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Background Lung cancer (LC) is a leading cause of mortality claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. Methods In this study, we have evaluated the changes in the metabolomic profile in serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different timepoints (1 month - A; 3–6 months - B) with respect to a group of healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), both mounted into an ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) was applied. Results A total of 33 altered metabolites belonging to carboxylic acids, organooxygen compounds, prenol lipids, fatty acyls, glycerolipids and glycerophospholipids classes were annotated comparing all the different studied groups. We found a group of metabolites altered in PRE (gabaculine, DG(14:0/22:1), stearamide, proline and E,e-carotene-3,3'-dione) whose levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, humulinic acid A and 3-galactosyllactose levels may predict an unsuccessful surgery because they remained altered after the intervention in some patients. In addition, tranexamic acid could be studied more exhaustively to be proposed for monitoring the postoperative recurrence of the LC because its levels seem to be close to controls after one month of the intervention, but may differ significantly after 3–6 months. Conclusions This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points with a wide metabolic coverage combining complementary analytical methods.

Selenium (Se) is a trace element crucial for human health. Recently, the impact of Se supplementation on gut microbiota has been pointed out as well as its influence on the expression of certain selenoproteins and gut metabolites. This study aims to elucidate the link between Se supplementation, brain selenoproteins and brain metabolome as well as the possible connection with the gut-brain axis. To this end, an in vivo study with 40 BALB/c mice was carried out. The study included conventional (n=20) and mice model with microbiota depleted by antibiotics (n=20) under a regular or Se supplemented diet. Brain selenoproteome was determined by a transcriptomic/gene expression profile, while brain metabolome and gut microbiota profiles were accomplished by untargeted metabolomics and amplicon sequencing, respectively. The total content of Se in brain was also determined. The selenoproteins genes Dio and Gpx isoenzymes, SelenoH, SelenoI, SelenoT, SelenoV, and SelenoW and 31 metabolites were significantly altered in the brain after Se supplementation in conventional mice, while 11 selenoproteins and 26 metabolites were altered in microbiota depleted mice. The main altered brain metabolites were related to glyoxylate and dicarboxylate metabolism, amino acid metabolism, and gut microbiota that have been previously related with the gut-brain axis (e.g., members of Lachnospiraceae and Ruminococcaceae families). Moreover, specific associations were determined between brain selenoproteome and metabolome, which correlated with the same bacteria, suggesting an intertwined mechanism. Our results demonstrated the effect of Se on brain metabolome through specific selenoproteins gene expression and gut microbiota., This work was supported by the projects: PG2018-096608-B-C21 and PID2021-123073NB-C21 from the Spanish Ministry of Science and Innovation (MICIN). Generación del Conocimiento. MCIN/ AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa”, UHU-1256905 and UHU-202009 from the FEDER Andalusian Operative Program 2014-2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). S.R.A. thanks the Spanish Ministry of Science and Innovation for a PhD scholarship (BES-2016-076364). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918). Funding for open access charge: Universidad de Huelva / CBUA.

The growing interest of our society for the environment, climate change, and the assurance of the quality of life and health has been the motor of new methodological proposals that allow a more comprehensive knowledge of the problems to be solved. In this sense, the potential of omic methodologies to study these problems from a global perspective represents a milestone in environmental studies. Therefore, the study of essential and toxic metals has a special interest, particularly in relation to toxicity issues and their association to biological interactions, transport, binding to biomolecules, and behavior in biological interfaces. These studies have promoted new instrumental platforms and methodological approaches that allow addressing these problems. Furthermore, to encompass the reality of molecule-atoms interactions in their completeness, combinations of omics have been tried, focusing on environment, food, and health issues. In this sense, the present work is situated, with the objective of reviewing the most recent methodological proposals in the field of the environment and their applications, considering not only the analytical approaches but also how they have to be applied, the use of bioindicators' exposure experiments in the laboratory, and the potential transfer of the findings from the laboratory to the field. This latter point is a true touchstone, which makes these new analytical methodologies in the necessary tools for understanding the environment and the consequences of its imbalance.

BACKGROUND AND OBJECTIVES: Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. METHODS: In N=1365 Hortega Study participants > 20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. RESULTS: The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 μg/g creatinine, and 84.9 μg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < −1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 μg/L, which became increasingly positive above ~105 μg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of selenium with the incidence of osteoporosis-related bone fractures, the positive association above ~105 μg/L was markedly stronger, compared to the cross-sectional analysis. CONCLUSIONS: Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.

Selenium (Se) is a vital trace element for many living organisms inclusive of aquatic species. Although the antagonistic action of this element against other pollutants has been previously described for mammals and birds, limited information on the join effects in bivalves is available. To this end, bivalves of the species Scrobicularia plana were exposed to Se and Cd individually and jointly. Digestive glands were analysed to determine dose-dependent effects, the potential influence of Se on Cd bioaccumulationas well as the possible recover of the oxidative stress and metabolic alterations induced by Cd. Selenium co-exposure decreased the accumulation of Cd at low concentrations. Cd exposure significantly altered the metabolome of clams such as aminoacyltRNA biosynthesis, glycerophospholipid and amino acid metabolism, while Se co-exposure ameliorated several altered metabolites such asLysoPC (14:0), LysoPE (20:4), LysoPE (22:6), PE (14:0/18:0), PE (20:3/18:4) andpropionyl-L-carnitine.Additionally, Se seems to be able to regulate the redox status of the digestive gland of clams preventing the induction of oxidativedamage in this organ. This study shows the potential Se antagonism against Cd toxicity in S. plana and the importance to study join effects of pollutants to understand the mechanism underlined the effects., This study has been carried out within the research projects (CTM2012-38720-C03-03 and CTM2016-75908-R) founded by the Spanish Ministry of Economy and Competitiveness, who also provided a pre-doc grant for Chiara Trombini (BES-2013-063426), and the project PGC-2018- 096608-B-C21 from the Spanish Ministry of Science and innovation (MCIN). (Generación del Conocimiento. MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa”). Authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. Rodríguez-Moro, G. thanks to Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) and European Union for a post-doctoral grant (DOC_01115). Funding for open access charge: Universidad de Huelva / CBUA.

Antibiotic (Abx) treatments or inadvertent exposure to Abx-contaminated food and water can adversely affect health. Many studies show strong correlations between Abx and liver damage pointing to gut dysbiosis as a contributing factor because the gut microbiota (GM) forms a complex network with liver. Selenium (Se) is a beneficial micronutrient able to shape the composition of the GM. We analyzed here the ability of a low dose (120 μg/kg bodyweight/day) Se-enriched diet to ameliorate the effects of a 7-day intervention with an Abx-cocktail over the global health and the homeostasis of cholesterol and bile acids in the mouse liver. We found that Se restored lipid metabolism preventing the increased synthesis and accumulation of cholesterol caused by Abx treatment. Integrating these results with previous metataxonomic and metabolomic data in same mice, we conclude that part of the effect of Se against liver dysfunction (cholesterol and bile acids metabolism and transport) could be mediated by the GM. We provide data that contribute to a more complete view of the molecular mechanisms underlying the beneficial action of Se on health, pointing to a possible use of low doses of Se as a functional food additive (prebiotic) to prevent the negative effects of antibiotics.

El selenio (Se) es un oligoelemento con funciones importantes para la salud debido a las propiedades antioxidantes de las selenoproteínas. Para analizar la interacción entre Se y la microbiota intestinal, se determinaron los perfiles metabolómicos intestinales en ratones convencionales (C) y con microbiota empobrecida (Abx) después de la suplementación con Se (Abx-Se) mediante metabolómica no dirigida, utilizando una multiplataforma analítica basada en GC-MS y UHPLC-QTOF-MS (MassIVE ID MSV000087829). El perfil de la microbiota intestinal se realizó mediante la secuenciación del amplicón del gen 16S rRNA. Se encontraron diferencias significativas en los niveles de aproximadamente el 70 % de los metabolitos intestinales determinados, incluidos los acilos grasos, los glicerolípidos, los glicerofosfolípidos y los esteroides, en Abx-Se en comparación con Abx, y solo el 30 % fue diferente entre Abx-Se y C, lo que sugiere un efecto importante de la suplementación con Se en el metabolismo de los ratones Abx. A nivel de género, el análisis de correlación mostró fuertes asociaciones entre los metabolitos y los perfiles bacterianos intestinales. Asimismo, una mayor abundancia de Lactobacillus spp., un género potencialmente beneficioso enriquecido tras la suplementación con Se, se asoció con niveles más altos de lípidos de prenol, fosfatidilgliceroles (C-Se), esteroides y diterpenoides (Abx-Se), y también con niveles más bajos de ácidos grasos (Abx-Se). Por lo tanto, observamos una interacción crucial entre la ingesta de Se-microbiota-metabolitos, aunque se necesitan más estudios para aclarar los mecanismos específicos. Este es el primer estudio sobre la metabolómica intestinal no dirigida después del agotamiento de la microbiota y la suplementación con Se., Selenium (Se) is an essential trace element with important health roles due to the antioxidant properties of selenoproteins. To analyze the interplay between Se and gut microbiota, gut metabolomic profiles were determined in conventional (C) and microbiota depleted mice (Abx) after Se-supplementation (Abx-Se) by untargeted metabolomics, using an analytical multiplatform based on GC-MS and UHPLC-QTOF-MS (MassIVE ID MSV000087829). Gut microbiota profiling was performed by 16S rRNA gene amplicon sequencing. Significant differences in the levels of about 70% of the gut metabolites determined, including fatty acyls, glycerolipids, glycerophospholipids, and steroids, were found in Abx-Se compared to Abx, and only 30% were different between Abx-Se and C, suggesting an important effect of Se-supplementation on Abx mice metabolism. At genus level, the correlation analysis showed strong associations between metabolites and gut bacterial profiles. Likewise, higher abundance of Lactobacillus spp., a potentially beneficial genus enriched after Se-supplementation, was associated with higher levels of prenol lipids, phosphatidylglycerols (C-Se), steroids and diterpenoids (Abx-Se), and also with lower levels of fatty acids (Abx-Se). Thus, we observed a crucial interaction between Se intake–microbiota–metabolites, although further studies to clarify the specific mechanisms are needed. This is the first study about untargeted gut metabolomics after microbiota depletion and Se-supplementation., This work was supported by the projects PG2018-096608-B-C21 f from the Spanish Ministry of Science and innovation (MCIN). Generación del Conocimiento. MCIN/ AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa” and UHU-1256905 from the FEDER Andalusian Operative Program 2014–2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). Authors would like to acknowledge the support from The Ramón Areces Foundation (ref CIVP19A5918). Authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1X10-1611. Funding for open access charge: Universidad de Huelva / CBUA

Cadmium is a ubiquitous and persistent metal, associated with different harmful health effects and with increased morbidity and mortality. Understanding the main sources of exposure is essential to identify at risk populations and to design public health interventions.To evaluate cadmium exposure in a random-sample of general adult population from three regions of Spain, assessed by the urinary cadmium (U-Cd) concentration, and to identify its potential determinants and sex-specific differences, including sociodemographic, lifestyle and dietary factors.We measured U-Cd (μg/g creatinine) in single urine spot samples from 1282 controls enrolled in the multicase-control study in common tumors in Spain (MCC-Spain) with inductively coupling plasma-mass spectrometry equipped with an octopole reaction systems (ICP-ORS-MS). The association between sociodemographic, lifestyle, and dietary characteristics and U-Cd concentrations was evaluated using geometric mean ratios (GMR) estimated by multiple log-linear regression models.Overall, geometric mean U-Cd concentration was 0.40 (95%CI: 0.38, 0.41) μg/g creatinine. Levels were higher in women than in men (GMR]: 1.19; 95%CI: 1.07, 1.32), and increased with age in males (pThese results confirmed that tobacco exposure is the main modifiable predictor of U-Cd concentrations, and remark that the role of dietary/sociodemographic factors on U-Cd levels may differ by sex.

Selenium is a well-known essential element with important roles in human reproductive health mainly due to its antioxidant character. This study aimed to investigate the potential role of selenoproteins on gut microbiota and male reproductive health. A new assay for the absolute quantification of selenoproteins in testicular tissue based on two dimensional chromatography with inductively coupled plasma mass spectrometry was performed for the first time. The gut microbiota profile was obtained by 16S rRNA gene sequencing. Numerous associations were found between testicular selenoproteins and gut microbiota (e.g. Mucispirillum, related with sperm activity and testosterone, was associated with glutathione peroxidase (GPx) and selenoalbumin (SeAlb), while Escherichia/Shigella, related to sex hormones, correlated with GPx, selenoprotein P (SelP) and SeAlb). The effects of Se-supplementation on testicular selenoproteins only occur in conventional mice, suggesting a potential selenoproteins-microbiota interplay that underlies testicular function. The selenoproteins GPx and SelP have been quantified for the first time in the testicles, and the novel identification of SeAlb, a protein with nonspecifically incorporated Se, is also reported. These findings demonstrate the significant impact of Se-supplementation on gut microbiota and male reproductive health. In addition, the analytical methodology applied here in selenoprotein quantification in testicular tissue opens new possibilities to evaluate their role in gut microbiota and reproductive health axis., This article was funded by the projects PGC 2018- 096608-B-C21 from the Spanish Ministry of Science and innovation (MCI) (Generación del Conocimiento. MCI/AEI/FEDER, EU “Una manera de hacer Europa”) and UHU-1256905 from the FEDER Andalusian Operative Program 2014-2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). S.R.A. thanks the Spanish Ministry of Economy and Competitiveness for a PhD scholarship (BES-2016-076364). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918).

Cadmium (Cd) has become one of the most important environmental pollutants in the world, derived from natural and industrial sources, which is known to be accumulated in the human body, producing serious health effects. On the other hand, Selenium (Se) is an essential element for mammals, which is well known for its antagonistic interaction against Cd toxicity, such as the prevention of oxidative stress induced by this element. For this reason, the use of complementary analytical methods to study the homeostasis of metals, "traffic" between different organs and massive information about metabolites altered by the exposure, is of great interest. To this end, a metabolomic workflow based on the use of direct infusion mass spectrometry (DIMS) and gas chromatography mass spectrometry (GC-MS) was applied in mice serum. On the other hand, metal homeostasis and traffic between different organs and serum of mice exposed to Cd and Se have been evaluated by determining the concentration of metals by inductively coupled plasma mass spectrometry. This work demonstrates for the first time that Cd exposure causes a decrease of all the elements studied in the lung except itself. On the other hand, Se provokes As trafficking from metabolically less active organs (brain, lung, and testes) to others with greater metabolic activity (kidney), which also facilitates its excretion. Moreover, when mice are only exposed to Se, it provokes the accumulation of almost all the elements in the kidney, except Cd that increases also in the liver and brain. However, when both elements are simultaneously administered, Se increases Cd concentration in all the organs except in the serum and especially in the testis. On the other hand, important metabolic alterations have been detected in the energy and amino acid metabolism, as well as degradation of phospholipidic membranes, and in free fatty acids. In summary, the results show the high potential of the combined use of organic and inorganic mass spectrometry to establish Cd and Se interaction and the biological impairments caused and to provide information about metal traffic and metabolomic changes in exposure experiments. This work has been financially supported by projects CTM2015-67902-C2-1-P and PG2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness and P12-FQM-0442 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). Gema Rodriguez Moro would like to thank the Spanish Ministry of Economy and Competitiveness for a PhD scholarship (BES-2013-064501). Finally, authors are grateful to FEDER (European Community) for the financial support, grant numbers UNHU13-1E-1611 and UNHU15-CE-3140.

Among organic contaminants, pesticides are one of the most important groups of chemicals due to their persistent character and toxicity. However, the biological systems are exposed to a complex environment in which the contaminants can interact in a synergistic/antagonistic fashion, and for this reason, the study of “chemical cocktails” is of great interest to fully understand the final biological effect. In this way, selenium is known for its antagonistic action against several toxicants. In this paper, metabolic impairments caused by the joint exposure of p,p′-dichloro diphenyl trichloroethane (DDE) and selenium (Se) have been issued for the first time. A metabolomic workflow was applied to mice fed DDE and DDE with Se diet, on the basis of the complementary use of two organic mass spectrometric techniques, combining direct infusion mass spectrometry (DI-ESI-QqQ-TOF MS) and gas chromatography–mass spectrometry (GC–MS). The results show a good classification between the studied groups caused by about 70 altered metabolites in the liver, kidney, or brain, including the pathways of energy metabolism, degradation of phospholipidic membrane, β-oxidation, and oxidative stress, which confirm the potential of combined metabolomic platforms in environmental studies., This work has been supported by projects CTM2015-67902-C2-1-P and PG2018-096608 B-C21 from the Spanish Ministry of Economy and Competitiveness and P12-FQM-0442 and B10-1657 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). G.R.-M. thanks the Spanish Ministry of Economy and Competitiveness for a PhD scholarship (BES-2013-064501). S.R.-A. thanks the Spanish Ministry of Economy and Competitiveness for a PhD scholarship (BES-2016-076364). Finally, the authors are grateful to FEDER (European Community) for financial support, Grant Nos. UNHU13-1E-1611 and UNHU15-CE-3140.

BackgroundThe association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain.MethodsUrine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting.ResultsIn single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities.ConclusionsUrine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

Background Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. Methods In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43–55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31–50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. Results The median for the sum of urine inorganic and methylated As species (ΣAs) (μg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (μg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. Conclusions While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels.

Human breast milk (HBM) has a beneficial impact on health programming, growth and neurodevelopment of newborns. Increase in iodine intake is recommended for pregnant women in order to produce enough thyroid hormones to meet foetal requirements. In this work, a combined analytical multiplatform based on gas chromatography coupled to mass spectrometry and ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry has been applied in the first metabolomic study of HBM of iodinedeficient women. In addition, the elemental composition of HBM has been determined by inductively coupled plasma triple quadrupole mass spectrometry. Remarkably, 31 metabolites with important biological roles (e.g.glycerophospholipids for neurodevelopment) were seen to be altered in the HBM of iodine-deficient women. The main metabolic pathways altered include lipid metabolism, amino acid cycle, the tricarboxylic acid cycle and glycolysis. Additionally, the concentration of selenium, zinc and copper were seen to be significantly lower in HBM of iodine-deficient women., PG2018-096608-B-C21 (Spanish Ministry of Science and innovation (MCIN). Generaci´on del Conocimiento. MCIN/ AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa”), UHU-1256905 and UHU-202009 from the FEDER Andalusian operative program (Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). Authors are grateful to FEDER (European Community) for financial support, Grants UNHU13-1E-1611 and UNHU15-CE-3140. Funding for open access charge: Universidad de Huelva / CBUA

Scope Lack of information about the impact of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the elemental and metabolomic profile of human milk (HM). Methods and results An observational study on HM from mothers with COVID-19 is conducted including a prepandemic control group. Maternal–infant clinical records and symptomatology are recorded. The absolute quantification of elements and untargeted relative metabolomic profiles are determined by inductively coupled plasma mass spectrometry and gas chromatography coupled to mass spectrometry, respectively. Associations of HM SARS-CoV-2 antibodies with elemental and metabolomic profiles are studied. COVID-19 has a significant impact on HM composition. COVID-19 reduces the concentrations of Fe, Cu, Se, Ni, V, and Aluminium (Al) and increases Zn compared to prepandemic control samples. A total of 18 individual metabolites including amino acids, peptides, fatty acids and conjugates, purines and derivatives, alcohols, and polyols are significantly different in HM from SARS-CoV-2 positive mothers. Aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine, and linoleic acid pathways are significantly altered. Differences are obtained depending on COVID-19 symptomatic and asymptomatic status. Conclusions This study provides unique insights about the impact of maternal SARS-CoV-2 infection on the elemental and metabolomic profiles of HM that warrants further research due the potential implications for infant health., This work was supported by the projects PG2018-096608-B-C21(Spanish Ministry of Science and innovation (MCIN). Generación delConocimiento. MCIN/ AEI /10.13039/501100011033/ FEDER “Una man-era de hacer Europa”), UHU-1256905 and UHU-202009 from the FEDERAndalusian operative program (Ministry of Economic Transformation, In-dustry, Knowledge and Universities, Andalusia, Spain), and a researchgrant from Fundación La Marató-TV3 (MilkCORONA, ref 202106). FJSCthanks Junta de Andalucía and University of Huelva for a predoctoralcontract (Ref. SNGJ5-TS-005, Garantía Juvenil). Funding for open accesscharge: Universidad de Huelva / CBUA. The authors are grateful to FEDER(European Community) for financial support through grants UNHU13-1E-1611 and UNHU15-CE-3140. The funding sources had no role in the de-sign and conduct of the study; collection, management, analysis, and in-terpretation of the data; preparation, review, or approval of the manuscript;and decision to submit the manuscript for publication

Lung cancer (LC) is the second most common cause of death in men after prostate cancer, and the third most recurrent type of tumor in women after breast and colon cancers. Unfortunately, when LC symptoms begin to appear, the disease is already in an advanced stage and the survival rate only reaches 2%. Thus, there is an urgent need for early diagnosis of LC using specific biomarkers, as well as effective therapies and strategies against LC. On the other hand, the influence of metals on more than 50% of proteins is responsible for their catalytic properties or structure, and their presence in molecules is determined in many cases by the genome. Research has shown that redox metal dysregulation could be the basis for the onset and progression of LC disease. Moreover, metals can interact between them through antagonistic, synergistic and competitive mechanisms, and for this reason metals ratios and correlations in LC should be explored. One of the most studied antagonists against the toxic action of metals is selenium, which plays key roles in medicine, especially related to selenoproteins. The study of potential biomarkers able to diagnose the disease in early stage is conditioned by the development of new analytical methodologies. In this sense, omic methodologies like metallomics, proteomics and metabolomics can greatly assist in the discovery of biomarkers for LC early diagnosis.

Determinación de metales y Selenoproteinas y su interacción con la Microbiota intestinal tras la ingesta de suplementos de selenio y la administración de antibióticos a ratones Mus musculus., Selenium (Se) is a micronutrient involved in important health functions and it has been suggested to shape gut microbiota. Limited information on Se assimilation by gut microbes and the possible link with selenoproteins are available. For this purpose, conventional and gut microbiota-depleted BALB/c mice were fed a Se-supplemented diet. The absolute quantification of mice plasma selenoproteins was performed for the first time using heteroatom-tagged proteomics. The gut microbiota profile was analyzed by 16S rRNA gene sequencing. Se-supplementation modulated the concentration of the antioxidant glutathione peroxidase and the Se-transporter selenoalbumin as well as the metal homeostasis, being influenced by microbiota disruption, which suggests an intertwined mechanism. Se also modulated microbiota diversity and richness and increased the relative abundance of some health- relevant taxa (e.g., families Christensenellaceae, Ruminococcaceae, and Lactobacillus genus). This study demonstrated the potential beneficial effects of Se on gut microbiota, especially after antibiotic-treatment and the first associations between specific bacteria and plasma selenoproteins., This work was supported by the projects PG2018-096608-BC21 from the Spanish Ministry of Science and innovation (MINECO) and UHU-1256905 from the FEDER Andalusian Operative Program 2014−2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). The authors would like to acknowledge thesupportfromTheRamonArecesFoundation(ref. CIVP19A5918). The authors are grateful to FEDER (European Community) for financial support, grant UNHU13-1E1611. Funding for open access charge: Universidad de Huelva / CBUA

Lung cancer (LC) is the second most common cause of death in men after prostate cancer, and the third most recurrent type of tumor in women after breast and colon cancers. Unfortunately, when LC symptoms begin to appear, the disease is already in an advanced stage and the survival rate only reaches 2%. Thus, there is an urgent need for early diagnosis of LC using specific biomarkers, as well as effective therapies and strategies against LC. On the other hand, the influence of metals on more than 50% of proteins is responsible for their catalytic properties or structure, and their presence in molecules is determined in many cases by the genome. Research has shown that redox metal dysregulation could be the basis for the onset and progression of LC disease. Moreover, metals can interact between them through antagonistic, synergistic and competitive mechanisms, and for this reason metals ratios and correlations in LC should be explored. One of the most studied antagonists against the toxic action of metals is selenium, which plays key roles in medicine, especially related to selenoproteins. The study of potential biomarkers able to diagnose the disease in early stage is conditioned by the development of new analytical methodologies. In this sense, omic methodologies like metallomics, proteomics and metabolomics can greatly assist in the discovery of biomarkers for LC early diagnosis.

Molecular and metabolomic tools were used to design and understand the biodegradation of phenolic compounds in real industrial streams. Bacterial species were isolated from an industrial wastewater treatment plant of a phenol production factory and identified using molecular techniques. Next, the biodegradation potential of the most promising strains was analyzed in the presence of a phenolic industrial by-product containing phenol, alfa-methylstyrene, acetophenone, 2-cumylphenol, and 4-cumylphenol. A bacterial consortium comprising Pseudomonas and Alcaligenes species was assessed for its ability to degrade phenolic compounds from the phenolic industrial stream (PS). The consortium adapted itself to the increasing levels of phenolic compounds, roughly up to 1750 ppm of PS; thus, becoming resistant to them. In addition, the consortium exhibited the ability to grow in the presence of PS in repeated batch mode processes. Results from untargeted metabolomic analysis of the culture medium in the presence of PS suggested that bacteria transformed the toxic phenolic compounds into less harmful molecules as a survival mechanism. Overall, the study demonstrates the usefulness of massive sequencing and metabolomic tools in constructing bacterial consortia that can efficiently biodegrade complex PS. Furthermore, it improves our understanding of their biodegradation capabilities, The research activities shown in this work were funded by CEPSA S.A.U. and Technological Corporation of Andalusia (CTA, Grant number 19/1002)

In this work, we describe for the first time the presence of selenoprotein P in human breast milk. To this end, a novel analytical method has been developed based on a two-dimensional column switching system, which consisted of three size exclusion columns and one affinity column coupled to inductively coupled plasma mass spectrometry (ICP-MS). The method combines the accurate quantification of selenoproteins and selenometabolites by species unspecific isotopic dilution ICP-MS, with unequivocal identification by quadrupole-time-of-flight mass spectrometry. Several selenopeptides, which contain the amino acid selenocysteine (U, SeCys), were identified after tryptic digestion followed by their separation. The results reveal that the relative selenium concentration in colostrum follows the order: glutathione peroxidase (GPX) ˜ selenoprotein P (SELENOP) > selenocystamine (SeCA) > other selenometabolites (SeMB), in contrast with previously published papers (GPX > SeCA > selenocystine > selenomethionine). A mean concentration of 20.1 ± 1.0 ng Se g-1 as SELENOP (1.45 µg SELENOP/g) was determined in colostrum (31% of total selenium). This work was supported by the projects UHU-1256905 from the FEDER Andalusian operative program (Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain) and PGC2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness (MINECO). Authors are grateful to FEDER (European Community) for financial support, Grants UNHU13-1E-1611 and UNHU15-CE-3140.

Introduction: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. Objectives: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8‑oxo‑7,8‑dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). Methods: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. Results: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03–1.27) for Mo, 1.17 (1.05–1.31) for Ba, 1.23 (1.04–1.46) for Cr and 1.18 (1.00–1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03–1.24) for Zn and 1.12 (1.02–1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01–1.23) for Zn and 1.09 (0.99–1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/ GSH but inverse for MDA. Conclusions: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation., This work was supported by the Strategic Action for Research in Health Sciences [CP12/03080, PI10/0082, PI13/01848, PI07/0497 and PI11/00726]; GRUPOS 03/101, PROMETEO/2009/029 and 2005/027, AMP07/075 and ACOMP/2013/039 from the Valencia Government; GRS/279/A/08 from Castilla-Leon Government; European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission; Retics (PREDIMED RD06/0045/0006); CIBER Fisiopatología Obesidad y Nutrición (CIBERobn) [CIBER-02-08-2009, CB06/03 and CB12/03/30016] and CIBER de Diabetes y Enfermedades Metabólicas Relacionadas (CIBERDEM CB07/0/018). The Strategic Action for Research in Health sciences, Retics, CIBEROBN and CIBERDEM are initiatives from Carlos III Health Institute Madrid and the Spanish Ministry of Economy and Competitiveness and co-funded with European Funds for Regional Development (FEDER). The authors declare they have no actual or potential competing financial interests., This work was supported by the Strategic Action for Research in Health Sciences [CP12/03080, PI10/0082, PI13/01848, PI07/0497 and PI11/00726]; GRUPOS 03/101, PROMETEO/2009/029 and 2005/027, AMP07/075 and ACOMP/2013/039 from the Valencia Government; GRS/279/A/08 from Castilla-Leon Government; European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission; Retics (PREDIMED RD06/0045/0006); CIBER Fisiopatologia Obesidad y Nutricion (CIBERobn) [CIBER-02-08-2009, CB06/03 and CB12/03/30016] and CIBER de Diabetes y Enfermedades Metabolicas Relacionadas (CIBERDEM CB07/0/018). The Strategic Action for Research in Health sciences, Retics, CIBEROBN and CIBERDEM are initiatives from Carlos III Health Institute Madrid and the Spanish Ministry of Economy and Competitiveness and co-funded with European Funds for Regional Development (FEDER). The authors declare they have no actual or potential competing financial interests.

The present review focus on the analytical platforms and the workflow for toxicometabolomics with a special emphasis on their strengths and pitfalls presenting as a case study the toxicometabolomics of arsenic in mammals. Although powerful analytical methods and techniques are currently available for metabolomics, the main “bottleneck” is still the absence of unified protocols for sample preparation (e.g. quenching, solvents used) as well as several important factors in toxicometabolomics, which drastically affect the metabolism (e.g. selection of model organisms, xenobiotic doses, chemical form of the xenobiotic, exposure route, biological sample). In this context, the applicability to complex samples, higher sensitivity, specificity and the possibility to perform quantitative analysis offered by MS is crucial to probe xenobiotic induced metabolic changes to evaluate the stress responses. Nowadays, the use of different metabolomic platforms allowed determining important changes in the metabolism induced by arsenic in mammals such as alterations in the energy (e.g. Glycolysis, Kreb's cycle), amino acid, lipid, nucleotide and androgen metabolisms.

Omic methodologies have become key analytical tools in a wide number of research topics such as systems biology, environmental analysis, biomedicine or food analysis. They are especially useful when they are combined providing a new perspective and a holistic view of the analytical problem. Methodologies for microbiota analysis have been mostly focused on genome sequencing. However, information provided by these metagenomic studies is limited to the identification of the presence of genes, taxa and their inferred functionality. To achieve a deeper knowledge of microbial functionality in health and disease, especially in dysbiosis conditions related to metal and metalloid exposure, the introduction of additional meta-omic approaches including metabolomics, metallomics, metatranscriptomics and metaproteomics results essential. The possible impact of metals and metalloids on the gut microbiota and their effects on gut-brain axis (GBA) only begin to be figured out. To this end new analytical workflows combining powerful tools are claimed such as high resolution mass spectrometry and heteroatom-tagged proteomics for the absolute quantification of metal-containing biomolecules using the metal as a “tag” in a sensitive and selective detector (e.g. ICP-MS). This review focus on current analytical methodologies related with the analytical techniques and procedures available for metallomics and microbiota analysis with a special attention on their advantages and drawbacks., This work was supported by the projects PG2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness (MINECO) and UHU-1256905 from the FEDER Andalusian Operative Program 2014–2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). S.R.A. thanks the Spanish Ministry of Science and Innovation for a PhD scholarship (BES-2016-076364). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918).

Background: The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels. Objectives: We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure. Methods: Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18–85years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30mg/g. Results: The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23–0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43–1.84) and 2.94 (95% CI, 2.58–3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1. Conclusions: Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects. Keywords: Urine cadmium, Albuminuria, Gene-environment interaction, Population-based survey

The trihalomethanes (TTHMs) and others disinfection by-products (DBPs) are formed in drinking water by the reaction of chlorine with organic precursors contained in the source water, in two consecutive and linked stages, that starts at the treatment plant and continues in second stage along the distribution system (DS) by reaction of residual chlorine with organic precursors not removed. Following this approach, this study aimed at developing a two-stage empirical model for predicting the formation of TTHMs in the water treatment plant and subsequently their evolution along the water distribution system (WDS). The aim of the two-stage model was to improve the predictive capability for a wide range of scenarios of water treatments and distribution systems. The two-stage model was developed using multiple regression analysis from a database (January 2007 to July 2012) using three different treatment processes (conventional and advanced) in the water supply system of Aljaraque area (southwest of Spain). Then, the new model was validated using a recent database from the same water supply system (January 2011 to May 2015). The validation results indicated no significant difference in the predictive and observed values of TTHM (R 2 0.874, analytical variance

Metals have important roles in biological systems due to their essential or toxic character, the participation in controlling numerous cellular and biological processes, and their effects on the metabolism that regulates numerous cellular processes. The study of metal-induced changes on metabolic pathways is fundamental to decipher the biological response related to environmental problems. In this context, the omics, such as metallomics and metabolomics, are powerful methodological tools to reach this aim by searching for biomarkers that act as a warning of harmful environmental situations. Generally, different bioindicator organisms (mice, clams, and crabs) have been used to evaluate the biological response associated with the presence of contaminants in the laboratory, which can be extrapolated to actual environmental issues in terrestrial and aquatic systems. Suitable exposure experiments and the application of multidimensional analytical techniques based on the coupling of chromatography with inductively coupled plasma mass spectrometry for very specific analysis of metal-containing biomolecules (metallomics), as well as the use of organic mass spectrometry, are considered for the nontargeted evaluation of metabolite changes caused by the contamination (metabolomics). Translational application of this methodology to natural spaces affected by contamination allows establishing, in a closer evaluation, the processes involved in the environment degradation and its assessment.

One of the most important causes of the high mortality rate and low life expectancy of lung cancer is the detection at advanced stages. Thus, there is an urgent need for early diagnosis and the search of new selective biomarkers. Selenium is an important constituent of selenoproteins and a powerful antioxidant able to protect against cancer. In this work, the absolute quantification of selenium in selenoproteins and the total content in selenometabolites has been performed for the first time in serum from lung cancer patients (LC) and healthy controls (HC). To this end, a method for the simultaneous speciation of selenoproteins using size exclusion chromatography (SEC) and affinity chromatography (AF) with detection by ICP-QQQ-MS, and quantification by isotopic dilution (IDA) (SEC-AF-HPLC-SUID-ICP-QQQ-MS) was developed to determine the selenium concentration in eGPx, SEPP1 and SeAlb, as well as total selenometabolites, to find alterations that may serve as biomarkers of this disease. In the same way, a method based on anion-exchange chromatography coupled to ICP-QQQ-MS was developed to quantify selenometabolites (SeCys2, SeMeSeCys, SeMet, selenite and selenate) in the same LC and HC serum samples. The results showed that the averaged concentrations of selenium in eGPx, SeAlb and selenite were significantly higher in LC patients (LC (eGPx: 21.24 +/- 0.77 ng g(-1); SeAlb: 49.56 +/- 3.16 ng g(-1) and Se(IV): 6.20 +/- 1.22 ng g(-1)) than in HC group (eGPx: 16.96 +/- 0.53 ng g(-1); SeAlb: 38.33 +/- 2.66 ng g(-1) and Se(IV): 3.56 +/- 0.55 ng g(-1)). In addition, the ratios between selenoproteins and selenometabolites have been calculated for the first to study their potential use as LC biomarkers. The rates eGPx/SEPP1, SEPP1/SeAlb, eGPx/Se(IV) and SEPP1/Se(IV) were significantly different between LC and HC groups. (C) 2020 Elsevier B.V. All rights reserved This research was funded by the projects PGC2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness, and P12-FQM-0442 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). Projects Neumosur (8/2012 and 9/2015) and SEPAR (124/2012 and 091/2016). Finally, authors are grateful to FEDER (European Community) for financial support, grants number UNHU13-1E-1611 and UNHU15-CE-3140.

Lung Cancer (LC) has a high mortality, because of the late diagnosis, which implies less probability of healing. During the development of the cancer some trace elements (metals or metalloids), have an important role activating or inhibiting enzymatic reactions. Our study is based on the study of trace elements as early biomarkers (BM) of LC; studying samples of blood, urine a bronchoalveolar lavage (BAL). We design a transversal study with 48 patients with LC and 39 controls divided in Healthy (C) and Lung Disease no Cancer (LDnC). We analyze concentrations of 11 metals of high and low molecular mass (V, Cr, Mn, Fe, Co, Cu, Zn, Se, Mo, Cd y Pb) in three kind of samples, using mass inductive-spectrometry technique. For statistics were used four different analyses: a)Mann-Whitney U test, to compare concentrations of different elements on the 3 groups. b)Spearman’s test to found correlations between altered element on LC group. c)Partial least squares-discriminant analysis, to determine which elements are more influents. d)Area under the curve to found specificity and sensibility of the altered metals and its role as BM. We obtained clear discrimination between groups on the 3 kind of samples, using over expressed or reduced levels of metals on LC group that could be used as BM. Vanadium and chrome are over expressed on LC group; and we know they’re related to metabolic process of cancer. Also we propose BM based on metal dyshomeostases, like in serum (V/Mn, V/Pb, V/Zn, Cr/Pb), in urine (Cr/Cd, Mn/Cd, V/Cd, Co/Cd, Cd/Pb) and in BAL (V/Cu). Correlations between different metal elements shown differences between patients with LC and the control groups (C, LDnC); what could imply that this elements could be used as early BM of LC.

Selenoprotein P contains most of the selenium in plasma and favours selenium retention in the brain over other organs. Recently, the presence of selenoprotein P in human breast milk has been demonstrated, filling the gap around the mother-offspring transfer of selenium during lactation and through cord serum. In this work, selenometabolites and selenoproteins have been accurately determined in human breast milk and cord and maternal sera. Using a heteroatom tagged proteomic method, twenty mother-child couples were analysed. The mean total concentration in maternal serum was 90 ± 10 ng Se g−1 (1.33 and 1.52-fold higher than that in cord serum and human breast milk, respectively). The concentration of selenoprotein P (ng Se g−1) follows the order: maternal serum (57.1 ± 8.8) > cord serum (33.6 ± 4.2) > breast milk (18.8 ± 5.1). Glutathione peroxidase was mainly transferred by breast milk, selenometabolites were transferred by breast milk and cord serum and selenocystamine was only present in breast milk.

A new analytical method was optimized to determine 18 disinfection by-products (DBPs) in drinking water, including four different chemical groups. For this purpose, spiral-shaped hollow-fibre liquid phase microextraction with 1-octanol as the acceptor solvent assisted by effervescence was applied using a homemade supporting device that was specifically designed for this application. The device was printed in a 3D printer and allows for an increased fibre surface even with a low sample volume, which significantly facilitates the extraction. The samples were analysed by gas chromatography coupled to both an electron capture detector and a mass spectrometer for the quantification and unequivocal identification of the analytes, respectively. Effervescence was generated using citric acid and bicarbonate at a molar ratio 1:2, which significantly improves the extraction efficiency and reduces mechanical operations, since stirring and modifiers are not required. The results showed enrichment factors ranging from 13.1 to 140.1. Satisfactory recoveries (80-113 %) were obtained, with relative standard deviations from 3 to 15 % and good linearity. The detection limits (ng L-1) ranged from 10 to 35 (trihalomethanes), 12 to 220 (halonitromethanes), 17 to 79 (haloacetonitriles) and 10 to 16 (haloketones). The applicability of the method was assessed in 6 local water distribution systems. The authors acknowledge the plant managers of GIAHSA and their employees for their valuable help in the water collection. This work has been supported by the projects PGC2018-16 096608-B-C21 from the Spanish Ministry of Economy and Competitiveness and Projects UHU 1256905 and P12-FQM-0442 from the Regional Department of Economy, Innovation, Science and Employment (Andalusian Government, Spain). The authors also acknowledge FEDER Funds (European Community), grants numbers UNHU13-1E-1611 and UNHU15-CE-3140.

A reliable and sensitive analytical approach has been optimized for the extraction of seven polychlorinated biphenyls (PCBs) from human breast milk. Hollow fiber liquid phase microextraction (HF-LPME) was applied for the first time for the extraction and pre-concentration of the analytes. Analytes were separated by gas chromatography with electron capture detector (GC-mu ECD) for the sensitive detection and mass spectrometry for the unequivocal identification. A rotable central composite design (RCCD) was performed for the multivariate optimization of the method. The best results were obtained at 40 degrees C during 30 min and 600 rpm of stirring speed using a hollow fiber length of 5 cm and toluene as an extractant phase and salt addition was not required. The detection limits were in the range 7-14 ng L-1 for PCBs. The coefficients of determination of the calibration curves indicated good linearity (R-2> 0.96) and the enrichment factors ranged from 74 to 143. This type of study is of great importance due to the deleterious effect that the presence of contaminants can produce in infants health related to the immature character of the defense system. Moreover, exclusive breastfeeding is recommended by neonatologists up to six months of life and as complementary food during the first two years. The authors thank projects UHU-1256905 (Operative program FEDER-Andalusia 2014-2020, Consejeria de Economia, Conocimiento, Empresa y Universidad, Spain) and PGC2018-096608-B-C21 (Ministry of Science and Innovation, Spain). Authors also thank European Community (FEDER) for financial support (UNHU15-CE-3140 and UNHU13-1E-1611). The authors thank Dr. Eduardo Garcia-Soblechero, Celia Perez-Serralbo and Dr. Elisabeth Gomez-Santos, from the Pediatric Unit of Juan Ramon Jimenez Hospital for the collection of samples.

This study aimed to assess the association between exposure to chromium and neuropsychological development among children. A cross-sectional study was conducted with 393 children aged 6–11 years old randomly selected from State-funded schools in two provinces in Southern Spain (Almeria and Huelva), in 2010 and 2012. Chromium levels in urine and hair samples were analyzed by inductively coupled plasma mass spectrometry with an octopole reaction system. Neuropsychological development was evaluated using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and three computerized tests from the Behavioural Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariable linear regression models adjusted for potential confounders, including heavy metals, were applied to examine the association between chromium levels and neuropsychological outcomes. A 10-fold increase in urine chromium levels was associated with a decrease of 5.99 points on the WISC-IV Full-Scale IQ (95% CI: 11.98 to −0.02). Likewise, a 10-fold increase in urine chromium levels in boys was associated with a decrease of 0.03 points in the percentage of omissions (95% CI: 0.0 to 0.05) in the SAT, with an increase of 68.35 points in latency (95% CI: 6.60 to 130.12) in the RTT, and with an increase in the number of trials with latencies > 1000 ms (β = 37.92; 95% CI: 2.73 to 73.12) in the RTT. An inverse significant association was detected between chromium levels in hair and latency in the SAT in boys (β = −50.53; 95% CI: 86.86 to −14.22) and girls (β = −55.95; 95% CI: 78.93 to −32.97). Excluding trials with latencies >1000 ms in the RTT increased latency scores by 29.36 points in boys (95% CI: 0.17 to 58.57), and 39.91 points in girls (95% CI: 21.25 to 58.59). This study is the first to show the detrimental effects of postnatal chromium exposure on neuropsychological development in school-aged children.

This is the Author’s Original Manuscript of an article published by Taylor & Francis in Expert Review of Proteomics on 18 Sep 2019, available online: http://www.tandfonline.com/10.1080/14789450.2019.1664292, Introduction: Selenium plays many key roles in health especially in connection with cancer and neurodegenerative diseases. However, it needs to be appreciated that the essentiality/toxicity of selenium depends on both, a narrow range of concentration and the chemical specie involved. In this context, selenoproteins are essential biomolecules against these disorders, mainly due to its antioxidant action. To this end, analytical methodologies may allow identifying and quantifying individual selenospecies in human biofluids and tissues. Areas covered: This review focus on the role of selenoproteins in medicine, with special emphasis in cancer and neurodegenerative diseases, considering the possible link with gut microbiota. In particular, this article reviews the analytical techniques and procedures recently developed for the absolute quantification of selenoproteins and selenometabolites in human biofluids and tissues. Expert commentary: The beneficial role of selenium in human health has been extensively studied and reviewed. However, several challenges remain unsolved as discussed in this article: (i) speciation of selenium (especially selenoproteins) in cancer and neurodegenerative disease patients; (ii) supplementation of selenium in humans using functional foods and nutraceuticals; (iii) the link between selenium and selenoproteins expression and the gut microbiota and (iv) analytical methods and pitfalls for the absolute quantification of selenoproteins and selenometabolites., This work was supported by the project PG2018-096608-B-C21 from the Spanish Ministry of Science, Innovation and Universities (MINECO), Project UHU-1256905 from the Regional Ministry of Economy, Knowledge, Business and University (Andalusian Government, Spain) and Project from The Ramón Areces Foundation. Finally, authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611.