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OBJECTIVES: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.
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Trastorno del Espectro Autista/tratamiento farmacológico , Buspirona/administración & dosificación , Desarrollo Infantil/efectos de los fármacos , Agonistas de Receptores de Serotonina/administración & dosificación , Buspirona/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Masculino , Tomografía de Emisión de Positrones , Serotonina/sangre , Agonistas de Receptores de Serotonina/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: We present a developmentally appropriate adolescent boy who presented with upper and lower extremity glove-and-stocking paresthesias, distal weakness, vertigo, high-pitched voice, inattention, ataxia, and binocular diplopia after a voluntary 59-kg weight loss over 5 months. CLINICAL INVESTIGATIONS: Extensive investigations revealed serum thiamine levels <2 nmol/L. Brain magnetic resonance imaging revealed symmetric abnormal T2 prolongation of the mammillary bodies. Nerve conduction studies were consistent with axonal, length-dependent polyneuropathy. Together, these findings were diagnostic for peripheral polyneuropathy and Wernicke encephalopathy secondary to thiamine deficiency. CONCLUSION: This patient illustrates that eating disorders can be an uncommon cause of rapidly progressive paresthesias, weakness, and neurological decline due to thiamine deficiency.
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Anorexia Nerviosa/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Deficiencia de Tiamina/complicaciones , Encefalopatía de Wernicke/etiología , Adolescente , Extremidades/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Tubérculos Mamilares/patología , Tiamina/sangreRESUMEN
BACKGROUND: Identification of gene regulatory networks is useful in understanding gene regulation in any organism. Some regulatory network information has already been determined experimentally for model organisms, but much less has been identified for non-model organisms, and the limited amount of gene expression data available for non-model organisms makes inference of regulatory networks difficult. RESULTS: This paper proposes a method to determine the regulatory links that can be mapped from a model to a non-model organism. Mapping a regulatory network involves mapping the transcription factors and target genes from one genome to another. In the proposed method, Basic Local Alignment Search Tool (BLAST) and InterProScan are used to map the transcription factors, whereas BLAST along with transcription factor binding site motifs and the GALF-P tool are used to map the target genes. Experiments are performed to map the regulatory network data of S. cerevisiae to A. thaliana and analyze the results. Since limited information is available about gene regulatory network links, gene expression data is used to analyze results. A set of rules are defined on the gene expression experiments to identify the predicted regulatory links that are well supported. CONCLUSIONS: Combining transcription factors mapped using BLAST and subfamily classification, together with target genes mapped using BLAST and binding site motifs, produced the best regulatory link predictions. More than two-thirds of these predicted regulatory links that were analyzed using gene expression data have been verified as correctly mapped regulatory links in the target genome.
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Biología Computacional/métodos , Redes Reguladoras de Genes , Arabidopsis/genética , Arabidopsis/metabolismo , Sitios de Unión , Proteínas Fúngicas/metabolismo , Genómica , Proteínas de Plantas/metabolismo , Proteínas de Unión al ARN/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with two sites for all members. RESULTS: We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem and therefore can be solved by an O(2k · n2) exact algorithm, where n is the number of members and k is the number of recombination events. CONCLUSIONS: Our work can therefore be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.
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BACKGROUND: Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with a small number of sites for all members. RESULTS: We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem with additional parity constraints. We solve this problem with an exact algorithm that runs in time, where n is the number of members, m is the number of sites, and k is the number of recombination events. CONCLUSIONS: This algorithm infers haplotypes for a small number of sites, which can be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.
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Abstract An O(nmα(m)) time algorithm is given for inferring haplotypes from genotypes of non-recombinant pedigree data, where n is the number of members, m is the number of sites, and α(m) is the inverse of the Ackermann function. The algorithm works on both tree and general pedigree structures with cycles. Constraints between pairs of heterozygous sites are used to resolve unresolved sites for the pedigree, enabling the algorithm to avoid problems previously experienced for non-tree pedigrees.
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Algoritmos , Haplotipos , Modelos Genéticos , LinajeRESUMEN
Secretin, a gastrointestinal (GI) hormone, was reported in a preliminary study to improve language and behavior in children with autism/pervasive developmental disorder (PDD) and chronic diarrhea. To determine the efficacy of secretin, we completed a double-blind, placebo-controlled, crossover (3 weeks) study in children with autism/PDD and various GI conditions using a single dose of intravenous porcine secretin. Children with chronic, active diarrhea showed a reduction in aberrant behaviors when treated with the secretin but not when treated with the placebo. Children with no GI problems are unaffected by either secretin or placebo. The improvement seen with secretin in children with autism/PDD and chronic diarrhea suggests that there may be a subtype of children with autism/PDD who respond to secretin.