Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.

Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.

Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.

Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Biomarkers in bipolar disorder : a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force

Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.

Peripheral vascular endothelial growth factor as a novel depression biomarker: a meta-analysis

BACKGROUND: The neurotrophic hypothesis of major depressive disorder (MDD) postulates that the pathology of this illness incorporates a down-regulation of neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless, emerging evidence has implicated the multi-competent angiogenic and neurogenic molecule - vascular endothelial growth factor (VEGF) - in hippocampal neurogenesis and depression pathophysiology. OBJECTIVE: To compare peripheral levels of VEGF between individuals with MDD and healthy controls. METHODS: We performed a systematic review and meta-analysis of original studies measuring peripheral levels of VEGF in participants with MDD compared to healthy controls. We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies published in any language through December 16th, 2014. RESULTS: Fourteen studies met eligibility criteria (N=1633). VEGF levels were significantly elevated in individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI: 0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide evidence of publication bias. A significant degree of heterogeneity was observed (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta-regression and subgroup analyses. Overall methodological quality, sample for assay (plasma versus serum), as well as the matching of MDD and control samples for age and gender emerged as significant sources of heterogeneity. CONCLUSIONS: Taken together, extant data indicate that VEGF shows promise as a biomarker for MDD, and supports that this mediator may be involved in neuroplasticity mechanisms underlying the pathophysiology of MDD.

Future directions for pharmacotherapies for treatment-resistant bipolar disorder

Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has historically been discovered through serendipity. There is now scope for new drug development, focused on the underlying biology of BD that is not targeted by current therapies. The need for novel treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate (NMDA)-receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by lack of corporate interest.

Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression

Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.

Aplicação do modelo de Rams para o estudo de um vórtice ciclônico que atingiu o município de Viamão

A partir de dados do CPTEC, utilizou-se o modelo numérico Regional Atmospheric Modeling System (RAMS) para simular as condições ambientais que originaram a formação e evolução de um ciclone no dia 11 de outubro de 2000, no município de Viamão, no estado do Rio Grande do Sul. Utilizou-se três grades aninhadas, com resolução progressivamente mais refinada e de forma simultânea. O modelo simulou com bastante precisão os campos de vento, pressão, umidade relativa e temperatura potencial. As simulações foram analisadas e comparadas à dados de superfície, imagens de satélite, cartas sinóticas e radiossondagens. A topografia e a brisa marítima exerceram forte influencia no sentido de intensificar o sistema convectivo que se formou sobre o Estado do Rio grande do Sul, bem como os altos valores de umidade relativa e o intenso cisalhamento vertical. Com estes procedimentos foi possível analisar e caracterizar o perfil atmosférico do sistema estudado e definir parâmetros meteorológicos que justificaram a formação de um tornado.

Circulações atmosféricas clássicas e não-clássicas na região metropolitana de Porto Alegre/RS

O Regional Atmospheric Modeling System (RAMS), versão 3b, foi utilizado para simular o escoamento na Região Metropolitana de Porto Alegre (RMPA) para explicar a influência de circulações clássicas e não clássicas devido as proximidades do oceano e da Lagoa dos Patos, e da ilha de calor formada pelas cidades. O RAMS foi utilizado em um domínio tridimensional com duas grades sendo utilizadas, a grade mais grossa com resolução horizontal de 8 Km, e a grade mais fina com resolução horizontal de 2 Km. A inicialização do modelo é homogênea e parte do repouso, em uma situação de verão. Foram realizados 3 experimentos; o primeiro deles com apenas a grade mais grossa e com a parametrização da vegetação sendo grama curta em todo o domínio; o segundo utilizando as duas grades, sendo que a área coberta pela grade mais fina é parametrizada como deserto, nas duas grades; o terceiro diferencia-se do segundo pela adição de uma forçante térmica no primeiro nível da área coberta pela grade mais fina durante o período da noite (após o pôr do sol). Os resultados mostram que circulação de brisa lacustre/terrestre é responsável por uma forte tendência meridional no escoamento resultante sobre a RMPA, só sendo atenuada pela componente zonal da circulação de brisa marítima à partir do final da tarde. A confluência dessas duas circulações provoca uma tendência a elevação da camada de mistura. A presença da ilha de calor aumenta o movimento convectivo, com maior transporte vertical de calor sensível, e também retardou o avanço da frente de brisa marítima, embora durante a noite a sua influência não tenha sido muito significante.

Natal como destino turístico : um estudo das imagens (re)veladas pela mídia, pelos turistas e suas implicações educacionais e culturais

This thesis is a result of a research on Natal/RN as a tourist destination. We understand that cities are chosen as tourist destinations beyond its cartographic localization, from other dimensions of meanings that, in its set, constitute images. These images are, probably, very different of the images constructed by native and resident populations, who possess relations of identity with the place. The knowledge of the meanings that others attribute to this city as tourist destination, bring us near to the symbolic bonds established by individuals or social groups on the act of their choices, as well as bring us near to the interaction process city-tourists where the expectations are confirmed or not. The images divulgated by the media also participate of the complex formation of the tourist image that is being constructed and available for the different public, in different social contexts. The tourism constitutes a symbolic asset of the modern society, being considered by the studious, as one of the most expressive phenomena of the modernity, for involving each year displacement and the interaction of thousand of people of different cultures in the entire world. All this people s mobilization points to practical social related to personal motivations, to the entailed desired to the idea to travel and to exceed borders. It is already consensus that tourism is a phenomenon of economic growth, generating jobs, income, professional, qualification, bringing improvements for the host cities. Since 1995, in Brazil, the tourism as a sector of the economy, passed to be considered one of the national priorities, and in this perspective, the national politics of the tourism invested in infrastructure of Brazilian cities with high tourist potential, objecting to increase the flows of Brazilian and foreign tourists. Owing to this fact, the country still invests in programs of tourist marketing, mainly divulging the images of the natural beauties of Brazil abroad. And for Brazilians, the campaigns appeal to rescue the feeling to be Brazilian, associating the idea to travel and know its country. Natal city possesses an excellent positioning in the tourist marketing, being predominantly divulgated in national and international level, for its naturalistic singularity, where the images of its natural enchantments as warm water beaches, white dunes, warm weather, constant breeze and an always blue sky are shown as the favorite scene on this city. From what was viewed above that the choice of a tourist destination articulates from a determined imaginary of a place, already constructed or in process of construction, we consider the knowledge of this imaginary a basic learning for the population of the city and especially, for educators, in the formation of professionals in this area and for tourism managers, elaborators of public politics. Based on this estimative, we developed this research that had as a general objective to identify the images that illustrate Natal city as a tourist destination - our objective of study, particularly the meanings and senses attributed by the tourist marketing (hotel s folders) and by the tourists that visited the city during this study. The discussions and reflections that had guided this research had been given from the theoretical link between imaginary and social representation, also considering some interfaces between the fields of communication and symbol. From the studied authors, Baczko (1985) clarifies that the study of social imaginary is directed for the mechanisms and structures of the social life, especially for the intervention accomplishes and efficient of the representations and symbols in the practical collectives, as well as in its direction and orientation . Following this same thought, Moscovici (1978) says that the social representation are produced in communicational and symbolic contexts, and these representations once that already constituted circulate socially as almost tangible entities. Based on this fundament and on the analyze of Barthes (1990), particularly in the approach given to the reading of photographic image, we could observe on hotel s folders that each page evidences senses and meanings of functionality of internal and external spaces, pointing to the way of leisure offered by the keepers of city which is the hotels. About, the leisure that they offer, it is directed to young public, giving meaning to the young myth of personalized leisure tourism on children, young and adults images. The image about security that hotels offer and the singular image of Natal city as a paradise place, provide an idealization of pleasure through the sun, dunes, and beaches and also due to the hospitability of the natives who are assigned as educated . For the tourist that participated on this research, Natal city is tied only by the imaginary of leisure and nature which constitute the emotional link of the relation media-city-tourist. And with such force and fullness of directions the city discloses without tensions and contradictions as a place protected by a mythical and sacred aura. The study also demonstrates us that the potiguar culture remains (almost) forgotten, due to the silenced in this imaginary. In this perspective, we highlight that this culture silence is very close related to the disvalue of education in its general meaning. We defend that the imaginary apprehended constitutes a new reading and a new looking and understanding the tourist reality that comes historically consolidating in this city. In this direction, we glimpse that this study and its future dismemberments can collaborate with the process of rescue the cultural values of the potiguar people, in the way that the meaning of tourist may be redefined, and the tourist image of the city can be also disclosed for its identities particularities of its culture

Características qualitativas de genótipos de cebola

Objetivou-se, com o trabalho, avaliar alguns atributos de qualidade de diferentes genótipos de cebola (Allium cepa L.), cultivados em Mossoró-RN. O experimento foi realizado na horta experimental no Departamento de Ciências Vegetais da Universidade Federal Rural do Semi-Árido (UFERSA), em delineamento de blocos casualizados completos e quatro repetições. Os tratamentos foram constituídos pelos genótipos de cebola CNPH 6415, CNPH 6047, CNPH 6244, CNPH 6400 Chata, CNPH 6400 Redonda, CPACT 1, CPACT 2, CPACT 3, Granex 429, Belém IPA 9, BRS Cascata, Crioula Alto Vale, Bola Precoce, Primavera, Régia, Valeouro IPA-11, Brisa e Alfa São Francisco. As características avaliadas foram teor de sólidos solúveis totais, acidez total titulável, teor de vitamina C e teor de ácido pirúvico (pungência). Foram observadas diferenças significativas entre os genótipos para todas as características avaliadas. Os genótipos apresentaram uma variação significativa para todas as características avaliadas, confirmando dessa forma que o fator genético é determinante na caracterização de cada material. O teor de sólidos solúveis totais variou de 6,67 a 11,63 (º Brix), vitamina C de 22,7 a 46,81 (mg ácido ascórbico/100 ml de suco) e a acidez total titulável de 0,19 a 0,45 (% de ácido pirúvico). Os genótipos apresentaram pungência intermediária com variação de 5,0 a 12,73 (µmol/g), sendo os menos pungentes Granex 429, CNPH 6047, Régia, Primavera e Belém IPA 9.

Um olhar semiótico sobre o processo de indexação: a questão da representação e do referente

The indexing process is determined the subject of the document and its relation with the representation information. To cultivate the interdisciplinary contributions is essential, especially when the relationship allows substantial additions to the area of research. Rehearse some contributions in this article of Semiotics of Charles Sanders Peirce in the field of study of the indexing process, in particular, the notions of representation and referent. It is concluded that the tripartite division of the sign provides basis for to understanding the process of thematic representation, discussing the relationship of the sign with the object and the phenomenon presented, in the indexer sees the documentary language as referent.

Aspectos da representação temática pela indexação de livros: análise de Assunto e suas concepções na diversificação de áreas do conhecimento em bibliotecas dos Institutos Federais de Educação, Ciência e Tecnologia (IF's)

Pós-graduação em Ciência da Informação - FFC