Caracterización clínica genética de pacientes con ataxias hereditarias en el estado de Portuguesa- Venezuela

Introduction: hereditary ataxias are neurodegenerative diseases that cause functional deterioration. As a consequence of their progressive nature, they lead to disability in affected individuals with severe psychological damage in their families. Objective: to characterize clinically and genetically the patients with hereditary ataxias in the Portuguese-Venezuela state in the period 2013-2015. Methods: an observational, descriptive cross-sectional study was carried out in patients with a diagnosis of hereditary ataxia. The universe consisted of 33 patients diagnosed in the study period, we worked with all of them. The individual and family health histories were reviewed. The data obtained were processed using the SPSS statistical program. Results: there was a predominance of the age group 25-29 years (18.18%) and the male sex (51.5%); as well as adult autosomal dominant spinocerebellar ataxias (SCA1 and SCA2) (82%). Stage 3 disease patients were the most prevalent (40%). The autosomal dominant type of inheritance predominated (69%) and the paternal inheritance path (63%). Conclusions: community genetics and genetic counseling contributed with therapeutic alternatives to improve the quality of life. In addition, the populations at risk were identified to outline preventive actions and reduce the recurrence of hereditary conditions.Introducción: las ataxias hereditarias son enfermedades neurodegenerativas que provocan deterioro funcional. Como consecuencia de su carácter progresivo conllevan a la discapacidad en los individuos afectados con una severa afectación psicológica en sus familias. Objetivo: caracterizar clínico y genéticamente los pacientes con ataxias hereditarias en el estado Portuguesa- Venezuela en el periodo 2013-2015. Métodos: se realizó un estudio observacional, descriptivo de corte transversal en pacientes con diagnóstico de ataxia hereditaria. El universo estuvo constituido por 33 pacientes diagnosticados en el periodo de estudio, se trabajó con todos ellos. Se realizó la revisión de las historias de salud individual y familiar. Los datos obtenidos fueron procesados mediante programa estadístico SPSS. Resultados: existió predominio del grupo de edad de 25-29 años (18.18 %) y del sexo masculino (51.5%); así como de las ataxias espinocerebelosas autosómicas dominantes del adulto (SCA1 y la SCA2) (82 %). Los pacientes en etapa 3 de la enfermedad fueron los más predominantes (40 %). Predominó el tipo de herencia autosómica dominante (69 %) y la vía de herencia paterna (63 %). Conclusiones: la genética comunitaria y el asesoramiento genético contribuyeron con alternativas terapéuticas para mejorar la calidad de vida. Además, quedaron identificadas las poblaciones de riesgo para trazar acciones preventivas y reducir la recurrencia de las afecciones hereditarias

Size effects in the magnetic behaviour of TbAl_2 milled alloys

The study of the magnetic properties depending upon mechanical milling of the ferromagnetic polycrystalline TbAl_2 material is reported. The Rietveld analysis of the X-ray diffraction data reveals a decrease of the grain size down to 14 nm and -0.15 % of variation of the lattice parameter, after 300 hours of milling time. Irreversibility in the zero field cooled - field cooled (ZFC-FC) DC-susceptibility and clear peaks in the AC susceptibility between 5 and 300 K show that the long-range ferromagnetic structure is inhibited in favour of a disordered spin arrangement below 45 K. This glassy behaviour is also deduced from the variation of the irreversibility transition with the field (H^{2/3}) and frequency. The magnetization process of the bulk TbAl_2 is governed by domain wall thermal activation processes. By contrast, in the milled samples, cluster-glass properties arise as a result of cooperative interactions due to the substitutional disorder. The interactions are also influenced by the nanograin structure of the milled alloys, showing a variation of coercivity with the grain size, below the crossover between the multi- and single-domain behaviours.Comment: 23 pages, 11 figures, to appear in J. Phys.: Condens. Ma

Epigenetic control of the EWS-FLI1 promoter in Ewing's sarcoma

Q2Q1Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra-osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS-FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS-FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS-FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS-FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS-FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS-FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.N/

Cytotoxicity effects of metal oxide nanoparticles in human tumor cell lines

Metallic and metal oxide nanoparticles (Nps) have a wide range of applications in various settings including household, cosmetics and chemical industries, as well as for coatings. Nevertheless, an in-depth study of the potential toxic effects of these Nps is still needed, in order to fulfill the mandatory requirement of ensuring the safety of workers, patients and the general public. In this study, Quick Cell colorimetric assays were used to evaluate the in vitro toxicity of different metal oxide Nps [Fe(II,III)Ox, TiOx, ZnO and CeO2] in several cell lines. The ZnO Nps were found to be highly toxic, with a lethal dose ≥100 μg/ml for all the cell lines studied. Western blot was also used to test the ability of the different Nps to activate the complement pathway. However, no activation of this cascade was observed when the Nps were added. In addition, the aggregation state and charge of the Nps in culture media was studied by dynamic light scattering (DLS) and measurement of zeta potential. Transmission Electron Microscopy was used to analyze Np uptake and localization at the cellular level

Magnetic and microstructural analysis of palladium nanoparticles with different capping systems

Palladium nanoparticles capped with different protective systems in a size range between 1.2 and 2.4 nm have been obtained by varying the preparation chemical method. Magnetization curves for all the samples show hysteresis loops, evidencing a ferromagnetic or a permanent magnetism in the nanoparticles. The microstructure of the nanoparticles has been analyzed by x-ray absorption and transmission electron microscopy. The nature of the magnetic behavior found for all these Pd nanoparticles (NPs) is different depending on their sizes and structural features and is explained on the basis of two different suggested mechanisms. The particles protected by means of a surfactant (tetralkylammonium salts), present a ferromagnetic order related to the factors increasing the density of states just below the Fermi level. Whereas, when the nanoparticles are stabilized by covalent bonds with protective species (thiol derivatized alkane chains or surface oxidized Pd NPs), the increase of the 4d density of holes, localized by the bonded atoms (S or O), is giving rise to the observed ferromagneticlike behavior

Assessing microplastic ingestion and occurrence of bisphenols and phthalates in bivalves, fish and holothurians from a Mediterranean marine protected area

Microplastic (MP) ingestion, along with accumulated plasticizers such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and phthalates represented by diethyl phthalate (DEP), dibutyl phthalate (DBP) and bis (2-ethylhexyl) phthalate (DEHP), were quantified in bivalves, fish, and holothurians collected from a coastal pristine area at the western Mediterranean Sea. MP ingestion in sediment-feeders holothurians (mean value 12.67 ± 7.31 MPs/individual) was statistically higher than ingestion in bivalves and fish (mean 4.83 ± 5.35 and 3 ± 4.44 MPs/individual, respectively). The main ingested polymers were polyethylene, polypropylene, and polystyrene. The levels of BPS, BPF, and DEHP were highest in bivalves' soft tissue; BPA and DBP had the highest levels in the holothurians’ muscle. In addition, the levels of all plasticizers assessed were lowest in fish muscle; only BPA levels in fish were higher than in bivalves, with intermediate values between those of bivalves and holothurians. This study provides data on exposure to MPs and plasticizers of different species inhabiting Cabrera Marine Protected Area (MPA) and highlights the differences in MP ingestion and levels of plasticizers between species with different ecological characteristics and feeding strategies.En prensa3,39

Reduction of the Yb valence in YbAl3 nanoparticles

Measurements of specific heat, dc magnetic susceptibility, and Yb LII and LIII x-ray absorption near-edge structure XANES and extended x-ray absorption fine structure EXAFS on YbAl3 milled alloys are reported. X-ray diffraction patterns are consistent with a reduction in particle size down to 10 nm and an increase in the lattice strain up to 0.4% for 120 h of milling time. A decrease in the mean valence from 2.86 for the unmilled alloy to 2.70 for 120 h milled YbAl3 is obtained from the analysis of XANES spectra. From the analysis of spectra in the EXAFS region, an increase in the mean-square disorder of neighbor distance with milling time is detected in good agreement with the results of x-ray diffraction. Size effects strongly influence the magnetic and thermal properties. The value for the maximum of the magnetic susceptibility decreases around 30% for 120 h milled alloy and an excess specific heat, with a peak around 40 K in the milled samples, is derived. These changes in the physical properties along the milled YbAl3 alloys are associated with the reduction in particle size. Such a reduction leads to the existence of a large number of Yb2+ atoms at the surface with respect to the bulk affecting the overall electronic state

PROLAPSO GENITAL SEVERO: CONSIDERACIONES CLÍNICAS, FISIOPATOLÓGICAS Y DE TÉCNICA QUIRÚRGICA AL MOMENTO DE SU CORRECCIÓN

El tratamiento quirúrgico actual del prolapso genital severo es el resultado de un mejor conocimiento y comprensión del piso pelviano. Se revisan los fundamentos anatómicos y fisiopatológicos implicados en el desarrollo del prolapso genital severo y de la cirugía reconstructiva del piso pélvic

Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases. Keywords: Alzheimer's disease; Huntington's disease; Parkinson's disease; epilepsy; multiple sclerosis; neurodegenerative diseases