Conselho Nacional de Desenvolvimento Científico e Tecnológico

<b><i>Background/Aims:</i></b> Anxious responses are evolutionarily adaptive, but excessive fear can become disabling and lead to anxiety disorders. Translational models of anxiety might be useful sources for understanding the neurobiology of fear and anxiety and can contribute to future proposals of therapeutic intervention for the disorders studied. Brain-derived neurotrophic factor (BDNF), which is known for its importance on neuroplasticity and contextual memory, has emerged as a relevant element for emotional memory. Recent studies show that the Val<sup>66</sup>Met BDNF polymorphism correlates with various psychiatric disorders, including anxiety, but there are several differences between experimental and clinical studies. <b><i>Methods:</i></b> In this work, we review the literature focused on the BDNF Val<sup>66</sup>Met polymorphism and anxiety, and discuss biological findings from animal models to clinical studies. <b><i>Results:</i></b> As occurs with other psychiatric disorders, anxiety correlates with anatomical, behavioral and physiological changes related to the BDNF polymorphism. In animal studies, it has been shown that a significant decrease in regulated secretion from both BDNF<sub>Val/Met</sub> and BDNF<sub>Met/Met</sub> neurons represented a significant decrease in available BDNF. <b><i>Conclusion:</i></b> These studies suggest that developing pharmacological strategies facilitating the release of BDNF from synapses or prolongation of the half-life of secreted BDNF may improve the therapeutic responses of humans expressing the BDNF polymorphism.

BACKGROUND: The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates. METHODS: We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta-analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta-regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates. RESULTS: We included 41 studies conducted in 27 countries from every world region. The worldwide-pooled prevalence of mental disorders was 13.4% (CI 95% 11.3-15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7-9.1), any depressive disorder was 2.6% (CI 95% 1.7-3.9), attention-deficit hyperactivity disorder was 3.4% (CI 95% 2.6-4.5), and any disruptive disorder was 5.7% (CI 95% 4.0-8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta-analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders. CONCLUSIONS: Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.

The contamination of soils and water with metals has created a major environmental problem, leading to considerable losses in plant productivity and hazardous health effects. Exposure to toxic metals can intensify the production of reactive oxygen species (ROS), which are continuously produced in both unstressed and stressed plants cells. Some of the ROS species are highly toxic and must be detoxified by cellular stress responses, if the plant is to survive and grow. The aim of this review is to assess the mode of action and role of antioxidants in protecting plants from stress caused by the presence of heavy metals in the environment.

Francis Martin and colleagues report genome sequences for 18 species of mycorrhizal fungi and a phylogenomic analysis including 32 other fungal genomes. The study identifies cell wall-degradation genes lost in all true ectomycorrhizal species and, using gene expression data, finds candidate genes for the establishment of symbiosis. To elucidate the genetic bases of mycorrhizal lifestyle evolution, we sequenced new fungal genomes, including 13 ectomycorrhizal (ECM), orchid (ORM) and ericoid (ERM) species, and five saprotrophs, which we analyzed along with other fungal genomes. Ectomycorrhizal fungi have a reduced complement of genes encoding plant cell wall–degrading enzymes (PCWDEs), as compared to their ancestral wood decayers. Nevertheless, they have retained a unique array of PCWDEs, thus suggesting that they possess diverse abilities to decompose lignocellulose. Similar functional categories of nonorthologous genes are induced in symbiosis. Of induced genes, 7–38% are orphan genes, including genes that encode secreted effector-like proteins. Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of mycorrhiza-induced genes.

Twenty-four multiparous dairy cows (eight with ruminal cannulae) were blocked by days in milk and assigned to six balanced 4 x 4 Latin squares with 21-d periods. The four diets, formulated from alfalfa silage plus a concentrate mix based on ground high moisture ear corn, contained (dry matter basis): 1) 20% concentrate, 80% alfalfa silage (24% nonfiber carbohydrate; NFC), 2) 35% concentrate, 65% alfalfa silage (30% NFC), 3) 50% concentrate, 50% alfalfa silage (37% NFC), or 4) 65% concentrate, 35% alfalfa silage (43% NFC). Soybean meal and urea were added to make diets isonitrogenous with equal nonprotein nitrogen (NPN) (43% of total N). Total urine was collected with indwelling Folley catheters for 24 h during each period. There was no effect of diet on urinary creatinine excretion (average 29 mg/kg of BW/d). There were quadratic effects of diet on total urinary ecretion of allantoin, uric acid, and purine derivatives (allantoin plus uric acid), and on ruminal synthesis of microbial N estimated from purine derivatives; maxima occurred at about 35% dietary NFC. Urinary excretion also was estimated with spot urine samples from creatinine concentration and the mean daily creatinine excretion. Daily excretion of allantoin, uric acid, and purine derivatives estimated from spot urine sampling followed the same pattern as that observed with total collection; differences between measured and estimated urine volume were significant only for 35% dietary concentrate. Spot urine sampling appeared to yield satisfactory estimates of purine derivative excretion. Maximal urea N excretion was estimated to occur at about 31% dietary NFC. Milk allantoin secretion increased linearly with concentrate and accounted for 4 to 6% of the total purine derivative excretion. Microbial yield was maximal at 35% dietary NFC, suggesting that this was the optimal level for utilization of dietary NPN from alfalfa silage and other sources.

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Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence.

BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. CONCLUSIONS: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.

The paradigmatic feature of long-term memory (LTM) is its persistence. However, little is known about the mechanisms that make some LTMs last longer than others. In rats, a long-lasting fear LTM vanished rapidly when the D1 dopamine receptor antagonist SCH23390 was injected into the dorsal hippocampus 12 hours, but not immediately or 9 hours, after the fearful experience. Conversely, intrahippocampal application of the D1 agonist SK38393 at the same critical post-training time converted a rapidly decaying fear LTM into a persistent one. This effect was mediated by brain-derived neurotrophic factor and regulated by the ventral tegmental area (VTA). Thus, the persistence of LTM depends on activation of VTA/hippocampus dopaminergic connections and can be specifically modulated by manipulating this system at definite post-learning time points.

Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric disorders exhibit all cardinal features of inflammation, including increased circulating levels of inflammatory inducers, activated sensors, and inflammatory mediators targeting all tissues. Inflammation may contribute to the pathophysiology and clinical progression of these disorders. Of note, proinflammatory cytokines modulate mood behavior and cognition by reducing brain monoamine levels, activating neuroendocrine responses, promoting excitotoxicity (increased glutamate levels), and impairing brain plasticity. What are the sources of this chronic inflammation? Increasing evidence indicates that changes in neuroendocrine regulation, metabolism, diet/microbiota, and negative health behaviors are important triggers of inflammation. Finally, recent data indicate that early-life stress is associated with overt inflammation prior to the development of neuropsychiatric disorders.

BACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.

This paper considers the problems of robust stability analysis and robust control design for a class of uncertain linear systems with a constant time-delay. The uncertainty is assumed to be norm-bounded and appears in all the matrices of the state-space model. We develop methods for robust stability analysis and robust stabilization. The proposed methods are dependent on the size of the delay and are given in terms of linear matrix inequalities.

The impact of El Niño and La Niña events (warm and cold phases of the Southern Oscillation) on rainfall over southern Brazil is investigated through the use of a large dataset of monthly precipitation from 250 stations. This region is partly dominated by rough orography and presents different climatic regimes of rainfall. As previous global studies on Southern Oscillation–precipitation relationships used data from only two stations in southern Brazil, this region was not included in the area of consistent Southern Oscillation–related precipitation in southeastern South America. The present analysis is based on the method by Ropelewski and Halpert, the sensitivity of which is assessed for this region. The spatial structure of the rainfall anomalies associated with warm (cold) events is analyzed and subregions with coherent anomalies are determined. Their distribution indicates the influence of relief, latitude, and proximity to the ocean. These areas are subjected to further analysis to determine the seasons of largest anomalies and assess their consistency during warm (cold) events. The whole of southern Brazil was found to have strong and consistent precipitation anomalies associated with those events. Their magnitude is even larger than in Argentina and Uruguay. All of the subregions have consistent wet anomalies during the austral spring of the warm event year, with a pronounced peak in November. The southeastern part also shows a consistent tendency to higher than average rainfall during the austral winter of the following year. There is also a consistent tendency to dryness in the year before a warm event. During the spring of cold event years strong consistent dry anomalies prevail over the whole region, also with maximum magnitude in November. They are even stronger and more consistent than the wet anomalies in warm event years. Consistent anomalies do not occur over large areas in the years before and after cold events. The wet anomalies during the austral spring of the warm event year weaken and even reverse during the following January. The same tendency, though not so clear, is observable in the dry anomalies of cold events. The seasons of largest anomalies disclosed by this study differ from those found by previous global studies for other regions in southeastern South America. This study expands the area of consistent warm (cold) event-related precipitation defined by previous studies in southeastern South America by including a region of larger anomalies, and provides a spatial and temporal refinement to the warm (cold) event–precipitation relationship.

Objetivou-se avaliar a influência do tempo de incubação in situ e do tamanho de partículas sobre as estimativas das frações indigestíveis da matéria seca (MSi), da fibra em detergente neutro (FDNi) e da fibra em detergente ácido (FDAi) em alimentos e fezes bovinas. Avaliaram-se amostras de fubá de milho, casca de soja, farelo de trigo, farelo de soja, farelo de algodão, silagem de milho, capim-elefante, cana-de-açúcar, feno de capim-braquiária, palha de milho e fezes de bovinos alimentados com dietas com alto ou baixo nível de concentrado. As amostras foram processadas em moinho com peneiras de porosidade 1, 2 ou 3 mm e acondicionadas (20 mg MS/cm² de superfície) em sacos de tecido não-tecido (100 g/m²) de dimensão 4 × 5 cm. Os materiais foram divididos em três grupos, de modo que as amostras de cada grupo foram incubadas no rúmen de três novilhas mestiças (Holandês × Zebu). O procedimento de incubação foi repetido três vezes e, a cada período, procedeu-se à incubação dos grupos em animais distintos. Foram utilizados os tempos: 0, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 e 312 horas. Os teores de MSi, FDNi e FDAi foram avaliados seqüencialmente para interpretação dos perfis de degradação por modelo logístico não-linear. Não houve efeito do tamanho de partículas sobre as estimativas de FDNi e FDAi. Verificaram-se efeitos dos tamanhos de partículas sobre a velocidade de degradação da MS da silagem de milho e do fubá de milho, da FDN da cana-de-açúcar, da silagem de milho e da palha de milho e sobre a velocidade de degradação da FDA da cana-de-açúcar. Para esses alimentos, o tamanho de partícula associou-se positivamente ao tempo necessário para estimar a fração indigestível. Tempos de incubação de 240 horas para MS e FDN e de 264 horas para FDA são recomendados para obtenção de estimativas exatas das frações indigestíveis. O uso de partículas de 2 mm é recomendado por proporcionar maior precisão das estimativas.

Summary This review presents a broader approach to the implementation and study of runs of homozygosity ( ROH ) in animal populations, focusing on identifying and characterizing ROH and their practical implications. ROH are continuous homozygous segments that are common in individuals and populations. The ability of these homozygous segments to give insight into a population's genetic events makes them a useful tool that can provide information about the demographic evolution of a population over time. Furthermore, ROH provide useful information about the genetic relatedness among individuals, helping to minimize the inbreeding rate and also helping to expose deleterious variants in the genome. The frequency, size and distribution of ROH in the genome are influenced by factors such as natural and artificial selection, recombination, linkage disequilibrium, population structure, mutation rate and inbreeding level. Calculating the inbreeding coefficient from molecular information from ROH ( F ROH ) is more accurate for estimating autozygosity and for detecting both past and more recent inbreeding effects than are estimates from pedigree data ( F PED ). The better results of F ROH suggest that F ROH can be used to infer information about the history and inbreeding levels of a population in the absence of genealogical information. The selection of superior animals has produced large phenotypic changes and has reshaped the ROH patterns in various regions of the genome. Additionally, selection increases homozygosity around the target locus, and deleterious variants are seen to occur more frequently in ROH regions. Studies involving ROH are increasingly common and provide valuable information about how the genome's architecture can disclose a population's genetic background. By revealing the molecular changes in populations over time, genome‐wide information is crucial to understanding antecedent genome architecture and, therefore, to maintaining diversity and fitness in endangered livestock breeds.

BACKGROUND: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. METHODS: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. RESULTS: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. LIMITATIONS: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. CONCLUSION: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.

INTRODUCTION: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. METHODS: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). RESULTS: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). CONCLUSIONS: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

The junction conditions are studied for a shear-free isotropic fluid undergoing radial heat flow with outgoing unpolarized radiation.

AIM: The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID-5-CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test-retest, joint interview, face-to-face vs telephone application) of the SCID-5-CV in a large sample of 180 non-prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience. METHODS: The SCID-5-CV was administered face-to-face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM-5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses. RESULTS: The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test-retest interviews. CONCLUSION: The SCID-5-CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.

Este trabalho traz a avaliação e adaptação da pirâmide alimentar elaborada nos Estados Unidos em 1992 à realidade profissional brasileira dos grupos de pesquisa em alimentação e nutrição. A Pirâmide Alimentar Adaptada foi construída com os alimentos distribuídos em oito grupos (cereais, frutas, vegetais, leguminosas, leite, carnes, gorduras e açúcares) de acordo com a contribuição de cada nutriente básico na dieta. Foram estabelecidas três dietas-padrão (1 600 kcal, 2 200 kcal e 2 800 kcal), com distribuição dos macronutrientes: carboidratos (50-60%), proteínas (10-15%), lipídios (20-30%). Cada nível foi apresentado em porções mínimas e máximas a serem consumidas de acordo com as dietas referidas. Para o cálculo das dietas e definição das porções utilizou-se o software "Virtual Nutri". A Pirâmide Alimentar Adaptada pode ser utilizada como instrumento para orientação nutricional de indivíduos e grupos populacionais, respeitando-se os hábitos alimentares e as diferentes realidades regionais e institucionais.