Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder

Objective: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naive adults with obsessive-compulsive disorder (OCD). Method: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. Results: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p = 0.008); higher verbal memory on the California Verbal Learning Test (p = 0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p = 0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p = 0.002). Conclusion: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context. (C) 2012 Elsevier Inc. All rights reserved.National Council for Scientific and Technological Development (CNPq: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [521369/96-7, 475919/2006-8, 481791/2004-3]Foundation for the Support of Research in the State of Sao Paulo (FAPESP: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [05/55628-08, 05/04206-6, 06/61459-7, 06/50273-0, 06/58286-3

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Dilatação dos confins: caminhos, vilas e cidades na formação da Capitania de São Paulo (1532-1822)

Este ensaio analisa a formação da rede urbana das capitanias de São Vicente e Santo Amaro, depois unidas na Capitania de São Paulo. Discute o processo de apropriação do sertão, a pulsação e dilatação dos confins ao sabor dos deslocamentos humanos e de interesses políticos. Interpreta o papel de capelas, freguesias, vilas e cidades no controle e produção de territórios metropolitanos em solos ultramarinos.This essay analyzes the development of urban networks in the Captaincies of São Vicente and Santo Amaro, later merged into the Captaincy of São Paulo. It discusses the process of appropriation of the sertão (backcountry), the commotion and expansion beyond the confines to the tune of population movements and political interests. The paper also interprets the role of chapels, parishes, villages and towns in initiatives to create and control metropolitan areas on overseas soil

Perfectionism and sensory phenomena: phenotypic components of obsessive-compulsive disorder

Background: The aim of the study was to investigate how perfectionism and sensory phenomena (SP) interact as possible phenotypic components of obsessive-compulsive disorder (OCD). Methods: Forty-seven adult outpatients, meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for OCD, and a control group of 41 community subjects were assessed using the Frost Multidimensional Perfectionism Scale (FM PS), the University of Sao Paulo-Sensory Phenomena Scale, and other standard measures of OCD severity. Results: Three of the FMPS subscales (""concern over mistakes,"" ""doubts about action,"" and ""parental criticism"") were significantly different between OCD patients and control subjects. All subtypes of SP were significantly more frequent and more severe in OCD than in control subjects. The ""incompleteness"" subtype of SP was associated with high scores on all dimensions of the FMPS, whereas the ""just-right"" subtype of SP was only associated with ""doubts about action,"" ""personal standards,"" and ""organization"" subscales of the FMPS. Conclusions: Presence and severity of SP and specific elements of perfectionism clearly distinguish OCD patients from healthy control subjects. Some SP subtypes are associated with specific FPMS subscale scores, whereas others are not. These results emphasize the relevance of assessing different subtypes of perfectionism and SP in OCD patients as important subcomponents of the OCD phenotype. (C) 2009 Elsevier Inc. All rights reserved.Downs International Health Student Travel Fellowship, Yale University (JCL)FAPESP Foundation for the Support of Research in the State of Sao Paulo[1999/08560-6]FAPESP Foundation for the Support of Research in the State of Sao Paulo[1998/15013-9]FAPESP Foundation for the Support of Research in the State of Sao Paulo[2003/07451-6]FAPESP Foundation for the Support of Research in the State of Sao Paulo[2005/55628-8]CNPq Brazilian Council for Scientific and Technological Development[521369/96-7]CNPq Brazilian Council for Scientific and Technological Development[133339/2004-1]National Institute of Mental Health (NIH)[K05MH076273

Características relatadas sobre animais agressores submetidos ao diagnóstico de raiva, São Paulo, Brasil, 1993-2007 Characteristics of biting animals submitted to rabies diagnosis, São Paulo State, Brazil, 1993-2007

As pesquisas relativas a agressões por animais baseiam-se em dados de registros de pacientes atendidos nos serviços de vigilância epidemiológica da raiva. Analisaram-se as características de animais agressores, obtidas a partir de dados de 10.616 fichas de envio de amostras para diagnóstico da raiva na região noroeste do Estado de São Paulo, Brasil, entre 1993-2007. Desse total de fichas, 61,5% continham informações sobre agressão e, dentre os animais agressores (25%), a maioria foi de cães (67%), seguidos por gatos (21,8%) e quirópteros (8,1%). Em 92,1% dos relatos as vítimas eram pessoas e 82,3% dos animais eram domiciliados. A maioria dos cães agressores tinha até um ano de idade. Houve associação significante (p < 0,0001) entre agressividade e sexo, sendo os machos mais agressores do que as fêmeas. Dos animais positivos para raiva, 75,9% (183/241) eram agressores. Os dados obtidos são importantes para a instituição de programas de prevenção de mordeduras, baseados no perfil não só da vítima, mas também do animal agressor, além de permitirem estabelecer fatores de risco para ocorrência de agressões.<br>Epidemiological factors related to animal bites in humans and other animals were obtained from a database with 10,616 records of animal specimens sent for rabies diagnosis in northwest São Paulo State, Brazil, from 1993 to 2007. Of this total, 61.5% contained information on the bites, and among the biting animals (25%), the majority were dogs (67%), followed by cats (21.8%), and bats (8.1%). In 92.1% of the reports the victims were humans, and 82.3% of the animals were home pets. The majority of the biting dogs were less than a year old. There was a significant association (p < 0.0001) between aggressiveness and gender (with male animals more aggressive than females). Of the rabies-positive animals, 75.9% (183/241) were biters. The data are important for establishing bite prevention programs based on the profile of both victims and biting animals, besides identifying risk factors for animal bites

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description Estudo de genética, imagem, cognição e resposta a tratamento em pacientes com TOC virgens de tratamento: métodos e descrição da amostra

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.<br>OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica

Resolution of Singularities: an Introduction.

International audienceThe problem of resolution of singularities and its solution in various contexts can be traced back to I. Newton and B. Riemann. This paper is an attempt to give a survey of the subject starting with Newton till the modern times, as well as to discuss some of the main open problems that remain to be solved. The main topics covered are the early days of resolution (fields of characteristic zero and dimension up to three), Zariski's approach via valuations, Hironaka's celebrated result in characteristic zero and all dimensions and its subsequent strenthenings and simplifications, existing resutls in positive characteristic (mostly up to dimension three), de Jong's approach via semi-stable reduction, Nash and higher Nash blowing up, as well as reduction of singuarities of vector fields and foliations. In many places, we have tried to summarize the main ideas of proofs of various results without getting too much into technical details