NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital.

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray®) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis.

Enrique Canals Infante, insigne estomatólogo pinareño en la guerra de independencia / Enrique Canals Infante: prominent dentist of Pinar del Río in the War of Independence

RESUMEN Introducción: en momentos cruciales de la nación cubana estuvieron presentes los estomatólogos que, por incorporarse a la lucha independentista, dieron su paso al frente para estar al lado del deber. Objetivo: la contribución de la actividad independentista de Enrique Canals Infante durante la época colonial, al desarrollo de la nación cubana y a la formación del modelo del profesional de la carrera de Estomatología. Métodos: se realizó una investigación histórica sustentada en el método materialista-dialéctico. Dentro del nivel teórico se emplearon métodos como el de análisis-síntesis, inducción-deducción e histórico-lógico. En el nivel empírico se realizó el análisis documental de 14 artículos bibliográficos procedentes de diferentes bases de datos, en el período de diciembre a enero 2019. Conclusiones: Enrique Canals Infante es un patriota insigne de la estomatología pinareña. Las características de la etapa colonial en Cuba y en Pinar del Río fueron determinantes para su actividad independentista, significativa en la formación de la nacionalidad cubana. Su actuar trascendió a la obra de otros revolucionarios como Isabel Rubio y Antonio Maceo, desde su espíritu de lucha contra la dominación extranjera. Los estudiantes de Estomatología son formados en los valores de patriotismo y humanismo heredados de figuras distintivas de la profesión como este héroe, con notables aportes al proceso de liberación nacional que lo convierte en un modelo a seguir para las presentes y futuras generaciones de vueltabajeros.

ABSTRACT Introduction: at crucial moments in the Cuban nation, dentists were present who, by joining the independence struggle, stepped forward to be on the side of duty. Objective: the contribution of the independence activity of Enrique Canals Infante during the colonial era to the development of the Cuban nation and to the training of a model of professional in dentistry studies. Methods: a historical research was carried out based on the materialistic-dialectic method. Within the theoretical level, methods such as analysis-synthesis, induction-deduction and historical-logical were applied. At the empirical level, the documentary analysis of 14 bibliographic articles from different databases was carried out between December and January 2019. Conclusions: Enrique Canals Infante is an outstanding patriot of Pinar del Río dentistry specialty. The characteristics of the colonial period in Cuba and in Pinar del Río were determinant for his significant independence activity in the development of Cuban nationality. His actions transcended the work of other revolutionaries as Isabel Rubio and Antonio Maceo, from his spirit of struggle against foreign domination. Dentistry students are trained in the values of patriotism and humanism inherited from distinctive figures of the profession such as this patriot, with notable contributions to the process of national emancipation; building a model to be followed for the present and future generations of Pinar del Río citizens.

Loss of function BMP4 mutation supports the implication of the BMP/TGF-ß pathway in the etiology of combined pituitary hormone deficiency.

Despite BMP4 signaling being critical to Rathke's pouch induction and maintenance during early stages of pituitary development, its implication in the etiology of combined pituitary hormone deficiency (CPHD) and other clinical presentations of congenital hypopituitarism has not yet been definitely demonstrated. We report here the first CPHD patient with a de novo pathogenic loss-of-function variant in BMP4. A 6-year-old boy, with macrocephaly, myopia/astigmatism, mild psychomotor retardation, anterior pituitary hypoplasia and ectopic posterior pituitary, clinically diagnosed with growth hormone deficiency, and central hypothyroidism, was referred for genetic analysis of CPHD. Targeted NGS analysis with a custom panel (n = 310 genes) identified a novel heterozygous de novo nonsense variant, NM_001202.5:c.794G > A, p.(Trp265*) in BMP4, which introduces a premature stop codon in the BMP4 pro-domain, impairing the transcription of the TGF-ß mature peptide domain. Additional relevant variants in other genes implicated in pituitary development signaling pathways such as SMAD4 and E2F4 (BMP/TGF-pathway), ALMS1 (NOTCH-pathway), and TSHZ1 (Prokineticin-pathway), were also identified. Our results support the implication of the BMP/TGF-ß signaling pathway in the etiology of CPHD and suggest that oligogenic contribution of additional inherited variants may modify the phenotypic expressivity of BMP4 pathogenic variants.

Conocimientos del personal estomatológico sobre la prevención de enfermedades transmisibles: Pinar del Río, 2007 / What the Dentistry personnel knows on prevention of contagious diseases: Pinar del Río, 2007

El presente estudio es una investigación analítica de corte transversal, que se realiza para evaluar los conocimientos sobre la prevención de enfermedades con riesgo de transmisión en Estomatología de los estomatólogos y técnicas de atención estomatológica (TAE), en las diferentes clínicas estomatológicas de la Ciudad de Pinar del Río entre los meses de Enero-Junio del año 2007. El universo de estudio coincide con la muestra y estuvo constituido por 60 estomatólogos y 60 técnicas de atención estomatológica, a los mismos se les aplicó un cuestionario. Una vez recogida la información se creó una base de datos con el programa Microsoft Excel, como medida resumen para los datos cualitativos se utilizó el porcentaje. Para analizar las diferencias entre grupos, se empleó el estadígrafo Chi cuadrado. Los datos se procesaran por el programa de tablas dinámicas de la hoja de calculo Excel y por el paquete estadístico SPSS, versión 8.0 para Windows, concluyendo que los estomatólogos y técnicas tienen gran necesidad de conocimientos sobre prevención de la transmisión de enfermedades con riesgo de propagación en la consulta. La mayoría de los estomatólogos y técnicos tienen evaluación de regular en la aplicación de las medidas de protección. Es contrastante que los estomatólogos en el cuestionario aplicado responden adecuadamente a las preguntas realizadas, sin embargo al observar el desempeño no se comportan de igual manera.

The present study is an analytical cross sectional study aimed at assessing what the dentistry personnel knows about the disease prevention at risk of contagious as well as the techniques in the different dental clinics in Pinar del Rio city between January and June, 2007. Universe coincides with sample and it is comprised of 60 dentists and of 60 dental care techniques using the same questionnaire in both. A data base was created using Microsoft Excel Program and the percentage method was used as a measure for the qualitative data.In order to study the differences between groups the Chi-square test was used.Data were processed using the dynamic table program from the Excel sheet and the satistical package SPSS version 8.0 Windows, it was concluded that dentists and dental techniques need to know about the prevention of the contagious disease at risk of spread to the dental care office.Most dentists and techniques are evaluated as regular according to the use of the protection measures, noting that dentists give a proper answer to the questionnaire applied and a different behaviour in the daily practice.

Caracterización de los valores de los estudiantes de primer año de estomatología / Characterization of values in 1st. year dental students

Se realiza una investigación descriptiva, cuya muestra estuvo formada por 25 estudiantes de primer año de la carrera de Estomatología de la Facultad de Ciencias Médicas Dr. Ernesto Che Guevara de la Serna de Pinar del Río, curso 2006-2007 y 6 estomatólogos docentes del ciclo clínico de dicha carrera. Con el objetivo de determinar los valores que sustentan los modos de actuación de los estudiantes de este año de la carrera, se aplicaron 2 pruebas y una dinámica grupal. Las pruebas consistieron en la redacción de una composición para determinar valores actuales y futuros y un ordenamiento de valores a partir de una hoja de recursos. A los estomatólogos se les aplicó también una prueba de ordenamiento de valores. La muestra se clasificó en 3 categorías según su estructura en relación con los valores. Se encontró una proyección psico- profesional de los estudiantes más orientada hacia los valores individuales que a los relacionados con la profesión, la proyección actual hacia el desarrollo de valores tuvo una mejor estructura que la proyección futura, por lo que se concluye la necesidad de reforzar en los estudiantes los valores propios de la profesión y los de compromiso social, con vistas a lograr un profesional integral.

A descriptive is done, whose sample comprised 25 1st. year dental students from "Dr. Ernesto Che Guevara de la Serna" Medical School (2006-2007) and 6 dental professors for such major, aimed at determining the values sustaining these students' way of performance. Two tests and a groupal dynamics were applied to them. Tests consisted of writing a composition to measure current and future values, and an ordering of values from a sheet of resources. The dental professors were also applied a test of ordering values. Students were classified into 3 categories according to their structure regarding values. It was found a psychoprofessional projection of the students more orientated towards individual values than those related to the profession. The current project towards developing values had a better structure that the future projection, that is why it is necessary to reinforce in students values related to the profession and those of social commitment, in order to achieve a comprehensive professional.

Caracterización de los valores de los estudiantes de primer año de Estomatología / Characterization of values in 1st year dental students

Se realiza una investigación descriptiva, cuya muestra estuvo formada por 25 estudiantes de primer año de la carrera de Estomatología de la Facultad de Ciencias Médicas Dr Ernesto Che Guevara de la Serna de Pinar del Río, curso 2006-2007 y 6 estomatólogos docentes del ciclo clínico de dicha carrera. Con el objetivo de determinar los valores que sustentan los modos de actuación de los estudiantes de este año de la carrera, se aplicaron 2 pruebas y una dinámica grupal. Las pruebas consistieron en la redacción de una composición para determinar valores actuales y futuros y un ordenamiento de valores a partir de una hoja de recursos. A los estomatólogos se les aplicó también una prueba de ordenamiento de valores. La muestra se clasificó en 3 categorías según su estructura en relación con los valores. Se encontró una proyección psico- profesional de los estudiantes más orientada hacia los valores individuales que a los relacionados con la profesión, la proyección actual hacia el desarrollo de valores tuvo una mejor estructura que la proyección futura, por lo que se concluye la necesidad de reforzar en los estudiantes los valores propios de la profesión y los de compromiso social, con vistas a lograr un profesional integral (AU)

A descriptive is done, whose sample comprised 25 1st year dental students from “Dr Ernesto Che Guevara de la Serna” Medical School (2006-2007) and 6 dental professors for such major, aimed at determining the values sustaining these students way of performance. Two tests and a groupal dynamics were applied to them. Tests consisted of writing a composition to measure current and future values, and an ordering of values from a sheet of resources. The dental professors were also applied a test of ordering values. Students were classified into 3 categories according to their structure regarding values. It was found a psychoprofessional projection of the students more orientated towards individual values than those related to the profession. The current project towards developing values had a better structure that the future projection, that is why it is necessary to reinforce in students values related to the profession and those of social commitment, in order to achieve a comprehensive professional (AU)