Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy

11 p.-4 fig.-4 tab.Introduction: The association between a change in proteinuria over time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure.Methods: Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure.Results: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥ 50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (HR: 0.79; 95% CI : 0.56-0.97; p < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up.Conclusion: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.This study was supported by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and PI19/1624, and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to M.P.), the Autonomous Region of Madrid (S2017/BMD-3673) (to M.P.); E.G.d.J. was supported by the Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (RYC-2013-13395 and RTI2018-095955-B-100); S.R.d.C. was supported by Ministerio de Economía y Competitividad/FEDER grant SAF2015-66287R and Autonomous Region of Madrid grant S2017/BMD3673.Peer reviewe

Preliminary crystallographic analysis of the ankyrin-repeat domain of Arabidopsis thaliana AKT1: Identification of the domain boundaries for protein crystallization

The Arabidopsis thaliana K+ transporter 1 (AKT1) participates in the maintenance of an adequate cell potassium (K+) concentration. The CBL-interacting protein kinase 23 (CIPK23) activates AKT1 for K+ uptake under low-K+ conditions. This process is mediated by the interaction between the cytosolic ankyrin-repeat (AR) domain of AKT1 and the kinase domain of CIPK23. However, the precise boundaries of the AR domain and the residues responsible for the interaction are still unknown. Here, the optimization procedure to obtain an AR domain construct suitable for crystallization and the preliminary crystallographic analysis of the obtained crystals are reported. The crystals belonged to space group P21212, with unit-cell parameters a = 34.83, b = 65.89, c = 85.44 Å, and diffracted to 1.98 Å resolution. © 2014 International Union of Crystallography All rights reserved.Peer Reviewe

Doce años después.... recuperamos el saber acumulado y elaboramos una nueva propuesta docente para los estudiantes de Tecnología educativa de la Universidad de Barcelona

En este artículo se relatan los cambios introducidos en nuestra propuesta docente de la asignatura de Tecnología Educativa en la Universidad de Barcelona y se intenta mostrar el trabajo, el conocimiento y el saber acumulado en todos estos años. El texto se divide en dos bloques. El primero, describe la propuesta actual y el recorrido realizado desde el curso 1993/94. Es una síntesis – con las limitaciones que conlleva – donde se destaca el sentido y algunos cambios significativos para las profesoras y profesores de la asignatura, en su intento de alejarse de una práctica docente de tradición reproductora, que la mayoría de las alumnas y los alumnos habían experimentado en propuestas educativas anteriores. El segundo, recoge algunas de sus voces y nos muestra como se han apropiado y han significado el trabajo realizado durante este curso 2004/05. La valoración de los alumnos y alumnas, es un mosaico de testimonios que nos permite comprender o, al menos, intuir el sentido que ha podido tener para ellas y ellos esta vivencia. Algunos de éstos son reveladores en cuanto confirman o desmienten tópicos o creencias, asumidas por el profesorado, y por mostrar elementos sutiles que quizás durante las sesiones de clase pasaron desapercibidos.In this article we describe the changes introduced in our educational proposal of the subject of Educational Technology in the University of Barcelona and we show the work and the knowledge accumulated in every year. The text is divided in two blocks. The first one, describes the current proposal and the journey carried out from the course 1993/94. It is a synthesis, where he/she stands out the sense and some significant changes for the teachers of the subject, in their intent of moving away from an educational practice of reproductional tradition that most of the students had experienced in previous educational proposals. The second, it picks up some of their voices and it shows us like they have appropriated and they have meant the work carried out during this course 2004/05. The valuation of the students, it is a mosaic of testimonies that allows us to understand this experience

The role of Food Safety Agencies in the evaluation, communication and management of risks associated with microplastics in food

A scientific report based on solid scientific data has been published by AESAN Identifying the most relevant dietary sources of microplastics, knowing the occurrence of the different molecules and polymers and their relevance in terms of exposure will contribute to focus future research projects, regulatory initiatives and monitoring programs. It is the interest of AESAN to promote research on MP and NP in the food supply and contribute to fill the identified knowledge gaps. Toxicokinetic; biomarkers of exposure; toxicity in experimental animals/models like acute toxicity, repeat dose and chronic toxicity; mode of action of the different MP and the observations in humans (Acute and Chronic effects); health based guidance values (dose response models and selection of critical reference points) Assessing the Spanish population dietary exposure to MP should be a challenge for our Food Safety experts and networking among the research groups should be promoted through our national food agencies and EFSA

Doce años después.... recuperamos el saber acumulado y elaboramos una nueva propuesta docente para los estudiantes de Tecnología Educativa de la Universidad de Barcelona

En este artículo se relatan los cambios introducidos en nuestra propuesta docente de la asignatura de Tecnología Educativa en la Universidad de Barcelona y se intenta mostrar el trabajo, el conocimiento y el saber acumulado en todos estos años. El texto se divide en dos bloques. El primero, describe la propuesta actual y el recorrido realizado desde el curso 1993/94. Es una síntesis – con las limitaciones que conlleva – donde se destaca el sentido y algunos cambios significativos para las profesoras y profesores de la asignatura, en su intento de alejarse de una práctica docente de tradición reproductora, que la mayoría de las alumnas y los alumnos habían experimentado en propuestas educativas anteriores. El segundo, recoge algunas de sus voces y nos muestra como se han apropiado y han significado el trabajo realizado durante este curso 2004/05. La valoración de los alumnos y alumnas, es un mosaico de testimonios que nos permite comprender o, al menos, intuir el sentido que ha podido tener para ellas y ellos esta vivencia. Algunos de éstos son reveladores en cuanto confirman o desmienten tópicos o creencias, asumidas por el profesorado, y por mostrar elementos sutiles que quizás durante las sesiones de clase pasaron desapercibidos

The consensus-Based approach for gene/enzyme replacement therapies and crystallization strategies: The case of human alanine-Glyoxylate aminotransferase

Protein stability is a fundamental issue in biomedical and biotechnological applications of proteins. Among these applications, gene- and enzyme-replacement strategies are promising approaches to treat inherited diseases that may benefit from protein engineering techniques, even though these beneficial effects have been largely unexplored. In the present study we apply a sequence-alignment statistics procedure (consensus-based approach) to improve the activity and stability of the human AGT (alanine-glyoxylate aminotransferase) protein, an enzyme which causes PH1 (primary hyperoxaluria type I) upon mutation. By combining only five consensus mutations, we obtain a variant (AGT-RHEAM) with largely enhanced in vitro thermal and kinetic stability, increased activity, and with no side effects on foldability and peroxisomal targeting in mammalian cells. The structure of AGT-RHEAM reveals changes at the dimer interface and improved electrostatic interactions responsible for increased kinetic stability. Consensus-based variants maintained the overall protein fold, crystallized more easily and improved the expression as soluble proteins in two different systems [AGT and CIPK24 (CBL-interacting serine/threonine-protein kinase) SOS2 (salt-overly-sensitive 2)]. Thus the consensus-based approach also emerges as a simple and generic strategy to increase the crystallization success for hard-to-get protein targets as well as to enhance protein stability and function for biomedical applications. © 2014 Biochemical Society.Peer Reviewe

Structural basis of the regulatory mechanism of the plant CIPK family of protein kinases controlling ion homeostasis and abiotic stress

10 páginas.-- 6 figuras.-- 77 referencias.-- This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1407610111/-/DCSupplementalData deposition: The atomic coordinates have been deposited in the Protein Data Bank (PDB), www.pdb.org (PDB ID codes 4CZT, 4CZU, and 4D28).© 2014, National Academy of Sciences. All rights reserved. Plant cells have developed specific protective molecular machinery against environmental stresses. The family of CBL-interacting protein kinases (CIPK) and their interacting activators, the calcium sensors calcineurin B-like (CBLs), work together to decode calcium signals elicited by stress situations. The molecular basis of biological activation of CIPKs relies on the calcium-dependent interaction of a self-inhibitory NAF motif with a particular CBL, the phosphorylation of the activation loop by upstream kinases, and the subsequent phosphorylation of the CBL by the CIPK. We present the crystal structures of the NAF-truncated and pseudophosphorylated kinase domains of CIPK23 and CIPK24/SOS2. In addition, we provide biochemical data showing that although CIPK23 is intrinsically inactive and requires an external stimulation, CIPK24/SOS2 displays basal activity. This data correlates well with the observed conformation of the respective activation loops: Although the loop of CIPK23 is folded into a well-ordered structure that blocks the active site access to substrates, the loop of CIPK24/SOS2 protrudes out of the active site and allows catalysis. These structures together with biochemical and biophysical data show that CIPK kinase activity necessarily requires the coordinated releases of the activation loop from the active site and of the NAF motif from the nucleotide-binding site. Taken all together, we postulate the basis for a conserved calcium-dependent NAF-mediated regulation of CIPKs and a variable regulation by upstream kinases.A.A. thanks Dr. Douglas Vinson Laurents for critical reading of the manuscript, and the European Syncrotron Radiation Facility (beamlines ID14-4 and ID23-2) and PETRAIII (beamline P13, BIOSTRUCTX_3100.5) for the access to the synchrotron radiation source. This work was funded by Ministerio de Economía y Competitividad Grants BFU2011-25384 and CSD2006-00015 (to A.A.), BIO2011-28184-C02-02 (toM.J.S.-B.), and BIO2012-36533 (to F.J.Q.), which was cofinanced by the European Regional Development Fund, and Comunidad de Madrid Grant S2010/BMD-2457 (to A.A.). A.C.-S. is supported by a Formación de Personal Investigador Predoctoral Fellowship, and M.J.S.-B. is supported by Ramón y Cajal Contract RYC-2008-03449 from MINECO.Peer Reviewe

Salud en red

Se describe el proyecto llevado a cabo en varios centros educativos de primaria y secundaria cuyo objetivo principal era que los alumnos adquirieran hábitos y costumbres saludables para su bienestar físico-mental y el de su entorno social. El proyecto se desarrolló sobre seis áreas temáticas: nutrición, consumo responsable y solidario, educación en igualdad de género entre hombres y mujeres, prevención del cáncer, salud y discapacidad, educación para la salud y salud medioambiental. Se detallan los objetivos de cada área, las actividades realizadas y un breve análisis de los resultados obtenidos.ExtremaduraConsejería de Sanidad y Dependencia; Calle Adriano, 4; 06800 Mérida (Badajoz); Tel. +34924004197; Fax +34924004122; [email protected]

Structural studies on the regulation of arabidopsis thaliana ion homeostasis through the cbl-cipk pathway

Resumen del Poster presentado en Environment Workshop 2013: Genomic, Physiological and Breeding Approaches for Enhancing Drought Resistance in Crops. Baeza (Spain), 23-25 September (2013)The regulation of ionic transport in plants is essential because it establishes the key physicochemical parameters for cell function. Under abiotic stress, the intracellular levels of pH, potassium (K+) and toxic cations, such as Na+, change and this affect multiple cellular systems. Consequently, the knowledge of the molecular mechanism that regulates the ionic transport is fundamental and provides opportunities to use plants to our benefit [1]. The plant cells use calcium-signaling pathways to activate certain ion channels providing the correct response to a particular stress situation. As the most abundant cation in a living plant cell, K+ is an essential ion for processes of growth, development, maintenance of turgor pressure, and plasma membrane polarization [2]. Plants living under low K+ conditions often adapt their K+ uptake through the CBL-CIPK calcium-signaling pathway, that mobilizes K+ uptake in roots [3]. Under K+ deficiency, a CBL calcium sensor activates a CIPK kinase [3] that in turn phosphorilates and activate the K+ channel. When K+ levels are restored, a phosphatase dephosphorilates and inactivates the channel (Fig. 1) [5]. We have carried out structural studies with the kinase domain and its binding partner, the interacting region of the K+ channel, to understand at molecular level how K+ uptake is regulated under stress conditions. [1] M.J. Sánchez-Barrena, M. Martínez-Ripoll, A. Albert Int. J. Mol. Sci. 2013, 14, 5734 [2] R.E. Hirsch, B.D. Lewis, E.P. Spalding, M.R. Sussman Science. 1998, 280, 127. [3] L.Li, B.G. Kim, Y.H. Cheong, G.K. Pandey, S. Luan Proc. Natl. Acad. Sci. USA, 2006,103, 12625 [4] J. Xu, H.D. Li, L.Q. Chen Y. Wnag, L.L. Liu, L. He, W.H. Wu Cell, 2006, 125, 1347. [5] S.C. Lee, W.Z. Lan, B.G. Kim, L.Li, Y.H. Cheong, G.K. Pandey, B.B. Buchanan, S. Luan Proc. Natl. Acad. Sci. USA, 2007, 40, 15959.Peer reviewe