Symposium on nutrition and cognition: towards research and application for different life stages. (Congress)

Asia Pacific Journal of Clinical Nutrition211104-12

Investigation of Prolactin Receptor Activation and Blockade Using Time-Resolved Fluorescence Resonance Energy Transfer

The prolactin receptor (PRLR) is emerging as a therapeutic target in oncology. Knowledge-based drug design led to the development of a pure PRLR antagonist (Del1-9-G129R-hPRL) that was recently shown to prevent PRL-induced mouse prostate tumorogenesis. In humans, the first gain-of-function mutation of the PRLR (PRLRI146L) was recently identified in breast tumor patients. At the molecular level, the actual mechanism of action of these two novel players in the PRL system remains elusive. In this study, we addressed whether constitutive PRLR activation (PRLRI146L) or PRLR blockade (antagonist) involved alteration of receptor oligomerization and/or of inter-chain distances compared to unstimulated and PRL-stimulated PRLR. Using a combination of various biochemical and spectroscopic approaches (co-IP, blue native electrophoresis, BRET1), we demonstrated that preformed PRLR homodimers are altered neither by PRL- or I146L-induced receptor triggering, nor by antagonist-mediated blockade. These findings were confirmed using a novel time-resolved fluorescence resonance energy transfer (TR-FRET) technology that allows monitoring distance changes between cell surface tagged receptors. This technology revealed that PRLR blockade or activation did not involve detectable distance changes between extracellular domains of receptor chains within the dimer. This study merges with our previous structural investigations suggesting that the mechanism of PRLR activation solely involves intermolecular contact adaptations leading to subtle intramolecular rearrangements

Evaluation du projet de l’Association Réseau Orientation Santé Social (AROSS)

Dans le cadre des travaux de la planification médico-sociale (PMS) du canton de Neuchâtel et afin d’améliorer l’orientation des personnes âgées de plus de 65 ans dans le réseau socio-sanitaire du canton, le rapport « Réseau et entretiens d’orientation » préconisait la création d’un dispositif d’information, d’orientation et de coordination à l’échelle cantonale, portée par un établissement autonome de droit public. La finalité annoncée de ce dispositif est « d’augmenter l’espérance de vie sans incapacité », par la détection et la prise en charge précoce et adaptée des personnes pré-fragiles et fragiles. Avant le déploiement à grande échelle de ce dispositif, l’État a souhaité l’expérimenter sur un territoire du canton. L’Association Réseau Orientation Santé Social (AROSS) a ainsi été créée en mars 2015 afin de promouvoir le développement d’un réseau socio-sanitaire assurant l’information, l’orientation et l’efficience de l’accompagnement des personnes âgées de plus de 65 ans, dans une optique de continuité des soins. Un projet-pilote, sous la forme d’une structure d’information et d’orientation destinée aux personnes âgées, à leurs proches et aux partenaires socio-sanitaires, a été mis en place depuis le 1er janvier 2016 sur les communes du Locle et des Brenets, puis étendu sur l’ensemble du district du Locle au 1er janvier 2017, afin de tester et valider l’approche

Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function

Background: Errors in address geocodes may affect estimates of the effects of air pollution on health.Objective: We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults.Methods: We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant's address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects.Results: Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: -0.56, -6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: -0.14, -3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted -2.81 (95% CI: -0.26, -5.35) using NavTEQ or 2.08 (95% CI -4.63, 0.47, p = 0.11) using Google Maps].Conclusions: Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model.Citation: Jacquemin B, Lepeule J, Boudier A, Arnould C, Benmerad M, Chappaz C, Ferran J, Kauffmann F, Morelli X, Pin I, Pison C, Rios I, Temam S, Künzli N, Slama R, Siroux V. 2013. Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function. Environ Health Perspect 121:1054-1060; http://dx.doi.org/10.1289/ehp.1206016

Exposure to Phthalates and Phenols during Pregnancy and Offspring Size at Birth

Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight

Non-infectious rhinitis is more strongly associated with early-rather than late-onset of COPD: data from the European Community Respiratory Health Survey (ECRHS)

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC < 0.7. A total of 5901 subjects were included. Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54). In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III. Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD

Residential surrounding greenspace and age at menopause: A 20-year European study (ECRHS)

Background: Menopause is associated with a number of adverse health effects and its timing has been reported to be influenced by several lifestyle factors. Whether greenspace exposure is associated with age at menopause has not yet been investigated. Objective: To investigate whether residential surrounding greenspace is associated with age at menopause and thus reproductive aging. Methods: This longitudinal study was based on the 20-year follow-up of 1955 aging women from a large, population-based European cohort (ECRHS). Residential surrounding greenspace was abstracted as the average of satellite-based Normalized Difference Vegetation Index (NDVI) across a circular buffer of 300m around the residential addresses of each participant during the course of the study. We applied mixed effects Cox models with centre as random effect, menopause as the survival object, age as time indicator and residential surrounding greenspace as time-varying predictor. All models were adjusted for smoking habit, body mass index, parity, age at menarche, ever-use of contraception and age at completed full-time education as socio-economic proxy. Results: An increase of one interquartile range of residential surrounding greenspace was associated with a 13% lower risk of being menopausal (Hazard Ratio: 0.87, 95% Confidence Interval: 0.79-0.95). Correspondingly the predicted median age at menopause was 1.4 years older in the highest compared to the lowest NDVI quartile. Results remained stable after additional adjustment for air pollution and traffic related noise amongst others. Conclusions: Living in greener neighbourhoods is associated with older age at menopause and might slow reproductive aging. These are novel findings with broad implications. Further studies are needed to see whether our findings can be replicated in different populations and to explore the potential mechanisms underlying this association

Identification of a new locus at 16q12 associated with time-to-asthma onset

International audienceBackground: Asthma is a heterogeneous disease in which age-of-onset plays an important role.Objective: We sought to identify the genetic variants associated with time-to-asthma onset.Methods: We conducted a large-scale meta-analysis of nine genome-wide association studies of time-to-asthma onset (total of 5,462 asthmatics with a broad range of age-of-asthma onset and 8,424 controls of European ancestry) performed using survival analysis techniques.Results: We detected five regions associated with time-to-asthma onset at genome-wide significant level (P<5x10-8). We evidenced a new locus in 16q12 region (near cylindromatosis turban tumor syndrome gene (CYLD)) and confirmed four asthma risk regions: 2q12 (IL1RL1), 6p21 (HLA-DQA1), 9p24 (IL33) and 17q12-q21 (ZPBP2-GSDMA). Conditional analyses identified two distinct signals at 9p24 (both upstream of IL33) and at 17q12-q21 (near ZPBP2 and within GSDMA). These seven distinct loci explained together 6.0% of the variance in time-to-asthma onset. In addition, we showed that genetic variants at 9p24 and 17q12-q21 were strongly associated with an earlier onset of childhood asthma (P≤0.002) whereas 16q12 SNP was associated with a later asthma onset (P=0.04). A high burden of disease risk alleles at these loci was associated with earlier age-of-asthma onset (4 years versus 9-12 years, P=10-4).Conclusion: The new susceptibility region for time-to-asthma onset at 16q12 harbors variants that correlate with the expression of CYLD and NOD2 (nucleotide-binding oligomerization domain 2), two strong candidates for asthma. This study demonstrates that incorporating the variability of age-of-asthma onset in asthma modeling is a helpful approach in the search for disease susceptibility genes

Body silhouettes as a tool to reflect obesity in the past

Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9-23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and self-reported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (±2y) or 45 (±2y) and body silhouettes in women and men were between 0.62-0.66 and correlations for self-reported BMI were between 0.58-0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (±2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men