Julia P. Genro

Bio: Julia P. Genro is an academic researcher from Universidade Federal de Ciências da Saúde de Porto Alegre. The author has contributed to research in topics: Attention deficit hyperactivity disorder & Methylphenidate. The author has an hindex of 24, co-authored 53 publications receiving 1774 citations. Previous affiliations of Julia P. Genro include Universidade Federal de Pelotas & Universidade Federal do Rio Grande do Sul.

The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

Abstract: Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.

Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric condition that affects approximately 5.3% of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on impairment in these two domains determining several problems in personal and academic life. Although it is known that genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. There seems to be a consensus in the literature that a fronto-subcortical dysfunction is responsible, at least in part, for the ADHD spectrum. Considering that these brain regions are rich in dopamine (DA), the DA hypothesis has an important role to understand ADHD pathophysiology. The main goal of the present review is to show evidence from different areas that support the idea that dysregulation in the DA system underlies ADHD. We discuss here evidences from animal models, pharmacology, brain imaging and genetics studies.

Association of the Adrenergic α2A Receptor Gene With Methylphenidate Improvement of Inattentive Symptoms in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Abstract: Context Preclinical studies have demonstrated the relevance of adrenergic α2A receptor on the attentional process and the mechanism of action of methylphenidate hydrochloride. Several molecular genetic investigations suggest a role for the adrenergic α2A receptor gene (ADRA2A) in attention-deficit/hyperactivity disorder (ADHD), especially in the inattentive dimension. However, the effect ofADRA2Ain the response to methylphenidate in humans has not been previously investigated, to our knowledge. Objective To evaluate the association between theADRA2A–1291 C>G polymorphism and the clinical response to methylphenidate treatment in children and adolescents with ADHD. Design A pharmacogenomic study was undertaken between November 1, 2002, and May 1, 2004, using a nonrandom assignment, quasi-experimental design. Setting An ADHD outpatient program at a university hospital in Brazil. Patients One hundred six patients consecutively diagnosed as having ADHD were genotyped for theADRA2A–1291 C>G polymorphism and were included in the analyses. Intervention Short-acting methylphenidate administered in increasing dosages until no further clinical improvement was detected or until limited adverse effects occurred. Main Outcome Measures The primary outcome measure was the parent-rated inattentive subscale of the Swanson, Nolan, and Pelham Scale version IV. Secondary outcome measures included the Barkley Side Effect Rating Scale and the parent-rated hyperactivity-impulsivity subscale of the Swanson, Nolan, and Pelham Scale version IV. Scales were applied by child psychiatrists blinded to genotype at baseline and at 1 and 3 months of treatment. Results A significant interaction effect between the presence of the G allele and treatment with methylphenidate over time on inattentive scores was detected during the 3 months of treatment (n = 106; F2,198 = 4.30;P = .02). Conclusions We documented the effect of the G allele at theADRA2A–1291 C>G polymorphism on the improvement of inattentive symptoms with methylphenidate treatment in children and adolescents with ADHD. Our findings provide clinical evidence for the involvement of the noradrenergic system in the modulation of methylphenidate action.

A current update on ADHD pharmacogenomics.

Abstract: Pharmacological treatment for attention deficit hyperactivity disorder, although highly effective, presents a marked variability in clinical response, optimal dosage needed and tolerability. Clinical and neurobiological investigations have juxtaposed findings on both response to medication and etiologic factors, generating the hypothesis that genetic factors may underlie differences in treatment outcome. Over the last decade, research has focused on the catecholaminergic system to investigate a potential role of genotype on pharmacological effect. Despite an increasing number of associations reported (for methylphenidate, nine in 2005, 24 in 2008 and 52 reported in the current article), the identification of clinically relevant genetic predictors of treatment response remains a challenge. At present, additional studies are required to allow for a shift from a trial-and-error approach to a more rational pharmacologic regimen that takes into account the likelihood of treatment effectiveness at the individual level.

No significant association between response to methylphenidate and genes of the dopaminergic and serotonergic systems in a sample of Brazilian children with attention‐deficit/hyperactivity disorder

Abstract: Few studies on pharmacogenetics of Attention-Deficit/Hyperactivity Disorder (ADHD) have been conducted. Most of them evaluated dopaminergic genes resulting in positive and negative findings. We assessed effects of polymorphisms in candidate dopaminergic (DRD4, DAT1) and serotonergic genes (HTR1B, HTR2A, and 5-HTT) on the response to treatment in 111 patients for whom methylphenidate (MPH) was prescribed. Outcome measures (Swanson, Nolan, and Pelham scale-version IV, Children Global Assessment Scale, Barkley's Stimulants Side Effects Rating Scale) were assessed at baseline and 1 month after the intervention. No significant association was detected between polymorphisms assessed and both response and side effects to MPH. Prospective multi-site controlled studies with larger sample sizes are needed in order to disentangle the role of candidate genes in response to ADHD treatment.

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

Modern Applied Statistics With S

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Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and can profoundly affect the academic achievement, well-being, and social interactions of children; the American Academy of Pediatrics first published clinical recommendations for the diagnosis and evaluation of ADHD in children in 2000; recommendations for treatment followed in 2001.