Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study.

BACKGROUND Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. CONCLUSIONS These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Dominant PRPF31 Mutations Are Hypostatic to a Recessive CNOT3 Polymorphism in Retinitis Pigmentosa: A Novel Phenomenon of "Linked Trans-Acting Epistasis".

Mutations in PRPF31 are responsible for autosomal dominant retinitis pigmentosa (adRP, RP11 form) and affected families show nonpenetrance. Differential expression of the wildtype PRPF31 allele is responsible for this phenomenon: coinheritance of a mutation and a higher expressing wildtype allele provide protection against development of disease. It has been suggested that a major modulating factor lies in close proximity to the wildtype PRPF31 gene on Chromosome 19, implying that a cis-acting factor directly alters PRPF31 expression. Variable expression of CNOT3 is one determinant of PRPF31 expression. This study explored the relationship between CNOT3 (a trans-acting factor) and its paradoxical cis-acting nature in relation to RP11. Linkage analysis on Chromosome 19 was performed in mutation-carrying families, and the inheritance of the wildtype PRPF31 allele in symptomatic-asymptomatic sibships was assessed-confirming that differential inheritance of wildtype chromosome 19q13 determines the clinical phenotype (P < 2.6 × 10(-7) ). A theoretical model was constructed that explains the apparent conflict between the linkage data and the recent demonstration that a trans-acting factor (CNOT3) is a major nonpenetrance factor: we propose that this apparently cis-acting effect arises due to the intimate linkage of CNOT3 and PRPF31 on Chromosome 19q13-a novel mechanism that we have termed "linked trans-acting epistasis."

Distinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.

Certain cell-surface receptors engage ligands expressed on juxtaposed cells and ligands on the same cell. The structural basis for trans versus cis binding is not known. Here, we showed that Ly49 natural killer (NK) cell receptors bound two MHC class I (MHC-I) molecules in trans when the two ligand-binding domains were backfolded onto the long stalk region. In contrast, dissociation of the ligand-binding domains from the stalk and their reorientation relative to the NK cell membrane allowed monovalent binding of MHC-I in cis. The distinct conformations (backfolded and extended) define the structural basis for cis-trans binding by Ly49 receptors and explain the divergent functional consequences of cis versus trans interactions. Further analyses identified specific stalk segments that were not required for MHC-I binding in trans but were essential for inhibitory receptor function. These data identify multiple distinct roles of stalk regions for receptor function.

Sequential analysis of trans-SNARE formation in intracellular membrane fusion.

SNARE complexes are required for membrane fusion in the endomembrane system. They contain coiled-coil bundles of four helices, three (Q(a), Q(b), and Q(c)) from target (t)-SNAREs and one (R) from the vesicular (v)-SNARE. NSF/Sec18 disrupts these cis-SNARE complexes, allowing reassembly of their subunits into trans-SNARE complexes and subsequent fusion. Studying these reactions in native yeast vacuoles, we found that NSF/Sec18 activates the vacuolar cis-SNARE complex by selectively displacing the vacuolar Q(a) SNARE, leaving behind a Q(bc)R subcomplex. This subcomplex serves as an acceptor for a Q(a) SNARE from the opposite membrane, leading to Q(a)-Q(bc)R trans-complexes. Activity tests of vacuoles with diagnostic distributions of inactivating mutations over the two fusion partners confirm that this distribution accounts for a major share of the fusion activity. The persistence of the Q(bc)R cis-complex and the formation of the Q(a)-Q(bc)R trans-complex are both sensitive to the Rab-GTPase inhibitor, GDI, and to mutations in the vacuolar tether complex, HOPS (HOmotypic fusion and vacuolar Protein Sorting complex). This suggests that the vacuolar Rab-GTPase, Ypt7, and HOPS restrict cis-SNARE disassembly and thereby bias trans-SNARE assembly into a preferred topology.

Perda da espontaneidade da ação: o desconforto de homens que sofreram infarto agudo do miocardio

Considerando que conforto - cuja promoção é uma das metas centrais da enfermagem -- e desconforto devem ser entendidos àluz das interações vivenciadas pelo paciente - e, portanto, vinculadas aos fatores objetivos das instituições, da nacionalidade epráticas que as fundamentam - este estudo investigou os significados de conforto e desconforto na perspectiva de homens quesofreram infarto agudo do miocárdio (IAM). Recorrendo ao Interacionismo Simbólico eàmetodologia da Teoria Fundamentadanos Dados, entrevistas foram feitas com 13 homens que sofreram IAM, em duas unidades de saúde na cidade de São Paulo. Aanálise permitiu construir um modelo teórico daqueles significados nessa experiência, caracterizada por três fenômenos eessencialmente permeada pelo desconforto de "padecer a perda da espontaneidade daação ".Este artigo resume o processopsicossocial básico da experiência, discutindo suas implicações para questionar o modelo clínico de intervenção, apontando apossibilidade de a enfermagem atuar na prevenção e propondo questões para aprimorar a formação do enfermeiro.

Homens e abortamento espontâneo: narrativas das experiências compartilhadas

Maior envolvimento masculino na saúde reprodutiva é um desafio da atualidade; em âmbito nacional e internacional existem recomendações para desenvolver pesquisas sob a perspectiva masculina. Objetivo: Compreender a experiência de homens que compartilharam do processo de abortamento espontâneo de suas parceiras. Método: Utilizou-se a abordagem qualitativa e a análise da narrativa foi o método empregado. Foram identificadas as similaridades nas experiências de nove homens entrevistados, que permitiram elaborar as seguintes categorias descritivas: Vivenciando a notícia da gravidez; identificando as possíveis causas do abortamento; expressando sentimentos relativos à experiência do abortamento; tomando atitudes em decorrência do abortamento; ponderando sobre a experiência vivida. Conclusão: Homens que compartilham da experiência do abortamento espontâneo requerem sensibilidade e envolvimento dos profissionais que os assistem, expressaram o desejo do acolhimento, o recebimento de suporte emocional e informações completas e precisas sobre o conjunto do processo.

Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies.

BACKGROUND: In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer's disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive supranuclear palsy but the molecular and cellular mechanisms supporting this progression are yet not known. These pathways appear to be associated with the intercellular transmission of pathology, as recently suggested in Tau transgenic mice. However, these conclusions remain ill-defined due to a lack of toxicity data and difficulties associated with the use of mutant Tau. RESULTS: Using a lentiviral-mediated rat model of hippocampal NFD, we demonstrated that wild-type human Tau protein is axonally transferred from ventral hippocampus neurons to connected secondary neurons even at distant brain areas such as olfactory and limbic systems indicating a trans-synaptic protein transfer. Using different immunological tools to follow phospho-Tau species, it was clear that Tau pathology generated using mutated Tau remains near the IS whereas it spreads much further using the wild-type one. CONCLUSION: Taken together, these results support a novel mechanism for Tau protein transfer compared to previous reports based on transgenic models with mutant cDNA. It also demonstrates that mutant Tau proteins are not suitable for the development of experimental models helpful to validate therapeutic intervention interfering with Tau spreading.

Pancreatic-specific expression of the glucose transporter type 2 gene: identification of cis-elements and islet-specific trans-acting factors.

A defect in glucose sensing of the pancreatic beta-cells has been observed in several animal models of type II diabetes and has been correlated with a reduced gene expression of the glucose transporter type 2 (Glut2). In a transgenic mouse model, expression of Glut2 antisense RNA in pancreatic beta-cells has recently been shown to be associated with an impaired glucose-induced insulin secretion and the development of diabetes. To identify factors that may be involved in the specific decrease of Glut2 in the beta-cells of the diabetic animal, an attempt was made to localize the cis-elements and trans-acting factors involved in the control of Glut2 expression in the endocrine pancreas. It was demonstrated by transient transfection studies that only 338 base pairs (bp) of the murine Glut2 proximal promoter are needed for reporter gene expression in pancreatic islet-derived cell lines, whereas no activity was detected in nonpancreatic cells. Three cis-elements, GTI, GTII, and GTIII, have been identified by DNAse I footprinting and gel retardation experiments within these 338 bp. GTI and GTIII bind distinct but ubiquitously expressed trans-acting factors. On the other hand, nuclear proteins specifically expressed in pancreatic cell lines interact with GTII, and their relative abundance correlates with endogenous Glut2 expression. These GTII-binding factors correspond to nuclear proteins of 180 and 90 kilodaltons as defined by Southwestern analysis. The 180-kilodalton factor is present in pancreatic beta-cell lines but not in an alpha-cell line. Mutation of the GTI or GTIII cis-elements decreases transcriptional activity directed by the 338-bp promoter, whereas mutation of GTII increases gene transcription. Thus negative and positive regulatory sequences are identified within the proximal 338 bp of the GLUT2 promoter and may participate in the islet-specific expression of the gene by binding beta-cell specific trans-acting factors.

(In)dependência funcional na dependente relação de homens tetraplégicos com seus (in)substituíveis pais/cuidadores

Objetivou-se identificar elementos da classificação internacional de funcionalidade, incapacidade e saúde, aplicáveis ao cuidado domiciliar de homens adultos tetraplégicos, com vistas à redução da dependência de ajuda de seus pais para as atividades da vida diária, e o autocuidado. Os dados foram coletados de junho de 2004 a março de 2005, a partir de entrevista semi-estruturada, realizada com 8 adultos acometidos de lesão medular alta, e com experiência de usuários do cuidado domiciliar. Optou-se pela análise de conteúdo, a partir das categorias de significados pautadas nos seguintes resultados: suporte familiar: segurança para as funções corporais do incapacitado; tecnologia assistiva: inventividades para promoção da qualidade do cuidado; medos, futuro incerto e perda dos pais: limiares e fragilidades humanas; e ganhos funcionais: respostas objetivas das funções corporais. Conclui-se que o apoio da família e, em especial, a presença dos pais, são fundamentais para enfrentar as limitações e reagir na busca de equilíbrio na deficiência, incapacidade, desvantagem e saúde dessa clientela, preparando-a para o alcance de gradativos ganhos funcionais e independência para atividades cotidianas e autocuidado.

The loss of GLUT2 expression in the pancreatic beta-cells of diabetic db/db mice is associated with an impaired DNA-binding activity of islet-specific trans-acting factors.

GLUT2 expression is reduced in the pancreatic beta-cells of several diabetic animals. The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. In these diabetic animals, insulin mRNA expression remains normal. The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. These data suggest that the decreased activity of GTIIa, in contrast to PDX-1, may be a major initial step in the development of the beta-cell dysfunction in this model of diabetes.

The transventricular-transseptal access to the aortic root : a new route for extrapleural trans-catheter aortic stent-valve implantation

Rapport de synthèseObjectif: le remplacement valvulaire aortique par voie transcathétère est, actuellement, une méthode fiable indiquée pour des patients à haut risque porteurs d'une sténose valvulaire aortique. La voie transfémorale est utilisable seulement en cas d'absence de maladie vasculaire et la voie transapicale est contrindiquée en cas de dysfonction pulmonaire chronique sévère. Une alternative pour ne pas passer a travers l'espace pleural serait par voie sous- xiphoïdienne et trans-septale à travers le ventricule droit.Méthode: une expérience animale a été amené au laboratoire de recherche du CHUV. Cinq cochons (poids : 52.3±10.9 kg) ont été endormi et, sous anesthésie générale, le ventricule droit a été préparé a travers un accès sous- xiphoïdien. Ensuite, sous guide fluoroscopique et avec l'utilisation d'une échocardiographie intracardiaque, un accès trans-septal a été crée entre le ventricule droit et le ventricule gauche en utilisant des dilatateur de diamètre croissant (de 8F à 26F). Par la suite, une valve stentée crée dans le laboratoire en utilisant un stent en nitinol et du péricarde a été chargé dans une cartouche et introduite dans le ventricule gauche à travers un introducteur trans-septal. Enfin, la valve a été amené dans la chambre de chasse du ventricule gauche et ensuite dans la racine aortique et puis déployé au bon endroit. Quand le système a été retiré, le septum ventriculaire a pu être réparé par mise en place d'un système d'occlusion septal Amplazer. Trente minutes après la procédure, les animaux ont été sacrifié et le coeur a été analysé pour étudier le positionnement da la valve stentée, l'efficacité de la fermeture du septum inter-ventriculaire et la fermeture de la paroi du ventricule droit.Résultat : les cinq cochon ont tous eu un parfait positionnement et pose de la prothèse en position aortique au premier essai (efficacité 100%). Les procédures ont duré, moyennement, 49±4 minutes et la progressive dilatation de l'accès trans-septale à donné lieu à une communication inter-ventriculaire mesurable après dilatation avec du 18F et plus. Toutes les valves stentées ont été déployées au bon endroit avec un bon résultat du fonctionnement des valves prothétiques et absence d'insuffisance para prothétique. Pendant les procédures, des battement prématurés ainsi que des épisodes isolées de tachycardie supra ventriculaire ont été détectés. Par contre, il n'y a pas eu de bloc atrio-ventriculaire. Les pertes sanguines pendant les procédures étaient de 280±10mL, et les systèmes d'occlusion Amplatzer étaient tous bien déployés sans shunts inter-ventriculaires résiduels.Conclusion: la technique d'introduction de valve stentées par voie extrapleural (trans-ventriculaire et trans-septale) est techniquement possible et elle jette les bases pour le remplacement valvulaire aortique trans-ventriculaire sous anesthésie locale.

Enfrentamentos experienciados por homens que vivem com HIV/Aids no ambiente de trabalho

Objetivou-se apreender situações de enfrentamento experienciadas por homens que vivem com HIV/aids no ambiente de trabalho. Estudo qualitativo realizado em ambulatório especializado em Fortaleza-Ceará, de março a junho de 2010, com onze homens infectados pelo vírus. Utilizou-se entrevista semiestruturada, audiogravada, sendo os depoimentos categorizados mediante análise de conteúdo, cujas categorias foram: Afastamento do trabalho em virtude da infecção; Subterfúgios para omissão da doença; Desrespeito ao sigilo no ambiente de trabalho; Sofrimento associado ao medo da rejeição e do preconceito; Formas de enfrentamento após o diagnóstico da doença e a importância do trabalho para a realização pessoal. Concluiu-se que os homens infectados pelo HIV enfrentam situações contraproducentes no ambiente de trabalho, evidenciadas principalmente pelo temor da descoberta da infecção e pelo preconceito. Associadas ao enfrentamento, as ausências para o acompanhamento em saúde interferiram no desempenho do trabalho que implicariam no risco de perda do emprego.

Impacto da incontinência urinária na vida de esposas de homens com incontinência: revisão integrativa

A incontinência urinária masculina tem sido relacionada a vários fatores, destacando-se a hiperplasia prostática benigna e o tratamento de câncer de próstata. A incontinência urinária gera implicações negativas tanto para o indivíduo incontinente, como para seus familiares e cuidadores. No presente estudo foi realizada uma revisão integrativa a fim de identificar o impacto na vida das parceiras de homens incontinentes. A busca dos artigos foi realizada nas bases de dados CINAHL, EMBASE, SCOPUS, MEDLINE e PubMed. Foram incluídos artigos na língua portuguesa, inglesa e espanhola, e excluídos os que não citavam esposas. A amostra final foi composta por 15 artigos, de sete países. Os artigos foram distribuídos nas categorias: Sofrimento Psíquico, Fadiga, Mudança na Vida Sexual, e Limitação da Vida Social. A categoria Sofrimento Psíquico esteve presente em todos os artigos e foi avaliada como a mais prejudicial na vida dessas mulheres.