Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from the prospective Pizarra study.

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Miltefosine induces programmed cell death in Leishmania amazonensis promastigotes

In the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in Leishmania amazonensis promastigotes. Miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-G0/G1 phase and DNA fragmentation into oligonucleosome-sized fragments. Despite the intrinsic variation that is detected in Leishmania spp, our results indicate that miltefosine causes apoptosis-like death in L. amazonensis promastigote cells using a similar process that is observed in Leishmania donovani.

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC).

BACKGROUND Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. METHODOLOGY/PRINCIPAL FINDINGS After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. CONCLUSIONS/SIGNIFICANCE Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.

Aider les étudiants en médecine à approcher la mort [Helping medical students to approach death].

A project recently launched by the Faculty of biology and medicine of Lausanne introduces the approach of facing death during both the dissection and the course of clinical activities. Existential questions relating to mortality are bound to arise sooner or later during the course of the study. For the sake of humanized clinical practice, these questions must be confronted. In response to a request by a student association, an accompanying curriculum with active student's contribution through encounters with death in anatomy and clinical situations was created in Lausanne. Students will benefit from this new program throughout their curriculum. This program is the first of its kind in Switzerland.

Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.

Social inequalities and mortality in Europe-results from a large multi-national cohort

BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

Magnetic pill tracking : a novel non-invasive tool for investigation of human digestive motility

RESUME Les améliorations méthodologiques des dernières décennies ont permis une meilleure compréhension de la motilité gastro-intestinale. Il manque toutefois une méthode qui permette de suivre la progression du chyme le long du tube gastro-intestinal. Pour permettre l'étude de la motilité de tout le tractus digestif humain, une nouvelle technique, peu invasive, a été élaborée au Département de Physiologie, en collaboration avec l'EPFL. Appelée "Magnet Tracking", la technique est basée sur la détection du champ magnétique généré par des matériaux ferromagnétiques avalés. A cet usage, une pilule magnétique, une matrice de capteurs et un logiciel ont été développés. L'objet de ce travail est de démontrer la faisabilité d'un examen de la motilité gastro-intestinale chez l'Homme par cette méthode. L'aimant est un cylindre (ø 6x7 mm, 0.2 cm3) protégé par une gaine de silicone. Le système de mesure est constitué d'une matrice de 4x4 capteurs et d'un ordinateur portable. Les capteurs fonctionnent sur l'effet Hall. Grâce à l'interface informatique, l'évolution de la position de l'aimant est suivie en temps réel à travers tout le tractus digestif. Sa position est exprimée en fonction du temps ou reproduite en 3-D sous forme d'une trajectoire. Différents programmes ont été crées pour analyser la dynamique des mouvements de l'aimant et caractériser la motilité digestive. Dix jeunes volontaires en bonne santé ont participé à l'étude. L'aimant a été avalé après une nuit de jeûne et son séjour intra digestif suivi pendant 2 jours consécutifs. Le temps moyen de mesure était de 34 heures. Chaque sujet a été examiné une fois sauf un qui a répété sept fois l'expérience. Les sujets restaient en décubitus dorsal, tranquilles et pouvaient interrompre la mesure s'ils le désiraient. Ils sont restés à jeûne le premier jour. L'évacuation de l'aimant a été contrôlée chez tous les sujets. Tous les sujets ont bien supporté l'examen. Le marqueur a pu être détecté de l'oesophage au rectum. La trajectoire ainsi constituée représente une conformation de l'anatomie digestive : une bonne superposition de celle-ci à l'anatomie est obtenue à partir des images de radiologie conventionnelle (CT-scan, lavement à la gastrografine). Les mouvements de l'aimant ont été caractérisés selon leur périodicité, leur amplitude ou leur vitesse pour chaque segment du tractus digestif. Ces informations physiologiques sont bien corrélées à celles obtenues par des méthodes établies d'étude de la motilité gastro-intestinale. Ce travail démontre la faisabilité d'un examen de la motilité gastro-intestinal chez l'Homme par la méthode de Magnet Tracking. La technique fournit les données anatomiques et permet d'analyser en temps réel la dynamique des mouvements du tube digestif. Cette méthode peu invasive ouvre d'intéressantes perspectives pour l'étude de motilité dans des conditions physiologiques et pathologiques. Des expériences visant à valider cette approche en tant que méthode clinique sont en voie de réalisation dans plusieurs centres en Suisse et à l'étranger. SUMMARY Methodological improvements realised over the last decades have permitted a better understanding of gastrointestinal motility. Nevertheless, a method allowing a continuous following of lumina' contents is still lacking. In order to study the human digestive tract motility, a new minimally invasive technique was developed at the Department of Physiology in collaboration with Swiss Federal Institute of Technology. The method is based on the detection of magnetic field generated by swallowed ferromagnetic materials. The aim of our work was to demonstrate the feasibility of this new approach to study the human gastrointestinal motility. The magnet used was a cylinder (ø6x7mm, 0.2 cm3) coated with silicon. The magnet tracking system consisted of a 4x4 matrix of sensors based on the Hall effect Signals from the sensors were digitised and sent to a laptop computer for processing and storage. Specific software was conceived to analyse in real time the progression of the magnet through the gastrointestinal tube. Ten young and healthy volunteers were enrolled in the study. After a fasting period of 12 hours, they swallowed the magnet. The pill was then tracked for two consecutive days for 34 hours on average. Each subject was studied once except one who was studied seven times. Every subject laid on his back for the entire experiment but could interrupt it at anytime. Evacuation of the magnet was controlled in all subjects. The examination was well tolerated. The pill could be followed from the esophagus to the rectum. The trajectory of the magnet represented a "mould" of the anatomy of the digestive tube: a good superimposition with radiological anatomy (gastrografin contrast and CT) was obtained. Movements of the magnet were characterized by periodicity, velocity, and amplitude of displacements for every segment of the digestive tract. The physiological information corresponded well to data from current methods of studying gastrointestinal motility. This work demonstrates the feasibility of the new approach in studies of human gastrointestinal motility. The technique allows to correlate in real time the dynamics of digestive movements with the anatomical data. This minimally invasive method is ready for studies of human gastrointestinal motility under physiological as well as pathological conditions. Studies aiming at validation of this new approach as a clinically relevant tool are being realised in several centres in Switzerland and abroad. Abstract: A new minimally invasive technique allowing for anatomical mapping and motility studies along the entire human digestive system is presented. The technique is based on continuous tracking of a small magnet progressing through the digestive tract. The coordinates of the magnet are calculated from signals recorded by 16 magnetic field sensors located over the abdomen. The magnet position, orientation and trajectory are displayed in real time. Ten young healthy volunteers were followed during 34 h. The technique was well tolerated and no complication was encountered, The information obtained was 3-D con-figuration of the digestive tract and dynamics of the magnet displacement (velocity, transit time, length estimation, rhythms). In the same individual, repea-ted examination gave very reproducible results. The anatomical and physiological information obtained corresponded well to data from current methods and imaging. This simple, minimally invasive technique permits examination of the entire digestive tract and is suitable for both research and clinical studies. In combination with other methods, it may represent a useful tool for studies of Cl motility with respect to normal and pathological conditions.

Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.

Productive HIV-1 infection of primary CD4+ T cells induces mitochondrial membrane permeabilization leading to a caspase-independent cell death.

We have explored in vitro the mechanism by which human immunodeficiency virus, type 1 (HIV-1) induces cell death of primary CD4+ T cells in conditions of productive infection. Although HIV-1 infection primed phytohemagglutinin-activated CD4+ T cells for death induced by anti-CD95 antibody, T cell death was not prevented by a CD95-Fc decoy receptor, nor by decoy receptors of other members of the TNFR family (TNFR1/R2, TRAILR1/R2/OPG, TRAMP) or by various blocking antibodies, suggesting that triggering of death receptors by their cognate ligands is not involved in HIV-induced CD4 T cell death. HIV-1 induced CD4 T cell shrinkage, cell surface exposure of phosphatidylserine, loss of mitochondrial membrane potential (Deltapsim), and mitochondrial release of cytochrome c and apoptosis-inducing factor. A typical apoptotic phenotype (nuclear chromatin condensation and fragmentation) only occurred in around half of the dying cells. Treatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a broad spectrum caspase inhibitor, prevented nuclear chromatin condensation and fragmentation in HIV-infected CD4+ T cells and in a cell-free system (in which nuclei were incubated with cytoplasmic extracts from the HIV-infected CD4+ T cells). Nevertheless, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone did not prevent mitochondrial membrane potential loss and cell death, suggesting that caspases are dispensable for HIV-mediated cell death. Our findings suggest a major role of the mitochondria in the process of CD4 T cell death induced by HIV, in which targeting of Bax to the mitochondria may be involved.

Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death.

Apoptosis is a normal component of the development and health of multicellular organisms. However, apoptosis is now considered a prerogative of unicellular organisms, including the trypanosomatids of the genera Trypanosoma spp. and Leishmania spp., causative agents of some of the most important neglected human diseases. Trypanosomatids show typical hallmarks of apoptosis, although they lack some of the key molecules contributing to this process in metazoans, like caspase genes, Bcl-2 family genes and the TNF-related family of receptors. Despite the lack of these molecules, trypanosomatids appear to have the basic machinery to commit suicide. The components of the apoptotic execution machinery of these parasites are slowly coming into light, by targeting essential processes and pathways with different apoptogenic agents and inhibitors. This review will be confined to the events known to drive trypanosomatid parasites to apoptosis.

Qualité des statistiques de causes de décès: problèmes actuels et perspectives. [Quality of statistics on causes of death: current problems and perspectives].

Statistics of causes of death remain an important source of epidemiological data for the evaluation of various medical and health problems. The improvement of analytical techniques and, above all, the transformation of demographic and morbid structures of populations have prompted researchers in the field to give more importance to the quality of death certificates. After describing the data collection system presently used in Switzerland, the paper discusses various indirect estimations of the quality of Swiss data and reviews the corresponding international literature.