ADRB2 and LEPR Gene Polymorphisms: Synergistic Effects on the Risk of Obesity in Japanese

The objective of the present study was to validate a recently reported synergistic effect between variants located in the leptin receptor (LEPR) gene and in the beta-2 adrenergic receptor (ADRB2) gene on the risk of overweight/obesity. We studied a middle-aged/ elderly sample of 4,193 nondiabetic Japanese subjects stratified according gender (1,911 women and 2,282 men). The LEPR Gln223Arg (rs1137101) variant as well as both ADRB2 Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms were analyzed. The primary outcome was the risk of overweight/obesity defined as BMI >= 25 kg/m(2), whereas secondary outcomes included the risk of a BMI >= 27 kg/m(2) and BMI as a continuous variable. None of the studied polymorphisms showed statistically significant individual effects, regardless of the group or phenotype studied. Haplotype analysis also did not disclose any associations of ADRB2 polymorphisms with BMI. However, dimensionality reduction-based models confirmed significant interactions among the investigated variants for BMI as a continuous variable as well as for the risk of obesity defined as BMI >= 27 kg/m(2). All disclosed interactions were found in men only. Our results provide external validation for a male specific ADRB2-LEPR interaction effect on the risk of overweight/obesity, but indicate that effect sizes associated with these interactions may be smaller in the population studied.

Multilocus Analyses of Seven Candidate Genes Suggest Interacting Pathways for Obesity-Related Traits in Brazilian Populations

We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity-related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African-derived populations (quilombos). Seven variants displaying conflicting results in previous reports and supposedly implicated in the susceptibility of obesity-related phenotypes were investigated: beta(2)-adrenergic receptor (ADRB2) (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome proliferator-activated receptor-gamma (PPARG) (Pro12Ala), and resistin (RETN) (-420C > G). Regression models as well as generalized multifactor dimensionality reduction (GMDR) were employed to test the contribution of individual effects and higher-order interactions to BMI and waist-hip ratio (WHR) variation and risk of overweight/obesity. The best multilocus association signal identified in the quilombos was further examined in an independent sample of 334 Brazilian subjects of European ancestry. In quilombos, only the PPARG polymorphism displayed significant individual effects (WHR variation, P = 0.028). No association was observed either with the risk of overweight/obesity (BMI >= 25 kg/m(2)), risk of obesity alone (BMI >= 30 kg/m(2)) or BMI variation. However, GMDR analyses revealed an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a third-order effect involving the latter two variants plus INSIG2 (P = 0.034) with overweight/obesity. Assessment of the LEPR-ADRB2 interaction in the second sample indicated a marginally significant association (P = 0.0724), which was further verified to be limited to men (P = 0.0118). Together, our findings suggest evidence for a two-locus interaction between the LEPR Gln223Arg and ADRB2 Arg16Gly variants in the risk of overweight/obesity, and highlight further the importance of multilocus effects in the genetic component of obesity.

Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women

Objective: To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. Methods: In this double-blind, placebo-controlled Study, 47 post menopausal women 47-66 v of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (11 = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student`s t-test. Within-group changes were determined by paired Student`s t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. Results: Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both,groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment: the reason for Such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. Conclusion: The results of the present Study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will he necessary to definitively assess the safety and efficacy of isoflavone. (C) 2008 Elsevier Inc. All rights reserved.

Leucine supplementation favors liver protein status but does not reduce body fat in rats during 1 week of food restriction

An important role in protein-energy metabolism has been attributed to leucine because of its long-term effects on body fat reduction and on the improvement of some indicators of protein status in rodents. The present study investigated the influence of leucine supplementation on the body composition and protein status of rats during the early phase of weight loss, which is characterized by a rapid loss of body weight. Thirty adult male Wistar rats were divided into 2 groups, a control and a leucine group (diet supplemented with 0.59% L-leucine), and were submitted to 1 week of 50% food restriction. The following parameters were evaluated: chemical carcass composition, protein and RNA content in liver and gastrocnemius muscle, and serum concentrations of insulin-like growth factor-1 and corticosterone. A higher liver weight and liver protein content were observed in the supplemented group (p < 0.05). However, no difference in body fat was found between groups (p > 0.05). The results indicate that low-dose leucine supplementation favors liver protein status but does not reduce body fat in rats during the early phase of rapid weight loss.

Robust inference in an heteroscedastic measurement error model

In this paper we deal with robust inference in heteroscedastic measurement error models Rather than the normal distribution we postulate a Student t distribution for the observed variables Maximum likelihood estimates are computed numerically Consistent estimation of the asymptotic covariance matrices of the maximum likelihood and generalized least squares estimators is also discussed Three test statistics are proposed for testing hypotheses of interest with the asymptotic chi-square distribution which guarantees correct asymptotic significance levels Results of simulations and an application to a real data set are also reported (C) 2009 The Korean Statistical Society Published by Elsevier B V All rights reserved

Revisão sistemática e meta-análise do uso de antidepressivos no transtorno de ansiedade generalizada

Revisão da Literatura: O Transtorno de Ansiedade Generalizada (TAG) é caracterizado por preocupação excessiva, persistente e incontrolável sobre diversos aspectos da vida do paciente. Tem prevalência entre 1,6% e 5,1% e índice de comorbidades de até 90,4%. As principais comorbidades são depressão maior (64%) e distimia (37%). Os antidepressivos podem ser eficazes no tratamento do TAG. A Medicina Baseada em Evidências (MBE) busca reunir a melhor evidência disponível com experiência clínica e conhecimentos de fisiopatologia. A melhor maneira disponível de síntese das evidências é a revisão sistemática e a meta-análise. Objetivos: Investigar a eficácia e tolerabilidade dos antidepressivos no tratamento do TAG através de uma revisão sistemática da literatura e meta-análise. Sumário do artigo científico: A revisão sistemática incluiu ensaios clínicos randomizados e controlados e excluiu estudos não-randomizados, estudos com pacientes com TAG e outro transtorno de eixo I. Os dados foram extraídos por dois revisores independentes e risco relativo, diferença da média ponderada e número necessário para tratamento (NNT) foram calculados. Antidepressivos (imipramina, paroxetina e venlafaxina) foram superiores ao placebo. O NNT calculado foi de 5,5. A evidência disponível sugere que os antidepressivos são superiores ao placebo no tratamento do TAG e bem tolerados pelos pacientes.

Educação a distância online: potencialidades para a formação de professores que ensinam matemática

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spatial patterns of species richness and phylogenetic diversity of woody plants in the neotropical savannas of Brazil

Savanna woody plant communities are widespread in Brazil, where this vegetation type can be divided into core-central and marginal areas within its range of distribution. The study of diversity patterns of plant communities can provide insights into the distribution, biogeography, and diversity of plant species in widespread biomes. The objectives of this study were to measure standard and phylogenetic indices of diversity in woody plant communities of the savanna vegetation of Brazil (Cerrado) throughout its extensive range. Based on a metaanalysis, the diversity indexes were compared using traditional statistical methods, a phylogenetic approach, and by mapping. Similar patterns were found for phylogenetic and traditional indexes of diversity in core and marginal areas, suggesting that both lower and higher diversity sites can occur within the Cerrado geographical area. The only difference was found in low diversity, disjunct savanna sites within the Amazon basin, which are isolated by the Amazon River from the more continuous central-southern Cerrado area.

Revisão sistemática do perfil de risco e profilaxia de tromboembolismo venoso no Brasil e no mundo

Pós-graduação em Bases Gerais da Cirurgia - FMB

Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography Main Results From the Randomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Background-It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury. Methods and Results-We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P = 0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P = 0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment. Conclusions-In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.

Combination of noninvasive brain stimulation with pharmacotherapy

Noninvasive brain stimulation (NIBS) techniques are being increasingly investigated as a therapeutic approach for neuropsychiatric disorders. One method is to combine NIBS with pharmacotherapy to enhance the clinical effects or avoid an increase in drug dosages to decrease the incidence of side effects. However, few studies to date have investigated the relative and combined efficacy of NIBS with pharmacotherapy. Based on a literature review of previous studies and meta-analyses for major depression, we identified four randomized, controlled trials that tested the combination of NIBS with a new drug and two trials that directly compared NIBS versus pharmacotherapy. There was no study designed to address the relative efficacy of each intervention against placebo and against combined therapy. We discuss the methods and rationale of NIBS-pharmacotherapy trials, addressing some methodological aspects, including factorial design, recruitment, blinding, blinding assessment, placebo effect and quantitative aspects, such as power analysis, statistics and interaction effects. Our review of the methodology underlying NIBS-drug trials provides insights for the further clinical research development of NIBS in major depression.

Clinical Predictors Associated With Duration of Repetitive Transcranial Magnetic Stimulation Treatment for Remission in Bipolar Depression A Naturalistic Study

Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and shown to be effective for unipolar depression. Although it has also been investigated for bipolar depression (BD), there are only few rTMS studies with BD. Here, we investigated 56 patients with BD who received rTMS treatment until remission (defined as Hamilton Depression Rating Scores <= 7). We used simple and multiple logistic regressions to identify clinical and demographic predictors associated with duration of treatment (defined as <15 vs. >15 rTMS sessions). Age, refractoriness, number of prior depressive episodes, and severe depression at baseline were associated with a longer rTMS treatment. In the multivariate analysis, refractoriness (likelihood ratio (LR) = 4.33; p < 0.01) and baseline severity (LR = 0.18, p < 0.01) remained significant predictors. Our preliminary study showed that, in remitted patients, refractoriness and severity of index episode are associated with the need of a longer rTMS treatment; providing preliminary evidence of important factors associated with rTMS parameters adjustment.

Behavior problems and prevalence of asthma symptoms among Brazilian children

Objective: Asthma is the most common chronic disease in childhood and has been designated a public health problem due to the increase in its prevalence in recent decades, the amount of health service expenditure it absorbs and an absence of consensus about its etiology. The relationships among psychosocial factors and the occurrence, symptomatology, and severity of asthma have recently been considered. There is still controversy about the association between asthma and a child`s mental health, since the pathways through which this relationship is established are complex and not well researched. This study aims to investigate whether behavior problems are associated with the prevalence of asthma symptoms in a large urban center in Latin America. Methods: It is a cross-section study of 869 children between 6 and 12 years old, residents of Salvador, Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC) instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior Checklist (CBCL) was employed to evaluate behavioral problems. Results: 19.26% (n = 212) of the children presented symptoms of asthma. 35% were classified as having clinical behavioral problems. Poisson`s robust regression model demonstrated a statistically significant association between the presence of behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% Cl: 1.10-1.85). Conclusion: These results suggest an association between behavioral problems and pediatric asthma, and support the inclusion of mental health care in the provision of services for asthma morbidity. (C) 2011 Elsevier Inc. All rights reserved.

Can the `yin and yang` BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are stilt mixed. Therefore new toots to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the `yin and yang` BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS. (C) 2008 Elsevier Ltd. All rights reserved.

Evaluation of the in vitro Activity of Dermaseptin 01, a Cationic Antimicrobial Peptide, against Schistosoma mansoni

Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of dermaseptin 01 (DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, on Schistosoma mansoni adult worms. DS 01 at a concentration of 100 mg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 mg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50-200 mu g/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a dermaseptin.