New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49)

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Z(max) = 3.43; theta = 0.00; P < 3.53 x 10(-5)). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients' fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions. Corral-Juan et al. describe a novel dominantly inherited spinocerebellar ataxia subtype, SCA49, caused by SAMD9L mutation characterized by polyneuropathy, distinctive cerebral demyelination with gaze-evoked nystagmus and hyperreflexia as initial clinical signs. The study demonstrates the mitochondrial location of human SAMD9L protein triggering mitochondrial and lysosomal alterations

Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers

Objective: In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). Methods: A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD. Results: Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. Conclusions: Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD

Evaluacion de riesgo en matadero de ovino en la Comunidad Valenciana

En el siguiente Trabajo de fin de máster nos hemos centrado en la evaluación de riesgos laborales de un matadero industrial de ovino situado en la Comunidad Valenciana. No se aportan nombres ni datos oficiales de la empresa con el fin de dar cumplimiento a Ley Orgánica 3/2018, de 5 de diciembre, de Protección de Datos Personales y garantía de los derechos digitales

Utilidad en enfermería de diferentes índices antropométricos y analíticos para valorar la existencia de síndrome metabólico con los criterios NCEP ATPIII e IDF en población mediterránea española

Introduction: Metabolic syndrome (MS) is a set of metabolic disorders related to lifestyle, genetic and environmental factors that increase the risk of cardiovascular disease. Objective: Determine the usefulness of different indices related to cardiovascular risk in predicting MS. Materials and methods: Cross-sectional study in 61283 workers in the Mediterranean area. The indices studied are: body mass index, ponderal index, waist to height ratio, waist to hip ratio, abdominal volume index, body adiposity index, visceral adiposity index, body shape index, body roundness index, conicity index, cholindex, lipid accumulation product and atherogenic indices. The MS is determined by the NCEP ATP III and IDF criteria. ROC curves and cutoff points of each of the indices that best predict SM are determined. Results: The indices that best predict the MS with the NCEP ATP III criteria are the atherogenic index triglycerides / HDL, visceral adiposity index and lipid accumulation product, whereas if we use the IDF criteria the best results are obtained with body roundness index, waist to height ratio, abdominal volume index and lipid accumulation product. The worst results are obtained with the body shape index. Conclusions: The analyzed indices are useful in predicting the onset of MS and could be an alternative to calculate MS. Being easy to get and cheap they are especially useful in the primary care levels.Introducción: El síndrome metabólico (SM) es un conjunto de alteraciones metabólicas relacionadas con el estilo de vida, factores genéticos y ambientales que aumentan el riesgo padecer una enfermedad cardiovascular. Objetivos: Determinar la utilidad de diferentes índices relacionados con el riesgo cardiovascular en la predicción de SM. Material y métodos: Estudio descriptivo transversal en 61283 trabajadores del área mediterránea. Los índices estudiados son: índice de masa corporal, índice ponderal, índice cintura/altura, índice cintura/cadera, índice de volumen abdominal, índice de adiposidad corporal, índice de adiposidad visceral, índice de forma del cuerpo, índice de redondez del cuerpo, índice de conicidad, cholindex, producto de acumulación de lípidos e índices aterogénicos. El SM se determina con los criterios NCEP ATP III e IDF. Se determinan las curvas ROC y los puntos de corte de cada uno de los índices que mejor predicen el SM. Resultados: Los índices que mejor predicen el SM con los criterios NCEP ATPIII son el índice aterogénico triglicéridos/HDL, índice de adiposidad visceral y producto de acumulación de lípidos, mientras que si empleamos los criterios IDF los mejores resultados se obtienen con índice de redondez del cuerpo, índice cintura altura, índice de volumen abdominal y producto de acumulación de lípidos. Los peores resultados se obtienen con el índice de forma del cuerpo. Conclusiones: Los índices analizados son útiles para predecir la aparición de SM y podrían ser una alternativa para calcular SM. Al ser fáciles de obtener y baratos son especialmente útiles en los niveles asistenciales primarios