Geographic and dietary differences of urinary uranium levels in the Strong Heart Family Study.

BACKGROUND: American Indian (AI) communities are affected by uranium exposure from abandoned mines and naturally contaminated drinking water. Few studies have evaluated geographical differences across AI communities and the role of dietary exposures. OBJECTIVE: We evaluated differences in urinary uranium levels by diet and geographical area among AI participants from the Northern Plains, the Southern Plains, and the Southwest enrolled in the Strong Heart Family Study (SHFS). METHODS: We used food frequency questionnaires to determine dietary sources related to urinary uranium levels for 1,682 SHFS participants in 2001-2003. We calculated adjusted geometric mean ratios (GMRs) of urinary uranium for an interquartile range (IQR) increase in self-reported food group consumption accounting for family clustering and adjusting for sociodemographic variables and other food groups. We determined the percentage of variability in urinary uranium explained by diet. RESULTS: Median (IQR) urinary uranium levels were 0.027 (0.012, 0.057) µg/g creatinine. Urinary uranium levels were higher in Arizona (median 0.039 µg/g) and North Dakota and South Dakota (median 0.038 µg/g) and lower in Oklahoma (median 0.019 µg/g). The adjusted percent increase (95% confidence interval) of urinary uranium levels per IQR increase in reported food intake was 20% (5%, 36%) for organ meat, 11% (1%, 23%) for cereals, and 14% (1%, 29%) for alcoholic drinks. In analyses stratified by study center, the association with organ meat was specific to North Dakota and South Dakota participants. An IQR increase in consumption of fries and chips was inversely associated with urinary uranium levels -11% (-19%, -3%). Overall, we estimated that self-reported dietary exposures explained 1.71% of variability in urine uranium levels. IMPACT: Our paper provides a novel assessment of self-reported food intake and urinary uranium levels in a cohort of American Indian participants. We identify foods (organ meat, cereals, and alcohol) positively associated with urinary uranium levels, find that organ meat consumption is only associated with urine uranium in North Dakota and South Dakota, and estimate that diet explains relatively little variation in total urinary uranium concentrations. Our findings contribute meaningful data toward a more comprehensive estimation of uranium exposure among Native American communities and support the need for high-quality assessments of water and dust uranium exposures in SHFS communities.

Breast cancer risk for the joint exposure to metals and metalloids in women: Results from the EPIC-Spain cohort.

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.

Blood Selenium Concentrations Are Inversely Associated with the Risk of Undernutrition in Older Adults.

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.

Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial.

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.

Association of genetic polymorphisms in detoxifying systems and urinary metal(loid) levels with excess body weight among Spanish children: A proof-of-concept study.

Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6-12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children.

Kisspeptin as potential biomarker of environmental chemical mixture effect on reproductive hormone profile: A pilot study in adolescent males.

BACKGROUND: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental 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 fungicides (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 associated 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.

Concentrations and predictors of aluminum, antimony, and lithium in breast milk: A repeated-measures study of donors.

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 µg/L. Sb and Li were detected in 72% and 79% of samples at median concentrations of 0.08 µg/L and 0.58 µg/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.

Passive exposure to electronic cigarette aerosol in pregnancy: A case study of a family.

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. Nitrosamines 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.

Exposure to secondhand aerosol from electronic cigarettes at homes: A real-life study in four European countries.

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.

Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.

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.

Serum Selenium and Incident Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Trial: Nested Case-Control Study.

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.

Estudio AHORA 6: Angioplastia coronaria con alta HOspitalaria RÁpida en 6 horas / Early Hospital Discharge (Within Six Hours) for Patients Undergoing Coronary Angioplasty

RESUMEN Introducción: Es de práctica habitual la internación durante 24 h en los pacientes (P) intervenidos con una angioplastia coronaria (ATC) programada. Experiencias previas proponen el alta post ATC en el mismo día en P seleccionados. Material y métodos: Estudio prospectivo, aleatorizado, controlado, simple ciego. Se incluyeron P de 18 a 75 años candidatos a una ATC programada por acceso radial, con posibilidad de acceder al sistema de emergencias en menos de 40 minutos. Se excluyeron los P con fracción de eyección ventricular izquierda < 30%, Creatinina > 1,5 mg/dL, insuficiencia cardíaca, enfermedad pulmonar obstructiva crónica, diabetes descompensada, o anatomía coronaria muy compleja. Se dividió a la población en dos grupos (G). G 1: alta en 6 horas. G2: alta al día siguiente. Punto final primario: muerte o necesidad de rehospitalización dentro de las 24 h de realizado el procedimiento. Se realizó seguimiento telefónico la noche del procedimiento y a la mañana siguiente, presencial a las 48 h, y telefónico al mes, seis meses y un año. Resultados: Se adjudicaron aleatoriamente 80 P. Seis P (7,5%) presentaron criterios de exclusión durante el procedimiento. No se produjo ninguna muerte ni evento cardiovascular mayor en ninguno de ambos grupos. Al año de seguimiento se detectó 3,75% de reestenosis intra stent. Se detectó elevación de troponina en 20 P (25%) de los cuales 4 habían sido excluidos por complicaciones durante la ATC. En los restantes 16, la elevación de la troponina no tuvo repercusión clínica. Conclusión: En una población de pacientes entre 55 y 75 años, en su mayoría de género masculino, con alta prevalencia de infarto de miocardio previo, y depresión de la función ventricular, pudo realizarse una angioplastia programada por acceso radial con alta en 6 horas, con un adecuado margen de seguridad.

ABSTRACT Background: 24-hour hospitalization is common practice in patients (P) who underwent scheduled coronary angioplasty (PCI). Previous experiences propose same-day discharge in selected P. Methods: Prospective, comparative, randomized, single-blind study. P aged 18 to 75 years were included as candidates for a scheduled radial-access PCI with the possibility of accessing the emergency system in less than 40 minutes. P with left ventricular ejection fraction <30%, creatinine >1.5 mg/dL, heart failure, chronic obstructive pulmonary disease, decompensated diabetes or very complex coronary anatomy were excluded. The population was divided in two groups (G). G 1: same-day discharge in 6 hours. G2: discharge the next day. Primary endpoint: death or need for rehospitalization within 24 hours of the procedure. Follow-up was carried out by phone the night of the procedure and the next morning, in person at 48 hours, and by telephone after a month, six months and a year. Continuous variables were expressed as median and their respective interquartile range, and qualitative variables as percentages. Results: 80 P were randomized. Six P (7.5%) presented exclusion criteria during the procedure. There were no deaths or major cardiovascular events in either groups. At one year of follow-up, 3.75% of in-stent restenosis was detected. Troponin elevation was detected in 20 P (25%); 4 were P excluded due to complications during PCI, in the remaining 16 it had no clinical repercussion. Conclusion: In a population of patients between 55 and 75 years old, mostly male, with a high prevalence of previous myocardial infarction, and ventricular function depression, a scheduled radial-access PCI could be performed with same day discharge in 6 hours, with an adequate safety margin.

Concentrations and determinants of lead, mercury, cadmium, and arsenic in pooled donor breast milk in Spain.

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 µg/L, 0.26 µg/L, 0.14 µg/L, and <0.04 µg/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.

Healthy lifestyle, metabolomics and incident type 2 diabetes in a population-based cohort from Spain.

BACKGROUND: The contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes. METHODS: A Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001-2003, and were followed-up to 2015 to ascertain incident type 2 diabetes. RESULTS: The HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and - 8.23 (95% CI, - 16.34, - 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes. CONCLUSIONS: The HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.

Cadmium exposure and growth differentiation factor-15 (GDF-15) levels in non-smoking older adults.

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 µg/L (0.09 in never- and 0.15 in former-smokers) and geometric mean GDF-15 was 1186.21 pg/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.

Effects of e-liquid flavor, nicotine content, and puff duration on metal emissions from electronic cigarettes.

Vaping is the action of inhaling and exhaling aerosols from electronic cigarettes. The aerosols contain various amounts of toxic chemicals, including metals. The purpose of this study was to evaluate factors that can influence metal levels, including flavor and nicotine content in the e-liquid, and puff duration. Aerosols were collected from both closed-system (cartridge-based) and open-system e-cigarettes using e-liquids with different flavors (fruit, tobacco, and menthol), nicotine content (0, 6, 24, and 59 mg/mL), and different puff durations (1, 2, and 4 s). The concentrations of 14 metals in the collected aerosols were measured using inductively coupled plasma mass spectroscopy. Aerosol concentrations of As, Fe, and Mn varied significantly among fruit, tobacco, and menthol flavors in both closed-system and open-system devices. Concentrations of Al, Fe, Sn, and U were significantly higher in tobacco or menthol flavored aerosols compared to fruit flavors in closed-system devices. Aerosol W levels were significantly higher in tobacco flavored aerosols compared to fruit flavors in open-system devices. Concentrations of As, Fe, and Mn were higher in tobacco flavored aerosols compared to menthol flavors in both types of devices. The median Pb concentration decreased significantly from 15.8 to 0.88 µg/kg when nicotine content increased from 0 to 59 mg/mL, and median Ni concentration was 9.60 times higher in aerosols with nicotine of 59 mg/mL compared to 24 mg/mL (11.9 vs. 1.24 µg/kg) for closed-system devices. No significant differences were observed in aerosol metal concentrations for different puff durations. Aerosol metal concentrations varied widely between different flavors and nicotine content but not by puff duration. Flavor and nicotine content of the e-liquid could be potential factors in metal emissions. Some elements showed higher concentrations under certain conditions, highlighting the urgent need of developing strict product regulations, especially on e-liquid composition and nicotine content to inform e-cigarette users about metal exposure through vaping.

Exposure to metals and metalloids among pregnant women from Spain: Levels and associated factors.

BACKGROUND: Humans are regularly exposed to metals and metalloids present in air, water, food, soil and domestic materials. Most of them can cross the placental barrier and cause adverse impacts on the developing foetus. OBJECTIVES: To describe the prenatal concentrations of metals and metalloids and to study the associated sociodemographic, environmental and dietary factors in pregnant Spanish women. METHODS: Subjects were 1346 pregnant women of the INMA Project, for whom the following metals arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), thallium (Tl) and zinc (Zn) were determined in urine, at both the first and the third trimesters of gestation. Sociodemographic, dietary and environmental information was collected through questionnaires during pregnancy. Multiple linear mixed models were built in order to study the association between each metal and metalloid concentrations and the sociodemographic, environmental and dietary factors. RESULTS: The most detected compounds were As, Co, Mo, Sb, Se and Zn at both trimesters. Zn was the element found in the highest concentrations at both trimesters and Tl was detected in the lowest concentrations. We observed significant associations between As, Cd, Cu, Sb, Tl and Zn concentrations and working situation, social class and age. Seafood, meat, fruits, nuts, vegetables and alcohol intake affected the levels of all the metals but Cd and Cu. Proximity to industrial areas, fields and air pollution were related to all metals except Cd, Sb and Se. CONCLUSIONS: This is the first large prospective longitudinal study on the exposure to metals and metalloids during pregnancy and associated factors to include several cohorts in Spain. The present study shows that some modifiable lifestyles, food intakes and environmental factors could be associated with prenatal exposure to metal(loid)s, which may be considered in further studies to assess their relationship with neonatal health outcomes.

Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment. OBJECTIVES: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males. METHODS: Data were gathered from 125 adolescents on: spot urine sample total concentrations of the neurotoxic metal(oid)s arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb); serum BDNF protein concentrations; and concurrent behavioral functioning according to the Child Behavior Check List (CBCL/6-18). In 113 of the participants, information was also collected on blood BDNF DNA methylation at six CpGs. Associations were evaluated by multivariate linear regression analysis adjusted for confounders. RESULTS: As, Cd, Hg, and Pb were detected in 100%, 98.5%, 97.0%, and 89.5% of urine samples, respectively. Median serum BDNF concentration was 32.6 ng/mL, and total percentage of BDNF gene methylation was 3.8%. In the adjusted models, urinary As was non-linearly associated with more internalizing problems and Cd with more externalizing behaviors. The percentage BDNF DNA methylation at CPGs #5 and the mean percentage CpG methylation increased across As tertiles (p-trend = 0.04 and 0.03, respectively), while 2nd tertile and 3rd tertile of Cd concentrations were associated with lower serum BDNF and higher CpG3 methylation percentage. Additionally, when BDNF was categorized in tertiles, serum BDNF at the 3rd tertile was associated with fewer behavioral problems, particularly withdrawn (p-trend = 0.04), social problems (p-trend = 0.12), and thought problems (p-trend = 0.04). CONCLUSION: Exposure to As and Cd was associated with BDNF gene DNA methylation BDNF gene and serum BDNF, respectively. Associations with DNA methylation may be attributable to a higher variability over time in circulating BDNF concentrations than in the methylation status of this gene. Caution should be taken when interpreting the results relating postnatal Pb and Hg to behavioral functioning. Further studies are needed to verify these findings.

Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats.

Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p > 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model.

Spatial relationship between well water arsenic and uranium in Northern Plains native lands.

Arsenic and uranium in unregulated private wells affect many rural populations across the US. The distribution of these contaminants in the private wells of most American Indian communities is poorly characterized, and seldom studied together. Here, we evaluate the association between drinking water arsenic and uranium levels in wells (n = 441) from three tribal regions in North Dakota and South Dakota participating in the Strong Heart Water Study. Groundwater contamination was extensive; 29% and 7% of wells exceeded maximum contaminant levels for arsenic and uranium respectively. 81% of wells had both arsenic and uranium concentrations at one-tenth of their human-health benchmark (arsenic, 1 µg/L; uranium 3 µg/L). Well arsenic and uranium concentrations were uncorrelated (rs = 0.06); however, there appeared to be a spatial correlation of wells co-contaminated by arsenic and uranium associated with flow along a geologic contact. These findings indicate the importance of measuring multiple metals in well water, and to understand underlying hydrogeological conditions. The underlying mechanisms for the prevalence of arsenic and uranium across Northern Plains Tribal Lands in the US, and in particular the occurrence of both elevated arsenic and uranium in drinking water wells in this region, demands further study.