.7%) and the most common painful area was the anterolateral shoulder region (100%). Women presented a more widespread pain distribution compared with men. Significant positive associations were obtained between pain extent and current pain intensity (rs = 0.421, p < 0.01), PCS (rs = 0.307, p < 0.05) and CSI (rs = 0.358, p < 0.05). The anterolateral region of the shoulder was the most common painful area in people with FS. Women with FS presented more extended areas of pain; and a more widespread distribution of pain was correlated with higher levels of pain, pain catastrophizing and pain sensitization