1031-1034delTAAC (Leu125Stop): a novel familial UBE3A mutation causing Angelman syndrome in two siblings showing distinct phenotypes

Background More than 50 mutations in the UBE3A gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect. Case Presentation We here describe a novel UBE3A frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same UBE3A mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features. Conclusions We hypothesized that the mutation Leu125Stop causes both severe and milder phenotypes. Potential mechanisms include: i) maybe the proband has an additional problem (genetic or environmental) besides the UBE3A mutation; ii) since the two siblings have different fathers, the UBE3A mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the UBE3A mutation causes the severe phenotype; iii) this UBE3A mutation alone can cause either typical AS or the severe clinical picture seen in the proband.

Adulthood with Turner Syndrome: Quality of life, psychosocial adjustment and clinical management in 70 Italian women

Abstract Background: Turner syndrome (TS) is a chromosomal abnormality (total or partial absence of one of the sexual chromosomes in some or all cells of the body), which affects approximately 1:2000 female. Principal characteristics are short stature and gonadal disgenesis. Clinical management consist of Growth Hormone (GH) treatment and oestrogen replacement therapy (HRT), to induce development of secondary characteristics and to avoid the sequelae of oestrogen deficiency. Aim of the study: To assess clinical management, quality of life (QoL) and general psychosocial adjustment of women with TS. Population: 70 adult Caucasian females with TS (mean age: 27.8, ± 7.6; range 18-48 y.). Setting: Specialist service for Rare Disease care, University Hospital. Methods: Subjects were required to fill in questionnaires collecting ASR, WHOQOL, and 8 open questions. Data were compared with those of the Italian population or to those collected in a comparison group (70 healthy females, mean age: 27.9, ±7.3, range 21-48 y.). Results: Women with TS are educated as well as the Italian Population, but they have a less successful professional life. They show good QoL in general, but they appeared less satisfied in social area. They had statistically higher scores than the comparison group for depression, anxiety and withdrawal. Are less involved in a love relationship. Diagnosis communication was mostly performed by doctors or parents, satisfaction was higher when information was given by parents. Main preoccupation about TS are infertility, feeling of being different and future health problem. Conclusions: Italian people with TS were generally well adapted and have a good QoL, but lived more often with parents and show impaired sentimental and sexual life. They have higher degree of psychological distress compared to a comparison group. Psychological intervention should firstly address parents in order to encourage an open communication on diagnosis issues and on sexual education.

The impact of body mass index on the development of systemic inflammatory response syndrome and sepsis in patients with polytrauma

PURPOSE: Obesity is a growing problem in industrial nations. Our aim was to examine how overweight patients coped with systemic inflammatory response syndrome (SIRS) after polytrauma. METHODS: A total of 651 patients were included in this retrospective study, with an ISS≥16 and age≥16 years. The sample was subdivided into three groups: body mass index (BMI; all in kg/m(2))<25, BMI 25-30 and BMI>30, or low, intermediate and high BMI. The SIRS score was measured over 31 days after admission together with measurements of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT). Data are given as the mean±SEM if not otherwise indicated. Kruskal-Wallis and χ(2) tests were used for statistical analysis and the significance level was set at p<.05. RESULTS: The maximum SIRS score was reached in the low BMI-group at 3.4±0.4, vs. 2.3±0.1 and 2.5±0.2 in the intermediate BMI-group and high BMI-group, respectively (p<.0001). However, the maximum SIRS score was reached earlier in the BMI 25-30 group at 1.8±0.2 days, vs. 3.4±0.4 and 2.5±0.2 days in the BMI<25 and BMI>30 groups, respectively (p<.0001). The incidence of sepsis was significantly higher in the low BMI group at 46.1%, vs. 0.2% and 0% in the BMI 25-30 and BMI>30 groups, respectively (p<.0001). No significant differences in the CRP, IL-6 or PCT levels were found between groups. CONCLUSIONS: A higher BMI seemed to be protective for these patients with polytrauma-associated inflammatory problems.

Is the metabolic syndrome a new childhood disease?

Overweight and obesity in children and adolescents have become a major public health problem in recent years throughout the world. The medical consequences of obesity may manifest as an increase in the prevalence of the metabolic syndrome in children and adolescents putting them at increased risk for future cardiovascular diseases. Obesity can cause insulin resistance and might disturb glucose homeostasis eventually leading to type 2 diabetes in susceptible patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia in obese children characteristically presenting as hypertriglyceridemia and low HDL cholesterol. Even elevated blood pressure might be present in obese kids. Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The diagnostic criteria of the metabolic syndrome in children and adolescents are discussed. Thoughts about pathophysiology and therapeutic options are offered.

Pitfall in pediatric dialysis: malposition of a dialysis catheter mimicking azygos continuation syndrome

Central venous catheters are established as vascular access in hemodialysis therapy. Vascular catheter misdirection may occur and is a well known problem. We present a rare catheter malposition in a young dialysis patient with consequent dilatation of the azygos vein system, simulating the appearance of an azygos continuation syndrome.

Unilateral hypoplastic breast in a male-to-female transsexual with Poland syndrome after gender reassignment--reconstructive considerations

Gender reassignment procedures are performed more frequently nowadays due to a multidisciplinary approach and improved techniques and selection process. Many male-to-female patients require bilateral breast augmentation as part of the transformation following the gender reassignment if they fail to develop female breast features after hormonal treatment. We report on a very rare incidence of male-to-female gender reassignment in a patient with Poland syndrome. A male-to-female transsexual on hormonal therapy for gender reassignment developed one normal female-shaped breast whereas the other breast remained hypoplastic. As a male, he was not aware of his chest wall deformity but it became a major issue after successful gender reassignment surgery. Our experience with the specific reconstructive considerations and recommendations regarding our surgical approach to this complex reconstructive problem are discussed.

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

New perspectives in long QT syndrome

Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk to sudden death secondary to ventricular dysrrhythmias. Was the first cardiac channelopathy described and is probably the best understood. After a decade of the sentinel identification of ion channel mutation in LQTS, genotype-phenotype correlations have been developed along with important improvement in risk stratification and genetic guided-treatment. Genetic screening has shown that LQTS is more frequent than expected and interestingly, ethnic specific polymorphism conferring increased susceptibility to drug induced QT prolongation and torsades de pointes have been identified. A better understanding of ventricular arrhythmias as an adverse effect of ion channel binding drugs, allow the development of more safety formulas and better control of this public health problem. Progress in understanding the molecular basis of LQTS has been remarkable; eight different genes have been identified, however still 25% of patients remain genotype-negative. This article is an overview of the main LQTS knowledge developed during the last years.

Approximate decoding approaches for network coded correlated data

This paper considers a framework where data from correlated sources are transmitted with the help of network coding in ad hoc network topologies. The correlated data are encoded independently at sensors and network coding is employed in the intermediate nodes in order to improve the data delivery performance. In such settings, we focus on the problem of reconstructing the sources at decoder when perfect decoding is not possible due to losses or bandwidth variations. We show that the source data similarity can be used at decoder to permit decoding based on a novel and simple approximate decoding scheme. We analyze the influence of the network coding parameters and in particular the size of finite coding fields on the decoding performance. We further determine the optimal field size that maximizes the expected decoding performance as a trade-off between information loss incurred by limiting the resolution of the source data and the error probability in the reconstructed data. Moreover, we show that the performance of the approximate decoding improves when the accuracy of the source model increases even with simple approximate decoding techniques. We provide illustrative examples showing how the proposed algorithm can be deployed in sensor networks and distributed imaging applications.

Decoding Delay Minimization in Inter-Session Network Coding

Intra-session network coding has been shown to offer significant gains in terms of achievable throughput and delay in settings where one source multicasts data to several clients. In this paper, we consider a more general scenario where multiple sources transmit data to sets of clients over a wireline overlay network. We propose a novel framework for efficient rate allocation in networks where intermediate network nodes have the opportunity to combine packets from different sources using randomized network coding. We formulate the problem as the minimization of the average decoding delay in the client population and solve it with a gradient-based stochastic algorithm. Our optimized inter-session network coding solution is evaluated in different network topologies and is compared with basic intra-session network coding solutions. Our results show the benefits of proper coding decisions and effective rate allocation for lowering the decoding delay when the network is used by concurrent multicast sessions.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Problem of Growing Magnitude.

Hepatocellular carcinoma (HCC) is a cancer with globally rising incidence. Growing evidence supports associations between metabolic syndrome and diabetes as well as obesity and HCC arising in patients with nonalcoholic fatty liver disease (NAFLD). This constitutes a problem of alarming magnitude given the rising epidemic of these conditions. The role of diabetes seems to be particularly important when associated with obesity or cirrhosis. Excess hepatic iron may be another potential risk factor for the development of NAFLD-associated HCC. In the context of NAFLD, HCC frequently develops in a not-yet cirrhotic liver. As there are no surveillance programs for these patients, diagnosis often occurs at a tumor stage beyond curative options. Clinical, tumor, and patient characteristics in NAFLD-associated HCC differ from other etiologies. Older age and cardiovascular comorbidities may limit treatment options further. The outcome in patients with NAFLD-associated early HCC is excellent and therefore aggressive treatment should be pursued in appropriate patients. Population-based prevention to reduce the culprit-NAFLD-early recognition through targeted surveillance programs in risk-stratified patients and effective treatment of HCC associated with NAFLD are urgently needed. In this review, the authors summarize the epidemiology, risk factors, features, and prevention of NAFLD-associated HCC.

Risk factors for metabolic syndrome among overweight and obese Hispanic children attending a pediatric clinic in New Braunfels, Texas

Childhood obesity is a persistent problem in the U.S., especially among Hispanics. Health complications like hypertension, type II diabetes, and metabolic syndrome (Met-S) are being seen at younger ages, and current screening procedures may be inadequate. This study sought to describe the risk factors for Met-S present in a sample of 106 overweight and obese Hispanic children, aged 5-14 years, participating in Nutrition and Exercise Start Today (NEST), a randomized weight management intervention trial at a rural health clinic in New Braunfels, Texas; and to determine associations between these factors and other clinical and socio-demographic characteristics linked to obesity. Baseline data was analyzed for the prevalence of large waist circumference (WC), elevated blood pressure (BP), high fasting serum glucose and serum triglycerides (TG), and low serum HDL cholesterol, in relationship with selected sample characteristics. Main findings included high baseline prevalence rates of large WC (77%), reduced HDL (57%), and elevated BP (30%). WC was significantly associated with BMI percentile and the serum liver function test alanine aminotransferase (ALT) by Fisher's exact test (p<0.001 and p=0.032, respectively), while there were significant relationships between HDL and both female gender and ALT. BMI percentile and ALT were associated with all sets of Met-S diagnostic criteria examined. BMI percentile also had a strong association (p=0.005) with total number of Met-S risk factors, while ALT had a weaker association (p=0.093). WC is a low-cost, simple measure whose use may improve clinic surveillance for childhood obesity and complications like Met-S. WC, BP, HDL and ALT may be used as part of targeted screening for obesity complications like Met-S, particularly in situations where resources are limited.^

Effects of diet and exercise on metabolic syndrome and the underlying factors = Efectos de la dieta y el ejercicio sobre el síndrome metabólico y sus factores

Introducción. El número de personas que padecen síndrome metabólico ha incrementado a nivel mundial durante las últimas dos décadas. Existen numerosos estudios que tratan de comparar prevalencias según los diferentes criterios y estimaciones del riesgo metabólico. De ellos se puede concluir que el principal hallazgo ha sido recalcar la necesidad de una definición estándar universal. A pesar de estas discrepancias no hay lugar a duda sobre el problema de salud pública que esto conlleva. Se necesitan medidas y estrategias urgentes para prevenir y controlar esta emergente epidemia global y para ello se debe prestar especial atención a los cambios en el estilo de vida, fundamentalmente dieta y ejercicio. A pesar de todo, existe a día de hoy una importante controversia sobre el tipo de ejercicio más efectivo y su combinación con la dieta para conseguir mejoras en la salud. Objetivos. Estudiar los índices de riesgo metabólico empleados en la literatura científica y las terapias basadas en dieta y ejercicio para el tratamiento de los factores del síndrome metabólico en adultos con sobrepeso. Diseño de investigación. Los datos empleados en el análisis de esta tesis son, primeramente un estudio piloto, y posteriormente parte del estudio “Programas de Nutrición y Actividad Física para el tratamiento de la obesidad” (PRONAF). El estudio PRONAF es un proyecto consistente en un estudio clínico sobre programas de nutrición y actividad física para el sobrepeso y la obesidad, desarrollado en España durante varios años de intervenciones. Fue diseñado, en parte, para tratar de comparar protocolos de entrenamiento de resistencia, cargas y combinado en igualdad de volumen e intensidad, con el objetivo de evaluar su impacto en los factores de riesgo y la prevalencia del síndrome metabólico en personas con sobrepeso y obesidad. El diseño experimental es un control aleatorio y el protocolo incluye 3 modos de ejercicio (entrenamiento de resistencia, con cargas y combinado) y restricción dietética sobre diversas variables determinantes del estado de salud. Las principales variables para la investigación que comprende esta tesis fueron: actividad física habitual, marcadores de grasa corporal, niveles de insulina, glucosa, triglicéridos, colesterol total, colesterol HDL, colesterol LDL, presión arterial y parámetros relacionados con el ejercicio. Conclusiones. A) Los índices de riesgo metabólico estudiados presentan resultados contradictorios en relación al riesgo metabólico en un individuo, dependiendo de los métodos matemáticos empleados para el cálculo y de las variables introducidas, tanto en mujeres sanas como en adultos en sobrepeso. B) El protocolo de entrenamiento combinado (de cargas y de resistencia) junto con la dieta equilibrada propuesto en este estudio fue la mejor estrategia para la mejora del riesgo de síndrome metabólico en adultos con sobrepeso. C) Los protocolos de entrenamiento supervisado de resistencia, con cargas y combinado junto con la restricción nutricional, no obtuvieron mejoras sobre el perfil lipídico, más allá de los cambios conseguidos con el protocolo de dieta y recomendaciones generales de actividad física habitual en clínica, en adultos con sobrepeso. Background. Over the past two decades, a striking increase in the number of people with the MetS worldwide has taken place. Many studies compare prevalences using different criteria and metabolic risk estimation formulas, and perhaps their main achievement is to reinforce the need for a standardized international definition. Although these discrepancies, there is no doubt it is a public health problem. There is urgent need for strategies to prevent and manage the emerging global epidemic, special consideration should be given to behavioral and lifestyle, mainly diet and exercise. However, there is still controversy about the most effective type of exercise and diet combination to achieve improvements. Objectives. To study the metabolic risk scores used in the literature and the diet and exercise therapies for the treatment of the MetS factors in overweight adults. Research design. The data used in the analysis was collected firstly in a pilot study and lately, as a part of the “Programas de Nutrición y Actividad física para el tratamiento de la obesidad” study (PRONAF). The PRONAF Study is a clinical research project in nutrition and physical activity programs for overweight and obesity, carried out in Spain (2008-2011). Was designed, in part, to attempt to match the volume and intensity of endurance, strength and combined training protocols in order to evaluate their impact on risk factors and MetS prevalence in overweight and obese people. The design and protocol included three exercise modes (endurance, strength and combined training) and diet restriction, in a randomized controlled trial concerning diverse health status variables. The main variables under investigation were habitual physical activity, markers of body fat, fasting serum levels of insulin, glucose, triglycerides, total, LDL and HDL cholesterol, blood pressure and diet and exercise parameters. Main outcomes. A) The metabolic risk scores studied presented contradictory results in relation to the metabolic risk of an individual, depending on the mathematical method used and the variables included, both in healthy women and overweight adults. B) The protocol proposed for combination of strength and endurance training combined with a balance diet was the optimal strategy for the improvement of MetS risk in overweight adults. C) The intervention program of endurance, strength or combined supervised training protocol with diet restriction did not achieved further improvements in lipid profile than a habitual clinical practice protocol including dietary advice and standard physical activity recommendations, in overweight adults.

Simultaneous A8344G heteroplasmy and mitochondrial DNA copy number quantification in Myoclonus Epilepsy and Ragged-Red Fibers (MERRF) syndrome by a multiplex Molecular Beacon based real-time fluorescence PCR

The association of a particular mitochondrial DNA (mtDNA) mutation with different clinical phenotypes is a well-known feature of mitochondrial diseases. A simple genotype–phenotype correlation has not been found between mutation load and disease expression. Tissue and intercellular mosaicism as well as mtDNA copy number are thought to be responsible for the different clinical phenotypes. As disease expression of mitochondrial tRNA mutations is mostly in postmitotic tissues, studies to elucidate disease mechanisms need to be performed on patient material. Heteroplasmy quantitation and copy number estimation using small patient biopsy samples has not been reported before, mainly due to technical restrictions. In order to resolve this problem, we have developed a robust assay that utilizes Molecular Beacons to accurately quantify heteroplasmy levels and determine mtDNA copy number in small samples carrying the A8344G tRNALys mutation. It provides the methodological basis to investigate the role of heteroplasmy and mtDNA copy number in determining the clinical phenotypes.

Convulsive ergotism: epidemics of the serotonin syndrome?

Between 1085 and 1927, epidemics of convulsive ergotism were widespread east of the Rhine in Europe due to consumption of grain contaminated with ergot, which is produced by the fungus Claviceps purpurea. West of the Rhine, consumption of ergot-contaminated food caused epidemics of gangrenous ergotism. The clinical features of convulsive ergotism-muscle twitching and spasms, changes in mental state, hallucinations, sweating, and fever lasting for several weeks-suggest serotonergic overstimulation of the CNS (ie, the serotonin syndrome). The ergot alkaloids are serotonin agonists. Dihydroergotamine binds to serotonin receptors in the dorsal horn of the spinal cord, which is the site of neuropathological changes in convulsive ergotism. Dihydroergotamine given to human beings can cause the serotonin syndrome. Ergots produced by different strains of Claviceps purpurea, and those growing in different soils, may have different ergot alkaloid compositions. An alkaloid, present in high concentrations in ergots from east of the Rhine, may have caused convulsive ergotism at a circulating concentration insufficient to produce peripheral ischaemia. The serotonin syndrome may, therefore, have been a public-health problem long before it was recognised as a complication of modem psychopharmacology.