Síndrome X frágil y otras patologías asociadas al gen FMR1 / Fragile X Syndrome and Other Pathologies Associated with the FMR1 Gene / Síndrome do X frágil e outras patologias associadas ao gene FMR1

Resumen: el síndrome X frágil es la causa más frecuente de retraso psicomotor vinculado al cromosoma X en niños, con una prevalencia de 1 : 5.000 en hombres y 1 : 4.000 - 8.000 en mujeres. Además, es la causa hereditaria más asociada al síndrome del espectro autista. Esta patología posee como base etiológica la expansión del triplete CGG en el extremo distal del gen FMR1, lo que causa su silenciamiento. Los pacientes afectados con este síndrome suelen padecer de problemas conductuales, neurológicos, cardíacos y ortopédicos. Este síndrome también se relaciona con la insuficiencia ovárica primaria asociada al X frágil, y el síndrome de temblor y ataxia asociado al X frágil que afectan a la madre y al abuelo materno, y que, por su reciente descripción, podrían ser desconocidos por el personal sanitario, lo que retrasa su diagnóstico y tratamiento. El objetivo de este artículo es analizar estas enfermedades, con el fin de describir el conocimiento actual sobre su etiología, las manifestaciones clínicas, el diagnóstico y el tratamiento. Esto se realizó mediante la recopilación de artículos en Pubmed, con algunas contribuciones de las bases de datos Scielo, Redalyc, Europe PMC, Science Direct, Google Académico y Genetics Home Reference. Entre las conclusiones principales se destaca que los fenotipos asociados a la premutación del gen FMR1 contemplan mecanismos fisiopatológicos diferentes al síndrome X frágil, a pesar de estar íntimamente relacionados.

Abstract: fragile X syndrome is the most common cause of X-linked psychomotor retardation in children, with a prevalence of 1 : 5.000 in males and 1 : 4.000 -8.000 in females. It is also the hereditary cause most associated with autism spectrum syndrome. The etiological basis of this pathology is the expansion of the CGG triplet at the distal end of the FMR1 gene, which causes its silencing. Patients affected with this syndrome usually suffer from behavioral, neurological, cardiac and orthopedic problems. This syndrome is also related to Fragile X-associated primary ovarian insufficiency, and Fragile X-associated tremor and ataxia syndrome affecting the mother and maternal grandfather, which, because of their recent description, may be unknown to health care providers, delaying their diagnosis and treatment. The objective of this article is to analyze these diseases, in order to describe the current knowledge about their etiology, clinical manifestations, diagnosis and treatment. This was done by collecting articles in Pubmed, with some contributions from Scielo, Redalyc, Europe PMC, Science Direct, Google Scholar and Genetics Home Reference databases. Among the main conclusions, it is highlighted that the phenotypes associated with FMR1 gene premutation involve different pathophysiological mechanisms to Fragile X syndrome, despite being closely related.

Resumo: a síndrome do X frágil é a causa mais comum de retardo psicomotor ligado ao cromossomo X em crianças, com prevalência de 1 : 5.000 em homens e 1 : 4.000 a 8.000 em mulheres. Além disso, é a causa mais hereditária associada à síndrome do espectro do autismo. Essa patologia tem como base etiológica a expansão do trigêmeo CGG na extremidade distal do gene FMR1, o que causa seu silenciamento. Pacientes com essa síndrome geralmente sofrem de problemas comportamentais, neurológicos, cardíacos e ortopédicos. Essa síndrome também está relacionada à insuficiência ovariana primária associada ao X frágil, à síndrome do tremor e à ataxia associada ao X frágil, que acometem a mãe e o avô materno, e que, devido à sua descrição recente, poderiam ser desconhecidas pelos profissionais de saúde, o que atrasa seu diagnóstico e tratamento. O objetivo deste artigo é analisar essas doenças, a fim de descrever o conhecimento atual sobre sua etiologia, manifestações clínicas, diagnóstico e tratamento. Isso foi feito através da recopilação de artigos no Pubmed, com algumas contribuições das bases de dados Scielo, Redalyc, Europe PMC, Science Direct, Google Academic e Genetics Home Reference. Dentre as principais conclusões, destaca-se que os fenotipos associados à premutação do gene FMR1 incluem outros mecanismos fisiopatológicos além da síndrome do X frágil, apesar de eles estarem intimamente relacionados.

A phosphoinositide-based model of actin waves in frustrated phagocytosis.

Phagocytosis is a complex process by which phagocytes such as lymphocytes or macrophages engulf and destroy foreign bodies called pathogens in a tissue. The process is triggered by the detection of antibodies that trigger signaling mechanisms that control the changes of the cellular cytoskeleton needed for engulfment of the pathogen. A mathematical model of the entire process would be extremely complicated, because the signaling and cytoskeletal changes produce large mechanical deformations of the cell. Recent experiments have used a confinement technique that leads to a process called frustrated phagocytosis, in which the membrane does not deform, but rather, signaling triggers actin waves that propagate along the boundary of the cell. This eliminates the large-scale deformations and facilitates modeling of the wave dynamics. Herein we develop a model of the actin dynamics observed in frustrated phagocytosis and show that it can replicate the experimental observations. We identify the key components that control the actin waves and make a number of experimentally-testable predictions. In particular, we predict that diffusion coefficients of membrane-bound species must be larger behind the wavefront to replicate the internal structure of the waves. Our model is a first step toward a more complete model of phagocytosis, and provides insights into circular dorsal ruffles as well.

Current state of iodine nutrition in Filipino school-aged children.

OBJECTIVES: Globally, although progress in eliminating iodine deficiency disorders (IDD) has been reported, IDD is still considered to be a global health problem. As school-aged children are the most accessible population group, their urinary iodine (UI) concentration data are accepted and used as an indicator of IDD for the general population. The aim of this study was to reassess the national, regional, and provincial estimates of UI as a measure of IDD among Filipino school-aged children. METHODS: Casual urine samples were collected from 22 588 children, 6 to 12 y of age, from participating households in the eighth National Nutrition Survey. UI was determined based on the catalytic action of iodine in the Sandell-Kolthoff reaction and IDD was evaluated using criteria from the World Health Organization, United Nations Children's Fund, International Council for Control of Iodine Deficiency Disorders criteria. RESULTS: The median UI level among Filipino school-aged children was 168 µg/L, corresponding to optimal iodine nutrition; whereas 23.2% had UI reflective of excessive iodine intake. Cjildren in the Zamboanga Peninsula Region had median UI level of 68 µg/L and 41.1% of participants had UI values <50 µg/L, which is indicative of mild iodine deficiency. Children from Guimaras and Zamboanga del Norte, or 2.4% of the provinces, had moderate iodine deficiency. CONCLUSION: Although the median UI level of school-age children was optimal, there are pockets of inadequacy and excessive intake that need special concern for targeted intervention.

Getting in shape and swimming: the role of cortical forces and membrane heterogeneity in eukaryotic cells.

Recent research has shown that motile cells can adapt their mode of propulsion to the mechanical properties of the environment in which they find themselves-crawling in some environments while swimming in others. The latter can involve movement by blebbing or other cyclic shape changes, and both highly-simplified and more realistic models of these modes have been studied previously. Herein we study swimming that is driven by membrane tension gradients that arise from flows in the actin cortex underlying the membrane, and does not involve imposed cyclic shape changes. Such gradients can lead to a number of different characteristic cell shapes, and our first objective is to understand how different distributions of membrane tension influence the shape of cells in an inviscid quiescent fluid. We then analyze the effects of spatial variation in other membrane properties, and how they interact with tension gradients to determine the shape. We also study the effect of fluid-cell interactions and show how tension leads to cell movement, how the balance between tension gradients and a variable bending modulus determine the shape and direction of movement, and how the efficiency of movement depends on the properties of the fluid and the distribution of tension and bending modulus in the membrane.

Miocardiopatía arritmogénica del ventrículo derecho / Arrytmogenic right ventricular dysplasia

La miocardiopatía arritmogénica del ventrículo derecho es una patología, en la mayoría de los casos de origen genético autosómico dominante caracterizado por el compromiso, tanto morfológico como funcional, del ventrículo derecho en el que se reemplaza el tejido del miocardio normal por tejido fibroadiposo, generando un sustrato arritmogénico. Se debe sospechar en todo paciente joven que presente síncope, taquiarritmia ventricular o paro cardiaco. Su diagnóstico se establece por la sumatoria de criterios que incluyen hallazgos morfológicos, electrocardiográficos y alteraciones funcionales. En la actualidad no hay un tratamiento único establecido; sin embargo, se sigue trabajando en el diagnóstico temprano y el uso de terapias más avanzadas. Se realiza una revisión de la literatura en el contexto de la presentación de un caso clínico diagnosticado en la ciudad de Bucaramanga en un adulto joven de género masculino. MÉD.UIS. 27(3):123-134.

Arrhythmogenic right ventricular dysplasia is a pathology, mostly genetic of dominant autosomic pattern characterized by both morphologic and functional compromise of the right ventricle in which normal myocardial tissue its replaced by fibrous and adipose tissue generating an arrhythmogenic substrate. It must be evaluated in all young patients presenting syncope, ventricular tachyarrhythmia or cardiac arrest. Its diagnosis it's established upon the consideration of morphological criteria, electrocardiographic findings and functional alterations. Currently there is not a definite treatment established; however there is ongoing research in early diagnosis and advanced therapies usage. In this article we provide a literature review in the context of a clinical case diagnosed in a male young adult from the city of Bucaramanga in Colombia. MÉD.UIS. 27(3):123-134.

Iron absorption from NaFeEDTA-fortified oat beverages with or without added vitamin C.

BACKGROUND: Food fortification is the best long-term approach for reducing the incidence of iron deficiency. OBJECTIVE: To determine iron absorption from NaFeEDTA-fortified oat beverages without and with vitamin C. MATERIALS AND METHODS: Iron absorption in 19 apparently healthy 6-year-old children was studied. Two oat beverages fortified with iron (labeled with stable isotopes of NaFeEDTA), zinc, and vitamin A, without and with vitamin C was consumed in two consecutive days in random order. Blood samples were taken 14 days later for stable isotope measurements. RESULTS: The mean fractional iron absorption from the fortified oat beverage without vitamin C (5.65 ± 0.54%) was significantly lower than that from the beverage with vitamin C (7.14 ± 0.90%; p < 0.05). CONCLUSION: Fortified oat beverages may offer a convenient and effective mechanism to improve the iron status of children. The addition of vitamin C improved iron absorption by an additional 1.5%.

Neuropatía multifocal motora en el oriente colombiano

Un hombre de 37 años de edad ingresó al Hospital Universitario Ramón González Valencia por presentar pie caído bilateral, debilidad muescular, fasciculaciones y calambres los cuales se presentaron inicialmente en miembros inferiores y luego en los superiores, sugiriendo inicialmente esclerosis lateral amiotrófica. Sin embargo, al efectuar diversos estudios neurofosiológicos se encontraron signos de desmielinización de nervios motores y prominentes bloqueos de conducción, más notorios a la altura del punto de Erb en el nervio cubital izquierdo. El cuadro clínico junto con estos hallazgos neurofisiológicos nos permitieron hacer el diagnóstico de neuropatía multifocal motora, la cual y hasta donde conocemos sería el primer caso descrito en la literatura colombiana

Transplante de tejido compuesto utilizando la técnica de anastomosis microvascular: estudio experimental

Se realizó un estudio experimental, en el cual 11 perros fueron sometidos a transplante de tejido compuesto, aplicándo la técnica de anastomosis microvascular bajo la visión de microscopio quirúrgico. Los tejidos transplantados fueron: yeyuno (1 caso), colon (1 caso), tiroides (1 caso, mama (1 caso), riñón (6 casos) y un caso de revascularización cerebral. Con el objeto de medir la eficiencia de la técnica se analizó la evolución y el reintegro de los transplantes. Todos los casos se siguieron basta la muerte o el sacrificio, para efectuar estudios post-morten. Los resultados demostraron que las causas de muerte no se dibieron al transplante en sí, sino al manejo anestésico, y desnutrición postoperatoria, excepto en un caso en que se encontró trombosis de la vena renal que sí pueda atribuirse a deficiencia de la anastomosis