Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia

Supplementary Materials: Supplementary Materials can be found at https://www.mdpi.com/1422 -0067/22/6/2990/s1.The project was approved by the Biomedical Research Ethics Committee of the Andalusian Public Health System in Granada, Spain on Oct. 29, 2015, (project identification code AP163052016). Data recording, sample collection and all in vitro experiments were conducted in accordance with ethical guidelines following the Nuremberg Code, Belmont Report, and the Declaration of Helsinki.Acknowledgments: We are grateful for the support and cooperation of the subjects, as well as their families.Ataxia in children is a common clinical sign of numerous neurological disorders consisting of impaired coordination of voluntary muscle movement. Its most common form, cerebellar ataxia, describes a heterogeneous array of neurologic conditions with uncountable causes broadly divided as acquired or genetic. Numerous genetic disorders are associated with chronic progressive ataxia, which complicates clinical management, particularly on the diagnostic stage. Advances in omics technologies enable improvements in clinical practice and research, so we proposed a multi-omics approach to aid in the genetic diagnosis and molecular elucidation of an undiagnosed infantile condition of chronic progressive cerebellar ataxia. Using whole-exome sequencing, RNA-seq, and untargeted metabolomics, we identified three clinically relevant mutations (rs141471029, rs191582628 and rs398124292) and an altered metabolic profile in our patient. Two POLR1C diagnostic variants already classified as pathogenic were found, and a diagnosis of hypomyelinating leukodystrophy was achieved. A mutation on the MMACHC gene, known to be associated with methylmalonic aciduria and homocystinuria cblC type, was also found. Additionally, preliminary metabolome analysis revealed alterations in our patient’s amino acid, fatty acid and carbohydrate metabolism. Our findings provided a definitive genetic diagnosis reinforcing the association between POLR1C mutations and hypomyelinating leukodystrophy and highlighted the relevance of multi-omics approaches to the disease.Fundación Mutua Madrileña, Spain XIII Call on Research Grants 2016, reference number AP16305201

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

Modulación por las distintas fuentes grasas de la dieta (aceites de oliva, girasol y pescado) de la apoptosis inducida por la Adriamicina: papel de la mitocondria

Incluye Resumen y Conclusiones en inglésTesis Univ. Granada. Departamento de Fisiología. Leída el 30 de enero de 200

Study needs of academic and professional guidance, Tutorial Action Plan BIOrienta2

Farmacia es la Licenciatura que ofrece una mejor formación curricular para aquellos profesionales que quieren desarrollarse en el campo de la Biomedicina. No existe ninguna otra Licenciatura que aúne conocimientos tan amplios en Ciencias de la Salud, Química, Microbiología, Parasitología, Biología Molecular y Biotecnología, y que aborde la enseñanza de los aspectos relacionados con el medicamento y las alteraciones fisio/patológicas a un nivel molecular como es la Licenciatura de Farmacia. Para valorar el conocimiento de los alumnos de esta Licenciatura en las diversas salidas profesionales en el área de Biomedicina, hemos realizado un estudio de las necesidades de los mismos basado en encuestas de opinión. Este trabajo ha puesto de manifiesto la necesidad de crear un Plan de Orientación Tutorial (PAT) enfocado a orientarlos sobre salidas profesionales en el área de Biomedicina, de tal manera que se cubran las principales carencias puestas de manifiesto: Motivación: si comprenden la utilidad de la Licenciatura en su futuro profesional se animarán más a trabajar. Orientación: Fundamentalmente en la elección de asignaturas e itinerarios profesionales relacionados con la Biomedicina. Información: Mediante charlas y conferencias en las que profesionales del área de la Biomedicina de entes públicos y privados los orienten sobre las carreras de investigador en ambos ámbitos. Nuestra experiencia como profesores e investigadores nos indica que aquellos alumnos que durante sus estudios de Licenciatura se vinculan a un Departamento como alumnos internos o al menos muestran algún interés por la investigación, no sólo se orientan profesionalmente mejor sino que aumentan su rendimiento académico significativamente. Este hecho justifica por sí solo la puesta en marcha del PAT.The Degree of Pharmacy offers the best instruction for those professionals that want to specialise in the field of Biomedicine. It doesn't exist any other Degree offering to the students so wide knowledge in Health Sciences, Chemistry, Microbiology, Parasitology, Molecular Biology and Biotechnology that deals with all the aspects related with drugs and physio/phatological alterations at a molecular level. We have carried out a study of the students’ requirements based on opinion surveys at the Granada University. This work has shown the necessity to create a PAT focused on the orientation of the students in their professional development in the area of Biomedicine, in such a way that the following needs are covered: Motivation: The understanding of the usefulness of the Degree in their professional future will encourage them to work more intensively. Orientation: Mainly in the election of subjects and professional itineraries related with the Biomedicine. Information: Professionals of Biomedicine from both public institutions and private companies will show them the different aspects of the research in both type institutions by means of chats and conferences. Our experience as professors and researchers shows that those students that are linked to a Department during their Degree or that show some interest for the research, significantly increase both their academic and professional performance. This fact justifies the initiation of the PAT

BIOrienta2: orientación a futuros farmacéuticos. La Investigación en biomedicina como carrera profesional

El Grado de Farmacia ofrece una formación idónea para personas que enfoquen su carrera profesional como investigadores en el área de Biomedicina. Ninguna otra formación de Pregrado aúna conocimientos tan amplios en Microbiología, Parasitología, Química, Biología Molecular y Biotecnología así como en aspectos relacionados con el mecanismo de acción de fármacos y con alteracions fisio/patológicas a nivel molecular. Por ello, nos hemos planteado realizar un Plan de Acción Tutorial enfocado a formar alumnos desde sus etapas iniciales en la investigación en Biomedicina: elección de su trayectoria curricular, requisitos para realizar una carrera científica y oportunidades de formación en esta áre