Determinants of smoking and cessation in older women

Résumé Introduction : Le tabagisme est le facteur de risque le plus important dans 7 des 14 premières causes de décès chez les personnes de plus de 65 ans. De nombreuses études ont démontré les bénéfices sur la santé d'un arrêt du tabagisme même à un âge avancé. Malgré cela, peu d'actions préventives sont entreprises dans cette population. Le but de ce travail est d'analyser les caractéristiques du tabagisme et de l'arrêt du tabagisme spécifiquement chez les fumeuses d'âge avancé afin de mieux les aider dans leur désir d'arrêter. Méthode : Nous avons évalué les caractéristiques tabagiques au sein d'une étude prospective de 7'609 femmes vivant en Suisse, âgées de plus de 70 ans et physiquement autonomes (étude Semof s'intéressant à la mesure de l'ostéoporose par ultrason osseux). Un questionnaire sur les habitudes tabagiques a été envoyé aux 486 fumeuses éligibles de la cohorte. Leurs stades de dépendance nicotinique et de motivation ont été évalués à l'aide respectivement des scores «Heavy Smoking Index» et « Prochaska ». Les participantes ayant cessé de fumer pendant le suivi ont été questionnées sur, les motivations, les raisons et les méthodes de leur arrêt. Résultats : 424 femmes ont retourné le questionnaire (taux de réponse de 87%) parmi lesquelles 372 ont répondu de façon complète permettant leur inclusion. L'âge moyen s'élevait à 74,5 ans. La consommation moyenne était de 12 cigarettes par jour, sur une moyenne de 51 ans avec une préférence pour les cigarettes dites « légères » ou « light ». Un peu plus de la moitié des participantes avait une consommation entre 1 et 10 cigarettes par jour et la grande majorité (78%) présentait un score de dépendance faible. Les raisons du tabagisme les plus fréquemment évoquées étaient la relaxation, le plaisir et l'habitude. Les principaux obstacles mentionnés : arrêter à un âge avancé n'a pas de bénéfice, fumer peu ou des cigarettes dites light n'a pas d'impact sur la santé et fumer n'augmente pas le risque d'ostéoporose. Le désir d'arrêter était positivement associé avec un début tardif du tabagisme, une éducation plutôt modeste et la considération que d'arrêter est difficile. Durant le suivi de 3 ans, 57 femmes sur 372 (15%) ont arrêté de-fumer avec succès. Le fait d'être une fumeuse occasionnelle (moins de 1 cigarette par jour) et de considérer que d'arrêter de fumer n'est pas difficile était associés à un meilleur taux d'arrêt du tabagisme. Seuls 11% des femmes ayant stoppé la cigarette signalaient avoir reçu des conseils de leur médecin. Conclusion : ces données illustrent le comportement tabagique spécifique des fumeuses d'âge avancé (consommation et dépendance plutôt faibles) et suggèrent que les interventions médicales pour l'aide à l'arrêt du tabagisme devraient intégrer ces caractéristiques. La volonté d'arrêter est associée à un niveau d'éducation plutôt modeste. Les obstacles les plus fréquemment mentionnés sont basés sur des appréciations erronées de l'impact du tabagisme sur la santé.

Sequence determinants of a microtubule tip localization signal (MtLS).

Microtubule plus-end-tracking proteins (+TIPs) specifically localize to the growing plus-ends of microtubules to regulate microtubule dynamics and functions. A large group of +TIPs contain a short linear motif, SXIP, which is essential for them to bind to end-binding proteins (EBs) and target microtubule ends. The SXIP sequence site thus acts as a widespread microtubule tip localization signal (MtLS). Here we have analyzed the sequence-function relationship of a canonical MtLS. Using synthetic peptide arrays on membrane supports, we identified the residue preferences at each amino acid position of the SXIP motif and its surrounding sequence with respect to EB binding. We further developed an assay based on fluorescence polarization to assess the mechanism of the EB-SXIP interaction and to correlate EB binding and microtubule tip tracking of MtLS sequences from different +TIPs. Finally, we investigated the role of phosphorylation in regulating the EB-SXIP interaction. Together, our results define the sequence determinants of a canonical MtLS and provide the experimental data for bioinformatics approaches to carry out genome-wide predictions of novel +TIPs in multiple organisms.

The CoLaus study : a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome

Rapport de synthèse : Les maladies cardio-vasculaires constituent les causes principales causes de morbidité et de mortalité dans les pays industrialisés. Des études épidémiologiques ont démontré l'implication de facteurs de risques comme l'hypertension, l'hypercholestérolémie, l'obésité abdominale, le diabète et le tabagisme dans le développement des affections cardiovasculaires comme l'infarctus du myocarde ou l'accident vasculaire cérébral. De larges études génétiques cas-contrôle ont contribué modestement à l'identification de gènes de susceptibilité au développement de ces FRCV. Une étude populationnelle offre par contre l'avantage d'effectuer des études associatives pour des traits phénotypiques continus correctement mesurés et aussi pour des traits de catégories utilisant des protocoles d'étude cas-contrôle très discordants. ~ Elle permet l'exploration des déterminants génétiques comme par exemple le syndrome métabolique. Cette approche permet également de procéder à des analyses de séquençage sur l'ADN des participants chez qui un trait phénotypique spécifique est étudié mais distribué de manière opposée. A titre d'exemple, le séquençage de l'ADN de participants à taux très élevé d'HDL-cholestérol versus très bas de ce marqueur lipidique permet d'identifier des variants génétiques rares localisés sur les parties codantes de gènes spécifiques associés aux dyslipidémies. Pour ce faire, nous avons recruté 6'188 personnes âgées de 35 à 75 ans, d'origine caucasienne et résidant en ville de Lausanne (3251 femmes et 2937 hommes). L'obtention d'un tel collectif a nécessité l'échantillonnage aléatoire de quelque 19'830 personnes de cette tranche d'âge. Les participants ont fait l'objet d'une anamnèse approfondie et d'un examen clinique. Le bilan était complété par une prise de sang pour le dosage de paramètres biologiques ainsi qu'une analyse .génétique. Cette dernière a été effectuée après extraction d'ADN au moyen d'une puce Affimetrix qui évalue la présence de quelques 500'000 SNPs. Les données récoltées lors de cette étude dévoilent que l'obésité (index de masse corporelle > 30 kg/m2), le tabagisme, l'hypertension (pression artérielle >_ 140/90 mmHg et/ou hypertension traitée), une dyslipidémie (LDL cholestérol élevé et/ou HDL cholestérol bas et/ou triglycéride élevé) et le diabète (glucose à jeun >_ 7 mmol/l et/ou traitement) affectent respectivement 947 (15,7%), 1673 (27%), 2268 (36,7%), 2113 (34,2%) et 407 (6,6%) participants. La prévalence de ces FRCV est plus marquée chez les hommes que chez les femmes. Dans les deux genres les prévalences de l'obésité, de l'hypertension et du diabète augmentent drastiquement avec l'âge. En conclusion la prévalence des FRCV est élevée au sein d'une population représentative de Lausanne âgée de 35 à 75 ans. A l'avenir, l'étude CoLaus constituera par la richesse de ses données phénotypiques et génétiques, une source unique pour investiguer l'épidémiologie et l'identification de gènes associés à ces FRCV.

Molecular determinants of vesicular storage and release of the gliotransmitter D-serine from cortical astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of 'gliotransmitters' such as glutamate, ATP or D-serine. A calcium-dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. Over the last years, we have been studying the molecular determinants governing D-serine release from glia using different approaches. Using a novel bioassay for D-serine, we have been able to show that D-serine release occurs mainly through a calcium- and SNARE proteindependent mechanism just supporting the idea that this amino acid is released by exocytosis from glia. We next have pursued our exploration by confocal imaging and tracking of the exocytotic routes for Dserine- mediated gliotransmission and have shown that D-serine releasable pools are confined to synaptobrevin2/cellubrevin-bearing vesicles. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2- positive vesicles from rat cortical astrocytes in culture while preserving their content in gliotransmitters. The purified organelles are clear round shape vesicles of excellent purity with homogeneous size (40 nm) as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles like synaptic vesicle protein 2 (SV2) and the proton pump H?-ATPase. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electrophoresis coupled to laser-induced fluorescence detection. The purified vesicles contain large amount of D-serine. We also detect peaks corresponding to unidentified compounds that may correspond to others amino acids. Postembedding immunogold labelling of the rat neocortex further revealed the expression of D-serine in astrocytes processes contacting excitatory synapses. Finally, we have examined the uptake properties for Dserine and glutamate inside the isolated glial vesicles. Our results provide significant support for the existence of an uptake system for D-serine in secretory glial vesicles and for the storage of chemical substances like D-serine and glutamate. 11th International Congress on Amino Acids, Peptides and Proteins 763 123

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Molecular determinants of desensitization in an ENaC/degenerin channel.

Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ∼20 Å above the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels.

Multiscale determinants of tree frog (Hyla arborea L.) calling ponds in western Switzerland

A tree frog (Hyla arborea L., 1758) metapopulation in western Switzerland was studied during spring 2001. All potential calling ponds in an area of 350 km(2) were searched for tree frog calling males. Twenty-nine out of 111 ponds sheltered between 1 and 250 callers. Most ponds were occupied by less than 12 males. Pond parameters were measured at three different levels using field analysis and a Geographical Information System (GIS). The first level was water chemistry and pond-associated measures. The second level was the surrounding land use in a 30 m buffer around the pond. The third level consisted of landscape indices on a broader scale (up to 2 km). Logistic regression was applied to identify parameters that can predict the presence of calling males in a pond. Response variable was the presence or absence of callers. Four significant parameters allowed us to explain about 40% of the total deviance of the observed occupational pattern. Urbanization around the pond had a highly negative impact on the probability of presence of calling males. Hours of direct sunlight on the pond was positively correlated with callers. Higher water conductivity was associated with a lesser probability of species presence. Finally, the further the closest two-lane road, the higher the probability of callers presence. Our results show that presence or absence of callers is influenced by factors acting at various geographical scales.

Frequency and determinants of urgent requests to home care agencies for community-dwelling elderly.

We analyzed a one-year case series and performed a longitudinal (4 month) cohort analysis of urgent requests made to home care agencies by and for their > or = 65 years old clients in order to estimate the frequency of unscheduled services delivered by home care agencies and to identify risk factors. All 40 home care agencies located in a Swiss region were included in the study and we registered 3,816 urgent requests (75/1,000 > or = 65 years residents per year). Among home care users, the presence of a urinary catheter, incontinence and the need for assistance in bathing were predictors of unscheduled services. Resources should be planned in order to help home care teams to handle unexpected, disruptive clusters of urgent requests that may compromise their scheduled activities.

Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.

Although all brain cells bear in principle a comparable potential in terms of energetics, in reality they exhibit different metabolic profiles. The specific biochemical characteristics explaining such disparities and their relative importance are largely unknown. Using a modeling approach, we show that modifying the kinetic parameters of pyruvate dehydrogenase and mitochondrial NADH shuttling within a realistic interval can yield a striking switch in lactate flux direction. In this context, cells having essentially an oxidative profile exhibit pronounced extracellular lactate uptake and consumption. However, they can be turned into cells with prominent aerobic glycolysis by selectively reducing the aforementioned parameters. In the case of primarily oxidative cells, we also examined the role of glycolysis and lactate transport in providing pyruvate to mitochondria in order to sustain oxidative phosphorylation. The results show that changes in lactate transport capacity and extracellular lactate concentration within the range described experimentally can sustain enhanced oxidative metabolism upon activation. Such a demonstration provides key elements to understand why certain brain cell types constitutively adopt a particular metabolic profile and how specific features can be altered under different physiological and pathological conditions in order to face evolving energy demands.

Determinants of Corporate Disclosure : A Multicountry, Multilevel Model

Abstract The complexity of the current business world is making corporate disclosure more and more important for information users. These users, including investors, financial analysts, and government authorities rely on the disclosed information to make their investment decisions, analyze and recommend shares, and to draft regulation policies. Moreover, the globalization of capital markets has raised difficulties for information users in understanding the differences incorporate disclosure across countries and across firms. Using a sample of 797 firms from 34 countries, this thesis advances the literature on disclosure by illustrating comprehensively the disclosure determinants originating at firm systems and national systems based on the multilevel latent variable approach. Under this approach, the overall variation associated with the firm-specific variables is decomposed into two parts, the within-country and the between-country part. Accordingly, the model estimates the latent association between corporate disclosure and information demand at two levels, the within-country and the between-country level. The results indicate that the variables originating from corporate systems are hierarchically correlated with those from the country environment. The information demand factor indicated by the number of exchanges listed and the number of analyst recommendations can significantly explain the variation of corporate disclosure for both "within" and "between" countries. The exogenous influences of firm fundamentals-firm size and performance-are exerted indirectly through the information demand factor. Specifically, if the between-country variation in firm variables is taken into account, only the variables of legal systems and economic growth keep significance in explaining the disclosure differences across countries. These findings strongly support the hypothesis that disclosure is a response to both corporate systems and national systems, but the influence of the latter on disclosure reflected significantly through that of the former. In addition, the results based on ADR (American Depositary Receipt) firms suggest that the globalization of capital markets is harmonizing the disclosure behavior of cross-boundary listed firms, but it cannot entirely eliminate the national features in disclosure and other firm-specific characteristics.

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study.

PURPOSE: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. METHODS: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. RESULTS: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. CONCLUSION: Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.

Resigned but satisfied: The negative impact of public service motivation and red tape on work satisfaction

This article examines the relationship between red tape, Public Service Motivation (PSM) and a particular work outcome labelled 'resigned satisfaction'. Using data from a national survey of over 3754 public servants working at the municipal level in Switzerland, this study shows the importance of looking more closely at the concept of work satisfaction and, furthermore, of thoroughly investigating the impact of the different PSM dimensions on work outcomes. Unsurprisingly, research findings show that red tape is the most important predictor of resignation. Nevertheless, when PSM dimensions are analysed separately, results demonstrate that 'commitment to public interest/civic duty' and, to a lesser extent, 'attraction to policy-making' decrease resignation, whereas 'compassion' and 'self-sacrifice' increase it. This study thus highlights some of the negative (or undesirable) effects of PSM that have not been previously addressed in PSM literature.