Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Molecular Mechanisms of Acute Brain Injury and Ensuing Neurodegeneration

Injury to the central nervous system (CNS), including stroke, traumatic brain injury andspinal cord injury, cause devastating and irreversible damage and loss of function. Forexample, stroke affects very large patient populations, results in major suffering for the patients and their relatives, and involves a significant cost to society. CNS damage implies disruption of the intricate internal circuits involved in cognition, the sensory-motor functions, and other important functions. There are currently no treatments available to properly restore such lost functions. New therapeutic proposals will emerge from an understanding of the interdependence of molecular and cellular responses to CNS injury, in particular the inhibitory mechanisms that block regeneration and those that enhanceneuronal plasticity...

Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Memòria, reorganització cerebral evidenciada amb fMRI i hipocamp

Aquesta pretén ser una revisió general dels processos cognitius normals i de la capacitat de reorganització cerebral en cas de dany cerebral adquirit (lesions i malalties neurodegeneratives).

Descripción de los circuitos de declaración y notificación de enfermedades profesionales en Cataluña

Objetivos. Investigar y definir los circuitos que deben seguir lostrabajadores/pacientes para el reconocimiento de su EP por la Administración, tras ser diagnosticados por médicos del trabajo de la UPL del PSMAR.Métodos. Serie de casos en la que se ha analizado la informaciónproporcionada por 32 casos diagnosticados de EP de la base de datos de la UPL del PSMAR.Resultados. Se contactó con 32 pacientes del total de 35 casos con sospecha firme de EP. De ellos, 26 se encontraban laboralmente en activo, de los cuales 5 no iniciaron el proceso de reconocimiento de EP. De los 6 pacientes que no estaban laboralmente en activo, dos no iniciaron el proceso de reconocimiento de EP. De los casos analizados, los cánceres supusieron el 15,6% (n=5), grupo donde se han reconocido el mayor número EP (12,5%, n=4). El grupodiagnóstico de hipoacusia/sordera fue el más numeroso (n= 15), en el cual se ha reconocido como EP el 9,4%. En este grupo se encuentra el mayor número de pacientes que no han iniciado el procedimiento (15,6%). El grupo de pacientes con problemas osteomusculares es el que cuenta con la mayoría de casos pendientes de resolución (21,9%).Conclusiones. La figura de un abogado en el procedimiento, ha facilitado favorablemente el reconocimiento de EP del trabajador/paciente. Los casos precisan de mayor información en los trámites e instancias a las que deben de acudir para el reconocimiento de su EP.

Differences in the evolutionary history of disease genes affected by dominant or recessive mutations

Background: Global analyses of human disease genes by computational methods have yielded important advances in the understanding of human diseases. Generally these studies have treated the group of disease genes uniformly, thus ignoring the type of disease-causing mutations (dominant or recessive). In this report we present a comprehensive study of the evolutionary history of autosomal disease genes separated by mode of inheritance.Results: We examine differences in protein and coding sequence conservation between dominant and recessive human disease genes. Our analysis shows that disease genes affected by dominant mutations are more conserved than those affected by recessive mutations. This could be a consequence of the fact that recessive mutations remain hidden from selection while heterozygous. Furthermore, we employ functional annotation analysis and investigations into disease severity to support this hypothesis. Conclusion: This study elucidates important differences between dominantly- and recessively-acting disease genes in terms of protein and DNA sequence conservation, paralogy and essentiality. We propose that the division of disease genes by mode of inheritance will enhance both understanding of the disease process and prediction of candidate disease genes in the future.

Aberrant repair and fibrosis development in skeletal muscle

The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.

Group motivational intervention in overweight/obese patients in primary prevention of cardiovascular disease in the primary healthcare area

Background The global mortality caused by cardiovascular disease increases with weight. The Framingham study showed that obesity is a cardiovascular risk factor independent of other risks such as type 2 diabetes mellitus, dyslipidemia and smoking. Moreover, the main problem in the management of weight-loss is its maintenance, if it is achieved. We have designed a study to determine whether a group motivational intervention, together with current clinical practice, is more efficient than the latter alone in the treatment of overweight and obesity, for initial weight loss and essentially to achieve maintenance of the weight achieved; and, secondly, to know if this intervention is more effective for reducing cardiovascular risk factors associated with overweight and obesity. Methods This 26-month follow up multi-centre trial, will include 1200 overweight/obese patients. Random assignment of the intervention by Basic Health Areas (BHA): two geographically separate groups have been created, one of which receives group motivational intervention (group intervention), delivered by a nurse trained by an expert phsychologist, in 32 group sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard program of diet, exercise, and the other (control group), receiving the usual follow up, with regular visits every 3 months. Discussion By addressing currently unanswered questions regarding the maintenance in weight loss in obesity/overweight, upon the expected completion of participant follow-up in 2012, the IMOAP trial should document, for the first time, the benefits of a motivational intervention as a treatment tool of weight loss in a primary care setting.

Actualización en los tratamientos alternativos en el síndrome de dolor-disfunción craneomandibular

Realizamos una revisión bibliográfica sobre los diferentes tipos de tratamiento alternativo en aquellos casos en los que fracasa la terapia convencional en el síndrome de dolor-disfunción craneomandibular y en los cuales la cirugía no sea la terapia de elección; haciendo una clasificación actualizada de los mismos, siendo estos: terapia psíquica (terapia de relajación muscular y control y manejo del estrés), terapia física realizada por el propio paciente y asistida por un fisioterapeuta, terapia mecánica (biofeedback electromiográfico, TENS, ionoforesis, ultrasonidos y láser blando) y terapia farmacológica.

Evolutionary analysis of genetic variants involved in rare diseases

Next-generation sequencing techniques such as exome sequencing can successfully detect all genetic variants in a human exome and it has been useful together with the implementation of variant filters to identify causing-disease mutations. Two filters aremainly used for the mutations identification: low allele frequency and the computational annotation of the genetic variant. Bioinformatic tools to predict the effect of a givenvariant may have errors due to the existing bias in databases and sometimes show a limited coincidence among them. Advances in functional and comparative genomics are needed in order to properly annotate these variants.The goal of this study is to: first, functionally annotate Common Variable Immunodeficiency disease (CVID) variants with the available bioinformatic methods in order to assess the reliability of these strategies. Sencondly, as the development of new methods to reduce the number of candidate genetic variants is an active and necessary field of research, we are exploring the utility of gene function information at organism level as a filter for rare disease genes identification. Recently, it has been proposed that only 10-15% of human genes are essential and therefore we would expect that severe rare diseases are mostly caused by mutations on them. Our goal is to determine whether or not these rare and severe diseases are caused by deleterious mutations in these essential genes. If this hypothesis were true, taking into account essential genes as a filter would be an interesting parameter to identify causingdisease mutations.

Comprender la experiencia de la mujer ingresada con pre-eclampsia y eclampsia

Introducción: La preeclampsia/eclampsia es una enfermedad del embarazo que puede producir cambios en el estado emocional de la mujer por su prolongado ingreso hospitalario. Objetivo: Conocer las experiencias vividas por las mujeres con preeclampsia/eclampsia durante el ingreso hospitalario. Los objetivos que se tendrán en cuenta serán conocer cómo se modifica el rol propio dentro de la organización familiar, conocer cómo impacta su ingreso respecto a suestado emocional, conocer cómo les afecta la estructura de la unidad a su estado emocional y conocer qué necesidades y/o cuidados terapéuticos reciben respeto al equipo sanitario. Ámbito: El estudio se realizará en el Hospital de la Vall d’ Hebrón de Barcelona. Metodología: Estudio fenomenológico. La muestra se escogerá intencionadamente que cumplirá con los criterios de inclusión (mujeres ingresadas por preeclampsia/eclampsia en launidad de materno infantil de la Vall d’ Hebrón de Barcelona), y se terminará hasta llegar al nivel de saturación teórico. Los datos se recogerán a través de entrevistas semi-estructuradas y de la observación participante. Consideraciones finales: Dada la baja incidencia que existe tanto a nivel nacional como internacional en estudios de este tipo, un estudio cualitativo que ayude a conocer las experiencias de las mujeres ingresadas por preeclampsia podría ayudar a mejorar la calidad y práctica asistencial enfermera.

Pycnodysostosis. A report of 3 clinical cases

Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. It is a genetic disorder, usually diagnosed at an early age. However, the diagnosis is sometimes late, made as a result of bone fracture, given the severe bone fragility resulting from increased bone density. Oral and maxillofacial manifestations of this disease are very clear. The head is usually large, the nose beaked, the mandibular angle obtuse, and both maxilla and mandible hypoplastic. Dental abnormalities and impaction are observed, as well as alterations in eruption and frequent dental crowding. The differential diagnosis is established with osteopetrosis, cleidocranial dysplasia and idiopathic acro-osteolysis. This article reviews the clinical and radiographic characteristics of pycnodysostosis based on three clinical cases of patients with this disease.

Adverse side effects of statins in the oral cavity

Increased plasma levels of cholesterol are high risk factors of cardiovascular disease. Statins are drugs that inhibit cholesterol synthesis at both pancreatic and extrahepathic levels, being the treatment of choice for hypercholesterolemia. Objective: To analyze the side effects of statins in the mouth cavity, and to analyze the symptoms after interruption of the treatment. Design: Observational study, preliminary. Material and methods: Patients aged 50-70, diagnosed with hypercholesterolemia and undergoing treatment with statins, referred from their primary care physician to the dentist"s office. Anamnesis over oral symptoms was performed in the first visit. Statin treatment was discontinued, followed by lab tests and control visits seven and fifteen days later. We monitored the improvement and/or remission of oral symptoms. Statin treatment was resumed, sending out a report of the patient evolution to the PCP. Symptoms were registered in sheet specially designed for the study. Exclusion criteria: patient refusal, use of drugs for dry mouth treatment, Sjögren"s syndrome. Results: n=26 patients. Dry mouth patients: improvement in 17 out of 23 patients (88.5%). Itchiness: 6 out of 15 cases improved (57.7%). Bitterness: improvement in 13 out of 14 patients (53.8%). Cough: improvement in 11 out of 12 patients (46.1%). Discussion: A high percentage of oral symptoms are associated to treatment with statins. There is a marked improvement after temporary interruption of the treatment. Little is known regarding the side effects of oral treatment with statins. This preliminary study includes a relatively small number of patients. The design of experimental treatments will be required to establish a true correlation between statin treatment and oral symptoms

Comparació entre dos mètodes d'estiraments ; estàtic i dinàmic, realitzats en l'escalfament de curses i entrenaments de 60, 100 i 110 metres tanques

Aquest estudi es basa en l'idea de que l'escurçament de la cadena musuclar posterior és una causa important del mal d'esquena en nens. És per aquest motiu que es planteja un tractament per a prevenir l'escurçament de la cadena muscular posterior i el mal d'esquena en forma de sessions de Stretching Global Actiu, mètode basat en la Reeducació Postural Global del mateix Ph.E. Souchard, que es posarà en pràctica en 3 escoles diferents de la comarca d'Osona. L'estudi té una durada de 3 cursos escolars (3r, 4t i 5è de primària) en el qual els nens seleccionats per al grup experimental (n=30) realitzaran classes de Stretching Global Actiu dues vegades a la setmana durant 3 mesos en cada curs escolar. Tres escoles més formaran el grup control (n=30) i s'espera que els nens que formen part del grup experimental millorin la flexibilitat de la cadena musuclar posterior (això es podrà observar a través dels resultats del test "sit and reach") i que no presentin mal d'esquena en el transcurs de 3 anys (durada de l'estudi).

Eficàcia de la teràpia amb aigua de mar isitònica nebulitzada en pacients amb MPOC. Beneficis respecte a l'ús del sèrum fisiològic convencional

Objectius: Establir l’eficàcia del tractament, en quant a la millora de la qualitat de vida relacionada amb la salut (CVRS) que podem obtenir, efectuant nebulitzacions amb aigua de mar isotònica versus el sèrum fisiològic, en pacients crònics respiratoris amb MPOC. Secundàriament vol determinar si hi ha una millora subjectiva de la tolerància a l’exercici físic, una reducció significativa dels símptomes, de les aguditzacions amb els conseqüents ingressos hospitalaris i una reducció de la despesa farmacèutica. - Metodologia: Assaig clínic aleatoritzat a doble cec sobre 3 grups (aigua de mar, sèrum fisiològic i placebo) de 60 pacients d’atenció primària diagnosticats de MPOC moderada segons els criteris GOLD que hagin superat els criteris d’inclusió i exclusió. Les teràpies s’autoadministraran al propi domicili. Els resultats seran avaluats mitjançant els següents instruments: el CRQ (Chronic Respiratory Questionnaire), l’escala de dispnea del British Medical Research Council (MRC), la prova de la marxa de 6 minuts, espirometria, analítica, gasometria arterial i pulsioximetria. - Limitacions de l’estudi: Manca de participació, incompliment terapèutic, abandonament de l’hàbit tabàquic durant el tractament i pèrdues per temporalitat.