Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

Acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral

RESUMEN El adecuado desempeño docente para atender la diversidad estudiantil en la disciplina Estomatología Integral, puede garantizarla formación con calidad del egresado en la carrera de Estomatología. El objetivo de este trabajo es diseñar un sistema de acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral en la Universidad de Ciencias Médicas de Las Tunas. Se realizó una investigación de desarrollo, principalmente cualitativa, en la institución antes declarada, desde septiembre de 2020 a febrero 2021. La investigación define como objeto el proceso de enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral y como campo las acciones docentes para atender diversidad estudiantil. La investigación se ejecutó en dos etapas, dedicadas a: revisar documentos rectores de la carrera, tesis, artículos, programas y elaborar las acciones. El sistema de acciones docentes para atender la diversidad estudiantil quedó estructurado por un objetivo general, acciones permanentes a realizar en el proceso de enseñanza-aprendizaje (relacionado con: superación docente, diagnóstico pedagógico integral y formación de valores); y acciones al planificar, ejecutar y controlar las clases. Las acciones propuestas promueven la unidad de la unidad de lo instructivo, educativo y desarrollador, de lo cognitivo y afectivo, de la formación del conocimiento y los valores, mediante un sistema didáctico integral y personalizado. Se proponen acciones docentes para atender la diversidad estudiantil, en el proceso enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral, al planificar, ejecutar y controlar.

ABSTRACT The appropriate educational acting to assist the student diversity in the discipline of Family Dentistry, it can guarantee the formation with quality of the students in the Dentistry career. To design a system of educational actions to assist the student diversity in the classes of the of Family Dentistry in the University of Medical Sciences of Las Tunas. A development investigation, mainly qualitative, before in the institution declared, from September of 2020 to February 2021. The investigation defines like object the process of teaching-learning of the classes of the Family Dentistry and I eat field the educational actions to assist student diversity. The investigation was executed in two stages, dedicated to: to revise documents rectors of the career, thesis, articles, programs and to elaborate the actions. The system of educational actions to assist the student diversity was structured by a general objective, permanent actions to carry out in the teaching-learning process (related with: educational preparation, integral pedagogic diagnosis, and values formation); and work when planning, to execute and to control the classes. The proposed actions promote the unit of the unit of the instructive, educational and developer, of the cognitive, and affective, of the formation of the knowledge and the values, by means of an integral and personalized didactic system. They intended educational actions to assist the student diversity, in the process teaching-learning of the classes of the discipline Family Dentistry, when planning, to execute and to control.

RESUMO Desempenho adequado de ensino para abordar a diversidade dos alunos na disciplina abrangente de estomatologia pode garantir treinamento de qualidade para graduados nacarreira de estomatologia. O objetivo deste trabalho é projetar um sistema de ações de ensino para abordar a diversidade dos alunos nas classes da abrangente disciplina estomatológica nas ciências da Universidade de Tunas. Uma pesquisa de desenvolvimento, principalmente qualitativa, foi realizada na instituição acima mencionada, a partir de 2020 a fevereiro de 2021. A pesquisa define como objeto o processo de ensino-aprendizagem das classes da disciplina abrangente de estomatologia e como um campo as ações de ensino para a diversidade estudantil. A pesquisa foi realizada em dois estágios, dedicada a: Revisar os documentos orientadores da carreira, tese, artigos, programas e elaborar as ações. O sistema de ações de ensino para abordar a diversidade dos alunos foi estruturado por um objetivo geral, ações permanentes a serem realizadas no processo de ensino-aprendizagem (relacionado a: melhoria dos professores, diagnóstico pedagógico abrangente e formação de valores); e ações ao planejar, executar e controlar as aulas. As ações propostas promovem a unidade da unidade instrutiva, educacional e de desenvolvedora, do cognitivo e afetivo, da formação de conhecimento e valores, através de um sistema didático abrangente e personalizado. As ações de ensino são propostas para abordar a diversidade do aluno, no processo de ensino-aprendizagem das classes da disciplina abrangente de estomatologia, ao planejar, executar e controlar.

Acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral / Work educational to assist the student diversity in the classes of the discipline of Family Dentistry

El adecuado desempeño docente para atender la diversidad estudiantil en la disciplina Estomatología Integral, puede garantizar la formación con calidad del egresado en la carrera de Estomatología. El objetivo de este trabajo es diseñar un sistema de acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral en la Universidad de Ciencias Médicas de Las Tunas. Se realizó una investigación de desarrollo, principalmente cualitativa, en la institución antes declarada, desde septiembre de 2020 a febrero 2021. La investigación define como objeto el proceso de enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral y como campo las acciones docentes para atender diversidad estudiantil. La investigación se ejecutó en dos etapas, dedicadas a: revisar documentos rectores de la carrera, tesis, artículos, programas y elaborar las acciones. El sistema de acciones docentes para atender la diversidad estudiantil quedó estructurado por un objetivo general, acciones permanentes a realizar en el proceso de enseñanza-aprendizaje (relacionado con: superación docente, diagnóstico pedagógico integral y formación de valores); y acciones al planificar, ejecutar y controlar las clases. Las acciones propuestas promueven la unidad de la unidad de lo instructivo, educativo y desarrollador, de lo cognitivo y afectivo, de la formación del conocimiento y los valores, mediante un sistema didáctico integral y personalizado. Se proponen acciones docentes para atender la diversidad estudiantil, en el proceso enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral, al planificar, ejecutar y controlar(AU)

The appropriate educational acting to assist the student diversity in the discipline of Family Dentistry, it can guarantee the formation with quality of the students in the Dentistry career. To design a system of educational actions to assist the student diversity in the classes of the of Family Dentistry in the University of Medical Sciences of Las Tunas. A development investigation, mainly qualitative, before in the institution declared, from September of 2020 to February 2021. The investigation defines like object the process of teaching-learning of the classes of the Family Dentistry and I eat field the educational actions to assist student diversity. The investigation was executed in two stages, dedicated to: to revise documents rectors of the career, thesis, articles, programs and to elaborate the actions. The system of educational actions to assist the student diversity was structured by a general objective, permanent actions to carry out in the teaching-learning process (related with: educational preparation, integral pedagogic diagnosis, and values formation); and work when planning, to execute and to control the classes. The proposed actions promote the unit of the unit of the instructive, educational and developer, of the cognitive, and affective, of the formation of the knowledge and the values, by means of an integral and personalized didactic system. They intended educational actions to assist the student diversity, in the process teaching-learning of the classes of the discipline Family Dentistry, when planning, to execute and to control(EU)

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that individuals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in individuals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients' diagnosis, follow-up, and longitudinal assessment in the clinical setting.

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual-motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.

Genetic Variation Underpinning ADHD Risk in a Caribbean Community.

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10-4), rs2282794-FGF1 (A allele; p = 1.33 × 10-2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10-2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

ADGRL3 (LPHN3) variants predict substance use disorder.

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community.

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.

Conglomerados de clases latentes en 408 miembros de 120 familias nucleares de Barranquilla con un caso índice afectado de trastorno de atención hiperactividad (TDAH) / Latent class clusters in 408 members of 120 nuclear families from Barranquilla with a proband attention deficit hyperactivity disorder (adhd) affected case

Resumen Introducción: el análisis de conglomerados de clases latentes (ACCL) es un procedimiento estadístico para agrupamientos, dependiendo de la respuesta a cada ítem. Se ha usado con el trastorno de atención hiperactividad (TDAH), para derivar tipos sutiles de casos en estudios genéticos. Objetivo: analizar los CCL de 408 miembros de 120 familias con un caso índice de TDAH, en relación con los síntomas registrados en la entrevista psiquiátrica. Pacientes y métodos: a partir de un caso índice (niño escolarizado de Barranquilla con diagnóstico estándar de oro de TDAH) se construyeron familias nucleares, las cuales de evaluaron para el diagnóstico de TDAH y comorbilidades. La muestra fue de 408 miembros de 120 familias, edad 26,6 ± 15,4 años. Con el programa para computador Latent-Gold 4,0 se hizo el ACCL con la respuesta nominal para cada síntoma de TDAH, y la presencia o no de comorbilidades con TOD y TDC. Se usó el sexo y la edad como covariables categóricas. Se hizo un análisis cruzado de cada conglomerado con el diagnóstico estándar de oro. Resultados: el mejor modelo (índices de verosimilitud) fue de 6 CCL (p Bootstrap = 0,08). El conglomerado 1 (32,5 %) son adultos, predominio de sexo femenino, probabilidad < 20 % de síntomas y comorbilidades. El segundo (17,4 %) son adultos y niños de sexo masculino con 40 a 80 % de síntomas de TDAH combinado. El grupo tres (15,7 %) son niños con ~100 % síntomas de TDAH combinado, TOD y TDC. El cuarto conglomerado (14,3 %) son adultos de ambos sexos con 20 a 50 % probabilidades de hiperactividad-impulsividad, TOD (70 %) y TDC (40 %). El grupo 5 (10,6 %) en un 80 % adultos con 30 a 90 % probabilidades de inatención sin comorbilidades. El conglomerado 6 (9,5 %) con altas probabilidades de síntomas de inatención. Conclusiones: se derivaron 6 CCL. Cuatro conglomerados son de afectados, 1 de no afectados y 1 con similar proporción de afectados y no afectados, los cuales podrían ser usados en análisis con marcadores genéticos de susceptibilidad para TDAH.

Summary Introduction: Latent class cluster analysis (LCCA) is a statistical procedure to sort a sample, according to item response of each member of a sample. It has been used with ADHD in order to derive mild cases for genetic studies. Objective: To analyze LCC from 408 members of 120 nuclear families with a ADHD proband, related to registered symptoms obtained with a structured psychiatric interview. Patient and methods: From a proband (school -gold standard- ADHD affected child from Barranquilla) nuclear families were recruited, which were assess for ADHD and comorbidities diagnoses. Sample was 408 members of 120 nuclear families, mean age 26,6 ± 15,4 years old. Using Latent Gold 4,0 software, an ACCL with each ADHD categorical symptoms, and comorbidities with ODD and CD was run. Gender and age were used as categorical active covariables. A cross tabulation analysis between LCC and ADHD gold standard diagnosis was done. Results: The best model (maximum likelihood index) was a 6 LCC (p Bootstrap = 0,08). Cluster 1 (32,5%) were predominantly female adults with low (< 20%) probability of ADHD symptoms. Cluster 2 (17,4%) were adults and children with 40 to 80% probabilities of combined ADHD symptoms. Cluster 3 (15,7%) were children with ~100% of ADHD combined symptoms with ODD and CD comorbidities. Cluster 4 (14,3%) were adults of both genders with 20 to 50% probabilities of hyperactivity - impulsivity and ODD (70%) and CD (40%). Cluster 5 (10,6%) were 80% adults with 30 to 90% probabilities of inattentive symptoms without comorbidities. Cluster 6 (9,5%) had high probabilities of inattentive symptoms. Conclusions: A 6 LCC model was obtained. Four LCC were ADHD affected, one was unaffected and one with similar proportion of affected and unaffected members, which would are able to be used for genetic analyses with ADHD susceptibility gene markers.

Déficit en habilidades sociales en niños con Trastorno por Déficit de Atención-Hiperactividad, evaluados con la Escala BASC / Déficit em habilidades sociais em crianças com Transtorno por Déficit de Atenção-Hiperatividade, avaliados com a escala BASC / Social skills deficits in children diagnosed with Attention Deficit Hyperactivity Disorder evaluated with the BASC scale

Se analizaron las Habilidades Sociales (HS) de 159 niños de ambos sexos, escolarizados, con Trastorno por Déficit de Atención-Hiperactividad (TDAH), entre los 6 y los 11 años de edad. La valoración de las HS se realizó con la escala Behavioral Assessment System for Children para padres y maestros. Los resultados mostraron que los niños con TDAH presentan puntajes más bajos en las dimensiones de habilidades sociales como escuchar, esperar turnos, reconocer señales sociales y tener capacidad de adaptabilidad. Sin embargo, en compañerismo, los participantes con TDAH combinado poseen habilidades semejantes a los no afectados. Esto replantea lo encontrado en la mayoría de los estudios en donde únicamente se evidencian deficiencias...

The study analyzed the Social Skills (SS) of 159 male and female school children between the ages of 6 and 11, suffering from Attention Deficit Hyperactivity Disorder (ADHD). The evaluation of SS was carried out with the Behavioral Assessment System for Children for use by parents and teachers. The results showed that children with ADHD feature lower scores in social skills such as listening, respecting turns, recognizing social signals, and adaptability. However, participants with ADHD proved to have companionship skills similar to those of unaffected children. This makes it necessary to rethink the findings of the majority of studies, which only reveal deficiencies...

Analisaram-se as Habilidades Sociais (HS) de 159 crianças, escolarizadas, com Transtorno por Déficit de Atenção-Hiperatividade (TDAH), entre 6 e 11 anos de idade. A valoração das HS se realizou com a escala Behavioral Assessment System for Children para pais e mestres. Os resultados mostraram que as crianças com TDAH apresentam pontuações mais baixas nas dimensões de HS como escutar, esperar a vez, reconhecer sinais sociais e ter capacidade de adaptabilidade. Contudo, em companheirismo, os participantes com TDAH combinado possuem habilidades semelhantes aos não afetados. Isso repropõe o encontrado na maioria dos estudos nos quais unicamente se evidenciam deficiências...

Uso de una escala comportamental Wender Utah para evaluar en retrospectiva trastorno de atención-hiperactividad en adultos de la ciudad de Barranquilla / Using a Wender Utah behavioral scale to assess with hindsight adults suffering from attention-hyperactivity disorder in the city of Barranquilla

Los cuestionarios comportamentales son herramientas eficaces para caracterizar el Trastorno por Déficit de Atención e Hiperactividad (TDAH) en la edad adulta. Se determinó de forma retrospectiva, las características conductuales de adultos afectados con TDAH, utilizando la Escala Wender Utah (WURS). La muestra estuvo compuesta por 102 adultos pertenecientes a 51 familias nucleares de la ciudad de Barranquilla. El diagnóstico de TDAH se realizó aplicando una entrevista estructurada psiquiátrica para adultos validada en Colombia y usada en estudios para genética del TDAH. Se realizó un examen neurológico y una evaluación neuropsicológica. Se analizaron las puntuaciones de corte y se calculó el tamaño del efecto, la sensibilidad y la especificidad de la escala, hallándose diferencias clínica y estadísticamente significativas en las puntuaciones de la WURS, mostrando tamaños del efecto de grandes a enormes. La escala permite diferenciar los sujetos afectados de los no afectados demostrando la existencia de síntomas del TDAH de manera retrospectiva. Es importante resaltar que la WURS puede ser usada como instrumento para el rastreo de síntomas de TDAH en el adulto, sin embargo se hace necesario complementar sus resultados con otros instrumentos para la comprobación multimodal del diagnóstico.

The behavioral questionnaires are effective tools to characterize the Attention Deficit Hyperactivity Disorder (ADHD) in adulthood. It was determined the behavioral characteristics of adults with ADHD in retrospect by using the Wender Utah Rating Scale (WURS). The sample consisted of 102 adults from 51 nuclear families in the city of Barranquilla. The diagnosis of ADHD was conducted using a structured psychiatric interview validated in Colombia, which is also used for genetic studies of ADHD. A neurological examination and a neuropsychological evaluation were made. The cutting scores were analyzed and the effect size, sensitivity and specificity of the scale were calculated. It was found that there are clinical and statistical significant differences in WURS scores, which showed large to enormous effect sizes. The scale distinguishes affected subjects from the unaffected ones, which proves the existence of ADHD symptoms in retrospect. It is important to highlight the WURS can be used as a tool for screening adult ADHD symptoms. However, it is necessary to complement its results with other tools for multimodal diagnostic testing.