Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Background: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. Methods: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. Results: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. Conclusions: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.This work was supported by the Strategic Action for Research in Health sciences [CP12/03080, PI15/00071, PI10/0082, PI13/01848, PI14/00874, PI16/01402, PI21/00506 and PI11/00726], CIBER Fisio patología Obesidad y Nutrición (CIBEROBN) (CIBER-02-08-2009, CB06/03 and CB12/03/30,016), the State Agency for Research (PID2019-108973RB- C21 and C22), the Valencia Government (GRUPOS 03/101; PROMETEO/2009/029 and ACOMP/2013/039, IDI FEDER/2021/072 and GRISOLIAP/2021/119), the Castilla-Leon Government (GRS/279/A/08) and European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission. The Strategic Action for Research in Health sciences, CIBERDEM and CIBEROBN are initiatives from Carlos III Health Institute Madrid and cofunded with European Funds for Regional Development (FEDER). The State Agency for Research and Carlos III Health Institute belong to the Spanish Ministry of Science and Innovation. ADR received the support of a fellowship from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). MGP received the support of a fellowship from “la Caixa” Foundation (ID 100010434, fellowship code LCFLCF/BQ/DI18/11660001). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.S

Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study

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

The archaeology of coding RNA

Different theories concerning the origin of RNA (and, in particular, mRNA) point to the concatenation and expansion of proto-tRNA−like structures. Different biochemical and biophysical tools have been used to search for ancient-like RNA elements with a specific structure in genomic viral RNAs, including that of the hepatitis C virus, as well as in cellular mRNA populations, in particular those of human hepatocytes. We define this method as “archaeological,” and it has been designed to discover evolutionary patterns through a nonphylogenetic and nonrepresentational strategy. tRNA-like elements were found in structurally or functionally relevant positions both in viral RNA and in one of the liver mRNAs examined, the antagonist interferon-alpha subtype 5 (IFNA5) mRNA. Additionally, tRNA-like elements are highly represented within the hepatic mRNA population, which suggests that they could have participated in the formation of coding RNAs in the distant past. Expanding on this finding, we have observed a recurring dsRNA-like motif next to the tRNA-like elements in both viral RNAs and IFNA5 mRNA. This suggested that the concatenation of these RNA motifs was an activity present in the RNA pools that might have been relevant in the RNA world. The extensive alteration of sequences that likely triggered the transition from the predecessors of coding RNAs to the first fully functional mRNAs (which was not the case in the stepwise construction of noncoding rRNAs) hinders the phylogeny-based identification of RNA elements (both sequences and structures) that might have been active before the advent of protein synthesis. Therefore, our RNA archaeological method is presented as a way to better understand the structural/functional versatility of a variety of RNA elements, which might represent “the losers” in the process of RNA evolution as they had to adapt to the selective pressures favoring the coding capacity of the progressively longer mRNAs

Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study.

Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. 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). 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. 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. 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.S

Social inequalities in health related behaviours in Barcelona

OBJECTIVE—This study describes social class inequalities in health related behaviours (tobacco and alcohol consumption, physical activity) among a sample of general population over 14 years old in Barcelona.
DESIGN—Cross sectional study (Barcelona Health Interview Survey).
SETTING—Barcelona city (Spain).
PARTICIPANTS—A representative stratified sample of the non-institutionalised population resident in Barcelona was obtained. This study refers to the 4171 respondents aged over 14.
DATA—Social class was obtained from a Spanish adaptation of the British Registrar General classification. In addition, sociodemographic variables such as family structure and employment status were used. As health related behaviours tobacco consumption, alcohol consumption, usual physical activity and leisure time physical activity were analysed. Age adjusted percentages were compared by social class. Multivariate analysis was performed using logistic regression models.
MAIN RESULTS—Women in the upper social classes were more likely to smoke, the adjusted odds ratio (OR) for social class V in reference to social class I was 0.36 (95% confidence intervals (95%CI): 0.19, 0.67), while the opposite occurred among men although it was not statistically significant in multivariate analysis. Smoking cessation was more likely among men in the higher classes (OR for class V 0.41, 95%CI: 0.18, 0.90). Excessive alcohol consumption among men showed no differences between classes, while among women it was greater in the upper classes. Engaging in usual physical activity classified as "light or none" in men decreased with lowering social class (OR class IVa: 0.55 and OR class IVb: 0.47). Women of social classes IV and V were less likely to have two or more health risk behaviours (OR for class V 0.33, 95% CI: 0.18, 0.62).
CONCLUSION—Health damaging behaviours are differentially distributed among social classes in Barcelona. Health policies should take into account these inequalities.


Keywords: health related behaviours; social class; health surve

Identification of plant cells in black pigments of prehistoric Spanish Levantine rock art by means of a multi-analytical approach. A new method for social identity materialization using chaîne opératoire

International audienc

Clinical presentation of influenza in children 6 to 35 months of age: findings from a randomized clinical trial of inactivated quadrivalent influenza vaccine

Background: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6–35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes. Methods: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011–2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018). Results: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44−0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39−0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case. Conclusions: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination

Cardiogenic shock code 2023: expert document for a multidisciplinary organization that allows quality care

[Resumen] Pese a los esfuerzos realizados para mejorar la atención al shock cardiogénico (SC), incluyendo el desarrollo de dispositivos de asistencia circulatoria mecánica (ACM), su pronóstico continúa siendo desfavorable. En este contexto surgen iniciativas de código SC, basadas en proporcionar una asistencia rápida y de calidad a estos pacientes. Este documento multidisciplinario trata de justificar la necesidad de implantar el código SC, definiendo su estructura/organización, criterios de activación, flujo de pacientes según nivel asistencial e indicadores de calidad. Sus propósitos concretos son: a) presentar las peculiaridades de esta enfermedad y el aprendizaje del código infarto y de experiencias previas en SC; b) detallar las bases para el abordaje de estos pacientes, la estructura de los equipos, su logística, la elección del tipo de ACM y el momento de su implante, y c) abordar los desafíos para la implantación del código SC, como la singularidad del código SC pediátrico. Urge desarrollar una asistencia protocolizada, multidisciplinaria y centralizada en hospitales con gran volumen y experiencia que permita minimizar la inequidad en el acceso a la ACM y mejorar la supervivencia de estos enfermos. Solo el apoyo institucional y estructural de las distintas administraciones permitirá optimizar la atención al SC.[Abstract] Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS