Las cláusulas “claims made”: ¿¿¿fin de la polémica???

Las conocidas como cláusulas de 'delimitación temporal de cobertura' –'Claims Made'– han sido objeto de distinto tratamiento por parte de la doctrina y de la jurisprudencia a lo largo de los años, ocasionando graves problemas en la práctica aseguradora. Una primera interpretación las consideró lesivas por ser desfavorables al asegurado, parte débil del contrato, y, por tanto, nulas. Ante las necesidades y presiones del mercado asegurador de RC, una reforma legislativa las incorporó al artículo 73 de la LCS, calificándolas como cláusulas 'limitativas' de los derechos de asegurado, condicionando su validez al cumplimiento de los requisitos establecidos en el art.3 de esta misma Ley. Mejor solución hubiese sido reconocer su función de delimitación del riesgo concertado en el contrato como venía sosteniendo una parte importante de la doctrina. El Proyecto de Código Mercantil elimina la calificación de 'limitativas', aunque no las define como 'delimitadoras'

Hacia un modelo de toma de decisiones compartida para el final de la vida

Decision making is a task all human beings have to face up to daily. The underlying basis for this practice is formed and marked by former experiences, every day applied or even automatized models that are never questioned. In the clinical setting, however, a critical reflexion is necessary when deciding procedures and criterias for making decisions, requiring analysis and effective and agile decisions. In our view, a highly interesting approach to tackle decisions in the ambit of the end-of-life is the Shared Decision-Making. In this paper we intend, at first, to conceptualize the most relevant variables according to that model, and then to propose a protocol to act as a facilitating tool for making difficult decisions to which the patients and their families may be exposed to.La toma de decisiones es una práctica diaria de todos los seres humanos. En dicha práctica los criterios que se utilizan se conforman en base a experiencias pasadas, modelos cotidianos o incluso inercias nunca cuestionadas. En el ámbito clínico, sin embargo, debe exigirse un quehacer crítico a la hora de discernir los procedimientos y criterios óptimos para la toma de decisiones, requiriéndose análisis y juicios efectivos y ágiles. A nuestro entender, un planteamiento altamente interesante para abordar decisiones en el ámbito del final de la vida es el de Toma de Decisiones Compartidas (TDC). En el presente texto se pretende, en un primer momento, conceptualizar las variables consideradas más relevantes en dicho modelo, para proponer posteriormente un protocolo que actúe como herramienta facilitadora de la toma de decisiones complicadas a las que pueden verse expuestos los pacientes y sus familiares

Isolation and identification by high resolution liquid chromatography tandem mass spectrometry of novel peptides with multifunctional lipid-lowering capacity

This work describes the isolation, characterization, and identification by RP-HPLC-ESI-Q-TOF of novel peptides that interfere in the fat digestion and absorption mechanisms by multiple pathways. Peptides were ultrafiltrated and peptides in the most active fraction were further separated by semipreparative RP-HPLC. Nine different subfractions were obtained observing a high amount of peptides in subfraction F3. Peptides in subfraction F3 could simultaneously reduce the solubility of cholesterol in micelles and inhibit pancreatic cholesterol esterase and pancreatic lipase, even after a simulated gastrointestinal digestion. The identification of lipid-lowering peptides has been scarcely performed and when done, low selectivity or sensitivity of employed identification techniques or conditions did not yield reliable results. Separation and detection of peptides by RP-HPLC-ESI-Q-TOF-MS was optimized and most favorable conditions were employed for the identification of peptides using de novo sequencing. Ten different peptides with 4-9 amino acids were identified. Main feature of identified peptides was the high acidity derived from a high presence of amino acids glutamic acid and aspartic acid in their sequences

Evaluation of the relationship between the peptide profile and the lipid-lowering properties of olive seeds hydrolysates as a tool for tunning hypocholesterolemic functionality

Olive processing generates large amounts of stones with high protein contents. Previous studies have demonstrated that Manzanilla variety olive seed proteins release peptides with lipid-lowering capacity. However, no work has demonstrated their roles in the overall hypolipidemic activity. Moreover, further studies using different olive varieties are required to propose a solid method for the exploitation of olive seeds. Twenty different olive varieties were employed in this work. Proteins were extracted using high-intensity focused ultrasound and digested with Alcalase. The released peptides were identified using proteomic techniques, and their capabilities to reduce the absorption of dietary cholesterol (by inhibiting cholesterol esterase enzyme, binding bile acids, and reducing micellar cholesterol solubility) or the biosynthesis of endogenous cholesterol were evaluated. Peptides with different lipid lowering capacities were obtained from all varieties although the genotype significantly affected the hypolipidemic characteristics. Univariate and multivariate statistical analyses showed strong correlations, positive and negative, between the presence of certain peptides in the hydrolysates and their capacity to reduce exogenous cholesterol absorption and endogenous cholesterol synthesis. Therefore, the selection of the olive seed genotype can direct its lipid-lowering properties,e.g., by promoting the reduction of dietary cholesterol absorption or the inhibition of cholesterol biosynthesis

Identification of Peptides Potentially Responsible for In Vivo Hypolipidemic Activity of a Hydrolysate from Olive Seeds

Previous studies demonstrated that peptides produced by the hydrolysis of olive seed proteins using Alcalase enzyme showed in vitro multifunctional lipid-lowering capability. This work presents a deeper insight into the hypolipidemic effect of olive seed peptides. The capability of olive seed peptides to inhibit endogenous cholesterol biosynthesis through the inhibition of HMGCoA reductase enzyme was evaluated observing a 38 ± 7% of inhibition. Two in vivo assays using different peptides concentrations (200 and 400 mg/kg/day) were designed to evaluate the hypolipidemic effect of olive seed peptides in male and female mice. A low concentration of hydrolysate reduced total cholesterol in male mice in a 20% after 11 weeks compared to the mice feeding with hypercholesterolemic diet. A higher hydrolysate concentration showed a greater reduction in total cholesterol (25%). The analysis of the olive seed hydrolysate by reverse phase high-performance liquid chromatography mass spectrometry (RP-HPLC-MS) enabled the identification of peptides that could be responsible for this hypolipidemic effect

Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer

Current chemotherapy for colorectal cancer (CRC) includes the use of oxaliplatin (Oxa), a first-line cytotoxic drug which, in combination with irinotecan/5-fluorouracil or biologic agents, increases the survival rate of patients. However, the administration of this drug induces side effects that limit its application in patients, making it necessary to develop new tools for targeted chemotherapy. MamC-mediated biomimetic magnetic nanoparticles coupled with Oxa (Oxa-BMNPs) have been previously demonstrated to efficiently reduce the IC50 compared to that of soluble Oxa. However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation. In this scenario, a further improvement of this nanoassembly was necessary. In the present study, Oxa-BMNPs nanoassemblies were enveloped in phosphatidylcholine unilamellar liposomes (both pegylated and non-pegylated). Our results demonstrate that the addition of both a lipid cover and further pegylation improves the biocompatibility and cellular uptake of the Oxa-BMNPs nanoassemblies without significantly reducing their cytotoxic activity in colon cancer cells. In particular, with the pegylated magnetoliposome nanoformulation (a) hemolysis was reduced from 5% to 2%, being now hematocompatibles, (b) red blood cell agglutination was reduced, (c) toxicity in white blood cells was eliminated. This study represents a truly stepforward in this area as describes the production of one of the very few existing nanoformulations that could be used for a local chemotherapy to treat CRC.Ministerio de Economia y Competitividad from Spain CGL2016-76723European Union (EU) CGL2016-76723Junta de Andalucia A-BIO-376-UGR18Unidad Cientifica de Excelencia of the University of Granada UCE-PP2016-05Junta de Andalucia PI-0102-2017Instituto de Salud Carlos III European Union (EU) PI19/01478Andalusian Government CTS-107Ministerio de Educacion, Ciencia y Deporte y Competitividad (Spain) FPU16_04580 FPU16_0171

Magnetic nanoparticles coated with carboxylate-terminated carbosilane dendrons as a reusable and green approach to extract/purify proteins

Extraction/purification of proteins, at both analytical and industrial levels, is a limiting step that usually requires the use of organic solvents and involves tedious work and a high cost. This work proposes a more sustainable alternative based on the use of magnetic nanoparticles (MNPs) coated with carboxylate-terminated carbosilane dendrons. MNPs coated with first- and second-generation carbosilane dendrons and bare MNPs were employed for the extraction of proteins with different molecular weights and charges. Interaction of proteins with MNPs significantly varied with the pH, the protein, and the dendron generation (different sizes and number of charges in the periphery). Optimal dendron:protein molar ratios and suitable conditions for disrupting interactions after protein extraction were also researched. Second-generation dendron-coated MNPs showed 100% retention capability for all proteins when using acidic conditions. They were reused without losing magnetism or interaction capacity after a disruption of protein-dendron interactions with 0.2% SDS at 100 degrees C for 10 min. The capacity of dendron-coated MNPs was successfully applied to the recovery/purification of proteins from two food byproducts, olive seeds and cheese whey

Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study

Conventional chemotherapy against colorectal cancer (CRC), the third most common cancer in the world, includes oxaliplatin (Oxa) which induces serious unwanted side effects that limit the efficiency of treatment. Therefore, alternative therapeutic approaches are urgently required. In this work, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC were coupled to Oxa to evaluate the potential of the Oxa–BMNP nanoassembly for directed local delivery of the drug as a proof of concept for the future development of targeted chemotherapy against CRC. Electrostatic interactions between Oxa and BMNPs trigger the formation of the nanoassembly and keep it stable at physiological pH. When the BMNPs become neutral at acidic pH values, the Oxa is released, and such a release is greatly potentiated by hyperthermia. The coupling of the drug with the BMNPs improves its toxicity to even higher levels than the soluble drug, probably because of the fast internalization of the nanoassembly by tumor cells through endocytosis. In addition, the BMNPs are cytocompatible and non-hemolytic, providing positive feedback as a proof of concept for the nanoassembly. Our study clearly demonstrates the applicability of Oxa–BMNP in colon cancer and offers a promising nanoassembly for targeted chemotherapy against this type of tumor.This work was also supported by the Consejería de Salud de la Junta de Andalucía (projects PI-0476-2016 and PI-0102-2017). Y.J. and B.G.-P. acknowledge FPU2016 grants (FPU16_04580 and FPU16_01716, respectively) from the Ministerio de Educación, Ciencia, y Deporte y Competitividad (Spain)

How are the ancient cystic fibrosis patients?: Cystic fibrosis diagnosed over 60 years-old

Background and aims To specify the prevalence of patients diagnosed with CF at age of ≥60 year-old and to analyze their characteristics. Patients and methods Observational study of CF patients which were diagnosed at age ≥60 year-old. The analyzed variables were: age, sex, nationality, lung function parameters, conditions present at diagnosis, microbiological characteristics and genetic findings. Results eight patients were included. 7 patients were female (87.5%) with a mean age of 70.6 years (median 71.5 years, range 60–78 years). The most important findings were: sweat test > 60 mEq/l; heterozygotes F508del; bronchiectasis in CT; methicillin-sensitive Staphylococcus aureus (50%) in sputum. The most patients presented a normal or mild obstructive lung function. Conclusions CF must also be considered a disease diagnosed in adulthood, incorporating the sweat test within the usual techniques of differential diagnosis in patients with different diseases associated with CF, because genetic counselling is esencial