Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

Aim: To identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians. Methods: 295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable. Results: Baseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels <= 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status. Conclusion: The whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Reciprocal Modulation of Cognitive and Emotional Aspects in Pianistic Performances

Background: High level piano performance requires complex integration of perceptual, motor, cognitive and emotive skills. Observations in psychology and neuroscience studies have suggested reciprocal inhibitory modulation of the cognition by emotion and emotion by cognition. However, it is still unclear how cognitive states may influence the pianistic performance. The aim of the present study is to verify the influence of cognitive and affective attention in the piano performances. Methods and Findings: Nine pianists were instructed to play the same piece of music, firstly focusing only on cognitive aspects of musical structure (cognitive performances), and secondly, paying attention solely on affective aspects (affective performances). Audio files from pianistic performances were examined using a computational model that retrieves nine specific musical features (descriptors) - loudness, articulation, brightness, harmonic complexity, event detection, key clarity, mode detection, pulse clarity and repetition. In addition, the number of volunteers' errors in the recording sessions was counted. Comments from pianists about their thoughts during performances were also evaluated. The analyses of audio files throughout musical descriptors indicated that the affective performances have more: agogics, legatos, pianos phrasing, and less perception of event density when compared to the cognitive ones. Error analysis demonstrated that volunteers misplayed more left hand notes in the cognitive performances than in the affective ones. Volunteers also played more wrong notes in affective than in cognitive performances. These results correspond to the volunteers' comments that in the affective performances, the cognitive aspects of piano execution are inhibited, whereas in the cognitive performances, the expressiveness is inhibited. Conclusions: Therefore, the present results indicate that attention to the emotional aspects of performance enhances expressiveness, but constrains cognitive and motor skills in the piano execution. In contrast, attention to the cognitive aspects may constrain the expressivity and automatism of piano performances.

Brazilian Adaptation of the Woodcock-Johnson III Cognitive Tests

An adaptation of the standard battery of Woodcock-Johnson III Tests of Cognitive Abilities (WJ-III) for Brazilian children and youth was investigated. The sample was composed of 1094 students (54 percent girls), ages 7-17, living in Sao Paulo state (91 percent). Items from Brazilian school books as well as from the WJ-III Spanish version (Bateria-R) were added to comprehension-knowledge tests. Brazilian words were adapted to the auditory tests according to syllabic division and stressed syllables. Items were examined through IRT and age differences through analysis of variance. Results indicated the need to remove items from all WJ-III subtests with the exception of the visual learning test. Analysis of Variance indicated significant age differences (p <= 0.001) for all tests. Thus, the importance of a Brazilian adaptation for the WJ-III was confirmed.

Identification of a juvenile hormone esterase-like gene in the honey bee, Apis mellifera L. - Expression analysis and functional assays

Tight control over circulating juvenile hormone (JH) levels is of prime importance in an insect`s life cycle. Consequently, enzymes involved in JH metabolism, especially juvenile hormone esterases (JHEs), play major roles during metamorphosis and reproduction. In the highly eusocial Hymenoptera, JH has been co-opted into additional functions, primarily in the development of the queen and worker castes and in age-related behavioral development of workers. Within a set of 21 carboxylesterases predicted in the honey bee genome we identified one gene (Amjhe-like) that contained the main functional motifs of insect JHEs. Its transcript levels during larval development showed a maximum at the switch from feeding to spinning behavior, coinciding with a JH titer minimum. In adult workers, the highest levels were observed in nurse bees, where a low JH titer is required to prevent the switch to foraging. Functional assays showed that Amjhe-like expression is induced by JH-III and suppressed by 20-hydroxyecdysone. RNAi-mediated silencing of Amjhe-like gene function resulted in a six-fold increase in the JH titer in adult worker bees. The temporal profile of Amjhe-like expression in larval and adult workers, the pattern of hormonal regulation and the knockdown phenotype are consistent with the function of this gene as an authentic JHE. (C) 2008 Elsevier Inc. All rights reserved.

Activity of the medial prefrontal cortex and amygdala underlies one-trial tolerance of rats in the elevated plus-maze

The anxiolytic effects of benzodiazepines are reduced after a single exposure of rats to elevated plus-maze test (EPM). Midazolam showed an anxioselective profile in animals submitted to one session (T1) but did not change the usual exploratory behavior of rats exposed twice (T2) to the EPM. In this study we examined further the one-trial tolerance by performing a factor analysis of the exploratory behavior of rats injected with saline before both trials as well as an immunohistochemistry study for quantification of Fos expression in encephalic structures after these sessions. Factor analysis of all behavioral categories revealed that factor I consisted of anxiety-related categories in T1 whereas these same behavioral categories loaded on factor 2 in T2. Risk assessment was also dissociated as it loaded stronger on T2 (factor 3) than on T1 (factor 4). Locomotor activity in T1 loaded on factor 5. Immunohistochemistry analyses showed that Fos expression predominated in limbic structures in T1 group. The medial prefrontal cortex and amygdala were the main areas activated in T2 group. These data suggest that anxiety and risk assessment behaviors change their valence across the EPM sessions. T2 is characterized by the emergence of a fear factor, more powerful risk assessment and medial prefrontal cortex activation. The amygdala functions as a switch between the anxiety-like patterns of T1 to the cognitive control of fear prevalent in T2. The EPM retest session is proposed as a tool for assessing the cognitive activity of rodents in the control of fear. (c) 2007 Elsevier B.V. All rights reserved.

Wavelet correlation between subjects: A time-scale data driven analysis for brain mapping using fMRI

Functional magnetic resonance imaging (fMRI) based on BOLD signal has been used to indirectly measure the local neural activity induced by cognitive tasks or stimulation. Most fMRI data analysis is carried out using the general linear model (GLM), a statistical approach which predicts the changes in the observed BOLD response based on an expected hemodynamic response function (HRF). In cases when the task is cognitively complex or in cases of diseases, variations in shape and/or delay may reduce the reliability of results. A novel exploratory method using fMRI data, which attempts to discriminate between neurophysiological signals induced by the stimulation protocol from artifacts or other confounding factors, is introduced in this paper. This new method is based on the fusion between correlation analysis and the discrete wavelet transform, to identify similarities in the time course of the BOLD signal in a group of volunteers. We illustrate the usefulness of this approach by analyzing fMRI data from normal subjects presented with standardized human face pictures expressing different degrees of sadness. The results show that the proposed wavelet correlation analysis has greater statistical power than conventional GLM or time domain intersubject correlation analysis. (C) 2010 Elsevier B.V. All rights reserved.

Analyzing the connectivity between regions of interest: An approach based on cluster Granger causality for NRI data analysis

The identification, modeling, and analysis of interactions between nodes of neural systems in the human brain have become the aim of interest of many studies in neuroscience. The complex neural network structure and its correlations with brain functions have played a role in all areas of neuroscience, including the comprehension of cognitive and emotional processing. Indeed, understanding how information is stored, retrieved, processed, and transmitted is one of the ultimate challenges in brain research. In this context, in functional neuroimaging, connectivity analysis is a major tool for the exploration and characterization of the information flow between specialized brain regions. In most functional magnetic resonance imaging (fMRI) studies, connectivity analysis is carried out by first selecting regions of interest (ROI) and then calculating an average BOLD time series (across the voxels in each cluster). Some studies have shown that the average may not be a good choice and have suggested, as an alternative, the use of principal component analysis (PCA) to extract the principal eigen-time series from the ROI(s). In this paper, we introduce a novel approach called cluster Granger analysis (CGA) to study connectivity between ROIs. The main aim of this method was to employ multiple eigen-time series in each ROI to avoid temporal information loss during identification of Granger causality. Such information loss is inherent in averaging (e.g., to yield a single ""representative"" time series per ROI). This, in turn, may lead to a lack of power in detecting connections. The proposed approach is based on multivariate statistical analysis and integrates PCA and partial canonical correlation in a framework of Granger causality for clusters (sets) of time series. We also describe an algorithm for statistical significance testing based on bootstrapping. By using Monte Carlo simulations, we show that the proposed approach outperforms conventional Granger causality analysis (i.e., using representative time series extracted by signal averaging or first principal components estimation from ROIs). The usefulness of the CGA approach in real fMRI data is illustrated in an experiment using human faces expressing emotions. With this data set, the proposed approach suggested the presence of significantly more connections between the ROIs than were detected using a single representative time series in each ROI. (c) 2010 Elsevier Inc. All rights reserved.

Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS): Description of a rare non-exon 3 and a novel CIAS1 missense mutation

We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

Optimizing the CAMCOG test in the screening for mild cognitive impairment and incipient dementia: saving time with relevant domains

Objective: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer`s disease (AD) in clinical practice. Methods: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. Results: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC = 0.80 +/- 0.03 for the reduced CAMCOG; AUC = 0.79 +/- 0.03 for the original CAMCOG). Conclusion: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice. Copyright (C) 2010 John Wiley & Sons, Ltd.

Higher Serum sTNFR1 Level Predicts Conversion from Mild Cognitive Impairment to Alzheimer`s Disease

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer`s disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor alpha (TNF-alpha) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-alpha and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-alpha, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 +/- 10.0 months. At baseline, there were no statistically significant differences in serum TNF-alpha, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-alpha and sTNFR2. Abnormal activation of TNF-alpha signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.

Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats

Several epidemiological studies have linked particulate matter exposure to numerous adverse health effects on the respiratory, cardiovascular, and reproductive systems (Braga et al., 1999; Zanobetti et al., 2000; Anderson et al., 2001; Farhat et al., 2005). More recently, ambient levels of black carbon were associated to impaired cognitive function in children (Suglia et al., 2008), suggesting that the central nervous system (CNS) may be a target of air pollutants. The present study was conducted to (a) determine whether chronic residual oil fly ash (ROFA) exposure promotes behavioral changes and lipid peroxidation in rat brain areas, and (b) determine whether N-acetylcysteine (NAC), a general antioxidant, prevents these effects. Forty-five-day-old male Wistar rats were exposed or not to ROFA by intranasal instillation and were treated or not with NAC (150 mg/kg) ip for 30 days. One day later, rats were submitted to the open field test to evaluate the motor/exploratory activities and emotionality followed by decapitation. Striatum and cerebellum were dissected to determine lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBARS). ROFA instillation induced an increase in lipid peroxidation level in striatum (p = .033) and cerebellum (p = .030), as compared with the control group. NAC treatment blocked these changes. ROFA promoted a decrease in the frequency of peripheral walking (p = .006) and a decrease in exploration (p = .001), which were not blocked by N-acetylcysteine. The present study provides evidence that toxic particles, administered by the respiratory route, induce oxidative stress in structures of the central nervous system, as well as behavioral alterations. The administration of NAC reduces lipid peroxidation at the striatum and cerebellum levels, but does not influence behavioral disturbances.

Screening for Alzheimer`s Disease Among Illiterate Elderly: Accuracy Analysis for Multiple Instruments

One of the challenges in screening for dementia in developing countries is related to performance differences due to educational and cultural factors. This study evaluated the accuracy of single screening tests as well as combined protocols including the Mini-Mental State Examination (MMSE), Verbal Fluency animal category (VF), Clock Drawing test (CDT), and Pfeffer Functional Activities Questionnaire (PFAQ) to discriminate illiterate elderly with and without Alzheimer`s disease (AD) in a clinical sample. Cross-sectional study with 66 illiterate outpatients diagnosed with mild and moderate AD and 40 illiterate normal controls. Diagnosis of AD was based on NINCDS-ADRDA. All patients were submitted to a diagnostic protocol including a clinical interview based on the CAMDEX sections. ROC curves area analyses were carried out to compare sensitivity and specificity for the cognitive tests to differentiate the two groups (each test separately and in two by two combinations). Scores for all cognitive (MMSE, CDT, VF) and functional assessments (PFAQ) were significantly different between the two groups (p < 0.001). The best screening instruments for this sample of illiterate elderly were the MMSE and the PFAQ. The cut-off scores for the MMSE, VF, CDT, and PFAQ were 17.5, 7.5, 2.5, and 11.5, respectively. The most sensitive combination came from the MMSE and PFAQ (94.1%), and the best specificity was observed with the combination of the MMSE and CDT (89%). Illiterate patients can be successfully screened for AD using well-known screening instruments, especially in combined protocols.

Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Objectives. Abnormalities in neurotrophic systems have been reported in Alzheimer`s disease (AD), as shown by decreased serum brain-derived neurotrophic factor (BDNF) levels and association with BDNF genetic polymorphisms. In this study, we investigate whether these findings can be detected in patients with mild cognitive impairment (MCI), which is recognized as a high risk condition for AD. We also address the impact of these variables on the progression of cognitive deficits within the MCI-AD continuum. Methods. One hundred and sixty older adults with varying degrees of cognitive impairment (30 patients with AD, 71 with MCI, and 59 healthy controls) were longitudinally assessed for up to 60 months. Baseline serum BDNF levels were determined by sandwich ELISA, and the presence of polymorphisms of BDNF and apolipoprotein E (Val66Met and APOE*E4, respectively) was determined by allelic discrimination analysis on real time PCR. Modifications of cognitive state were ascertained for non-demented subjects. Results. Mean serum BDNF levels were reduced in patients with MCI and AD, as compared to controls (509.2 +/- 210.5; 581.9 +/- 379.4; and 777.5 +/- 467.8 pg/l respectively; P < 0.001). Baseline serum BDNF levels were not associated with the progression of cognitive impairment upon follow-up in patients with MCI (progressive MCI, 750.8 +/- 463.0; stable MCI, 724.0 +/- 343.4; P = 0.8), nor with the conversion to AD. Although Val66Met polymorphisms were not associated with the cross-sectional diagnoses of MCI or AD, the presence of Met-BDNF allele was associated with a higher risk of disease-progression in patients with MCI (OR = 3.0 CI(95%) [1.2-7.8], P = 0.02). We also found a significant interaction between the APOE*E4 and Met-BDNF allele increasing the risk of progression of cognitive impairment in MCI patients (OR = 4.4 CI(95%) [1.6-12.1], P = 0.004). Conclusion. Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.

Behavioral disturbances in Noonan Syndrome: Brazilian preliminary data

Different from other countries Of Europe and North American, studies about the behavioral profile of Noonan syndrome`s patients are inexistent. The objective of this study was to report the profiles of behavioral functions of 10 participants (4 females and 6 males), with mutations in the PTPN11 gene. For this assessment it was used the Inventory of Behaviors of Children and Adolescents from 6 to 18 years (CBCL/6-18) and the Inventory of Auto-Evaluation for Adults from 18 to 59 years (ASR). The main results point that in Adaptive Functioning Scale all the participants were in the normality range. In the Syndrome Scale the adult participants were in normality range and the children were in clinical range to the sub-scales anxious/depressed, somatic complaints and aggressive behavior. In the DSM-Oriented Scale, 25% of the adult patients were in the borderline clinical range and clinical range, respectively, for Avoidant Personality Problems and Antisocial Personality Problems. About the both children in this scale were in the clinical range of Affective Problems and Anxiety Problems. This relatively homogenous sample, regarding the PTPN11 gene, shows a normal adult behavioral profile, on the average. However, the individual children anti adult profiles show diverse internalizing and externalizing behavioral disturbances.

Diagnostic transitions in mild cognitive impairment subtypes

Background: At least for a subset of patients, the clinical diagnosis of mild cognitive impairment (MCI) may represent an intermediate stage between normal aging and dementia. Nevertheless, the patterns of transition of cognitive states between normal cognitive aging and MCI to dementia are not well established. In this study we address the pattern of transitions between cognitive states in patients with MCI and healthy controls, prior to the conversion to dementia. Methods: 139 subjects (78% women, mean age, 68.5 +/- 6.1 years; mean educational level, 11.7 +/- 5.4 years) were consecutively assessed in a memory clinic with a standardized clinical and neuropsychological protocol, and classified as cognitively healthy (normal controls) or with MCI (including subtypes) at baseline. These subjects underwent annual reassessments (mean duration of follow-up: 2.7 +/- 1.1 years), in which cognitive state was ascertained independently of prior diagnoses. The pattern of transitions of the cognitive state was determined by Markov chain analysis. Results: The transitions from one cognitive state to another varied substantially between MCI subtypes. Single-domain MCI (amnestic and non-amnestic) more frequently returned to normal cognitive state upon follow-up (22.5% and 21%, respectively). Among subjects who progressed to Alzheimer`s disease (AD), the most common diagnosis immediately prior conversion was multiple-domain MCI (85%). Conclusion: The clinical diagnosis of MCI and its subtypes yields groups of patients with heterogeneous patterns of transitions between one given cognitive state to another. The presence of more severe and widespread cognitive deficits, as indicated by the group of multiple-domain amnestic MCI may be a better predictor of AD than single-domain amnestic or non-amnestic deficits. These higher-risk individuals could probably be the best candidates for the development of preventive strategies and early treatment for the disease.