Physical activity of urban adults: A general population survey in Geneva

Summary: Objectives: Describing the distribution of physical activity in populations is of major importance for developing public health campaigns to prevent sedentarism. Methods: A population-based survey conducted during 1997-1999 in Geneva, Switzerland, included 3410 randomly selected men (n=1707) and women (n=1703), aged 35 to 74 years. Percentiles P10, P50, and P90 summarised the distributions of the total energy expenditure and of the percents used in moderate intensity activities (3 to 3.9 times the basal metabolism rate (BMR), e.g., normal walking, household chores), and in high and very high intensity activities (≥ 4 BMR, e.g., brisk walking, sports). Results: The total energy expenditure (median 2929 kcal/day in men, 2212 kcal/day in women) decreased with age. Prevalence of sedentarism, defined as less than 10% of total energy expended in ≥4 BMR activities, was 57% in men and 70% in women. Men expended 12% (median) of their total energy in 3 to 3.9 BMR and 8% in ≥4 BMR activities. Corresponding percentages in women were 11% and 5%. The highest prevalence of sedentarism was in older age, women, and lower socio-economic status persons. Conclusion: Most of Geneva population is sedentary. Promoting physical activity should target children, adults and elderly, and physical activity should target children, adults and elderly, and physical activities which would be both attractive and financially affordable by most peopl

Lifetime Exposure to Environmental Tobacco Smoke among Urban Women: Differences by Socioeconomic Class

This study sought to determine cumulative lifetime exposure to environmental tobacco smoke (ETS) among urban women in relation to sociodemographic factors. In a population survey carried out in Geneva, Switzerland, during 1993-1995, a representative sample of 1, 883 women aged 35-74 years answered interview questions on lifetime ETS exposure. Exposed women were defined as those who had spent at least 1 hour daily in a smoky environment during 1 or more years. The prevalence of current ETS exposure was 31.0% among 1, 458 never or former smokers. Lifetime prevalence was 58.3% among 1, 061 never smokers. The home (42.1%) and the workplace (39.6% of employed women) were the most frequent sources of ETS exposure, leisure time activity being a secondary source. Throughout a lifetime, work accounted for the greatest average intensity of exposure (on average, 19 hours of exposure per week), while the longest duration of exposure (on average, 18 years) was in the home. Cumulative lifetime exposure (intensity (in hours/week) x duration) from all sources combined was 308 hours/week-years, which can correspond to 30.8 hours/week over a period of 10 years or 20.5 hours/week over a period of 15 years. Women from low socioeconomic classes had more intense and longer exposures than women from higher socioeconomic classes, mainly because of work exposure. Both the intensity and the duration of lifetime ETS exposure were greater than previously suspected. Reduction of ETS exposure in the workplace should be a public health priority. Am J Epidemiol 1998; 148: 1040-

Can the declining prevalence of left-handedness with age be due to smoking?

The objective of this study was to assess whether smoking habits can explain the decline in left-handedness prevalence with age. Subjects participating in a population-based survey (n=3,071) in Geneva, Switzerland, completed a questionnaire on innate hand preference, current hand preference for writing and smoking habits. The prevalence of innate left-handedness in the Geneva population was 9.4% in men and 7.4% in women. There was no association between smoking and left-handedness. It is concluded that smoking is not associated with hand preference and is an unlikely cause of overmortality in left-handed subject

A population survey of bowel habits in urban Swiss men

The aim of this study was to determine the prevalence of symptoms related to constipation in urban Swiss men and to identify associated sociodemographic factors and health habits. A sample of 773 men aged between 35 and 74 years randomly selected from the Geneva population answered a questionnaire on bowel habits during a personal interview in a mobile epidemiological unit. ‘Constipation' was reported by more than 6% of subjects, difficulties in stool evacuation by approximately 5% and less than three stools per week by approximately 2%. These symptoms appeared less prevalent in subjects with post-baccalaureate education (the excess prevalence of self-reported constipation, difficulty in stool evacuation and frequent daily defecation was greater than 5%). Smokers were more likely to have a frequency of 3-7 stools per week and were less affected by frequent daily defecation. Self-reported constipation was more prevalent in subjects with a higher dietary fibre intake. No statistically significant effects of age, nationality, dietary fat or physical activity were observed. These results are consistent with national surveys in US populations. Factors related to socioeconomic status or education may be a cause of constipation in men, but they still need to be elucidate

The neurogenic basic helix–loop–helix transcription factor NeuroD6 confers tolerance to oxidative stress by triggering an antioxidant response and sustaining the mitochondrial biomass

Preserving mitochondrial mass, bioenergetic functions and ROS (reactive oxygen species) homoeostasis is key to neuronal differentiation and survival, as mitochondria produce most of the energy in the form of ATP to execute and maintain these cellular processes. In view of our previous studies showing that NeuroD6 promotes neuronal differentiation and survival on trophic factor withdrawal, combined with its ability to stimulate the mitochondrial biomass and to trigger comprehensive antiapoptotic and molecular chaperone responses, we investigated whether NeuroD6 could concomitantly modulate the mitochondrial biomass and ROS homoeostasis on oxidative stress mediated by serum deprivation. In the present study, we report a novel role of NeuroD6 as a regulator of ROS homoeostasis, resulting in enhanced tolerance to oxidative stress. Using a combination of flow cytometry, confocal fluorescence microscopy and mitochondrial fractionation, we found that NeuroD6 sustains mitochondrial mass, intracellular ATP levels and expression of specific subunits of respiratory complexes upon oxidative stress triggered by withdrawal of trophic factors. NeuroD6 also maintains the expression of nuclear-encoded transcription factors, known to regulate mitochondrial biogenesis, such as PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α), Tfam (transcription factor A, mitochondrial) and NRF-1 (nuclear respiratory factor-1). Finally, NeuroD6 triggers a comprehensive antioxidant response to endow PC12-ND6 cells with intracellular ROS scavenging capacity. The NeuroD6 effect is not limited to the classic induction of the ROS-scavenging enzymes, such as SOD2 (superoxide dismutase 2), GPx1 (glutathione peroxidase 1) and PRDX5 (peroxiredoxin 5), but also to the recently identified powerful ROS suppressors PGC-1α, PINK1 (phosphatase and tensin homologue-induced kinase 1) and SIRT1. Thus our collective results support the concept that the NeuroD6–PGC-1α–SIRT1 neuroprotective axis may be critical in co-ordinating the mitochondrial biomass with the antioxidant reserve to confer tolerance to oxidative stress

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

The international EAACI/GA(2)LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria

Publisher Copyright: © 2021 GA²LEN. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.Peer reviewe

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc