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Rett syndrome caused by MECP2 variants is characterized by a heterogenous clinical spectrum accounted for in 60% of cases by hot-spot variants. Focusing on the most frequent variants, we generated in vitro iPSC-neurons from the blood of RTT girls with p.Arg133Cys and p.Arg255*, associated to mild and severe phenotype, respectively, and of an RTT male harboring the close to p.Arg255*, p.Gly252Argfs*7 variant. Truncated MeCP2 proteins were revealed by Western blot and immunofluorescence analysis. We compared the mutant versus control neurons at 42 days for morphological parameters and at 120 days for electrophysiology recordings, including girls’ isogenic clones. A precocious reduced morphological complexity was evident in neurons with truncating variants, while in p.Arg133Cys neurons any significant differences were observed in comparison with the isogenic wild-type clones. Reduced nuclear size and branch number show up as the most robust biomarkers. Patch clamp recordings on mature neurons allowed the assessment of cell biophysical properties, V-gated currents, and spiking pattern in the mutant and control cells. Immature spiking, altered cell capacitance, and membrane resistance of RTT neurons, were particularly pronounced in the Arg255* and Gly252Argfs*7 mutants. The overall results indicate that the specific markers of in vitro cellular phenotype mirror the clinical severity and may be amenable to drug testing for translational purposes.

Abstract Background Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array‐based detection rate. Methods The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. Results Non‐polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non‐syndromic neurodevelopmental signs and non‐syndromic congenital malformations to a decreased detection rate. Conclusions Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease, mainly affecting the motor neurons (MNs) and without effective therapy. Drug screening is hampered by the lack of satisfactory experimental and pre-clinical models. Induced pluripotent stem cells (iPSCs) could help to define disease mechanisms and therapeutic strategies as they could be differentiated into MNs, otherwise inaccessible from living humans. In this study, given the seminal role of TDP-43 in ALS pathophysiology, MNs were obtained from peripheral blood mononuclear cells-derived iPSCs of an ALS patient carrying a p.A382T TARDBP mutation and a healthy donor. Venous samples were preferred to fibroblasts for their ease of collection and no requirement for time consuming extended cultures before experimentation. iPSCs were characterized for expression of specific markers, spontaneously differentiated into primary germ layers and, finally, into MNs. No differences were observed between the mutated ALS patient and the control MNs with most of the cells displaying a nuclear localization of the TDP-43 protein. In conclusion, we here demonstrated for the first time that human TARDBP mutated MNs can be successfully obtained exploiting the reprogramming and differentiation ability of peripheral blood cells, an easily accessible source from any patient. Keywords: Amyotrophic Lateral Sclerosis (ALS), Induced Pluripotent Stem Cells (iPSCs), Peripheral blood, TDP43, Motor neuron

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutation in either the CREBBP (RSTS1) or EP300 (RSTS2) genes. We generated an induced pluripotent stem cell line from an RSTS2 patient's blood mononuclear cells by Sendai virus non integrative reprogramming method. The iPSC line (IAIi001RSTS2-65-A) displayed iPSC morphology, expressed pluripotency markers, possessed trilineage differentiation potential and was stable by karyotyping. Mutation and western blot analyses demonstrated in IAIi001RSTS2-65-A the patient's specific non sense mutation in exon 23 c.3829A > T, p.(Lys 1277*) and showed reduced quantity of wild type p300 protein.

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutations in either CREBBP (RSTS1) or EP300 (RSTS2) genes. We characterized 3 iPSC lines generated by Sendai from blood of RSTS1 patients with unique non sense c.4435G > T, p.(Gly1479*), c.3474G > A, p.(Trp1158*) and missense c.4627G > T, p.(Asp1543Tyr) CREBBP mutations. All lines displayed iPSC morphology, pluripotency markers, trilineage differentiation potential, stable karyotype and specific mutations. Western-blot using a CREB-Binding Protein N-terminus antibody demonstrated the same amount of full length protein as control in the missense mutation line and reduced amount in lines with stop mutations.

Satellited non-acrocentric autosomal chromosomes (ps–qs-chromosomes) are the result of an interchange between sub- or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carriers of this type of translocation may or may not display phenotypic abnormalities. With the aim to understand the causative mechanism, we revised all the ps–qs-chromosomes identified in five medical genetics laboratories, which used the same procedures for karyotype analysis, reporting 24 unrelated cases involving eight chromosomes. In conclusion, we observed three different scenarios: true translocation, benign variant and complex rearrangement. The detection of translocation partners is essential to evaluate possible euchromatic unbalances and to infer their effect on phenotype. Moreover, we emphasize the importance to perform both, molecular and conventional cytogenetics methods, to better understand the behavior of our genome.

El presente trabajo tuvo como objetivo diseñar estrategias de marketing para el posicionamiento de productos agroturísticos en la provincia de Manabí, Ecuador. En la metodología aplicada se consideró como primera fase el diagnóstico turístico para la identificación de las actividades productivas asociadas al agroturismo, las mismas que están vinculadas a la producción de la tierra, la ganadería, el comercio y la manufactura, con base en productos primarios, frutas tropicales, cultivo de camarón y al turismo. En la segunda fase se estableció el estudio de mercado; mediante la segmentación se evidenció un nicho de turismo familiar que en época de vacaciones se moviliza a los diferentes sitios de interés, estos informan y comparten experiencias a través de las redes sociales. Se detectaron 4 productos turísticos con potencial localizados en la zona centro oeste de Manabí: la ruta del abuelo, del encanto, de los sentidos y el circuito de cacao fino de aroma. En la última fase se desarrolló un plan de acción el cual se apoyó en la técnica de la entrevista a los actores y gestores locales. Asimismo, se diseñaron 4 estrategias direccionadas al posicionamiento de los productos; al precio como determinante de atractividad; la competitividad entre el precio-calidad, a través de convenios y alianzas estratégicas; se esbozan canales de distribución y la promoción de la marca de los productos. A partir de las estrategias se plantearon 4 programas que contemplan 16 proyectos enmarcados en la mezcla de mercadotécnica (marketing mix), con el fin de fortalecer, innovar y posicionar el agroturismo en Manabí.

Socializaremos aquí los resultados de una investigación desarrollada en el Archivo General de los Tribunales de Córdoba (Argentina), orientada al relevamiento, la sistematización y el análisis de las guardas y adopciones tramitadas en los juzgados civiles y de menores de la ciudad de Córdoba entre 1975 y 1983. Sus objetivos fueron: establecer la vinculación de la identidad biológica y adoptiva de los niños adoptados en esos años, e identificar posibles apropiaciones ilegales vinculadas al Terrorismo de Estado. En ese marco, presentaremos aquí las hipótesis a las que se arribó en el primer trabajo realizado en nuestro país con un fondo documental completo de estas características, respecto de algunas prácticas judiciales de aquel período en relación al derecho a la identidad. En particular, y en cuanto al abordaje de éstas al momento de indagar en torno al plan sistemático de apropiación ilegal de niños desarrollado durante la última dictadura en Argentina, intentaremos mostrar: por una parte, que no era necesario fraguar el procedimiento en relación a la gestión judicial de menores para lograr la sustitución o supresión de su identidad biológica y, por la otra, que el conjunto de mecanismos y dispositivos que facilitaban la inscripción de los niños como hijos propios, funcionaban también al interior de los procesos judiciales.

Resumen En este artículo, se buscó conocer la prevalencia de riesgo de deterioro cognitivo y su relación con factores demográficos, sociales y funcionales en las personas mayores de las subregiones de Antioquia, Colombia. Se trata de un estudio cuantitativo, transversal analítico, con fuente de información primaria. La muestra fue probabilística y se determinó el riesgo de deterioro cognitivo con la escala minimental. Así se encontró que el 83,1% de los mayores presenta algún riesgo de deterioro cognitivo, principalmente las mujeres, y está asociado significativamente con vivir en la subregión del Magdalena Medio y Medellín, tener mayor edad, no tener pareja, no tener escolaridad, tener escasos recursos sociales, no participar en grupos comunitarios, tener mala percepción de la calidad de vida, estar insatisfecho con la salud y tener dependencia funcional para realizar las actividades básicas. Estos resultados permiten orientar los programas de salud pública relacionados con la inclusión de las personas mayores hacia programas educativos, la participación en grupos comunitarios, la tamización constante en los servicios de salud, el fortalecimiento de los recursos sociales y el fomento de la actividad física en la vejez, para lograr un envejecimiento saludable con mejor calidad de vida.

Objective The health needs of older adults constitute challenges for health monitoring and care, resulting in increased costs. The present study therefore sought to analyze the health status of the elderly to enable targeting and intervention, in the pursuit of healthy aging for all. Method A quantitative observational cross-sectional study using a primary source was performed in 2012. A total of 4,248 adults aged over 60 years of age residing in the nine regions of Antioquia, Colombia, and the capital city were surveyed. Univariate, bivariate and multivariate analysis was performed of statistical and epidemiological measures, based on confidence intervals and statistical tests under 5%. Results One in four individuals had a risk of depression, one in three were at risk of anxiety, eight out of ten had cognitive impairment, mainly mild, and the same proportion were at nutritional risk. The elderly persons suffered from all types of abuse, notably psychological. Conclusions Thehealth status ofelderly personsis more affectedbymental than physical healthrisks, indicatingthatpublic policy anda better distribution ofresourcesshould be aimed at seeking animprovement in qualityof life anddignified aging, differentiated byregion.