"Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure"

Background: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.

Genetic basis of Sjögren's syndrome. How strong is the evidence?

Sjögren's syndrome (SS) is a late-onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex-dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder.

Experience in the Surgical Management of Abdominal Compartment Syndrome in the Hospital Occidente de Kennedy

The abdominal compartment syndrome (ACS) is the result of various physiological alterations produced by an abnormal increase of the intra-abdominal pressure. Some of these patients will undergo a surgical procedure for its management. Methods: This is a retrospective case series of 28 patients with ACS who required surgical treatment at the Hospital Occidente de Kennedy between 1999 and 2003. We assessed retrospectively the behavior of McNelis’s equation for prediction of the development of the ACS. Results: The leading cause of ACS in our study was intraabadominal infection (n=6 21,4%). Time elapsed between diagnosis and surgical decompression was less than 4 hours in 75% (n=21) of the cases. The variables that improved significantly after the surgical decompression were CVP (T: 4,0 p: 0,0001), PIM (T: 2,7; p: 0,004), PIA (T1,8; p:0,034) and Urine Output (T:-2,4; p:0,02). The values of BUN, Creatinine and the cardiovascular instability did not show improvement. The ICU and hospital length of stay were 11 days (SD: 9) and 18 days (SD13) respectively. Global mortality was 67,9% (n=19) and mortality directly attributable to the syndrome was 30% (n=8). The behavior of the McNelis’s equation was erratic. Conclusions: The demographic characteristics as well as disease processes associated with ACS are consistent with the literature. The association between physiological variables and ACS is heterogeneous between patients. Mortality rates attributable to ACS in our institution are within the range described world-wide. The behavior of the McNelis’s equation seems to depend greatly upon fluid balance.

Senescence-associated β-galactosidase activity in the in vitro ovarian stromal fibroblasts

Introduction: A growing biological research field is the cellular senescence, a mechanism that has been associated, under certain circumstances, with malignant transformation. Given the high incidence of ovarian cancer and its main origin from the ovarian surface epithelium, as well as the possibility that an epithelial-mesenchymal transition occurs, we evaluated both the in vitro growth of stromal fibroblasts from the ovarian cortex and their β-galactosidase activity at pH 6, enzyme whose expression is considered as a marker of replicative senescence. Methods: 48 samples of ovarian cortical fibroblasts from donors without a history of cancer were serially cultured until the end of their replicative life. β-galactosidase activity at pH 6 was quantified in each passage by the chemiluminiscent method. As control, we used ovarian epithelial cell cultures from the same donors. The enzyme activity was also evaluated in fibroblasts previously induced to senescence by exposure to hydrogen peroxide. Results: The analysis of the enzyme activity and the replicative capacity taken together showed that the fibroblast cultures reached the senescent state at passages 4-5, as what happened with the control epithelial cells. Fibroblasts induced to senescence showed high variability in the values of enzymatic activity. Conclusions: The similarity between both types of cells in reaching the senescent state deserves to be taken into account in relation to the epithelialmesenchymal transition that has been proposed to explain their behavior in the genesis of cancer arising from ovarian surface epithelium. Low β-galactosidase activity values at pH 6 would suggest possible inactivation of the response pathways to oxidative stress.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Búsqueda de selección en el polimorfismo 677C>T (c.665C>T) del gen de la metilentetrahidrofolato reductasa (MTHFR) en una población Colombiana

Se realizó un estudio genético – poblacional en dos grupos etarios de población colombiana con la finalidad de evaluar las diferencias genéticas relacionadas con el polimorfismo MTHFR 677CT en busca de eventos genéticos que soporten la persistencia de este polimorfismo en la especie humana debido que este ha sido asociado con múltiples enfermedades. De esta manera se genotipificaron los individuos, se analizaron los genotipos, frecuencias alélicas y se realizaron diferentes pruebas genéticas-poblacionales. Contrario a lo observado en poblaciones Colombianas revisadas se identificó la ausencia del Equilibrio Hardy-Weinberg en el grupo de los niños y estructuras poblacionales entre los adultos lo que sugiere diferentes historias demográficas y culturales entre estos dos grupos poblacionales al tiempo, lo que soporta la hipótesis de un evento de selección sobre el polimorfismo en nuestra población. De igual manera nuestros datos fueron analizados junto con estudios previos a nivel nacional y mundial lo cual sustenta que el posible evento selectivo es debido a que el aporte de ácido fólico se ha incrementado durante las últimas dos décadas como consecuencia de las campañas de fortificación de las harinas y suplementación a las embarazadas con ácido fólico, por lo tanto aquí se propone un modelo de selección que se ajusta a los datos encontrados en este trabajo se establece una relación entre los patrones nutricionales de la especie humana a través de la historia que explica las diferencias en frecuencias de este polimorfismo a nivel espacial y temporal.  

Asperger syndrome pocketbook.

Recurso de bolsillo que ayuda a los profesores y al personal de apoyo a entender las dificultades de los alumnos con síndrome de Asperger y les ofrece estrategias para superar los retos que plantean en el aula. El primer capítulo explica exactamente lo que es, y lo que no es, el citado síndrome, enumera sus características y destaca las complicaciones y los placeres de tener un alumno con estas dificultades en clase. Los capítulos siguientes hacen frente a desafíos específicos: deterioro social; intereses obsesivos; problemas con el cambio; la etapa de la rabia, la etapa de recuperación. Tiene ejemplos ilustrativos y soluciones prácticas. Hace referencia a recursos adicionales, programas de enseñanza, sitios web.

Simple strategies that work! : helpful hints for all educators of students with Asperger syndrome, high-functioning autism, and relates disabilities.

Recurso que ofrece enfoques y estrategias que los profesores pueden utilizar para ayudar a sus estudiantes con síndrome de Asperger y autismo en el camino hacia el éxito. Analiza los problemas que pueden surgir en el aula de inclusión y cómo los educadores pueden hacer adaptaciones para atender a sus alumnos con autismo sin interferir en las rutinas del aula estándar. Incluye información sobre lo que puede causar ansiedad en el estudiante con estas discapacidades, los posibles incrementos en los problemas de comportamiento, y lo que el profesor puede hacer para ayudar. Cuenta con diez estrategias acompañadas de ejemplos y razones por las que son importantes usarlas.

Incidence of Meares-Irlen/visual stress syndrome in reading and learning disorders : Does fluorescent lighting in classrooms affect literacy and numeracy?

Resumen tomado de la publicación

Pathomechanics of posterior ankle impingement syndrome in female ballet dancers

A dança é uma actividade de grande exigência atlética, que pode conduzir a um elevado número de lesões, particularmente na região do tornozelo, possivelmente devido à amplitude extrema do movimento articular de flexão plantar do mesmo, que os bailarinos, especialmente do sexo feminino possuem, para realizar a ponta e meia ponta tão características do ballet clássico (Kadel, 2006; Motta-Valencia, 2006; Russel, Kruse, Koutedakis, McEwan, Wyon, 2010). Estas posições de flexão plantar extrema produzem força excessiva na região posterior do tornozelo, o que muitas vezes pode resultar em conflito, dor e incapacidade, representando na maioria das vezes um desafio de diagnóstico. O síndrome do conflito posterior do tornozelo refere-se a um grupo de entidades patológicas que resultam da flexão plantar forçada do tornozelo, de forma repetitiva ou traumática, causando um conflito das estruturas ósseas e/ou de tecidos moles (Hamilton, Geppert, Thompson, 1996; Hamilton, 2008) . Os objectivos deste projecto são compreender os quais os factores de risco, mecânicos e funcionais que contribuem para a mecânica patológica da lesão descritos na literatura, e proceder a uma avaliação biomecânica do movimento de flexão plantar do tornozelo. Método. Realizar uma revisão sistemática de literatura dirigida á mecânica patológica do síndrome do conflito posterior do tornozelo em bailarinas e conduzir um estudo caso-controlo, cujo objectivo é avaliar, comparar e descrever o movimento da flexão plantar do tornozelo realizado ao efectuar os movimentos de ponta e meia-ponta, em bailarinas pré-profissionais com e sem lesão recorrente resultante do conflito posterior do tornozelo. Resultados. Não foram encontrados estudos relacionados especificamente com a mecânica patológica do tornozelo, no entanto vários estudos foram encontrados considerando as características clínicas e anatómicas assim como os procedimentos de tratamento, indicando que os principais factores de risco relacionados com a lesão se dividem em factores mecânicos e funcionais que quando combinados entre si e associados ao sobre-uso podem resultar no conflito posterior do tornozelo. Na avaliação do movimento foram observadas diferenças na actividade muscular entre os sujeitos com lesão e controlos, tendo sido possível a observação de um padrão na sequência de activação para um dos movimentos testados. Na oscilação postural e na rigidez do tornozelo foram também observadas diferenças entre os sujeitos bem como entre as posições realizadas. Conclusão. Concluiu-se que não sendo possível alterar a anatomia do bailarino, por vezes é possível intervir a nível funcional melhorando a capacidade técnica de forma obter um melhor desempenho e a actuar preventivamente em relação às lesões, uma vez que estas podem apresentar padrões cinéticos próprios, relacionados com a função muscular, a estabilidade postural e a rigidez articular.

Sociodemographic characteristics and clinical features of patients with adult polycystic kidney disease undergoing hemodialysis

Aims:To analyze the socio-demographic and clinical characteristics of patients with adult polycystic kidney disease admitted to hemodialysis services in Northwestern Paraná state,Brazil. Methods: This was an observational, descriptive and retrospective longitudinal study. Medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th Regional Health Region of Paraná state where analyzed. Results:We found that 10.3% of hemodialysis patients had polycystic kidney disease as a leading cause of stage 5 of chronic kidney disease. The mean age of patients was 54.9±9.4 years (ranging between 27 and 74 years), with equal gender distribution and Caucasian predominance (72.9%). The average age of dialysis initiation was 50±10.2 years. The most common comorbidity was systemic hypertension (66.7%). Liver cyst was the main extra-renal manifestation (10.4%). Twenty-five percent of the patients required renal transplantation, and (22.9%) undergone nephrectomy. The most widely used classes of antihypertensive drugs were β-blockers (41.7%) and drugs that act on the renin-angiotensin system (31.3%), while 56.3% of patients were treated with recombinant human erythropoietin. Conclusions:This is a pioneering epidemiological study in Northwestern Paraná state. We found in this population a sociodemographic and clinical profile of adult polycystic kidney disease similar to that of North America and Europe, probably because the ethnic constitution of the sample was predominantly of Euro-descendants.

Autosomal dominant polycystic kidney disease in hemodialysis patients in southern Brazil

Introduction: Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. Objective: To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. Methods: This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. Results: The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. Conclusion: The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe.

Acoustic reflex measurements in normals and Meniere's Syndrome using pulsed stimuli

This paper reviews a study to determine the maximum rate the acoustic reflex can follow pulsed stimuli in normal hearing subjects and in subjects with Meniere's Syndrome.

Acoustic reflex measurements in normals and Meniere's Syndrome using pulsed stimuli

This paper reviews a study to determine the maximum rate the acoustic reflex can follow pulsed stimuli in normal hearing subjects and in subjects with Meniere's Syndrome.