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Stress shielding and osseointegration are two main challenges in bone regeneration, which have been targeted successfully by chemical and physical surface modification methods. Direct irradiation synthesis (DIS) is an energetic ion irradiation method that generates self-organized nanopatterns conformal to the surface of materials with complex geometries (e.g., pores on a material surface). This work exposes porous titanium samples to energetic argon ions generating nanopatterning between and inside pores. The unique porous architected titanium (Ti) structure is achieved by mixing Ti powder with given amounts of spacer NaCl particles (vol % equal to 30%, 40%, 50%, 60%, and 70%), compacted and sintered, and combined with DIS to generate a porous Ti with bone-like mechanical properties and hierarchical topography to enhance Ti osseointegration. The porosity percentages range between 25% and 30% using 30 vol % NaCl space-holder (SH) volume percentages to porosity rates of 63%–68% with SH volume of 70 vol % NaCl. Stable and reproducible nanopatterning on the flat surface between pores, inside pits, and along the internal pore walls are achieved, for the first time on any porous biomaterial. Nanoscale features were observed in the form of nanowalls and nanopeaks of lengths between 100 and 500 nm, thicknesses of 35-nm and heights between 100 and 200 nm on average. Bulk mechanical properties that mimic bone-like structures were observed along with increased wettability (by reducing contact values). Nano features were cell biocompatible and enhanced in vitro pre-osteoblast differentiation and mineralization. Higher alkaline phosphatase levels and increased calcium deposits were observed on irradiated 50 vol % NaCl samples at 7 and 14 days. After 24 h, nanopatterned porous samples decreased the number of attached macrophages and the formation of foreign body giant cells, confirming nanoscale tunability of M1–M2 immuno-activation with enhanced osseointegration.

Pentraxin-3 has been reported as a promising biomarker of pre-eclampsia and its severity; however, available studies have small sample sizes, and analyses are not always adjusted for confounders. The aim of this study is to establish the strength of the association between maternal Pentraxin-3 level and pre-eclampsia or HELLP syndrome. It was a case-control study. Women with pre-eclampsia or HELLP syndrome were defined as cases, and women with healthy pregnancies at term (>37 weeks) were classified as controls. Plasma concentrations of Pentraxin-3 were determined at the time of delivery by quantitative enzyme immunoassay. Associations between Pentraxin-3 and pre-eclampsia and HELLP syndrome were assessed by multinomial logistic regression. Subsidiary analysis for the time of disease onset was also carried out. Odds ratios and 95% confidence intervals are reported. A total of 1024 pregnant women were included (461 controls, 368 pre-eclampsia, 195 HELLP). A positive log-linear relationship was found between the top pentraxin-3 quintile and HELLP syndrome. After adjustment for confounders (maternal age, ethnicity, socioeconomic position, date and place of recruitment, family history of pre-eclampsia, smoking, body mass index at beginning of pregnancy, gestational age and multiple pregnancy), the strength of the association was higher for HELLP syndrome [OR 1.13 (95% CI 1.08; 1.18)] than for pre-eclampsia [OR 1.03 (95% CI 1.03; 1.10)]. No difference according to time of onset or pentraxin-3 level was found. In summary, pentraxin-3 level was associated with pre-eclampsia, but it was more strongly associated with HELLP syndrome. Longitudinal studies with a lower probability of residual confounding are necessary to improve our knowledge about the role of pentraxin-3 in pre-eclampsia.

Bacterial cellulose is a naturally occurring polysaccharide with numerous biomedical applications that range from drug delivery platforms to tissue engineering strategies. BC possesses remarkable biocompatibility, microstructure, and mechanical properties that resemble native human tissues, making it suitable for the replacement of damaged or injured tissues. In this review, we will discuss the structure and mechanical properties of the BC and summarize the techniques used to characterize these properties. We will also discuss the functionalization of BC to yield nanocomposites and the surface modification of BC by plasma and irradiation-based methods to fabricate materials with improved functionalities such as bactericidal capabilities.

En el siguiente articulo se analiza la cinematica del lanzamiento y trayectoria del frisbee utilizando la plataforma Arduino con un acelerometro. Ademas, se implementa el analisis de videos digitales mediante el software cinematico Kinovea®. Por medio de estos se obtienen las aceleraciones y velocidades que toma el disco en tres diferentes tipos de lanzamientos: Backhand , forehand y elevator pass . Se hallo que tanto el lanzador como el tipo de lanzamiento presentan diferencias que permiten su reconocimiento. Los resultados obtenidos muestran que el lanzador tuvo dificultades en garantizar la repetitividad en el lanzamiento backhand, con aceleraciones entre 23m/s 2 y 64m/s 2 , lo cual mejoro en el caso del elevator pass entre 22m/s 2 y 52m/s 2 y en el forehand entre 50m/s 2 y 73m/s 2 . Finalmente, se concluye como estos instrumentos describen la cinematica del lanzamiento.

One of the major limitations during titanium (Ti) implant osseointegration is the poor cellular interactions at the biointerface. In the present study, the combined effect of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) and nanopatterned Ti6Al4V fabricated with Directed irradiation synthesis (DIS) is investigated in vitro. This environmentally-friendly plasma uses ions to create self-organized nanostructures on the surfaces. Nanocones (≈36.7 nm in DIS 80°) and thinner nanowalls (≈16.5 nm in DIS 60°) were fabricated depending on DIS incidence angle and observed via scanning electron microscopy. All samples have a similar crystalline structure and wettability, except for sandblasted/acid-etched (SLA) and acid-etched/anodized (Anodized) samples which are more hydrophilic. Biological results revealed that the viability and adhesion properties (vinculin expression and cell spreading) of DIS 80° with BMP-2 were similar to those polished with BMP-2, yet we observed more filopodia on DIS 80° (≈39 filopodia/cell) compared to the other samples (&lt, 30 filopodia/cell). BMP-2 increased alkaline phosphatase activity in all samples, tending to be higher in DIS 80°. Moreover, in the mineralization studies, DIS 80° with BMP-2 and Anodized with BMP-2 increased the formation of calcium deposits (&gt, 3.3 fold) compared to polished with BMP-2. Hence, this study shows there is a synergistic effect of BMP-2 and DIS surface modification in improving Ti biological properties which could be applied to Ti bone implants to treat bone disease.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavioral issue for children. One of the sleeping disorders most frequently related to ADHD is the Restless Legs Syndrome (RLS), characterized by an irresistible urge to move the legs, something that is generally associated with paresthesias and motor restlessness. The prevalence rate of RLS in children diagnosed with ADHD is close to 18%, but in Colombia, these cases have been hardly studied. Objective: To determine the frequency of RLS, in children with ADHD. Methods: A cross-sectional study, filled out by parents of children diagnosed with ADHD, were analyzed. This questionnaire contained clinical criteria for classifying ADHD according to the DSM-IV, as well as diagnostic criteria for RLS by the National Institutes of Health (2003). Results: A predominance rate of 65.6% in combined ADHD was observed in children with RLS criteria. Upon carrying out an exploratory data analysis, it was found that having a family history of RLS and belonging to the middle or low socioeconomic strata are conditions associated with the presence of RLS in children with ADHD, with a significant p (p < 0.000) and a PR of 4.47 (3.16-6.32). Conclusions: The prevalence of RLS was similar to the findings of other clinical investigations. However, it highlights new prevalence values in relation to the comorbidity between ADHD and RLS, suggesting the need for new clinical and therapeutic alternatives amidst the presence of both syndromes Introducción: El trastorno de hiperactividad con déficit de atención (TDAH) es el problema de comportamiento más común en la infancia. Uno de los trastornos de sueño que más se ha relacionado el TDAH es el síndrome de piernas inquietas (SPI) el cual conlleva un deseo irresistible de mover las piernas que, en general, se asocia con parestesias e inquietud motora. La prevalencia del SPI en la población infantil diagnosticada con TDAH es de cerca del 18 %. Sin embargo, en Colombia han sido escasamente estudiados. Objetivo: Determinar la frecuencia de SPI en niños con TDAH. Método: se realizó un estudio de corte transversal, con el uso de cuestionarios diligenciados por los padres de niños con diagnóstico de TDAH. Dicho cuestionario contenía criterios clínicos para la clasificación del TDAH según el DSM-IV, y criterios diagnósticos para SPI del National Institutes of Health pediatric restless legs syndrome (2003). Resultados: Los niños con criterios de SPI tuvieron predominio del TDAH combinado en un 65.6%. Al realizar el análisis exploratorio se encontró que tener historia familiar de SPI y estrato medio o bajo se asocian con la presencia del SPI en niños con TDAH, con una p significativa (p < 0.000) y una RP de 4.47 (3.16-6.32). Conclusiones: La prevalencia de SPI fue similar a los hallazgos de otras investigaciones clínicas, sin embargo, resalta nuevos valores de prevalencia en relación a la comorbilidad entre el TDAH y el SPI, sugiriendo la necesidad de habilitar nuevas alternativas clínicas y terapéuticas en la presencia de ambos síndromes

In order to estimate the mean heterosis, mid parent heterosis and heterobeltiosis (HB), three diallel crossings of Cucúrbita moschata were evaluated, each formed by six parents with three levels of inbreeding (S0, S1, S2). A randomized complete block experimental design was used with four replicates, arranged in split plots. The variables yield per plant (YPP) and average fruit weight (AFW) were analyzed. The hybrids between S1 or S2 inbred lines presented heterotic superiority regarding to those between S0 parents for the variables YPP and AFW. Likewise, the hybrids between S2 inbred lines reported heterotic superiority in comparison to those among S1 inbred lines, for such variables. The hybrids between S2 inbred lines that reported the highest expression levels of HB for YPP were P1xP3, P2xP6 and P1xP2, with values ranging between 131.42 and 98.24%; while the hybrids among S1 inbred lines that recorded the highest values of HB, for this same variable, were P3xP5 and P1xP5 with values of 191.71 and 139.29%, respectively. Furthermore, the hybrids between S2 and S1 inbred lines that registered the highest level of HB for AFW were P1xP3 and P1xP5 with values of 108 and 83.7%, respectively. RESUMEN Para estimar la heterosis promedia, heterosis relativa y hete-robeltiosis (HB) se evaluaron tres cruzamientos dialélicos de Cucurbita moschata, conformados cada uno por seis progenitores con tres niveles de endogamia (S0, S1, S2). Se utilizó el diseño experimental de bloques completos al azar con cuatro repeticiones y arreglo en parcelas divididas. Se analizaron las variables producción por planta (PFP) y peso promedio del fruto (PPF). Los híbridos producidos entre líneas endogámicas S2 o S1 presentaron superioridad heterótica en comparación a los híbridos formados entre padres S0 para PFP y PPF. igualmente, los híbridos entre líneas endogámicas S2 reportaron para dichas variables superioridad heterótica con respecto a los híbridos entre líneas endogámicas S1. Los híbridos entre líneas endogámicas S2 que presentaron los mayores niveles de expresión de HB para PFP fueron P1xP3, P2xP6 y P1xP2 con valores entre 131.42 y 98.24%, respectivamente; mientras que los híbridos entre líneas endogámicas S1 que registraron los niveles más altos de HB para dicha variable fueron P3xP5 y P1xP5 con 191.71 y 139.29%, respectivamente. Por otro lado, los híbridos entre líneas endogámicas S2 y S1 que registraron los niveles más altos de HB para PPF fueron P1xP3 y P1xP5, con valores de 108 y 83.7%, respectivamente.

Pentraxin-3 has been reported as a promising biomarker of pre-eclampsia and its severity; however, available studies have small sample sizes, and analyses are not always adjusted for confounders. The aim of this study is to establish the strength of the association between maternal Pentraxin-3 level and pre-eclampsia or HELLP syndrome. It was a case-control study. Women with pre-eclampsia or HELLP syndrome were defined as cases, and women with healthy pregnancies at term (37 weeks) were classified as controls. Plasma concentrations of Pentraxin-3 were determined at the time of delivery by quantitative enzyme immunoassay. Associations between Pentraxin-3 and pre-eclampsia and HELLP syndrome were assessed by multinomial logistic regression. Subsidiary analysis for the time of disease onset was also carried out. Odds ratios and 95% confidence intervals are reported. A total of 1024 pregnant women were included (461 controls, 368 pre-eclampsia, 195 HELLP). A positive log-linear relationship was found between the top pentraxin-3 quintile and HELLP syndrome. After adjustment for confounders (maternal age, ethnicity, socioeconomic position, date and place of recruitment, family history of pre-eclampsia, smoking, body mass index at beginning of pregnancy, gestational age and multiple pregnancy), the strength of the association was higher for HELLP syndrome [OR 1.13 (95% CI 1.08; 1.18)] than for pre-eclampsia [OR 1.03 (95% CI 1.03; 1.10)]. No difference according to time of onset or pentraxin-3 level was found. In summary, pentraxin-3 level was associated with pre-eclampsia, but it was more strongly associated with HELLP syndrome. Longitudinal studies with a lower probability of residual confounding are necessary to improve our knowledge about the role of pentraxin-3 in pre-eclampsia.

Here, titanium porous substrates were fabricated by a space holder technique. The relationship between microstructural characteristics (pore equivalent diameter, mean free-path between pores, roughness and contact surface), mechanical properties (Young’s modulus, yield strength and dynamic micro-hardness) and bacterial behavior are discussed. The bacterial strains evaluated are often found on dental implants: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The colony-forming units increased with the size of the spacer for both types of studied strains. An antibiofouling synthetic coating based on a sulfonated polyetheretherketone polymer revealed an effective chemical surface modification for inhibiting MRSA adhesion and growth. These findings collectively suggest that porous titanium implants designed with a pore size of 100–200 µm can be considered most suitable, assuring the best biomechanical and bifunctional anti-bacterial properties. University of Seville VI Plan Propio de Investigación y Transferencia—US 2018, I.3A2

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavioral issue for children. One of the sleeping disorders most frequently related to ADHD is the Restless Legs Syndrome (RLS), characterized by an irresistible urge to move the legs, something that is generally associated with paresthesias and motor restlessness. The prevalence rate of RLS in children diagnosed with ADHD is close to 18%, but in Colombia, these cases have been hardly studied. Objective: To determine the frequency of RLS, in children with ADHD. Methods: A cross-sectional study, filled out by parents of children diagnosed with ADHD, were analyzed. This questionnaire contained clinical criteria for classifying ADHD according to the DSM-IV, as well as diagnostic criteria for RLS by the National Institutes of Health (2003). Results: A predominance rate of 65.6% in combined ADHD was observed in children with RLS criteria. Upon carrying out an exploratory data analysis, it was found that having a family history of RLS and belonging to the middle or low socioeconomic strata are conditions associated with the presence of RLS in children with ADHD, with a significant p (p < 0.000) and a PR of 4.47 (3.16-6.32). Conclusions: The prevalence of RLS was similar to the findings of other clinical investigations. However, it highlights new prevalence values in relation to the comorbidity between ADHD and RLS, suggesting the need for new clinical and therapeutic alternatives amidst the presence of both syndromes. Resumen Introducción: El trastorno de hiperactividad con déficit de atención (TDAH) es el problema de comportamiento más común en la infancia. Uno de los trastornos de sueño que más se ha relacionado el TDAH es el síndrome de piernas inquietas (SPI) el cual conlleva un deseo irresistible de mover las piernas que, en general, se asocia con parestesias e inquietud motora. La prevalencia del SPI en la población infantil diagnosticada con TDAH es de cerca del 18 %. Sin embargo, en Colombia han sido escasamente estudiados. Objetivo: Determinar la frecuencia de SPI en niños con TDAH. Método: se realizó un estudio de corte transversal, con el uso de cuestionarios diligenciados por los padres de niños con diagnóstico de TDAH. Dicho cuestionario contenía criterios clínicos para la clasificación del TDAH según el DSM-IV, y criterios diagnósticos para SPI del National Institutes of Health pediatric restless legs syndrome (2003). Resultados: Los niños con criterios de SPI tuvieron predominio del TDAH combinado en un 65.6%. Al realizar el análisis exploratorio se encontró que tener historia familiar de SPI y estrato medio o bajo se asocian con la presencia del SPI en niños con TDAH, con una p significativa (p < 0.000) y una RP de 4.47 (3.16-6.32). Conclusiones: La prevalencia de SPI fue similar a los hallazgos de otras investigaciones clínicas, sin embargo, resalta nuevos valores de prevalencia en relación a la comorbilidad entre el TDAH y el SPI, sugiriendo la necesidad de habilitar nuevas alternativas clínicas y terapéuticas en la presencia de ambos síndromes.

RESUMEN: La presente tesis doctoral constituye un análisis sobre los conocimientos ticuna en torno a la especie vegetal Carapa guianensis y la incidencia de estos con una dimensión política, en Puerto Nariño, Amazonas colombiano, respondiendo a la pregunta sobre la relación entre principios culturales y conflictos socioecológicos en zonas estratégicas de conservación de la biodiversidad a nivel mundial. Por medio del método etnográfico y desde los aportes de la etnoecología y la ecología política se analizan: (i) las representaciones ticuna de la naturaleza y Carapa guianensis, (ii) los actores sociales en torno a la naturaleza y al territorio, (iii) las relaciones y los conflictos entre dichos actores sociales, y (iv) la incidencia de los conocimientos tradicionales en la reivindicación de la naturaleza y el territorio. En el Amazonas, zona estratégica de conservación de carácter internacional, convergen diferentes actores sociales alrededor a la naturaleza y al territorio: el Estado y el sector privado con sus agendas extractivistas, los actores de la investigación, del ecodesarrollo y la conservación de la biodiversidad y, los actores de base (comunidades indígenas). La sociedad ticuna es de tipo animista con filiación totémica. Su sistema de parentesco se funda en la filiación entre mitades exógamas pertenecientes a un clan determinado por un epónimo animal o vegetal. Los resultados evidencian que, dado el alto grado de aculturación de los ticuna de Puerto Nariño, existe una coexistencia entre ontologías sociales (representaciones del mundo) animistas y naturalistas. Esto resulta ser fuente de tensiones entre actores sociales con intereses en torno a la naturaleza en razón de una oposición entre los modelos tecnocráticos y modelos organicistas del ecodesarrollo. Así, por parte de las comunidades, existen reticencias hacia las agendas institucionales y estatales de investigación sobre recursos biológicos, y se reivindica la gestión de la naturaleza y del territorio desde el discurso de la ancestralidad. Se concluye finalmente sobre la necesidad de generar programas de desarrollo y conservación que incluyan estos parámetros culturales. ABSTRACT: This doctoral thesis is an analysis of Ticuna’s knowledge of the plant species Carapa guianensis and the incidence of these with a political dimension, in Puerto Nariño, Colombian Amazon, in response to the question on the relationship between cultural principles and socioecological conflicts in strategic areas of biodiversity conservation at the global level. Through the ethnographic method and from the contributions of ethnology and political ecology are analyzed: (i) the representations Ticuna of nature and Carapa guianensis, (ii) the social actors around nature and territory, (iii) the relations and conflicts between these social actors, and (iv) the impact of traditional knowledge on the vindication of nature and territory. In the Amazon, a strategic area of international conservation, different social actors converge around nature and territory: the State and the private sector with their extractives’ agendas, research, Ecodevelopment and biodiversity conservation actors and grassroots actors (indigenous communities). Ticuna society is of animist type with totemic filiation. Their kinship system is based on filiation between exogamous halves belonging to a clan determined by an animal or vegetable eponym. The results show that, given the high degree of acculturation of the Ticuna of Puerto Nariño, there is a coexistence between social ontologies (world representations) animists and naturalists. This turns out to be a source of tension between social actors with interests around nature due to an opposition between technocratic models and Ecodevelopment organizing models. Thus, on the part of the communities, there is reticence towards the institutional and state agendas of research on biological resources, and the management of nature and territory is demanded from the discourse of ancestry. Finally, it concludes on the need to generate development and conservation programs that include these cultural parameters.

Maestría en Educación desde la Diversidad, Facultad de Ciencias Sociales y Humanas. El presente artículo condensa un trabajo investigativo cuyo objetivo central fue comprender las posibles formas de construir pensamiento crítico en los niños y las niñas de la Institución Educativa “La Pamba” de Popayán (Cauca) a través de una adecuada educación musical, que contribuya a los procesos de transformación social. Este estudio es parte de un proyecto nacional denominado “Práctica pedagógica transformadora: hacia una construcción de pensamiento crítico en la escuela Caucana” vinculado al Grupo de Investigación Educación y Pedagogía: Saberes, Imaginarios e Intersubjetividades en la línea de Investigación en Educación y Pedagogía de la Universidad de Manizales Metodológicamente se configuró como una investigación cualitativa de corte hermenéutico, en la cual los niños y las niñas actuaron en una serie de talleres y encuentros, que nos permitieron indagar, registrar e interpretar información, a través de algunas técnicas propias de la etnografía como la observación participante y la entrevista, que posibilitaran comprender cómo se está construyendo pensamiento crítico en el aula escolar. En esas aproximaciones con los y las estudiantes se examinaron algunos planteamientos respecto a la teoría y la pedagogía crítica y se analizaron categorías relacionadas con la educación musical, que nos permitieran percibir la manera de aportar, desde la educación, a la formación de sujetos reflexivos, capaces de transformar y cuestionar los preceptos que la sociedad les plantea. De dicho análisis se concluye que la música, como herramienta empleada en la praxis pedagógica, puede apoyar a la transformación social; sin embargo, los métodos tradicionales de enseñanza, que continúan imponiéndose, ignoran su trascendencia y no la aprovechan como alternativa para generar pensamiento crítico que posibilite la formación de sujetos pensantes, capaces de reflexionar frente al sistema dominante y actuar para liberarse del mismo.

A robotic arm able to reproduce the tremor characteristics of Parkinson Disease (PD) and Essential Tremor (ET), both in time and frequency domain, is presented. To obtain the tremor signals, an acquisition system with inertial sensors has been developed and implemented in affected patients. Different strategies for digital signal processing were considered to characterize the tremor. Neural networks demonstrated to be the best fit for modeling the highly non-lineal behavior of the analyzed system. The constructed mechatronic simulator was thought as a dynamic tool for developing and proving new approaches for active cancelation of tremor (ACT) as a hope for improving everyday life of people suffering from this disability.

RESUMEN: ¿Cómo se distribuye la población rural de la región del Este de Antioquia, Colombia?, y ¿qué efectos tiene para el desarrollo local de la región esta distribución? son las preguntas de este artículo. Para responderlas se usó una metodología cualitativa basada en un estudio de caso interpretativo y comparativo, empleando técnicas como la revisión documental y la entrevista semi estructurada. Se compone de una primera parte que incluye algunos aportes teóricos del tema; en la segunda se presentan los resultados y en la tercera parte se exponen las conclusiones. Los resultados indican que hay una población rural significativa (47%) con una desigual distribución de la propiedad y la renta rural (Gini de 0.50) y con diferentes estilos de vida y formas de consumo. En conclusión, las obras de infraestructura en conjunto con la renta rural están generando una segregación socio espacial local e intra regional en el Este de Antioquia. ABSTRACT: How is the eastern Antioquia´s Rural population distributed throughout the region? What eff ect does this distribution have for the region local development? Those are the questions for this article. A comparative and interpretative case study was used for qualitative methodology to answer the question above. Documental revision and semistructured interviews were techniques used during research. This article is composed in three parts: the first part is a basic presentation of some theories that contribute to the issues. The second part is comprised of result and third part includes conclusions. The result indicates that there is a significant rural population (47%) with an uneven of property and rural rent (Gini of 0.50) and diff erent lifestyle and consuming habits. This leads to the conclusion that the infrastructure works and rural rent are creating region of Antioquia zones of spatial segregation inside the Eastern region of Antioquia.

Here, titanium porous substrates were fabricated by a space holder technique. The relationship between microstructural characteristics (pore equivalent diameter, mean free-path between pores, roughness and contact surface), mechanical properties (Young&rsquo, s modulus, yield strength and dynamic micro-hardness) and bacterial behavior are discussed. The bacterial strains evaluated are often found on dental implants: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The colony-forming units increased with the size of the spacer for both types of studied strains. An antibiofouling synthetic coating based on a sulfonated polyetheretherketone polymer revealed an effective chemical surface modification for inhibiting MRSA adhesion and growth. These findings collectively suggest that porous titanium implants designed with a pore size of 100&ndash, 200 &micro, m can be considered most suitable, assuring the best biomechanical and bifunctional anti-bacterial properties.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P

Introducción: La hiperglicinemia no cetósica (HGNC) es un error innato del metabolismo del grupo de las aminoacidopatías, de carácter autosómico recesivo, causado por un defecto en el sistema de clivaje de la glicina. Es una entidad rara y no se conoce su incidencia en Colombia. Objetivo: Describir características clínicas, bioquímica e imagenológicas en una cohorte de pacientes diagnosticados con hiperglicinemia no cetósica clásica Materiales y métodos: Estudio de tipo descriptivo, ambispectivo, en el periodo enero 2000-2014, en varios centros de Medellín. Resultados: Se incluyeron 20 pacientes que cumplían criterios de inclusión, de los 35 pacientes que cumplían con el criterio de búsqueda, en su mayoría de sexo femenino y con un Apgar adecuado al nacer. El promedio de inicio de los síntomas fue de 2,6 días; somnolencia, hipoactividad, apnea, convulsiones y singulto fueron los principales síntomas, y las convulsiones de tipo focal las más frecuentes. La relación glicina LCR/plasma en promedio fue 0,42. El patrón estallido-supresión en el electroencefalograma y la ausencia o retraso en la mielinización de la sustancia blanca supratentorial en la resonancia magnética fueron hallazgos comunes. Conclusión: La HGNC es frecuente en nuestro medio, por lo cual es necesario que se disponga de pruebas bioquímicas y moleculares necesarias para diagnóstico oportuno, manejo integral y asesoría genética. Introduction: Nonketotic Hyperglycinemia is an inborn error of metabolism in a group of aminoacidopathies, autosomal recessive, caused by a defect in the system of the glycine cleavage. It is rare, and the incidence is unknown in Colombia. Objective:To describe clinical, biochemical and imaging characteristics in a cohort of patients diagnosed with classical nonketotic hyperglycinemia. Materials and methods: This is a descriptive-ambispective study during the period January 2000 - 2014 in some centers of Medellin. Results: There were 35 patients who met the search criteria and finally 20 patients who met inclusion criteria. We found in this cohort more girls than boys, and most of them with a good APGAR. The average onset of symptoms was 2.6 days, with drowsiness, hypoactivity, apnea, seizures and singultus the main symptoms. The focal seizures were the most frequent type. The average value of CSF glycine to plasma glycine ratio was 0.42. The burst suppression pattern in the EEG and the absence or delayed myelination in the supratentorial white matter on MRI were common findings. All patients received dextromethorphan as part of their treatment and the vast majority of sodium benzoate. Conclusion: HGNC is common in our environment. It´s necessary to have available biochemical and molecular evidence for timely diagnosis, comprehensive management and genetic counseling.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures., Author Summary Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome (TS) and obsessive compulsive disorder (OCD). However, efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful. One possible explanation for this is that many genetic variations scattered throughout the genome each contribute a small amount to the overall risk. For TS and OCD, the genetic architecture (characterized by the number, frequency, and distribution of genetic risk factors) is presently unknown. This study examined the genetic architecture of TS and OCD in a variety of ways. We found that rare genetic changes account for more genetic risk in TS than in OCD; certain chromosomes contribute to OCD risk more than others; and variants that influence the level of genes expressed in two regions of the brain can account for a significant amount of risk for both TS and OCD. Results from this study might help in determining where, and what kind of variants are individual risk factors for TS and OCD and where they might be located in the human genome.