The doctor-patient relationship in primary healthcare organizations in Spain. A qualitative approach

Antecedentes. La relación médico-paciente es aquella que se produce durante la interacción entre el usuario y el profesional. Esta ha ido cambiando a lo largo de la historia. En la actualidad, el paradigma emergente es el que autonomiza y empodera al usuario, en contraposición al tradicional paradigma paternalista. Objetivo. El objetivo de este trabajo es averiguar el estado del fenómeno sociológico del empoderamiento del paciente en España, desde el punto de vista de los profesionales sanitarios. Metodología. Se realizó un estudio exploratorio mediante una metodología cualitativa. La recolección de datos se basó en entrevistas estructuradas no estandarizadas. Se procedió al análisis del contenido a través de un proceso circular simultáneamente a la recolección de datos. Se complementó con un estudio de fuentes documentales bibliográficas a propósito de la temática abordada. Resultados. Los profesionales muestran una actitud positiva hacia el fenómeno del empoderamiento del paciente. Todavía se muestran escépticos ante la fiabilidad de la información sobre salud que se encuentra en internet y del criterio de los propios pacientes. Aun así, el máximo de autonomía del paciente, el consentimiento informado, sigue siendo considerado como una herramienta de protección del profesional. Discusión. Tras este estudio exploratorio se ha podido observar un cambio de actitud en el profesional respecto a la percepción que tiene sobre la evolución en la relación con el paciente. Se empieza a constatar que el fenómeno social se encuentra en un estado en el que los actores adquieren posturas más simétricas jerárquicamente.Background. The doctor-patient relationship, which happens during the interaction between the user and the professional, has been changing throughout history. The currently emerging paradigm is the one making the user autonomous and empowering him, rather than the traditional paternalistic paradigm. Objective. The objective of this research is to figure out the status of the sociological phenomenon of patient empowerment in Spain, from the vantage point of the healthcare professionals. Methodology. An exploratory study was conducted, using qualitative methodology. Data were gathered based on non-standardized structured interviews. Contents were analyzed through a circular process, at the same time as the data were gathered. This was complemented by a bibliographical documentary sources study with regards to the themes discussed. Results. The professionals show a positive attitude towards the patient empowerment phenomenon. They are still skeptical of the reliability of the health information that can be found on the Internet and of the patient’s own criteria. Even so, the greatest representative of patient autonomy, informed consent, continues to be regarded as a tool for protecting the professional. Discussion. After this exploratory study, it has been possible to observe a change in attitude for the professionals, regarding the perception they have on the evolution of the relationship with patients. It is starting to show that the social phenomenon is at a point where the actors acquire more hierarchically symmetrical positions

Exposición prenatal a manganeso y a arsénico y efectos en el desarrollo neuropsicológico en niños y niñas participantes en la cohorte INMA

Introducción: El manganeso (Mn) es un elemento esencial, indispensable para el desarrollo durante la etapa fetal. Por su parte, el arsénico (As) es un tóxico para el ser humano, siendo su forma inorgánica (iAs) la considerada más tóxica. La principal vía de exposición a ambos compuestos en población general es a través de la dieta. Una vez es absorbido, el iAs es biotransformado en ácido monometilarsónico (MMA) y ácido dimetilarsínico (DMA). Diversos estudios epidemiológicos han relacionado la exposición prenatal a estos metales con efectos adversos en el desarrollo neuropsicológico durante la infancia, aunque la evidencia actual no es concluyente. Además, la mayoría de estos estudios se han realizado en áreas con una alta exposición ambiental a estos compuestos, por lo que la evidencia en zonas con menores niveles en el ambiente, incluyendo agua y alimentos, es todavía escasa. El objetivo general de la presente tesis es estudiar la relación entre la exposición prenatal a Mn y a As y la aparición de efectos adversos en el desarrollo neuropsicológico infantil en los participantes de dos cohortes materno-infantiles, así como evaluar los factores asociados a dichas exposiciones. Metodología: este trabajo forma parte del proyecto multicéntrico de cohortes Infancia y Medio Ambiente (INMA). La población de estudio fue de 807, 1017 y 1179 pares madre-hijo/a de las cohortes de Gipuzkoa y Valencia (2004-2008), según el estudio. Durante el primer trimestre del embarazo se recogieron muestras de suero y orina en las que se analizaron las concentraciones de Mn y As total (TAs) y sus metabolitos (MMA, DMA, As inorgánicos [iAs] y arsenobetaína [AB]), respectivamente. El desarrollo neuropsicológico de los niños y niñas se evaluó mediante las Escalas de Desarrollo Infantil de Bayley (BSID) al año de edad y a través de las Escalas de Habilidades Infantiles McCarthy (MSCA) a los 4-5 años de edad. Se recogió información sociodemográfica, de estilos de vida y dietética mediante cuestionarios, así como otros biomarcadores maternos (ferritina sérica y zinc (Zn) urinario, entre otros). La eficiencia de metilación del As se determinó a través de los porcentajes de los metabolitos y utilizando el análisis de componentes principales. Se utilizaron modelos de regresión lineal multivariante para evaluar los factores asociados a las variables de exposición, así como para evaluar la relación entre la exposición prenatal a Mn, a As y sus metabolitos, así como la eficiencia en la metilación del As y las puntuaciones en las pruebas neuropsicológicas. Finalmente se examinó la linealidad de las relaciones y se exploró la posible modificación del efecto relacionada con diversas variables. Resultados: la media geométrica (MG) e intervalo de confianza del 95% (IC95%) de las concentraciones de Mn en suero durante el primer trimestre del embarazo fue de 1,50 µg/L (1,48-1,53). El único factor dietético asociado (relación directa) a estas concentraciones fue el consumo de frutos secos. Las madres trabajadoras presentaron menores concentraciones de Mn en suero. Por su parte, la MG (IC95%) de las concentraciones de TAs, AB, ∑As (suma de DMA, MMA e iAs), DMA, MMA e iAs en orina fue de 35,55 (33,10-38,19), 20,17 (18,34-22,19), 7,74 (7,41-8,09), 6,82 (6,52-7,14), 0,34 (0,32-0,36) y 0,33 (0,31-0,35) μg/g creatinina, respectivamente. El consumo de arroz se asoció de forma directa con las concentraciones urinarias de todos los metabolitos de As, excepto con la AB. De la misma manera, el consumo de pescado se asoció positivamente con las concentraciones de todos los metabolitos evaluados excepto con el MMA y el iAs. Otros factores asociados con las concentraciones de ciertas especies de As fueron el área de estudio, el país de origen de la madre, la clase social parental y el índice de masa corporal materno (IMC). Respecto a la eficiencia en la metilación del As durante el embarazo, las medianas (IC del 95%) del porcentaje de metabolitos de As fueron 89,7 (89,3-90,2) para %DMA, 5,1 (4,8-5,3) para %MMA y 4,7 (4,5-5,0) para %iAs. Las mujeres nacidas en Latinoamérica y aquellas con un mayor IMC presentaron una mejor metilación del iAs (indicado por mayor %DMA y menor %MMA y %iAs). En este estudio de cohortes multicéntrico no se encontró asociación entre la exposición prenatal a Mn y el desarrollo mental (β [IC95%] = −0,39 [−2,73 a 1,95]), ni con el desarrollo psicomotor (β [IC95%] = −0.92 [−3,48 a 1,65]) de los niños y niñas al año de edad. Respecto a la exposición prenatal a As, en el presente trabajo se observó una relación negativa entre las concentraciones urinarias de MMA durante el primer trimestre del embarazo y las puntuaciones de las escalas general, verbal, cuantitativa, de memoria, de función ejecutiva y de memoria de trabajo del MSCA a los 4-5 años de edad (por ejemplo, β [IC95%] = −1,37 [−2,33 a −0,41] para la escala general). Además, el %MMA se asoció de manera negativa con la subescala de memoria. Finalmente, se observó que los niños y niñas cuyas madres presentaron concentraciones más bajas de Mn, Zn y ferritina obtuvieron puntuaciones más bajas en varias escalas de MSCA con una eficiencia de metilación decreciente. Conclusiones: Los niveles de Mn, As y sus metabolitos analizados en nuestra población son más bajos que los observados en la mayoría de los estudios publicados. Ciertos factores dietéticos, de estilo de vida y ambientales influyen tanto en las concentraciones de Mn y de especies de As, así como en la eficiencia de metilación del As en nuestra población. Este estudio no muestra asociación entre los niveles maternos prenatales de Mn y el desarrollo neuropsicológico al año del nacimiento. No obstante, sí se ha observado una asociación inversa entre las concentraciones de MMA y el desarrollo neuropsicológico de los niños y niñas a los 4-5 años de edad. Además, los niveles maternos de Mn, Zn y ferritina modificaron la asociación entre la eficiencia de metilación del As y las puntuaciones de MSCA.Introduction: Manganese (Mn) is an essential element that is indispensable for correct development during the foetal stage. Arsenic (As) is toxic to humans, its inorganic form (iAs) being considered the most toxic. The main route of exposure to both compounds in the general population is through diet. Once absorbed, iAs is biotransformed into monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Several epidemiological studies have linked prenatal exposure to these metals to adverse effects on neuropsychological development during childhood, although the current evidence is inconclusive. Moreover, most of these studies have been conducted in areas with high environmental exposure to these compounds and evidence in areas with lower levels in the environment, including food and water, is still scarce. The general aim of the present thesis is to study the relationship between prenatal exposure to Mn and As and the occurrence of adverse effects on child neuropsychological development in participants from two maternal-infant cohorts, as well as to evaluate the factors associated with these exposures. Methods: This study is part of the multicentre cohort-based INMA (Infancia y Medio Ambiente [Environment and Childhood]) project. The study population was 807, 1017 and 1179 mother– child pairs from the Gipuzkoa and Valencia cohorts (2004-2008), according to the study. During the first trimester of pregnancy, serum and urine samples were collected and analysed to determine the concentrations of Mn and total As (TAs) and its metabolites (monomethylarsonic acid [MMA], dimethylarsinic acid [DMA], inorganic As [iAs] and arsenobetaine [AB]), respectively. The children's neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 1 year of age and the McCarthy Scales of Children's Abilities (MSCA) at 4-5 years of age. Sociodemographic, lifestyle and dietary information was collected by questionnaires, together with other maternal biomarkers (serum ferritin and urinary zinc [Zn], among others). The As methylation efficiency was determined through metabolite percentages and using principal component analysis. Multivariate linear regression models were used to evaluate factors associated with exposure variables, as well as to assess the relationship between prenatal exposure to Mn, to As and its metabolites, and As methylation efficiency and neuropsychological test scores. Finally, the linearity of the relations and the possible effect modification related to several variables was explored. Results: The geometric mean (GM) and 95% confidence interval (95%CI) of serum Mn concentrations during the first trimester of pregnancy was 1.50 µg/L (1.48-1.53). The only dietary factor associated with these concentrations was the consumption of nuts. Working mothers had lower serum Mn concentrations. The GM (95% CI) of TAs, AB, ∑As (sum of DMA MMA and iAs), DMA, MMA and iAs concentrations in urine were 35.55 (33.10-38.19), 20.17 (18.34-22.19), 7.74 (7.41-8.09), 6.82 (6.52-7.14), 0.34 (0.32-0.36) and 0.33 (0.31-0.35) μg/g creatinine, respectively. Rice consumption was directly associated with urinary concentrations of all As metabolites except AB. Similarly, fish consumption was positively associated with concentrations of all the metabolites assessed except MMA and iAs. Other factors associated with the concentrations of certain As species were study area, maternal country of origin, parental social class and maternal body mass index (BMI). Regarding As methylation efficiency during pregnancy, the medians (95%CI) of the percentage of As metabolites were 89.7 (89.3- 90.2) for %DMA, 5.1 (4.8-5.3) for %MMA and 4.7 (4.5-5.0) for %iAs. Women born in Latin America and those with a higher BMI had better iAs methylation (indicated by higher %DMA and lower %MMA and %iAs). In this multicentre cohort study, no association was found between prenatal Mn exposure and mental development (β [95% CI] = −0.39 [−2.73, 1.95]) or with psychomotor development (β [95% CI] = −0.92 [−3.48, 1.65]) of children at one year of age. Regarding prenatal As exposure, in the present work, a negative relationship was observed between urinary MMA concentrations during the first trimester of pregnancy and scores on the general, verbal, quantitative, memory, executive function and working memory scales of the MSCA at 4-5 years of age (e.g. β [95% CI] = −1.37 [−2.33, −0.41] for the general scale). In addition, %MMA was negatively associated with the memory subscale. Finally, it was observed that children whose mothers had lower concentrations of manganese, zinc and ferritin scored lower on several MSCA scales with decreasing methylation efficiency. Conclusions: The levels of Mn, As and its metabolites analysed in our population are lower than those observed in most of the studies published to date. Certain dietary, lifestyle and environmental factors influence both the concentrations of Mn and As species and the As methylation efficiency in our population. This study shows no association between prenatal maternal Mn levels and neuropsychological development at one year after birth. However, an inverse association between MMA concentrations and the neuropsychological development of children aged 4-5 years has been observed. In addition, maternal Mn, Zn and ferritin levels modified the association between As methylation efficiency and MSCA scores

Maternal copper status and neuropsychological development in infants and preschool children

Introduction Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development. Methods Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development. Results The mean ± standard deviation of maternal Cu concentrations was 1606 ± 272 μg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = −0.051; 95% confidence intervals [CI]: −0.102, −0.001) and the MSCA verbal scale (beta = −0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938μg/L). Conclusion The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy

Gestational phthalate exposure and lung function during childhood: A prospective population-based study

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV1 at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (-0.02 (-0.04, 0)) and FEV1 z-scores (-0.02 (-0.04,-0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV1 at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV1, especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure.The INMA study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1) , and from Spain: Instituto de Salud Carlos III and Ministry of Health (Red INMA G03/176; CB06/02/0041; PI041436, PI081151, PI06/0867, PS09/00090, PI13/02187; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI12/01890, PI13/1944, PI13/2032, PI14/00891, PI14/1687, PI17/01194, and PI17/00663; MV16/00015; predoctoral grant PFIS - FI14/00099, pre-doctoral grant PFIS FIS-FSE: 17/00260, FIS19/1338, MV16/00015, Miguel Servet-FEDER: CP11/0178, and Miguel Servet-FSE: MS13/00054, MSII16/00051, and MS16/00128) , CIBERESP; Department of Health of the Basque Government (2005111093 and 2009111069) ; the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001) ; and the Generalitat de Catalunya-CIRIT (1999SGR 00241) . ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX 2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program

Urinary Arsenic Species and Methylation Efficiency During Pregnancy: Concentrations and Associated Factors in Spanish Pregnant Women

Background: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. Objectives: To describe the urinary concentrations of the different As species and evaluate the methylation effi-ciency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. Methods: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003 & ndash;2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Socio-demographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. Results: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 lig/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., beta [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). Discussion: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.This study was supported by grants from Instituto de Salud Carlos III, Spain [FIS-FEDER: 07/0314; FIS 11/01007, 13/1944, 16/1288, 19/1338; Miguel Servet-FEDER: CP15/0025, CPII20/00006; FIS-FSE: 17/00260; Miguel Servet-FSE: MS15/0025, MS20/0006; PI06/0867 and FIS-PI18/01142 incl. FEDER funds] , Generalitat Valenciana, Spain BEST/2020/059, Department of Health of the Basque Government, Spain (2005111093) , Provincial Government of Gipuzkoa (DFG06/002) , and annual agreements with the municipalities in the study area (Zumarraga, Urretxu, Legazpi, Azkoitia, Azpeitia and Beasain)

Postnatal exposure to mercury and neuropsychological development among preschooler children

The objective of this study was to describe the postnatal exposure to Hg and to evaluate its association with neuropsychological development among preschool children. The study population are 4–5 years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4 years of age (2008–2012). Neuropsychological development was assessed using the McCarthy Scales of Children’s Abilities (MSCA). Information on covariates and possible confounders was obtained by questionnaires during pregnancy and childhood. Generalized additive and linear regression models were built in order to assess the relationship between MSCA scores and Hg exposure. We also evaluated the magnitude of the possible bias generated from measurement error in seafood intake estimate from questionnaire and Hg determination. The geometric mean of hair Hg was 0.98 μg/g [95% confidence interval (CI) 0.94, 1.03]. In the regression analysis, the association between Hg and the MSCA scores was positive for all the scales and statistically significant for the verbal (β = 0.89; 95%CI 0.38, 1.39), memory (β = 0.42; 95%CI 0.09, 0.76) and general cognitive scales (β = 1.35; 95%CI 0.45, 2.25). However, these associations were clearly attenuated when we adjusted by the children’s fish intake variables or when took into account theoretical scenarios of low precision in fish intake and Hg measurements. Hg levels in this Spanish population were high in comparison with other European countries; however, we did not observe adverse effects on child neuropsychological development associated with this postnatal exposure to Hg

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort

Background: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. Methods: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. Results: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). Conclusions: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations

Prenatal Metals Exposure and pre-adolescents’ Emotional and Behavioral Problems

Emotional and behavioral problems during childhood raise the risk of subsequent developmental of mental disorders. Our aim was to study the association between maternal metal and trace element concentrations during gestation and these problems in 9 year-old children. The study sample comprised Spanish mother-child pairs in the INMA project (n = 1003). Metals and trace elements (As, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Tl and Zn) were measured in urine samples collected during pregnancy. Inorganic As metabolites were speciated in a subsample (n = 729). Emotional and behavioral problems were assessed using the Child Behavior Checklist (CBCL) composed of three scales: internalizing, externalizing and total problems. Sociodemographic, dietary and exposure to other environmental pollutants were obtained through questionnaires. Single nucleotide polymorphisms in brain- and metabolism-related genes APOE, BDNF, GSTP1, and PON1 were determined in cord blood. Multivariate negative binomial models were used. The interaction with sex and genotypes was evaluated including interaction terms. A multi-element analysis was carried out by a principal component analysis. Higher concentrations of Cu, monomethylarsonic acid, and Pb during pregnancy were associated with an increased incidence ratio risk (IRR) between 4.6 and 7.5% for internalizing and externalizing problems for all three CBCL scales in the children. Increasing Mo, Ni and Co concentrations were associated with higher IRR for internalizing problems (up to 8%), and Cd for externalizing problems (6.7%). Modifications by sex and genotypes were found for several associations. Multi-element analysis associated multiple metals and trace elements (Ni, Cu, Se, Cd and Pb) with higher internalizing problems.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. We are grateful to all the participants and their families for taking part in this study. We also appreciate the generous contribution in the study of all INMA members. A full roster of the INMA Project researchers can be found at http://www.proyectoinma.org/presentacion-inma/listado-investigadores/en_listado-investigadores.html. This study was supported by grants from Spanish government through the Ministry of Universities under the grant CAS21/00008 and grant for the requalification of the Spanish University, financed by the European Union, NextGeneration EU, Instituto de Salud Carlos III [FIS-FEDER: 13/1944, 16/1288, 17/00663 and 19/1338; FIS-FSE: 17/00260; Miguel Servet-FSE: MSII20/0006, FIS-PI06/0867, FIS-PI09/00090, CPII18/00018], CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089, 2015111065), Generalitat Valenciana [BEST/2020/059, AICO/2020/285 and CIAICO/2021/132] and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221 and DFG 89/17). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.Peer reviewe

Los Batanes: A trap for the Pyrenean wild goat during the Late Pleistocene (Spain)

Los Batanes cave (1025 m.a.s.l.) is a karstic system formed by pressure ducts, near the locality of Biescas in the Upper Gallego Valley (Huesca, Spain). Many fossil remains were retrieved from the cave sediments. The minimum sediment calendar age was determined to be 12.770 ± 60 BP. This date indicates that the deposit was formed before the Late Pleistocene-Early Holocene transition at the Pyrenees. Here we analyze the faunal assemblage of the site that is only conformed by remains of Pyrenean wild goat (Capra pyrenaica pyrenaica), which is a recently extinct subspecies of Iberian wild goat (C. pyrenaica). In the site, 1079 remains of Iberian wild goat have been recovered being one of the most numerous both in minimum number of individuals (MNI) and number of identified specimens (NISP) recovered until now in a natural trap in the Spanish Pyrenees. The population of Los Batanes shows a wide range of ages between juvenile and senile individuals and the MNI estimated from the number of right metatarsus is nine. The taphonomic features indicate that the cave acted as a trap for the goats which inhabited the vicinity of the cave. These goats probably stumbled and fell to the bottom of the pit and they could not get out, dying inside. Due to the origin of the accumulation numerous complete bones have been recovered. These fossil allow us to perform a biometric analysis that indicates that population of Los Batanes is in the range size of other goats from Late Pleistocene of Iberian Peninsula