Dictamen Jurídic Dret de Successions. Cas 18-A

Treballs Finals del Màster d'Advocacia, Facultat de Dret, Universitat de Barcelona, Curs: 2019-2020, Tutor: Rubio Gimeno, Gemm

Desarrollo de una metodología de diseño del sistema de encendido por pre-cámara en motores de encendido provocado para automoción

[ES] Hoy en día, los efectos negativos del calentamiento global generan una gran preocupación sobre las emisiones de los gases de efecto invernadero y sus consecuencias. Debido al consumo de combustibles fósiles en el sector del transporte, las emisiones de CO2 están aumentando de forma alarmante, siendo este uno de los principales contribuyentes. Además, el uso de estos combustibles también genera una serie de emisiones contaminantes nocivas para el ser humano que degradan la calidad del aire localizadas en las zonas de alta habitabilidad; entre los más conocidos están los óxidos de nitrógeno (NOx) y las partículas de hollín. En este contexto, la optimización de los actuales motores de encendido provocado (MEP) muestra ciertas ventajas respecto a sus principales competidores; los motores de encendido por compresión (MEC). Aunque estos últimos cuentan con un mayor rendimiento térmico que se traduce en menos emisiones de CO2, las futuras normativas anticontaminación están forzando a los fabricantes de motores a evaluar otras alternativas. La integración de un sistema de encendido por precámara en MEP ofrece ciertas ventajas en términos de rendimiento térmico y CO2 sin comprometer el coste del motor en exceso. Sin embargo, la complejidad añadida al incorporar este sistema de encendido hace necesario el desarrollo de nuevas estrategias de diseño que permitan acelerar el desarrollo y la optimización del concepto. Por tanto, en este trabajo se ha desarrollado una metodología de diseño para este novedoso sistema de encendido en un MEP de nueva generación. La metodología se basa en tres herramientas numéricas con diferente grado de complejidad. En primer lugar, un modelo de acción de ondas se utiliza para estimar los flujos entre la precámara y la cámara de combustión. Además, se ha utilizado un modelo unidimensional de chorro para predecir las características de éstos. Y, por último, se ha utilizado un modelo avanzado basado en la dinámica de fluidos computacional (CFD) para validar los anteriores modelos y realizar un análisis detallado del concepto. Los resultados muestran una buena correlación con las medidas experimentales, demostrando la validez y aplicabilidad de la metodología. En base a éstos, se ha propuesto un diseño óptimo del sistema que aumenta el rango de operación y la flexibilidad del concepto.[VL] Les creixents emissions dels gasos d'efecte d'hivernacle estan creant una gran preocupació sobre l’escalfament global i les seues conseqüències. Un dels principals sectors de consum de petroli en el món és el del transport de persones. Per a això s’utilitzen motors de combustió interna alternatius que necessiten combustibles fòssils per al seu funcionament, els quals generen una gran quantitat de CO₂, nociva per al medi ambient. Tot això comporta una degradació de la qualitat de l'aire que respirem i l'augment de malalties respiratòries. La preocupació per la salut i el medi ambient continua creixent a causa a les continues millores de la indústria. Especialment ha sigut el sector de l'automoció el que s'ha vist afectat per la dura normativa anti-contaminació. En aquest marc, els efectes negatius de la contaminació ambiental i sonora estan arribant a límits realment preocupants, sent aquests especialment aparents en els principals nuclis urbans, on les autoritats estan, fins i tot, restringint la circulació dels vehicles tèrmics. Per tant, en aquest treball s'ha desenvolupat una metodologia de disseny per a un nou sistema d'encesa en un motor d'encesa provocada de nova generació. La metodologia es basa en tres eines numèriques amb diferent grau de complexitat. En primer lloc, un model d'acció d'ones s'utilitza per a estimar els fluxos entre la pre-cambra i la cambra de combustió. A més, s'ha utilitzat un model unidimensional per a predir les característiques de l’intercanvi de massa entre les cambres. I, finalment, s'ha utilitzat un model més avançat basat en la dinàmica de fluids computacional (CFD) per a validar els anteriors models i entendre millor el concepte. Els resultats mostren una bona correlació amb les mesures experimentals, demostrant la validesa i utilitat de la metodologia. Utilitzant aquesta metodologia, s'ha proposat un disseny òptim del sistema que augmenta el rang d'operació i la flexibilitat del concepte.[EN] Nowadays, the negative effects of global warming are causing great concern about greenhouse gas emissions and their consequences. Due to the consumption of fossil fuels in the transport sector, CO2 emissions are increasing at a critical rate, with the transport sector being one of the main contributors. In addition, the use of these fuels also generates a number of pollutant emissions harmful to humans that degrade the air quality in areas of high habitability; being nitrogen oxides (NOx) and soot particles among the best known. In this context, the optimization of existing Spark-Ignition (SI) engines shows certain advantages over their main competitor, the Compression-Ignition (CI) engines. Although the latter have a higher thermal efficiency resulting in lower CO2 emissions, future anti-pollution regulations are forcing engine manufacturers to evaluate other alternatives. The integration of a pre-chamber ignition system in SI engines offers advantages in terms of thermal efficiency and CO2 without compromising the cost of the engine in excess. However, the added complexity of incorporating this ignition system requires the development of new design strategies to accelerate the development and optimization of the concept. Therefore, in this work a design methodology has been developed for this novel ignition system in a new generation MEP. The methodology is based on three numerical tools with different degrees of complexity. Firstly, a wave action model is used to estimate the flows between the prechamber and the combustion chamber. In addition, a one-dimensional jet model has been used to predict the characteristics of these. And finally, an advanced model based on computational fluid dynamics (CFD) has been used to validate the previous models and to perform a detailed analysis of the concept. The results show a good correlation with the experimental measurements, demonstrating the validity and applicability of the methodology. Based on these, an optimal system design has been generated that increases the operating range and flexibility of the pre-chamber ignition concept.Fortea Marzo, RM. (2020). Desarrollo de una metodología de diseño del sistema de encendido por pre-cámara en motores de encendido provocado para automoción. http://hdl.handle.net/10251/157320TFG

Screening of Suitable Plant Regeneration Protocols for Several Capsicum spp. through Direct Organogenesis

[EN] Peppers (Capsicum spp.) are recalcitrant to in vitro culture regeneration, making the application of in vitro-based breeding strategies difficult. We evaluated the impact of different combinations of auxins, cytokinins and micronutrients on the induction of direct organogenesis in cotyledon and hypocotyl explants of C. annuum, C. baccatum and C. chinense. We found variation in the regeneration response among species and type of explant. In this way, the average numbers of shoots per cotyledon and hypocotyl explant were, respectively, 1.44 and 0.28 for C. annuum, 4.17 and 3.20 for C. baccatum and 0.08 and 0.00 for C. chinense. Out of the six media, the best overall results were obtained with the medium Pep1, which contained 5 mg/L BAP (6-benzylaminopurine), 0.5 mg/L IAA (indole-3-acetic acid) and 0.47 mg/L CuSO4, followed by a subculture in the same medium supplemented with 10 mg/L AgNO3 (medium Pep1.2). The best result for the Pep1 + Pep1.2 medium was obtained for C. baccatum using cotyledon explants, with 8.87 shoots per explant. The explants grown in medium Pep1 + Pep1.2 were the ones with greener tissue, while overall the hypocotyl explants were greener than the cotyledon explants. Our results indicate that there is wide variation among Capsicum species in terms of regeneration. Our results suggest that the synergistic effect of copper and silver resulted in a higher regeneration rate of Capsicum explants. Explants with shoots were transferred to different media for elongation, rooting and acclimatization. Although acclimatized plantlets were obtained for C. baccatum and C. chinense, an improvement in these latter stages would be desirable for a high throughput regeneration pipeline. This work contributes to the improvement of Capsicum regeneration protocols using specific combinations of medium, explant and genotype, reaching the levels of efficiency required for genetic transformation and of gene editing technologies for other crops.This research was funded by Universitat Politecnica de Valencia, research line 20200268.Martínez-López, M.; García-Pérez, A.; Gimeno -Páez, E.; Prohens Tomás, J.; Vilanova Navarro, S.; García-Fortea, E. (2021). Screening of Suitable Plant Regeneration Protocols for Several Capsicum spp. through Direct Organogenesis. Horticulturae. 7(9):1-17. https://doi.org/10.3390/horticulturae7090261S1177

Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Portal sinusoidal vascular disease is a presinusoidal cause of portal hypertension (PHT) of unknown etiology, characterized by typical manifestations of PHT (esophageal varices, ascites, portosystemic collaterals), plaquetopenia and splenomegaly with a gradient of portal pressure slightly increased, according to the presinusoidal nature of the PHT. A few cases in the literature have shown a relationship between oxaliplatin and the development of presinusoidal portal hypertension, years after the chemotherapy for colorectal cancer (therefore, different to sinusoidal obstruction syndrome). There are three mechanisms through which oxaliplatin can cause sinusoidal damage: 1) damage at the level of endothelial cells and stimulates the release of free radicals and depletion of glutathione transferase, with altering the integrity of the sinusoidal cells. The damage in the endothelial sinusoidal cells allows to erythrocytes to across into the Dissé space and formation of perisinusoidal fibrosis, 2) the appearance of nodular regenerative hyperplasia is favored by the chronic hypoxia of the centrilobular areas and, finally, 3) oxaliplatin can generate an obliteration of the blood capillaries and zones of parenchymal extinction. These three facts can develop, in a minority of cases, the appearance of a presinusoidal increase of portal pressure, which typically appears years after the completion of chemotherapy and sometimes is underdiagnosed until variceal bleeding, ascites or encephalopathy appear. The knowledge of this pathology is essential to be able to perform an early diagnostic and consult to the hepatologist.Funding: This research received an external funding of CI18/67/02 Acuerdo de cooperación en el programa de becas de investigación científica de IDIVAL de JANSSEN-CILAG, S.A

Acute Stress Regulates Sex-Related Molecular Responses in the Human Jejunal Mucosa: Implications for Irritable Bowel Syndrome

Estrés agudo; Barrera intestinal; SexoEstrès agut; Barrera intestinal; SexeCute stress; Intestinal barrier; SexIrritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder linked to intestinal barrier dysfunction and life stress. We have previously reported that female sex per se determines an increased susceptibility to intestinal barrier dysfunction after cold pain stress (CPS). We aimed to identify sex-related molecular differences in response to CPS in healthy subjects to understand the origin of sex bias predominance in IBS. In 13 healthy males and 21 females, two consecutive jejunal biopsies were obtained using Watson’s capsule, at baseline, and ninety minutes after CPS. Total mucosal RNA and protein were isolated from jejunal biopsies. Expression of genes related to epithelial barrier (CLDN1, CLDN2, OCLN, ZO-1, and ZO-3), mast cell (MC) activation (TPSAB1, SERPINA1), and the glucocorticoid receptor (NR3C1) were analyzed using RT-qPCR. NR3C1, ZO-1 and OCLN protein expression were evaluated through immunohistochemistry and western blot, and mucosal inflammation through MC, lymphocyte, and eosinophil numbering. Autonomic, hormonal, and psychological responses to CPS were monitored. We found an increase in jejunal MCs, a reduced CLDN1 and OCLN expression, and an increased CLDN2 and SERPINA1 expression 90 min after CPS. We also found a significant decrease in ZO-1, OCLN, and NR3C1 gene expression, and a decrease in OCLN protein expression only in females, when compared to males. CPS induced a significant increase in blood pressure, plasma cortisol and ACTH, and subjective stress perception in all participants. Specific and independent sex-related molecular responses in epithelial barrier regulation are unraveled by acute stress in the jejunum of healthy subjects and may partially explain female predominance in IBS.Supported in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economiá y Competitividad: CM08/00229 (BL); CM10/00155 (MP); EII2011-0035, CD15/00010, and MV17-00043 (BKRJ.); FI12/00254 (ESR.), PI17/0190 (JS), PI12/00314 and PI15/00301 (CAC), CIBEREHD CB06/04/0021 (JS, CAC.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2014-018 (MF), PRED-VHIR-2016-53 34 (CPC.)

Is Routine Prophylaxis Against Pneumocystis jirovecii Needed in Liver Transplantation? A Retrospective Single-Centre Experience and Current Prophylaxis Strategies in Spain

In liver transplant (LT) recipients, Pneumocystis jirovecii pneumonia (PJP) is most frequently reported before 1992 when immunosuppressive regimens were more intense. It is uncertain whether universal PJP prophylaxis is still applicable in the contemporary LT setting. We aimed to examine the incidence of PJP in LT recipients followed at our institution where routine prophylaxis has never been practiced and to define the prophylaxis strategies currently employed among LT units in Spain. All LT performed from 1990 to October 2019 were retrospectively reviewed and Spanish LT units were queried via email to specify their current prophylaxis strategy. During the study period, 662 LT procedures were carried out on 610 patients. Five cases of PJP were identified, with only one occurring within the first 6 months. The cumulative incidence and incidence rate were 0.82% and 0.99 cases per 1000 person transplant years. All LT units responded, the majority of which provide prophylaxis (80%). Duration of prophylaxis, however, varied significantly. The low incidence of PJP in our unprophylaxed cohort, with most cases occurring beyond the usual recommended period of prophylaxis, questions a one-size-fits-all approach to PJP prophylaxis. A significant heterogeneity in prophylaxis strategies exists among Spanish LT centres.Funding: This study was supported by the Health Research Institute Marqués de Valdecilla. IDIVAL. Santander. NEXT VAL17/07 grant to José Ignacio Fortea Ormaechea

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibresDisfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosaDisfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosaIrritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.)

Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction

Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBSD. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS

A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.</p

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation