Reference values for plasma and urine trace elements in a Swiss population-based cohort.

OBJECTIVES: Trace elements (TEs) are ubiquitous. TE concentrations vary among individuals and countries, depending on factors such as living area, workplaces and diet. Deficit or excessive TEs concentrations have consequences on the proper functioning of human organism so their biomonitoring is important. The aim of this project was to provide reference values for TEs concentrations in the Swiss population. METHODS: The 1,078 participants to the SKiPOGH cohort included in this study were aged 18-90 years. Their 24-h urine and/or plasma samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine 24 TEs concentrations: Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, I, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Se, Sn, Tl, V and Zn. Statistical tests were performed to evaluate the influence of covariates (sex, age, BMI, smoking) on these results. Reference intervals for the Swiss adult population were also defined. RESULTS: TEs concentrations were obtained for respectively 994 and 903 persons in plasma and urine matrices. It was possible to define percentiles of interest (P50 and P95) for almost all the TEs. Differences in TEs distribution between men and women were noticed in both matrices; age was also a cofactor. CONCLUSIONS: This first Swiss biomonitoring of a large TEs-panel offers reference values in plasma and in urine for the Swiss population. The results obtained in this study were generally in line with clinical recommendations and comparable to levels reported in other population-based surveys.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

BACKGROUND: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. METHODS: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept. RESULTS: There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers. DISCUSSION: This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological 'wear and tear' and a further biomarker (PEF) that could usefully be included in future data collection.

Prevalence of SARS-CoV-2 infection and associated risk factors among asylum seekers living in asylum centres: A cross-sectional serologic study in Canton of Vaud, Switzerland.

Background: Understanding the factors influencing SARS-CoV-2 transmission in asylum seekers and refugees living in centres is crucial to determine targeted public health policies protecting these populations fairly and efficiently. In response, this study was designed to explore the pandemic's spread into asylum centres during the first wave of the pandemic in Switzerland. Specifically, it aimed to identify the risk factors associated with a positive anti-SARS-CoV-2 seroprevalence test after the first semi-confinement period (16 March to 27 April 2020) amongst asylum seekers and refugees living in centres. Methods: This research is part of SérocoVID, a seroepidemiologic study of SARS-CoV-2 infection conducted in the canton of Vaud, Switzerland. Migrants living in two asylum centres, one known to have had an epidemic outbreak, were invited to participate in this study. Anti-SARS-CoV-2 IgG and IgA antibodies targeting the spike viral protein were measured in all participants using a Luminex immunoassay. Each participant also completed a questionnaire measuring socio-demographic characteristics, medical history (comorbidities, smoking status, BMI, flu-like symptoms), health literacy, public health recommendations (wearing a masque in a public area, social distancing and hands cleaning), behaviours and exposures (daily life activities, number of contacts weekly). The association of these independent variables with the serologic test result were estimated using a multivariable logistic regression model. Findings: A total of 124 participants from the two asylum centres took part in the study (Centre 1, n = 82; Centre 2, n = 42). The mean participation rate was 36.7%. The seroprevalence in Centres 1 and 2 were 13% [95% CI 0.03, 0.14] and 50% [0.34, 0.65], respectively. Next, 40.63% of SARS-CoV-2 positive people never developed symptoms (asymptomatic cases), and no one had severe forms of the Covid-19 disease requiring hospitalisation. Participants report high compliance with public health measures, especially hygiene rules (96.3% of positive answers) and social distancing (88.7%). However, only 11.3% said they always wore a masque in public. After adjusting for individual characteristics, infection risk was lower amongst people with high health literacy (aOR 0.16, p = 0.007 [0.04, 0.60]) and smokers (aOR 0.20, p = 0.013 [0.06, 0.69]). Conclusion: Despite the lack of severe complications of Covid-19 disease in this study, findings suggest that developing targeted public health measures, especially for the low health literacy population, would be necessary to limit the risk of outbreaks in asylum centres and improve this population's safety. Further investigations and qualitative approach are required to understand more finely how living conditions, risks and behaviours such as tobacco consumption, and the adoption of protective measures impact SARS-CoV-2 infection.

Blood DNA methylation signatures of lifestyle exposures: tobacco and alcohol consumption.

BACKGROUND: Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic changes incurred with differing levels of lifestyle exposures. This study describes and validates two novel epigenetic signatures of tobacco (EpiTob) and alcohol (EpiAlc) consumption and investigates their association with disease outcomes. METHODS: The epigenetic signatures, EpiTob and EpiAlc, were developed using data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) (N = 689). Epigenetic and phenotypic data available from the 1921 (N = 550) and 1936 (N = 1091) Lothian Birth Cohort (LBC) studies, and two publicly available datasets on GEO Accession (GSE50660, N = 464; and GSE110043, N = 94) were used to validate the signatures. A multivariable logistic regression model, adjusting for age and sex, was used to assess the association between self-reported tobacco or alcohol consumption and the respective epigenetic signature, as well as to estimate the association between CVD and epigenetic signatures. A Cox proportional hazard model was used to estimate the risk of mortality in association with the EpiTob and EpiAlc signatures. RESULTS: The EpiTob signature was positively associated with self-reported tobacco consumption for current or never smokers with explained variance ranging from 0.49 (LBC1921) to 0.72 (LBC1936) (pseudo-R2). In the SKIPOGH, LBC1921 and LBC1936 cohorts, the epigenetic signature for alcohol consumption explained limited variance in association with self-reported alcohol status [i.e., non-drinker, moderate drinker, and heavy drinker] (pseudo-R2 = 0.05, 0.03 and 0.03, respectively), although this improved considerably when measuring self-reported alcohol consumption with standardized units consumed per week (SKIPOGH R2 = 0.21; LBC1921 R2 = 0.31; LBC1936 R2 = 0.41). Both signatures were associated with history of CVD in SKIPOGH and LBC1936, but not in LBC1921. The EpiTob signature was associated with increased risk of all-cause and lung-cancer specific mortality in the 1936 and 1921 LBC cohorts. CONCLUSIONS: This study found the EpiTob and EpiAlc signatures to be well-correlated with self-reported exposure status and associated with long-term health outcomes. Epigenetic signatures of lifestyle exposures may reduce measurement issues and biases and could aid in risk stratification for informing early-stage targeted interventions.

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND: Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS: We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS: During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION: With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance.

Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking.

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case-control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.

Genetic insights into biological mechanisms governing human ovarian ageing.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

Intraocular Pressure Reduction after Femtolaser Assisted Cataract Surgery and Its Association with the Use of Ultrasound.

Background and Objectives: To quantify the change in intraocular pressure (IOP) after phacoemulsification in patients having undergone femtolaser assisted cataract surgery (FLACS), and study the influence of the use of ultrasound on this change. Setting: Jules-Gonin Eye Hospital, University Department of Ophthalmology, Lausanne, Switzerland. Materials and Methods: Interventional study. Methods: All consecutive cases operated with FLACS and with complete data for the studied parameters were selected for inclusion in the study. Data had been prospectively collected and was analysed retrospectively. Linear regression was performed to explore the association of change in IOP with time of measure, ultrasound use, sex, age, and duration of surgery. Results: There was a mean decrease in intraocular pressure of 2.5 mmHg (CI 95% -3.6; -1.4, p < 0.001) postoperatively. No association between the change in intraocular pressure and ultrasound time or effective phaco time was observed when the data were analyzed one at a time or in a multiple linear regression model. There was no association with sex, age, nuclear density, presence of pseudoexfoliation, duration of surgery, and time of ocular pressure measurement. Eyes with preoperative IOP ≥ 21 mmHg had a more significant IOP reduction after surgery (p < 0.0001) as did eyes with an anterior chamber depth <2.5 mm (p = 0.01). Conclusion: There was a decrease in intraocular pressure six months after FLACS in our study similar to that in the published literature for standard phacoemulsification. The use of ultrasound may not influence the size of the decrease, whereas the preoperative IOP and anterior chamber depth do. FLACS may be as valuable as standard phacoemulsification for cases where IOP reduction is needed postoperatively.

Dietary Intake and Diet Quality of Adult Survivors of Childhood Cancer and the General Population: Results from the SCCSS-Nutrition Study.

Childhood cancer survivors (CCSs) are at increased risk of developing chronic health conditions. This may potentially be reduced by a balanced diet. We aimed to compare dietary intake and diet quality using the Alternative Healthy Eating Index (AHEI) of adult CCSs and the general Swiss population. A food frequency questionnaire (FFQ) was completed by CCSs with a median age of 34 (IQR: 29-40) years. We compared dietary intake of 775 CCSs to two population-based cohorts who completed the same FFQ: 1276 CoLaus and 2529 Bus Santé study participants. CCSs consumed particular inadequate amounts of fiber and excessive amounts of sodium and saturated fat. Dietary intake was similar in CCSs and the general population. The mean AHEI was low with 49.8 in CCSs (men: 47.7, women: 51.9), 52.3 in CoLaus (men: 50.2, women: 54.0), and 53.7 in Bus Santé (men: 51.8, women: 54.4) out of a maximum score of 110. The AHEI scores for fish, fruit, vegetables, and alcohol were worse in CCSs than in the general population, whereas the score for sugar-sweetened beverages was better (all p < 0.001). Diet quality at follow-up did not differ between clinical characteristics of CCSs. Long-term CCSs and the general population have poor dietary intake and quality in Switzerland, which suggests similar population-based interventions for everyone.

Residential radon - Comparative analysis of exposure models in Switzerland.

Residential radon exposure is a major public health issue in Switzerland due to the known association between inhaled radon progeny and lung cancer. To confirm recent findings of an association with skin cancer mortality, an updated national radon model is needed. The aim of this study was to derive the best possible residential radon prediction model for subsequent epidemiological analyses. Two different radon prediction models were developed (linear regression model vs. random forest) using ca. 80,000 measurements in the Swiss Radon Database (1994-2017). A range of geographic predictors and building specific predictors were considered in the 3-D models (x,y, floor of dwelling). A five-fold modelling strategy was used to evaluate the robustness of each approach, with models developed (80% measurement locations) and validated (20%) using standard diagnostics. Random forest consistently outperformed the linear regression model, with higher Spearman's rank correlation (51% vs. 36%), validation coefficient of determination (R2 31% vs. 15%), lower root mean square error (RMSE) and lower fractional bias. Applied to the population of 5.4 million adults in 2000, the random forest resulted in an arithmetic mean (standard deviation) of 75.5 (31.7) Bq/m3, and indicated a respective 16.1% and 0.1% adults with predicted radon concentrations exceeding the World Health Organization (100 Bq/m3) and Swiss (300 Bq/m3) reference values.

Clinical Profiles and Factors Associated with a Low Sodium Intake in the Population: An Analysis of the Swiss Survey on Salt.

As a part of the salt controversy, it has been suggested that people with a low sodium intake have an increased risk of cardiovascular events. However, there is no clear explanation for this increased risk. We examined the socio-demographic, clinical profile, and behavioral factors associated with a low sodium intake in the Swiss subjects who participated in the Swiss Survey on Salt. Only 13.3% of the Swiss population eat less than 5 g of salt daily and among them 78.2% are women. Subjects with a low sodium intake eat and drink less as reflected by lower intakes of proteins, potassium, and calcium and a smaller urine volume. In addition, a low blood pressure, a normal body mass index, a low prevalence of obesity, a low serum uric acid, and less alcohol and cigarette consumption characterized this group, suggesting a rather low cardiovascular risk profile. Being single and doing most of the cooking at home are associated with a low intake of sodium, as well as a less frequent consumption of meat and fish when eating less than 5 g salt per day. However, the awareness of the effects of salt on health and cardiovascular risk, health concerns, and physical activity are similar in subjects eating more or less salt. In conclusion, we could not evidence clinical or behavioral factors that could significantly increase the risk of developing cardiovascular events in low salt eaters.

[New law for cancer registration in Switzerland†: opportunities and challenges]. / Nouvelles exigences légales dans le domaine de l'enregistrement du cancer†: opportunités et défis.

The new federal Act on registration of oncological diseases requires since January 1st 2020 institutions and treating physicians to transmit regulated data on all Swiss cancer cases and some precancerous pathologies to the competent tumour registry, and to inform their patients about it. This legal basis is intended to enlarge cancer data collection and registration in a traceable, better standardized, more complete and rapid manner. These legal provisions are expected to improve the reliability and efficiency of the analysis of the data, which is crucial for the epidemiological surveillance of cancer in Switzerland, for the benefit of public health policy, clinical management and for the population.

La Loi fédérale sur l'enregistrement des maladies oncologiques, entrée en vigueur le 1er janvier 2020, contraint désormais institutions et médecins traitants à transmettre des données réglementées sur les cancers et certaines pathologies précancéreuses au registre des tumeurs compétent, et d'en informer leurs patient·e·s. Cette base légale est destinée à amplifier la collecte et l'enregistrement des données concernant les maladies oncologiques, ceci de manière traçable, mieux standardisée, plus complète et rapide. Il est attendu de ces dispositions légales une amélioration de la fiabilité et de l'efficacité de l'analyse des données recueillies, analyse déterminante pour la surveillance épidémiologique du cancer en Suisse au bénéfice des politiques de santé publique, de la prise en charge clinique et de la population.

Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study.

BACKGROUND: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1ß and tumor necrosis factor α- in 6 European cohort studies. METHODS: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation. RESULTS: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1ß and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1ß and tumor necrosis factor α. CONCLUSIONS: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health.

Uranium exposure of the Swiss population based on 24-hour urinary excretion.

AIM OF THE STUDY: Important regional differences in uranium exposure exist because of varying uranium concentrations in soil, water and food. Comprehensive data on the exposure of the general population to uranium is, however, scarce. Based on the 24-hour urinary excretion, the uranium exposure of the adult Swiss population was assessed in relation to age, sex, place of residence, body mass index (BMI), smoking habit and type of drinking water, as well as risk factors in relation to kidney impairment and indicators of a possible renal dysfunction. METHODS: Uranium was quantified in 24-hour urine from a nationwide population-based sample (n = 1393). The ratio 238U/233U was measured for isotope dilution calibration with a sector field inductively coupled plasma mass spectrometer (HR-ICP-MS). RESULTS: Overall median and 95th percentile were 15 and 67 ng/24 h, respectively. The place of residence significantly influenced urinary uranium excretion. However, most of the highest urinary uranium excretion levels could not be associated to areas known for their elevated uranium concentrations in the drinking water. Sources other than the local drinking water (e.g., bottled water) might be important, too. Gender as well as albumin excretion also had a significant effect on uranium excretion. The latter was, however, strongly dependent on the presence of diabetes mellitus. No association was found for age, BMI, smoking habit or the other examined kidney related variables. CONCLUSIONS: On the basis of uranium exposure, assessed via 24-hour urinary uranium excretion, and current knowledge of the toxicity of naturally occurring uranium, a substantial corresponding health risk for the general adult population is unlikely. However, as long as no specific sensitive biomarker for the biological impact of low-dose chronic uranium exposure has been identified and validated, assessing subtle health impact of such exposure will remain difficult.

Mechanisms of life-course socioeconomic inequalities in adult systemic inflammation: Findings from two cohort studies.

Disadvantaged socioeconomic conditions in childhood heighten systemic inflammatory levels in adulthood; however, life-course mechanisms underlying this association are largely unknown. In the present observational study, we investigated the roles of adulthood socioeconomic and lifestyle factors in mediating this association. Participants were from two prospective Swiss population-based cohorts (N = 5,152, mean age 60 years). We estimated the total effect of paternal occupational position on adult heightened systemic inflammatory levels (C-reactive protein>3 mg/L), and the indirect effects via adulthood socioeconomic positions (SEPs: education and occupational position), financial hardship, and lifestyle factors (body mass index, smoking status, physical inactivity, and alcohol consumption). We estimated odds ratio (OR) and proportion mediated using counterfactual-based mediation models. Individuals whose father had a low occupational position had an OR of 1.51 [95% confidence interval (CI): 1.25, 1.84] for heightened inflammation compared to their more advantaged counterparts. This was jointly mediated (33 [95% CI: 14, 69]%) by adulthood SEPs, whereby the pathway through education followed by occupational position mediated 30 [95% CI: 11, 64]%, while the pathway via occupational position only mediated 3 [95% CI: 4, 13]%. Individuals with the lowest life-course SEPs had an OR of 2.27 [95% CI: 1.71, 2.98] for heightened inflammation compared to having the highest life-course SEPs. This was jointly mediated (63 [95% CI: 44, 97]%) by financial hardship and lifestyle factors. Our study supports a cumulative effect of life-course SEPs on adult heightened systemic inflammation along the pathway paternal occupational position -> education -> adult occupational position. Financial hardship and lifestyle factors in adulthood mediate half of that effect.

Caffeine Consumption in Switzerland: Results from the First National Nutrition Survey MenuCH.

Caffeine is a natural psychostimulant with a potentially positive impact on health when consumed in moderation and a negative impact at high dose (> 400 mg/day). So far, no study has examined self-reported caffeine consumption in Switzerland. Our objectives were to determine 1) the caffeine consumption per adult, 2) the main sources of caffeine intake in the Swiss diet, and 3) the timing of caffeine consumption during the day. We used data from the 2014-2015 national nutrition survey menuCH (adults aged 18 to 75 years old, n = 2057, weighted n = 4,627,878), consisting of two 24-hour dietary recalls. Caffeine content in consumed foods was systematically assessed using laboratory analyses in samples of Swiss caffeinated beverages, information from food composition databases, and estimations from standard recipes. Mean (± SD) daily caffeine consumption per person and percentile 95 were 191 mg/day (± 129) and 426 mg/day, respectively. We observed differences in mean caffeine consumption across age groups (18-34 y: 140 mg/day; 50-64 y: 228 mg/day), linguistic regions (German-speaking: 204 mg/day; French-speaking: 170 mg/day, Italian-speaking: 136 mg/day), and smoking status (never smokers: 171 mg/day; current smokers: 228 mg/day). The three main sources of caffeine intake were 1) coffee (83% of total caffeine intake), 2) tea (9%) and 3) soft drinks (4%). Caffeine consumption was highest between 06:00 and 09:00 (29%) and the circadian rhythm slightly differed across linguistic regions and age groups. The mean caffeine consumption in the Swiss adult population was similar to that reported in neighbouring countries.

Sodium and Potassium Intakes and Cardiovascular Risk Profiles in Childhood Cancer Survivors: The SCCSS-Nutrition Study.

Risk of cardiovascular disease (CVD), common in childhood cancer survivors (CCSs), may be affected by diet. We assessed sodium (Na) and potassium (K) intake, estimated from food frequency questionnaires (FFQs) and morning urine spots, and its associations with cardiovascular risk in CCSs. We stratified CCSs into three risk profiles based on (A) personal history (CVD, CVD risk factors, or CVD risk-free), (B) body mass index (obese, overweight, or normal/underweight), and (C) cardiotoxic treatment (anthracyclines and/or chest irradiation, or neither). We obtained an FFQ from 802 and sent a spot urine sample collection kit to 212, of which 111 (52%) returned. We estimated Na intake 2.9 g/day based on spot urine and 2.8 g/day based on FFQ; the estimated K intake was 1.6 g/day (spot urine) and 2.7 g/day (FFQ). CCSs with CVD risk factors had a slightly higher Na intake (3.3 g/day), than CCSs risk free (2.9 g/day) or with CVD (2.7 g/day, p = 0.017), and obese participants had higher Na intake (4.2 g/day) than normal/underweight CCSs (2.7 g/day, p < 0.001). Daily Na intake was above, and daily K intake below, the national recommended levels. Adult survivors of childhood cancer need dietary assistance to reduce Na and increase K intake.

Nutritional Assessment of Childhood Cancer Survivors (the Swiss Childhood Cancer Survivor Study-Nutrition): Protocol for a Multicenter Observational Study.

BACKGROUND: Childhood cancer survivors are at high risk of developing adverse late health effects. Poor nutritional intake may contribute to this risk, but information about dietary intake is limited. OBJECTIVE: This study will assess childhood cancer survivors' dietary intake and compare two dietary assessment tools: a self-reported food frequency questionnaire, and dietary measurements from urine spot samples. METHODS: In a substudy of the Swiss Childhood Cancer Survivor Study (SCCSS), SCCSS-Nutrition, we assessed childhood cancer survivors' dietary intake via a validated food frequency questionnaire. We sent a urine spot collection kit to a subset of 212 childhood cancer survivors from the French-speaking region of Switzerland to analyze urinary sodium, potassium, urea, urate, creatinine, and phosphate content. We will compare the food frequency questionnaire results with the urine spot analyses to quantify childhood cancer survivors' intake of various nutrients. We collected data between March 2016 and March 2018. RESULTS: We contacted 1599 childhood cancer survivors, of whom 919 (57.47%) returned a food frequency questionnaire. We excluded 11 childhood cancer survivors who were pregnant or were breastfeeding, 35 with missing dietary data, and 71 who had unreliable food frequency questionnaire data, resulting in 802 childhood cancer survivors available for food frequency questionnaire analyses. To a subset of 212 childhood cancer survivors in French-speaking Switzerland we sent a urine spot collection kit, and 111 (52.4%) returned a urine sample. We expect to have the results from analyses of these samples in mid-2019. CONCLUSIONS: The SCCSS-Nutrition study has collected in-depth dietary data that will allow us to assess dietary intake and quality and compare two dietary assessment tools. This study will contribute to the knowledge of nutrition among childhood cancer survivors and is a step toward surveillance guidelines and targeted nutritional recommendations for childhood cancer survivors in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT03297034; https://clinicaltrials.gov/ct2/show/NCT03297034. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14427.

Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation.

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease is independently associated with all-cause mortality. Since inflammation is characteristic of chronic kidney disease and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of chronic kidney disease showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of chronic kidney disease.