The incidence of precocious puberty (PP) and its variants in girls has increased over recent decades. Early-life exposure to endocrine disrupting chemicals (EDCs) may contribute to this trend. The purpose of this study is to investigate the association of exposure to several phenolic EDCs and metal(loid)s, both individually and as a mixture, with the risk of early puberty in Spanish girls. This multicentric case-control study recruited 182 girls aged 4-8 years diagnosed with PP (n = 101) or manifesting any sign of early puberty (premature thelarche: n = 74, other: n = 7) and 128 controls in six Spanish hospitals. Bisphenol, paraben, benzophenone (BzP), and metal(loid) concentrations were quantified in spot urine samples. Adjusted logistic regression and quantile g-computation models were used to assess associations of individual chemicals and their mixture, respectively, with risk of early puberty. Increased bisphenol A (BPA) exposure was associated with higher risk of overall early puberty [OR (95

BACKGROUND:Chronic exposure to low levels of lead (Pb) remains a widespread public health issue, especially among older adults. While its neurotoxic and cardiovascular effects are well recognized, its potential role in accelerating age-related musculoskeletal decline is less understood. Emerging evidence suggests Pb may contribute to sarcopenia, but epidemiological data, especially regarding the most informative biomarkers of exposure, are limited. METHODS:We analysed data from 11 842 participants aged ≥ 60 years across four population-based studies (NHANES III, NHANES 1999-2006, NHANES 2011-2012 and Seniors-ENRICA-2). Sarcopenia indicators included muscle strength (grip strength and chair stand test), muscle mass (dual-energy X-ray absorptiometry, calf circumference and arm circumference) and muscle function (gait speed and Short Physical Performance Battery scores). Sarcopenia was defined in the Seniors-ENRICA-2 using the European Working Group on Sarcopenia in Older People 2 criteria. Associations between Pb exposure (serum and whole blood) and sarcopenia indicators were estimated using multivariable regression and meta-analyses. RESULTS:Pb levels were associated with residential environmental exposures such as traffic proximity, industrial emissions and soil contamination, explaining approximately 11% of variability in whole blood Pb and 9% in serum Pb. Both whole blood and serum Pb showed dose-dependent inverse associations with muscle sarcopenia indicators, including measures of strength, mass and function. Associations with lower limb outcomes were generally stronger for serum Pb compared with whole blood Pb. An interquartile range increase in serum Pb was associated with a 1.33-fold increase in the odds of confirmed or severe sarcopenia (95% CI: 1.02, 1.70), compared with a 1.20-fold increase for whole blood Pb (95% CI: 1.06, 1.36). CONCLUSIONS:Environmental Pb exposure is associated with detrimental effects on musculoskeletal health and contributes to sarcopenia in older adults. Serum Pb may be a more sensitive biomarker of musculoskeletal aging than whole blood Pb and should be considered in future research and surveillance strategies.

To assess whether the role of selenium on pre-diabetes is differential by age, given comorbidities and decreased β-cell function in older adults. We evaluated the cross-sectional association of blood selenium with the homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) in middle-aged (Aragon Workers Health Study [AWHS], N = 1186), and older (Seniors ENRICA [Study on Nutrition and Cardiovascular Risk in Spain]-2 [SEN-2], N = 915) diabetes-free adults. A subsample of participants from AWHS (N = 571) and SEN-2 (N = 603) had glucose and insulin repeated measurements for longitudinal analysis. We validated the cross-sectional dose–response associations in the 2011–2018 National Health and Nutrition Examination Survey (NHANES, N = 1317 middle age and N = 960 older) participants. Selenium was measured in whole blood with ICP-MS in AWHS, SEN-2 and NHANES. The cross-sectional geometric mean ratios (95% confidence intervals) per two-fold selenium increase were 1.09 (1.01, 1.19) for HOMA-IR and 1.15 (1.06, 1.24) for HOMA-β in AWHS; and 1.13 (0.98, 1.31) and 1.03 (0.90, 1.18), in SEN-2. The cross-sectional dose-response associations were consistent in NHANES, with mostly increasingly positive trends for both HOMA endpoints in younger adults and a plateau at levels >~150 μg/L in older adults. The longitudinal dose–response consistently showed positive associations at high selenium dose for both HOMA endpoints in the younger, but not the older, study population. Increased blood selenium was associated with increased insulin resistance and β-cell function in middle-aged, but not in older individuals, especially for β-cell function. The results suggest that selenium-associated insulin resistance might induce compensatory increased β-cell function at younger ages, being this compensatory capacity decreased with aging.

Safety concerns continue to arise as lead and other potentially toxic metals are found in the aerosols of modern disposable e-cigarettes.

Epidemiological studies focusing on metal(oid) exposure and excess body weight among children show inconsistent results and the influence of metal(loid) mixtures has been little studied. We aimed to explore the effect of 10 metal(loid)s, individually and in combinations, on overweight and obesity among children aged 6–12. Urinary levels of these metal(oid)s from 92 controls and 51 cases with overweight and obesity were analyzed. Metal(loid) levels were log-transformed and categorized into tertiles according to the control group cutoff points. Two logistic regression models and weighted quantile sum regressions (WQS) were run: model 1 adjusting for age, sex, creatinine, energy intake and physical activity and model 2 additionally adjusting for maternal education, rice and fish consumption. In the single metal(oid) exposure model, there was a trend of significant negative association for urinary cobalt (Co), where children in the third tertile had lower odds of present overweight and obesity than those in the first (Odds Ratio, OR = 0.43; 95

Processed meat products could constitute a relevant source of cadmium (Cd) and other toxic elements in the diet as they could contain organ meats (e.g. kidneys, liver) known to accumulate metals. Additionally, these products could be contaminated due to metal transfer from the machinery during processing and, in the case of canned meats, metal migration from the container could also occur. We analyzed Cd together with arsenic (As), chromium (Cr), copper (Cu), iron (Fe), nickel (Ni), lead (Pb), tin (Sn) and zinc (Zn) in heavily processed meat products from low, medium, and high-cost US supermarkets (n = 75). These elements were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and the results were expressed on a wet weight basis. The limits of detection (LOD) for the elements analyzed were: 2.8 mu g/kg for As, 0.46 mu g/kg for Cd, 2.3 mu g/kg for Cr, 7.0 mu g/kg for Cu, 41 mu g/kg for Fe, 2.4 mu g/kg for Ni, 0.83 mu g/kg for Pb and 4.3 mu g/kg for Sn and 5.6 mu g/kg for Zn. Cd was detected in the vast majority of the samples presenting an overall median (IQR) concentration of 3.71 (2.10, 5.34) mu g/kg. The products with the highest median Cd concentrations were beef franks and pork cheese sausages from the low-cost supermarket, while spam (from the low and medium-cost supermarkets) presented the lowest. The elements As, Sn and Pb were mainly undetectable. Cr and Ni were detected in most of the samples displaying overall median (IQR) concentrations of 18.39 (8.26, 36.18) mu g/kg and 22.25 (12.66, 54.85) mu g/kg, respectively. Cu, Fe and Zn were detectable in all the samples with overall median (IQR) concentrations of 312 (235, 493) mu g/kg, 10.84 (7.36, 13.57) mg/kg and 13.73 (11.42, 18.12) mg/kg, respectively. Metal composition of these products does not evidence addition of organ meat nor Cd contamination during processing. Metal migration in canned meat (spam) is also unlikely. All processed meat samples presented metal concentrations below the maximum levels set by the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) and the European Union (EU). The estimated Cd intake due to the consumption of these products represented a minimal percentage of the tolerable weekly intake (TWI). Processed meat products from the low and medium-cost supermarkets generally had higher levels of Cd and, in similar products, lower levels of Fe and Zn than those from the high-cost supermarket.

Environmental pollution represents one of the current major problems in food contamination. The release of heavy metals and metalloids from emissions, toxic discharges, etc., is one of the main consequences of industrial pollution. Due to their cumulative properties and toxicity, heavy metal and metalloid concentrations could reach levels that are potentially harmful to human health. In fact, the International Agency for Research on Cancer (IARC) has classified certain metals and metalloids (As, Cd, Cr, and Ni) as carcinogenic to humans due to their ability to induce DNA damage. This chapter deals with the main heavy metals and metalloids of interest in Food Toxicology, including lead, mercury, cadmium, nickel, tin, copper and arsenic.

Background: Selenium is an essential trace element with an antioxidant and anti-inflammatory capacity that has been associated in experimental studies with beneficial effects on appetite control, the regulation of the gut microbiota, and control of the anabolic–catabolic balance. The main aim of the present study was to evaluate the association between circulating selenium concentrations and the risk of developing undernutrition in older adults. Methods: This was a cohort study with 1398 well-nourished community-dwelling individuals aged ≥ 65 years residing in Spain in 2017, who were followed for a mean of 2.3 years. Whole blood selenium was measured at baseline using inductively coupled plasma-mass spectrometry. Undernutrition was assessed at baseline and at follow-up, and defined as having at least one of the three GLIM phenotypic criteria (involuntary weight loss, a low body mass index, and a reduced muscle mass) and at least one of the two etiologic criteria (reduced food consumption or nutrient assimilation and inflammation/disease burden). Results: During the follow-up, 142 participants (11%) developed moderate undernutrition and 113 (8.8%) severe undernutrition. The standardized relative risks of moderate and severe undernutrition at the 75th percentile of Se levels versus the 25th were 0.90 and 0.70, respectively. In dose–response analyses, the risk of severe undernutrition decreased linearly with increasing selenium concentrations. This association was independent of protein intake or diet quality and was stronger among participants with a diagnosis of a musculoskeletal disorder. Conclusions: The results suggest that an adequate dietary selenium status is needed to prevent undernutrition in older adults. Also, this may open the door for clinical trials with selenium supplementation, at doses considered as safe, to prevent undernutrition.

BACKGROUND AND AIM:Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. METHODS AND RESULTS:We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 μg/L to 1450 μg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 μg/L than in controls 959.3 μg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION:In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.

Emotional and behavioral problems during childhood raise the risk of subsequent developmental of mental disorders. Our aim was to study the association between maternal metal and trace element concentrations during gestation and these problems in 9 year-old children. The study sample comprised Spanish mother-child pairs in the INMA project (n = 1003). Metals and trace elements (As, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Tl and Zn) were measured in urine samples collected during pregnancy. Inorganic As metabolites were speciated in a subsample (n = 729). Emotional and behavioral problems were assessed using the Child Behavior Checklist (CBCL) composed of three scales: internalizing, externalizing and total problems. Sociodemographic, dietary and exposure to other environmental pollutants were obtained through questionnaires. Single nucleotide polymorphisms in brain- and metabolism-related genes APOE , BDNF , GSTP1 , and PON1 were determined in cord blood. Multivariate negative binomial models were used. The interaction with sex and genotypes was evaluated including interaction terms. A multi-element analysis was carried out by a principal component analysis. Higher concentrations of Cu, monomethylarsonic acid, and Pb during pregnancy were associated with an increased incidence ratio risk (IRR) between 4.6 and 7.5% for internalizing and externalizing problems for all three CBCL scales in the children. Increasing Mo, Ni and Co concentrations were associated with higher IRR for internalizing problems (up to 8%), and Cd for externalizing problems (6.7%). Modifications by sex and genotypes were found for several associations. Multi-element analysis associated multiple metals and trace elements (Ni, Cu, Se, Cd and Pb) with higher internalizing problems.

Background: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some envi-ronmental chemicals adversely affect the human reproductive system.Objective: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent males.Methods: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals (arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6-methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fun-gicides (ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15-17 years from the INMA-Granada cohort. In blood samples collected on the same day, KISS1 gene DNA methylation was measured at four CpGs from the Exon IV, as well as serum levels of kiss54 protein, total testosterone (T), estradiol (E2), sex hormone binding-globulin, dehydroepiandrosterone sulfate, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Multiple linear regression and mixture (quantile g-computation) models were fit.Results: Urinary MDA and DCCA concentrations were associated with higher kiss54 levels [% change (95%CI) for each log-unit increase in concentration = 2.90 (0.32;5.56), and 1.93 (0.45,3.43), respectively]; IMPy with lower DNA methylation percentage at CpG1 and total CpGs [% change (95%CI) = -1.15 (-1.96;-0.33): -0.89 (-1.73;-0.01), respectively]; and BP3 and DCCA with lower total CpGs methylation [-0.53 (-1.04;-0.01) and - 0.69 (-1.37;-0.01), respectively]. The pesticide mixture and the whole chemical mixture were associated with higher kiss54 [% change (95%CI) = 9.09 (3.29;15.21) and 11.61 (3.96;19.82), respectively] and lower methylation levels at several CpGs. Additionally, serum kiss54 in the third tertile was associated with higher LH levels [% change (95%CI) = 28.69 (3.75-59.63)], and third-tertile CpG1, CpG2, and total CpG methylation percentages were associ-ated with lower FSH and E2.Conclusion: The findings of the present study and the negative correlation between serum kiss54 levels and KISS1 DNA methylation percentages suggested that kisspeptin may be a promising effect biomarker.

Background: Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. Methods: This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. Results: Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitro-samines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old.Conclusions: We detected low but not negligible concentrations of e-cigarette-related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.

Environmental factors play a role in breast cancer development. While metals and metalloids (MMs) include some carcinogens, their association with breast cancer depends on the element studied. Most studies focus on individual MMs, but the combined effects of metal mixtures remain unclear. The aim of this study was to analyze the relationship between the joint exposure to MMs and the risk of developing female breast cancer.We conducted a case-control study within the multicenter prospective EPIC-Spain cohort. Study population comprised 292 incident cases and 286 controls. Plasma concentrations of 16 MMs were quantified at recruitment. Potential confounders were collected using a questionnaire and anthropometric measurements. Mixed-effects logistic regression models were built to explore the effect of individual MMs. Quantile-based g computation models were applied to identify the main mixture components and to estimate the joint effect of the metal mixture.The geometric means were highest for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher Cu concentrations (p = 0.010) and significantly lower Zn concentrations (p < 0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (-0.61) and W (-0.16) showed the highest negative weights. The joint effect of the metal mixture was estimated at an OR = 4.51 (95%CI = 2.32-8.79), suggesting a dose-response relationship. No evidence of non-linearity or non-additivity was found.An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer. Further studies are warranted to confirm these findings.

Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015-2018) and analyzed for Al, Sb, and Li concentrations. Mixed-effect linear regression was used to investigate the association of breast milk concentrations of these elements with the sociodemographic profile of the women, their dietary habits and utilization of personal care products (PCPs), the post-partum interval, and the nutritional characteristics of milk samples, among other factors. Al was detected in 94% of samples, with a median concentration of 57.63 mu g/L. Sb and Li were detected in 72% and 79% of samples at median concen-trations of 0.08 mu g/L and 0.58 mu g/L, respectively. Concentrations of Al, Sb, and Li were not associated with post-partum time. Al was positively associated with total lipid content of samples, weight change since before pregnancy, and coffee and butter intakes and inversely with meat intake. Li was positively associated with intake of chocolate and use of face cream and eyeliner and inversely with year of sample collection, egg, bread, and pasta intakes, and use of hand cream. Sb was positively associated with fatty fish, yoghurt, rice, and deep-fried food intakes and use of eyeliner and inversely with egg and cereal intakes and use of eyeshadow. This study shows that Al, Sb, and Li, especially Al, are widely present in donor breast milk samples. Their concentrations in the milk samples were most frequently associated with dietary habits but also with the lipid content of samples and the use of certain PCPs.

Electronic cigarette (e-cigarette) use emits potentially hazardous compounds and deteriorates indoor air quality. Home is a place where e-cigarettes may frequently be used amid its increasing prohibition in public places. This study assessed the real-life scenario of bystanders' exposure to secondhand e-cigarette aerosol (SHA) at home. A one-week observational study was conducted within the TackSHS project in four countries (Greece, Italy, Spain, and the United Kingdom) in 2019 including: 1) homes of e-cigarette users living together with a non-user/non-smoker; and 2) control homes with no smokers nor e-cigarette users. Indoor airborne nicotine, PM2.5, and PM1.0 concentrations were measured as environmental markers of SHA. Biomarkers, including nicotine and its metabolites, tobacco-specific nitrosamines, propanediol, glycerol, and metals were measured in participants' saliva and urine samples. E-cigarette use characteristics, such as e-cigarette refill liquid's nicotine concentration, e-cigarette type, place of e-cigarette use at home, and frequency of ventilation, were also collected. A total of 29 e-cigarette users' homes and 21 control homes were included. The results showed that the seven-day concentrations of airborne nicotine were quantifiable in 21 (72.4 %) out of 29 e-cigarette users' homes; overall, they were quite low (geometric mean: 0.01 μg/m3; 95 % CI: 0.01–0.02 μg/m3) and were all below the limit of quantification in control homes. Seven-day concentrations of PM2.5 and PM1.0 in e-cigarette and control homes were similar. Airborne nicotine and PM concentrations did not differ according to different e-cigarette use characteristics. Non-users residing with e-cigarette users had low but significantly higher levels of cotinine, 3′-OH-cotinine and 1,2-propanediol in saliva, and cobalt in urine than non-users living in control homes. In conclusion, e-cigarette use at home created bystanders' exposure to SHA regardless of the e-cigarette use characteristics. Further studies are warranted to assess the implications of SHA exposure for smoke-free policy.

Background: Selenium is an essential trace mineral with potential interest for cardiovascular disease (CVD) prevention owing to its antioxidant properties. Epidemiological data on selenium status and CVD remain inconsistent. The objective of this study was to ascertain whether low serum selenium (SSe) concentrations are related to an increased risk of a first CVD event in a population at high cardiovascular risk. Methods: We undertook a case-control study nested within the “PREvención con DIeta MEDiterránea” (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke, or cardiovascular death) during the follow-up period (2003–2010) were matched by sex, age, and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. SSe levels were determined using inductively coupled plasma mass spectrometry analysis. Covariates were assessed through validated questionnaires, in-person interviews, and medical record reviews. Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (ORs). Results: Among women, the mean SSe concentration was lower in cases than in controls (98.5 μg/L vs. 103.8 μg/L; p = 0.016). In controls, SSe levels were directly associated with percentage of total energy intake from proteins and fish intake (p for linear trend < 0.001 and 0.049, respectively), whereas SSe concentrations were inversely associated with age, body mass index, and percentage of total energy intake from carbohydrates (p for linear trend < 0.001, 0.008 and 0.016 respectively). In the total group, we observed an inverse dose–response gradient between SSe levels and risk of CVD in the fully-adjusted model (highest vs. lowest quartile: OR = 0.47, 95% CI: 0.27–0.81; ptrend = 0.003). Conclusions: Among elderly individuals at high cardiovascular risk, high SSe concentrations within population reference values are associated with lower first CVD incidence.

Increased brain iron content has been consistently reported in sporadic Parkinson's disease (PD) patients, and an increase in cytosolic free iron is known to cause oxidative stress and cell death. However, whether iron also accumulates in susceptible brain areas in humans or in mouse models of familial PD remains unknown. In addition, whilst the lysosome functions as a critical intracellular iron storage organelle, little is known about the mechanisms underlying lysosomal iron release and how this process is influenced by lysosome biogenesis and/or lysosomal exocytosis. Here, we report an increase in brain iron content also in PD patients due to the common G2019S-LRRK2 mutation as compared to healthy age-matched controls, whilst differences in iron content are not observed in G2019S-LRRK2 knockin as compared to control mice. Chemically triggering iron overload in cultured cells causes cytotoxicity via the endolysosomal release of iron which is mediated by TRPML1. TFEB expression reverts the iron overload-associated cytotoxicity by causing lysosomal exocytosis, which is dependent on a TRPML1-mediated increase in cytosolic calcium levels. Therefore, approaches aimed at increasing TFEB levels, or pharmacological TRPML1 activation in conjunction with iron chelation may prove beneficial against cell death associated with iron overload conditions such as those associated with PD.

Aim: To measure concentrations of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in longitudinally collected donor breast milk samples and to determine associated factors. Methods: Pb, Hg, Cd, and As concentrations were measured in 242 pooled breast milk samples from 83 donors to a Human Milk Bank in Spain, in 2015-2018, determining their association with the donors' sociodemographic profile, dietary and lifestyle habits, and post-partum time, among other factors, and with the nutritional characteristics of samples. Mixed-effect linear regression was used to identify predictors of Hg and As concentrations in breast milk and mixed-effect logistic regression to identify predictors of the presence of Pb and Cd. Results: As was the element most frequently detected in milk samples (97.1%), followed by Hg (81.2%), Pb (50.6%), and Cd (38.0%). Their median breast milk concentrations were 1.49 mu g/L, 0.26 mu g/L, 0.14 mu g/L, and <0.04 mu g/L, respectively. Concentrations of As were higher in breast milk from primiparous donors, while Hg was higher in donors with a greater intake of fatty fish and meat and lower in samples collected after a longer post-partum time and with higher lactose content. Detection of Pb was higher among multiparous donors, those gaining weight since before pregnancy, and ex-smokers and was lower in samples collected more recently and from donors with greater intake of red meat and eggs. Cd detection was higher for donors with university education and those with greater intake of fried and canned food and more frequent use of hand cream and was lower for donors with greater bread intake. Conclusions: These findings reveal relatively high As concentrations, moderate Hg concentrations, and low Pb and Cd concentrations in pooled donor breast milk. Several factors including post-partum time, parity, smoking habit, and the intake of certain food items were associated with the metal content of milk samples.

Background: Cadmium (Cd) exposure is a risk factor for cardiovascular disease (CVD); however, understanding the effects of Cd at the cellular level remains incomplete. Since growth differentiation factor-15 (GDF-15) is a cytokine produced in many cell types in response to tissue injury and inflammation that may capture several pathways between Cd and CVD, this study examined the relationship between blood Cd levels and serum GDF-15 concentrations in community-dwelling older adults. Methods: Cd and GDF-15 were measured in 1942 non-smoking individuals aged 65+ with no previous history of CVD. The association of Cd with GDF-15 was evaluated in linear regression models that adjusted for sociodemographic, lifestyle and biological risk factors, inflammatory biomarkers (IL-6, C-reactive protein and neutrophil to lymphocyte ratio), and markers of vascular damage (NTproBNP and cTnT-hs). Results: Geometric mean Cd exposure was 0.11 mu g/L (0.09 in never- and 0.15 in former-smokers) and geometric mean GDF-15 was 1186.21 mu g/mL (1182.67 in never- and 1191.66 in former-smokers). In multivariable analyses, we found a dose-response association between Cd levels and GDF-15: adjusted mean percentage differences in GDF-15 (95% confidence interval) per 2-fold increase in Cd concentrations in the overall non-smoking population and in never smokers were, respectively, 2.54% (1.01, 4.06) and 2.50% (0.47, 4.54). In spline regression, the dose-response relationship was progressive over the range of Cd concentrations with no significant departures from linearity. Conclusions: Cd exposure may be related to enhanced GDF-15 expression. Future studies with repeated GDF-15 measurements should confirm the present findings to better understand the biological mechanisms underlying this association.

Objectives: Major depressive disorder (MDD) is a multifactorial syndrome with significant interactions between genetic and environmental factors. This study specifically investigates the association between family history of alcohol problems (FHAP) and family history of depression (FHD), and how these relate to different clusters of depressive symptoms. Methods: Correlations between FHAP and FHD and different clusters of the Beck Depression Inventory (BDI) were studied. We sampled 333 employees from a general hospital who had been receiving a psychiatric consultation between 2005 and 2012. Analysis of variance (ANOVA) and Analysis of covariance (ANCOVA) models were conducted to explore these correlations. Results: There was a significant positive correlation between FHAP and BDI affective score. This result remained significant even after the adjustment for other variables considered as important factors for MDD, such as gender, age, marital status, education, ethnic group and FHD. More specifically, FHAP was correlated with dissatisfaction and episodes of crying among the affective symptoms. FHAP showed no statistical difference in any of the other clusters score or in the BDI total score. Moreover, as expected, we found a correlation between FHD and BDI total score and Somatic and Cognitive clusters. Conclusion: FHAP should be routinely investigated in individuals presenting with depressive symptoms. This is especially important in cases presenting with dissatisfaction and episodes of crying in patients who do not endorse criteria for MDD. Due to study limitations, the findings require replication by neurobiological, epidemiological and clinical studies.