Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries.

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling.

Rapid ovarian transcript changes during the onset of premature ovarian insufficiency.

The manuscript has been submitted without altering abstract in line with Reproduction's Flexible Submission Process. The abstract is extended and thus does not fit this space.

The Enigmatic Reissner's Fiber and the Origin of Chordates.

Reissner's fiber (RF) is a secreted filament that floats in the neural canal of chordates. Since its discovery in 1860, there has been no agreement on its primary function, and its strong conservation across chordate species has remained a mystery for comparative neuroanatomists. Several findings, including the chemical composition and the phylogenetic history of RF, clinical observations associating RF with the development of the neural canal, and more recent studies suggesting that RF is needed to develop a straight vertebral column, may shed light on the functions of this structure across chordates. In this article, we will briefly review the evidence mentioned above to suggest a role of RF in the origin of fundamental innovations of the chordate body plan, especially the elongation of the neural tube and maintenance of the body axis. We will also mention the relevance of RF for medical conditions like hydrocephalus, scoliosis of the vertebral spine and possibly regeneration of the spinal cord.

Clinical, radiological, and molecular diagnosis of progressive fibrodysplasia ossificans / Diagnóstico clínico, radiológico y molecular de fibrodisplasia osificante progresiva

Abstract Background: Progressive fibrodysplasia ossificans is a rare genetic disease with heterozygous mutations (autosomal dominant inheritance) in the ACVR1 gene, which causes progressive heterotopic ossification in muscles, tendons, and ligaments, usually secondary to trauma. The ossification foci generate pain, joint ankyloses, and restricted movement. Congenital shortening and medial deviation first metatarsal of the foot is a distinctive feature. This report aimed to present an educational value case of a patient with clinical, imaging, and molecular diagnosis of progressive fibrodysplasia ossificans, recognized as a rare condition that severely affects the quality of life. Case report: We present the case of a 6-year-old female patient with lumps in the right scapular and dorsal region, progressive joint rigidity, and short first metatarsal medially deviated since birth. By imaging studies, we established the diagnosis of progressive fibrodysplasia ossificans. Sanger sequencing of ACVR1 reported c.617G>A (p.Arg206His). Conclusions: Confirmation of the diagnosis allowed genetic counseling, including a comprehensive explanation of the disease’s natural history and measures to prevent its rapid progression.

Resumen Introducción: La fibrodisplasia osificante progresiva es una enfermedad genética poco frecuente, causada por variantes patogénicas en estado heterocigoto (herencia autosómica dominante) en el gen ACVR1, que provoca osificación heterotópica progresiva en músculos, tendones y ligamentos, comúnmente secundaria a traumatismos. Los focos de osificación generan dolor, anquilosis articular y restricción del movimiento. Es característico el acortamiento congénito y la desviación medial del primer metatarsiano del pie. El objetivo de este reporte es presentar un caso de alto valor educativo de una paciente con diagnóstico clínico, imagenológico y molecular de fibrodisplasia osificante progresiva, reconocida como una condición infrecuente y que afecta de manera grave la calidad de vida. Caso clínico: Paciente de sexo femenino con tumoraciones induradas en la región dorsal y escapular, detectadas a los 6 años de vida. Cursaba además con rigidez articular progresiva y primer metatarsiano del pie acortado y con desviación en sentido medial desde el nacimiento. Por estudios de imagen se estableció el diagnóstico de fibrodisplasia osificante progresiva. Por secuenciación Sanger se reportó c.617G>A (p.Arg206His) en ACVR1. Conclusiones: La confirmación del diagnóstico permitió ofrecer un asesoramiento genético integral, incluyendo una amplia explicación de la evolución natural del padecimiento y de las medidas preventivas para disminuir su rápida progresión.

Clinical, radiological, and molecular diagnosis of progressive fibrodysplasia ossificans.

BACKGROUND: Progressive fibrodysplasia ossificans is a rare genetic disease with heterozygous mutations (autosomal dominant inheritance) in the ACVR1 gene, which causes progressive heterotopic ossification in muscles, tendons, and ligaments, usually secondary to trauma. The ossification foci generate pain, joint ankyloses, and restricted movement. Congenital shortening and medial deviation first metatarsal of the foot is a distinctive feature. This report aimed to present an educational value case of a patient with clinical, imaging, and molecular diagnosis of progressive fibrodysplasia ossificans, recognized as a rare condition that severely affects the quality of life. CASE REPORT: We present the case of a 6-year-old female patient with lumps in the right scapular and dorsal region, progressive joint rigidity, and short first metatarsal medially deviated since birth. By imaging studies, we established the diagnosis of progressive fibrodysplasia ossificans. Sanger sequencing of ACVR1 reported c.617G>A (p.Arg206His). CONCLUSIONS: Confirmation of the diagnosis allowed genetic counseling, including a comprehensive explanation of the disease's natural history and measures to prevent its rapid progression.

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes.

Although the cerebral hemispheres are among the defining characters of vertebrates, each vertebrate class is characterized by a different anatomical organization of this structure, which has become highly problematic for comparative neurobiology. In this article, we discuss some mechanisms involved in the generation of this morphological divergence, based on simple spatial constraints for neurogenesis and mechanical forces generated by increasing neuronal numbers during development, and the different cellular strategies used by each group to overcome these limitations. We expect this view to contribute to unify the diverging vertebrate brain morphologies into general, simple mechanisms that help to establish homologies across groups.

Identification of genomic copy number variations in lung benign metastasizing leiomyomatosis.

OBJECTIVES: Lung metastasizing leiomyomatosis (LML) is an infrequently diagnosed pathology developed after sexual maturation, commonly preceded by uterine myomas. Symptoms can include difficulties to breathe, cough, dyspnea and pain, because of mechanical obstruction exerted by expanding local growing leiomyomas. Lung leiomyomas are normally detected by imaging studies, but nowadays the precise diagnosis demands histological characterization of biopsies obtained from the affected tissues. The purpose of the present study was to determine the presence of genomic alterations in circulating cells of LML. METHODS: Immunohistochemical characterization of a lung biopsy extracted by thoracoscopy was performed. Pathologic proliferative smooth muscle cells were observed in a major lung metastasizing nodule, with a growing pattern similar to a uterine myoma. The presence of cellular linages different to smooth muscle cells was discarded by testing the presence of a battery of molecular markers. Also, a normal karyotype was determine by GTG-banding cytogenetic study, but a high density microarray analysis revealed six submicroscopic chromosomal regions displaying genomic abnormalities: microduplications were detected on chromosomes 4, 14, 17 and 22; and microdeletions on chromosomes 8 and 10. CONCLUSION: This study remarks the relevance of submicroscopic chromosomal analysis of unusual pathologic conditions such as Benign Metastasizing Leiomyomatosis. This propitiate a better understanding of the molecular basis on the development of the pathology, in order to reckon on minimally invasive diagnostic methods, and to design appropriate treatments.

Ciberacoso Sexual en adolescentes: creencias erróneas / Sexual cyberbullying in adolescents: wrong beliefs

El objetivo de este estudio ha sido identificar las creencias erróneas sostenidas por los adolescentes sobre el fenómeno del Ciberacoso Sexual Juvenil a partir de la realización de 5 grupos de discusión con un total de 37 estudiantes valencianos de Secundaria y Bachiller entre 14 y 18 años. El análisis interpretativo de los datos revela que los estudiantes entienden el fenómeno como una dinámica interaccional con varias fases mediante las que un adulto fácilmente identificable ("mito del viejo verde") emplea estrategias predominantemente agresivas pretende obtener beneficios de tipo sexual contactándoles a través de Internet. Los participantes reconocen que es una situación habitual pero evitable si se detectan ciertas señales de alarma ("mito de la detectabilidad" y "falacia de control") que derivan únicamente de su sentido común ("mito de la invencibilidad"), por lo que consideran a las víctimas responsables de su situación y atribuyen su silencio al "miedo razonable", a la reprobación social, la estigmatización y el castigo. Además, interpretan los intentos de protección de los adultos como faltas de confianza y amenazas para su libertad de acción online, rechazando por ello su supervisión y/o saltándose las normas. En conclusión, existen creencias erróneas que podrían contribuir al inicio y mantenimiento de la dinámica de victimización cuya identificación puede servir para diseñar programas de prevención más eficaces y estrategias de intervención más específicas.

The main objective of this study was to identify misconceptions of teenagers about online sexual harassment. In order to do this five discussion groups were held with a total of 37 high-school students from Valencia, between 14 and 18 years of age. Interpretative analysis of the data reveals that teenagers understand the phenomenon as an interactional dynamics with several phases through which an easily identifiable man ("myth of the dirty old man") that contacts them through Internet intends to obtain sexual benefits by using predominantly aggressive strategies. They recognize this is a very frequent yet easily avoidable situation if certain signs of alarm are detected ("detectability myth" and "control fallacy") by using one's own common sense ("the myth of invincibility") -this is why they consider the victim responsible for his/her own situation and attribute the victim's silence to the "reasonable fear" of social disapproval, stigmatization and punishment. In addition, teenagers interpret any adult attempt of protection as a lack of trust and as a threat to their freedom regarding their online-activity, so they reject this supervision and/or break the rules. In conclusion, misconceptions that might contribute to the onset and maintenance of the dynamics of victimization exist and their identification can help design more effective prevention programs and more specific intervention strategies

Patrón alimentario de pacientes mexicanas con cáncer de mama y obesidad / Dietary patterns of Mexican patients with breast cancer and obesity

Introducción: La dieta ha sido implicada en muchos mecanismos relacionados con el desarrollo de carcinogénesis, incluyendo apoptosis, diferenciación del ciclo celular, inflamación y angiogénesis. Objetivo: Evaluar la asociación del patrón del consumo de alimentos con el cáncer de mama en pacientes con obesidad. Métodos: Estudio transversal comparativo en 98 mujeres obesas con menopausia y cáncer de mama de reciente diagnóstico y 95 mujeres obesas sin cáncer de mama, con menopausia. Se aplicó un cuestionario semi-cuantitativo de 116 ítems de frecuencia de consumo de alimentos, se evaluó edad, IMC, antecedentes ginecoobstétricos, tabaquismo y alcohol. Se realizó ajuste de modelos multivariados de regresión logística utilizando el software STATA V 11. Resultados: El hallazgo principal fue que las pacientes que tenían un consumo de vitamina B2 por debajo de la recomendación, tuvieron 6,74 veces la posibilidad de presentar cáncer de mama, con un valor de p=0,06 comparada con mujeres que tenían un consumo adecuado de vitamina B2. El modelo de regresión fue ajustado por edad, IMC, glucosa, triglicéridos séricos y dieta. Discusión: Los resultados muestran asociación marginalmente significativa entre el consumo de vitamina B2 por debajo de la recomendación con la presencia de cáncer de mama. Hallazgo similar a lo reportado por otros autores, quienes encontraron evidencia débil de una asociación inversa entre el riesgo de cáncer de mama y la ingestión de riboflavina. La metionina, vitamina B12, vitamina B6, riboflavina están involucradas en el metabolismo de grupos metilo. Conclusiones: Los resultados de este estudio sustentan la necesidad de seguir fortaleciendo los esfuerzos sobre los procesos para comprender la complejidad y los problemas que constituyen el uso de las estimaciones individuales de la ingestión de nutrimentos individuales y potencial papel de las vitaminas del complejo B como protectoras contra este tipo de cáncer (AU)

Introduction: Diet has been implicated in many mechanisms related to the development of carcinogenesis, including apoptosis, cell cycle differentiation, inflammation and angiogenesis. Objective: To evaluate the association of the pattern of food consumption with breast cancer in obese patients. Methods: Comparative cross-sectional study in 98 obese women with menopause and newly diagnosed breast cancer and 95 obese women without breast cancer, with menopause. A semi-quantitative questionnaire of 116 items of food consumption frequency was applied, age, BMI, gyneco- obstetric history history, smoking and alcohol were evaluated. Adjustment of multivariate logistic regression models using the STATA V 11 software. Results: The main finding was that patients who had a vitamin B2 intake below the recommendation had a 6.74-fold chance of developing breast cancer, with a value of p = 0.06 compared to women who had adequate intake Of vitamin B2. The regression model was adjusted for age, BMI, glucose, serum triglycerides and diet. Discussion: The results show a marginally significant association between vitamin B2 intake below the recommendation with the presence of breast cancer. Findings similar to those reported by other authors, who found weak evidence of an inverse association between breast cancer risk and riboflavin intake. Methionine, vitamin B12, vitamin B6, riboflavin are involved in the metabolism of methyl groups. Conclusions: The results of this study support the need to further strengthen efforts on processes to understand the complexity and problems of using individual estimates of individual nutrient intakes and the potential role of B vitamins as protectors against this Type of cancer (AU)

Intramolecular radical non-reductive alkylation of ketones via transient enamines.

Radical cyclization of dichloroacetamide-tethered ketones using pyrrolidine, AIBN and TTMSS under microwave activation gave 2-azabicyclo[3.3.1]nonan-3,6-diones. In a five-minute one-pot process, after the generation of an enamine, intramolecular addition of a carbamoylchloromethyl radical, and oxidation of the α-aminoalkyl radical intermediate, the resulting iminium salt evolved to the corresponding enamine and, after a workup, to the alkylated ketone.

From sauropsids to mammals and back: New approaches to comparative cortical development.

Evolution of the mammalian neocortex (isocortex) has been a persisting problem in neurobiology. While recent studies have attempted to understand the evolutionary expansion of the human neocortex from rodents, similar approaches have been used to study the changes between reptiles, birds, and mammals. We review here findings from the past decades on the development, organization, and gene expression patterns in various extant species. This review aims to compare cortical cell numbers and neuronal cell types to the elaboration of progenitor populations and their proliferation in these species. Several progenitors, such as the ventricular radial glia, the subventricular intermediate progenitors, and the subventricular (outer) radial glia, have been identified but the contribution of each to cortical layers and cell types through specific lineages, their possible roles in determining brain size or cortical folding, are not yet understood. Across species, larger, more diverse progenitors relate to cortical size and cell diversity. The challenge is to relate the radial and tangential expansion of the neocortex to the changes in the proliferative compartments during mammalian evolution and with the changes in gene expression and lineages evident in various sectors of the developing brain. We also review the use of recent lineage tracing and transcriptomic approaches to revisit theories and to provide novel understanding of molecular processes involved in specification of cortical regions.

Asociación de factores de riesgo de preeclampsia en mujeres mexiquenses / Association preeclampsia risk factors in mexiquenses women

Introducción: La preeclampsia es aún uno de los mayores problemas obstétricos en países en vías de desarrollo.Objetivo: Identificar los principales factores de riesgo para desarrollar preeclampsia en mujeres mexiquenses atendidas en el Hospital Materno Perinatal "Mónica Pretelini Sáenz".Material y métodos: Estudio de casos y controles, se incluyeron dos grupos, el grupo A casos (n=138) y el grupo B controles (n=276) con relación caso-control de 1:2.Los criterios de definición para los casos fueron: mujeres con diagnóstico inicial de preeclampsia y que cuenten con las siguientes mediciones: Tensión Arterial Sistólica (TAS)=140 ó Tensión Arterial Diastólica (TAD)=90 mmHg más una de las siguientes: concentración de proteínas en orina de 24 h =300 ó Proteinuria =++. El grupo de controles quedó conformado por mujeres que acudieron al hospital para atención del embarazo sin preeclampsia. Resultados: La media de edad fue de 27.5±8.0 para los casos (grupo A) y 25.3±6.7 para los controles (grupo B) (P<0.01). El tener 1 o más óbitos (P<0.045), las cifras iniciales y finales de TAS y TAD, el índice de masa corporal pregestacional (IMCPG), el peso al final del embarazo, y la hipertensión arterial sistémica crónica (P<0.01) así como el haber padecido preeclampsia en algún embarazo previo fueron estadísticamente significativo (P<0.01) para tener preeclampsia. Conclusiones: En nuestra población, además de los factores de riesgo tradicionales para preeclampsia se agrega el antecedente de óbitos como otro factor de riesgo para padecer preeclampsia.

Introduction: Preeclampsia is still a major obstetric problem in developing countries. Objective: To identify the main risk factors to develop preeclampsia in women from the State of Mexico attended at the Maternal Perinatal Hospital "MónicaPreteliniSáenz". Materials and methods: In this case-control study, two groups were included, group A patients (n = 138) and B controls (n = 276) with a case-control ratio of 1: 2. The criteria for defining cases were women initially diagnosed with preeclampsia and who had the following measurements: Systolic Blood Pressure (SBP) =140 or diastolic blood pressure (DBP) =90 mmHg plus one of the following: =300 protein concentration in a 24-h urine sample or proteinuria = ++. The control group was made up of women attended at the hospital who did not develop preeclampsia. Results: The mean age was 27.5 ± 8.0 years for the cases (group A) and 25.3 ± 6.7 years for controls (group B) (P <0.01). Having 1 or more stillbirth (P <0.045), initial and final measures of SBP and DBP, the pre-pregnancy body mass index (IMCPG), weight in late pregnancy, and chronic hypertension (P <0.01) as well as having had preeclampsia in a previous pregnancy were statistically significant (P <0.01) to have preeclampsia. Conclusions: In our population, in addition to the traditional risk factors for preeclampsia, history of stillbirthswas is another risk factor to develop preeclampsia.

Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.

We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.

Olfaction, navigation, and the origin of isocortex.

There are remarkable similarities between the brains of mammals and birds in terms of microcircuit architecture, despite obvious differences in gross morphology and development. While in reptiles and birds the most expanding component (the dorsal ventricular ridge) displays an overall nuclear shape and derives from the lateral and ventral pallium, in mammals a dorsal pallial, six-layered isocortex shows the most remarkable elaboration. Regardless of discussions about possible homologies between mammalian and avian brains, a main question remains in explaining the emergence of the mammalian isocortex, because it represents a unique phenotype across amniotes. In this article, we propose that the origin of the isocortex was driven by behavioral adaptations involving olfactory driven goal-directed and navigating behaviors. These adaptations were linked with increasing sensory development, which provided selective pressure for the expansion of the dorsal pallium. The latter appeared as an interface in olfactory-hippocampal networks, contributing somatosensory information for navigating behavior. Sensory input from other modalities like vision and audition were subsequently recruited into this expanding region, contributing to multimodal associative networks.

Pallial patterning and the origin of the isocortex.

Together with a complex variety of behavioral, physiological, morphological, and neurobiological innovations, mammals are characterized by the development of an extensive isocortex (also called neocortex) that is both laminated and radially organized, as opposed to the brain of birds and reptiles. In this article, we will advance a developmental hypothesis in which the mechanisms of evolutionary brain growth remain partly conserved across amniotes (mammals, reptiles and birds), all based on Pax6 signaling or related morphogens. Despite this conservatism, only in mammals there is an additional upregulation of dorsal and anterior signaling centers (the cortical hem and the anterior forebrain, respectively) that promoted a laminar and a columnar structure into the neocortex. It is possible that independently, some birds also developed an upregulated dorsal pallium.