Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency

Mutations in the creatine (Cr) transporter (CrT; Slc6a8) gene lead to absence of brain Cr and intellectual disabilities, loss of speech, and behavioral abnormalities. To date, no mouse model of CrT deficiency exists in which to understand and develop treatments for this condition. The purpose of this study was to generate a mouse model of human CrT deficiency. We created mice with exons 2–4 of Slc6a8 flanked by loxP sites and crossed these to Cre:CMV mice to create a line of ubiquitous CrT knockout expressing mice. Mice were tested for learning and memory deficits and assayed for Cr and neurotransmitter levels. Male CrT−/y (affected) mice lack Cr in the brain and muscle with significant reductions of Cr in other tissues including heart and testes. CrT−/y mice showed increased path length during acquisition and reversal learning in the Morris water maze. During probe trials, CrT−/y mice showed increased average distance from the platform site. CrT−/y mice showed reduced novel object recognition and conditioned fear memory compared to CrT+/y. CrT−/y mice had increased serotonin and 5-hydroxyindole acetic acid in the hippocampus and prefrontal cortex. Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder

Conversações sobre a "boa morte": o debate bioético acerca da eutanásia Conversations on the "good death": the bioethical debate on euthanasia

A despeito das grandes discussões hodiernas sobre a eutanásia, permanecem ainda muitos pontos em aberto, aparentemente insolúveis, aguardando que um melhor tratamento conceitual seja desenvolvido. Neste âmbito podem ser incluídos os "preconceitos e fundamentalismos" em relação ao tema — a eutanásia ainda é vista como tabu em boa parte da sociedade, especificamente no caso do Brasil —, as imprecisões semânticas do vocábulo e as acérrimas tensões argumentativas em torno do tema — levando-se em consideração os princípios da sacralidade da vida, da qualidade de vida e da autonomia e o argumento da assim chamada "ladeira escorregadia" ou slippery slope. Compor o horizonte de indagação acerca da eutanásia, partindo dos antecedentes históricos em direção a um melhor equacionamento do problema — e delimitação de perspectivas vindouras necessárias à sua melhor compreensão — é, pois, o objetivo do presente ensaio.<br>Despite extensive current debate on euthanasia, many open and apparently unsolvable issues persist, awaiting a better conceptual treatment. The area includes "prejudices and fundamentalisms" in relation to the theme, still viewed as taboo by a major share of society, specifically in the case of Brazil, while semantic imprecision in the term and argumentative tensions surround the issue, focusing on the principles of sacredness of life, quality of life, and autonomy and the so-called "slippery slope" argument. The purpose of the current essay is thus to serve as a sphere of inquiry concerning euthanasia, moving from historical antecedents towards a better solution to the problem and the demarcation of necessary future perspectives for enhanced understanding of the issue

Self-perceived health and clinical characteristics in young adult students from the brazilian northeast

Objective To analyze the association between socioeconomic situation, clinical characteristics referred and the family history of cardiovascular disease, with the Self-perceived health of young adults education and their implications for clinical characteristics observed. Method Analytical study conducted with 501 young adults who are students in countryside city in the Brazilian Northeast. We used binary logistic regression. Results The final model explained 83.3% of the self-perceived positive health, confirming the association of Self-perceived health with male, residence in the community, have excellent/very good lifestyle and does not have or do not know that there are cases of stroke in the family. Conclusion Health perception was often optimistic, being important to identify devices to be worked closer to their perception of their actual health condition, increasing the effectiveness of health promotion activities undertaken by professionals

Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo

In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment

Prevalência e características associadas à síndrome metabólica em nipo-brasileiros com e sem doença periodontal Prevalence and characteristics associated with metabolic syndrome in Japanese-Brazilians with and without periodontal disease

Verificou-se, num estudo transversal, a relação entre as doenças periodontais e a síndrome metabólica. Foram analisados dados de 1.315 nipo-brasileiros com idade entre 30 e 92 anos. Os indivíduos foram submetidos a exames físicos, odontológicos e laboratoriais. Os dados foram descritos através de médias e porcentagens e a associação entre as variáveis foi verificada por meio de regressão logística. Do total de sujeitos examinados, 215 (16,4%) apresentaram higidez periodontal, 484 (36,8%) edentulismo total, 513 (39%) gengivites, 85 (6,5%) periodontite inicial ou moderada e 18 (1,4%) periodontite avançada. A prevalência de síndrome metabólica entre os nipo-brasileiros foi 54,3%, e apesar de esta ter sido maior entre os que apresentaram periodontites quando comparados aos sem nenhum comprometimento da saúde bucal (51,5% vs. 48,8%) essa associação não foi estatisticamente significante. Neste estudo os indivíduos com síndrome metabólica se caracterizaram por pior perfil antropométrico e metabólico.<br>This cross-sectional study focused on the relationship between periodontal disease and metabolic syndrome. Data were analyzed from 1,315 Japanese-Brazilians ranging from 30 to 92 years of age, submitted to physical, laboratory, and dental exams. Means and percentages were used in the data description and logistic regression pattern in the analysis of associations among variables. 484 (36.8%) of the 1,315 were edentulous, 215 (16.4%) enjoyed periodontal health, 513 (39%) had gingivitis, 85 (6.5%), showed initial or moderate periodontitis, and 18 (1.4%) suffered from chronic periodontits. Prevalence of metabolic syndrome was 54.3%, higher among individuals with periodontitis than in the healthy (51.5% vs. 48.8%), but this association was not statistically significant. Individuals with metabolic syndrome showed a worse metabolic and anthropometric profile