Associations of multiple exposures to persistent toxic substances with the risk of hyperuricemia and subclinical uric acid levels in BIOAMBIENT.ES study

Hyperuricemia is becoming a serious public health issue, which is highly influenced by environmental factors, although there is still controversial information on the potential influence of the exposure to Persistent Toxic Substances (PTSs) in the general population. In this study we aimed to assess the association. PTS exposure with uric acid homeostasis in a sample of the Spanish population. Participants were recruited during 2009–2010 in all the main geographical areas of Spain. Exposure to 34 PTSs was estimated by chemical analyses of serum levels of 6 Polychlorinated Biphenyls (PCBs, n=950), 13 Organochlorine Pesticides (OCPs, n=453), 6 Perfluoroalkyl Substances (PFAs, n=755), 7 Polybrominated Diphenyl Ethers (PBDEs, n=365), urinary Cadmium (n=926), and Lead in whole blood (n=882). The two study outcomes were defined as the prevalence of hyperuricemia in the study population and uric acid levels, the latter only in individuals with no previous diagnosis of hyperuricemia. Statistical analyses were performed by means of binomial logistic regression and linear regression, and mixture effects were screened using Weighted Quantile Sum Regression (WQS). Serum concentrations of γ-HCH, o,p´-DDE, PCB-138, PCB-153, PFOA, and urinary Cadmium were associated with an increased risk of hyperuricemia, while PBDE-153 showed an inverse association with the effect. Furthermore, exposure to Cadmium, PCB-138, and to PCB-153 was positively associated with uric acid levels. Results were consistent after lipid adjustment or standardization. WQS analyses revealed a major contribution of PCB-153 within the PCB mixture on both the risk of hyperuricemia and uric acid levels. Sensitivity analyses were performed by adjusting for dietary habits, fasting glucose and estimated glomerular filtration rate. Overall, we found novel associations between human exposure to mixtures of PTSs and disturbances in uric acid homeostasis. However, we cannot completely rule out potential residual confounding effect or reversedcausality related to the cross-sectional design.This work was funded as part of a research agreement between the Ministerio de Agricultura, Alimentación y Medioambiente, Spain and the Instituto de Salud Carlos III, Madrid , Spain (Project N_ SEG 1251/ 07, 1210/10 and 1321/15)

Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

The study was supported by the Swedish Research Council (No. 2017-00822). We acknowledge the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research for providing facilities and experimental support (Swedish Research Council No. 2017-00644). The computations were performed on resources provided by Swedish National Infrastructure for Computing Sensitive Personal Data through the Uppsala Multidisciplinary Center for Advanced Computational Science under project SIMP2019015. Dr Arrebola is under contract within the Ramón y Cajal Program, Ministerio de Economía, Industria y Competitividad, Madrid, Spain.Importance: Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population. Objective: To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population. Design, Setting, and Participants: This prospective nested case-control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023. Exposures: A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography-triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included. Main Outcomes and Measures: Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD. Results: Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes. Conclusions and Relevance: In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.Swedish Research Council 2017-00822, 2017-00644Uppsala Multidisciplinary Center for Advanced Computational Science SIMP2019015Ramón y Cajal Program, Ministerio de Economía, Industria y Competitividad, Madrid, Spai

Perception and Demands of Pregnant and Breastfeeding Women Regarding Their Role as Participants in Environmental Research Studies

A significant proportion of scientific studies consider pregnant and breastfeeding women as vulnerable subjects. The objective of this study was to analyse the perception of pregnant and breastfeeding women regarding their participation in environmental research studies. Our work is a descriptive and interpretative observational study that has been developed under the qualitative research paradigm following a phenomenological and ethnographic perspective. The study involved 173 women selected intentionally in two Spanish autonomous communities. To obtain the primary data, we relied upon 111 interviews, four focused ethnographies and eight focus groups. The data encoding and analysis was carried out with the help of NVivo 12 software (QSR International, Boston, MA, USA). We evidenced the need of pregnant and breastfeeding women for more detailed and accurate information on the risk of environmental pollutant exposure during their crucial life stage. In addition, these women claimed for a more participatory role in research studies. Pregnant and breastfeeding women in Spain ask for greater interaction with researchers and propose a dialogical relationship between valid partners. We conclude that our pregnant and breastfeeding women claim more research focused on their collective, as well as clearer, more accessible and structured information on the risks of exposure to environmental contaminants. In addition, they do not want to simply be informants; rather, they ask to be active and empowered members by providing their opinions and arguments throughout the research process.Fundación Pública Andaluza Progreso y Salud de la Junta de Andalucía, Spain (reference: AP-0139-2017)Ministry of Health of the Junta de Andalucía, Spain - A-0043-2018Ramón y Cajal programme (RYC-2016-20155, of the Ministry of Economy, Industry and Competitiveness, Spain)

Human health risks associated with urban soils in mining areas

We thank Ms. I. Martinez Segura and Mr. M.J. Roman Alpiste for their assistance in laboratory work. Additionally, Dr. A. Parviainen acknowledges the `Juan de la Cierva-Incorporaci ' on' fellowship (grant number IJCI-2016-27412); and Dr. J.P. Arrebola acknowledges the Ram ' on y Cajal program (grant number RYC-2016-20155) from the Spanish Ministry of Science, Innovation and Universities. Research performed at the UGR was supported by the Project RTI 2018-094327-B-I00, funded by the Ministry of Science, Innovation and Universities. The European Regional Development Fund (ERFD) and the European Social Fund (ESF) of the European Commission (co)funded the fellowships, research and infrastructure endeavors involved in this research performed at the Instituto Andaluz de Ciencias de la Tierra (UGR-CSIC).We studied the chemical composition of As and Pb in total (<2 mm) and fine fractions (<50 μm) of 52 urban soil samples from Minas de Riotinto (mining area) and Aracena (non-exposed area) in SW Spain. In addition to a soil phytotoxicity bioassay using Lactuca Sativa L., we modelled and performed carcinogenic and non-carcinogenic human health risk assessment, later comparing our data with relative cancer mortality rates reported at the municipal level. This study demonstrates that mineralized bedrock and natural soil-forming processes affect the geochemistry of natural (in-situ) urban soils, which in many cases surpass the regulatory levels for As (36 mg/kg) and Pb (275 mg/kg). Fine fractions of in-situ and mixed urban soils —susceptible of inhalation— are significantly enriched in As and Pb with respect to fine fractions of aggregate materials (ex-situ soils of chalky sands and gravel) in Minas de Riotinto. The soils in Minas de Riotinto are significantly enriched in As (total and fine fractions) and Pb (total fraction) with respect to Aracena. Despite elevated bulk concentrations of As and Pb, only one in-situ sample exhibits phytotoxic effects of the soil-water extracts on Lactuca Sativa L. seeds. Health risk assessment of these towns as exposure areas indicates that the soils of Minas de Riotinto are indeed a health risk to the residents, whereas there is no potential risk in Aracena. The reported relative mortality rates in Minas de Riotinto show a greater mortality of carcinogenic tumors potentially related to As and Pb exposure, including lung cancer. Both soil type and use must be considered when administrators or policy-makers evaluate health risks involved in urbanistic decision-making. To minimize exposure risk and adverse health outcomes, we recommend that insitu soils surpassing regulatory levels for As and Pb in public playgrounds and passing areas should be covered with aggregate materials.'Juan de la Cierva-Incorporacion' fellowship IJCI-2016-27412Spanish Government RYC-2016-20155Ministry of Science, Innovation and Universities RTI 2018-094327-B-I00European Regional Development Fund (ERFD) of the European Commission European Social Fund (ESF) of the European Commissio

Human health risks associated with urban soils in mining areas

samples from Minas de Riotinto (mining area) and Aracena (non-exposed area) in SW Spain. In addition to a soil phytotoxicity bioassay using Lactuca Sativa L., we modelled and performed carcinogenic and non-carcinogenic human health risk assessment, later comparing our data with relative cancer mortality rates reported at the municipal level. This study demonstrates that mineralized bedrock and natural soil-forming processes affect the geochemistry of natural (in-situ) urban soils, which in many cases surpass the regulatory levels for As (36 mg/kg) and Pb (275 mg/kg). Fine fractions of in-situ and mixed urban soils —susceptible of inhalation— are significantly enriched in As and Pb with respect to fine fractions of aggregate materials (ex-situ soils of chalky sands and gravel) in Minas de Riotinto. The soils in Minas de Riotinto are significantly enriched in As (total and fine fractions) and Pb (total fraction) with respect to Aracena. Despite elevated bulk concentrations of As and Pb, only one in-situ sample exhibits phytotoxic effects of the soil-water extracts on Lactuca Sativa L. seeds. Health risk assessment of these towns as exposure areas indicates that the soils of Minas de Riotinto are indeed a health risk to the residents, whereas there is no potential risk in Aracena. The reported relative mortality rates in Minas de Riotinto show a greater mortality of carcinogenic tumors potentially related to As and Pb exposure, including lung cancer. Both soil type and use must be considered when administrators or policy-makers evaluate health risks involved in urbanistic decision-making. To minimize exposure risk and adverse health outcomes, we recommend that insitu soils surpassing regulatory levels for As and Pb in public playgrounds and passing areas should be covered with aggregate materials

Psychological and cognitive factors related to prehospital delay in acute coronary syndrome: A systematic review

We would like to thank Yolanda Ramírez Casas for her help with data collection. This research is part of the PhD thesis of Mercedes Arrebola Moreno (Programa de Doctorado en Psicología, Universidad de Granada).Background: In acute coronary syndrome the time elapsed between the start of symptoms and the moment the patient receives treatment is an important determinant of survival and subsequent recovery. However, many patients do not receive treatment as quickly as recommended, mostly due to substantial prehospital delays such as waiting to seek medical attention after symptoms have started. Objective: To conduct a systematic review with meta-analysis of the relationship between nine frequently investigated psychological and cognitive factors and prehospital delay. Design: A protocol was preregistered in PROSPERO [CRD42018094198] and a systematic review was conducted following PRISMA guidelines. Data sources: The following databases were searched for quantitative articles published between 1997 and 2019: Medline (PubMed), Web of Science, Scopus, Psych Info, PAIS, and Open grey. Review methods: Study risk of bias was assessed with the NIH Quality Assessment Tool for Observational, Cohort, and Cross-Sectional Studies. A best evidence synthesis was performed to summarize the findings of the included studies. Results: Forty-eight articles, reporting on 57 studies from 23 countries met the inclusion criteria. Studies used very diverse definitions of prehospital delay and analytical practices, which precluded meta-analysis. The best evidence synthesis indicated that there was evidence that patients who attributed their symptoms to a cardiac event (n = 37), perceived symptoms as serious (n = 24), or felt anxiety in response to symptoms (n = 15) reported shorter prehospital delay, with effect sizes indicating important clinical differences (e.g., 1.5–2 h shorter prehospital delay). In contrast, there was limited evidence for a relationship between prehospital delay and knowledge of symptoms (n = 18), concern for troubling others (n = 18), fear (n = 17), or embarrassment in asking for help (n = 14). Conclusions: The current review shows that symptom attribution to cardiac events and some degree of perceived threat are fundamental to speed up help-seeking. In contrast, social concerns and barriers in seeking medical attention (embarrassment or concern for troubling others) may not be as important as initially thought. The current review also shows that the use of very diverse methodological practices strongly limits the integration of evidence into meaningful recommendations. We conclude that there is urgent need for common guidelines for prehospital delay study design and reporting.Juan de la Cierva Fellowship from the Spanish Ministry of Science FJCI-2016-28279Ministerio de Economia y Competitividad (Spain) PSI2014-51842-RAndalusian Regional Goverment SOMM17-6103-UGREuropean Union (EU) SOMM17-6103-UGRMinisterio de Economia, Industria y Competitividad, Spain RYC-2016-2015

Associations of serum phthalate metabolites with thyroid hormones in GraMo cohort, Southern Spain

These results would not have been achieved without the selfless collaboration of the staff from Santa Ana and San Cecilio Hospitals and the participants who took part in the study. Dr. JP Arrebola is under contract within the Ramon y Cajal Program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain) and Dr. C Donat-Vargas is under contract within the Atraccion de Talento (from the community of Madrid, Spain) . This study was supported by research grants from Instituto de Salud Carlos III (PI20/01568, PI16/01858) .The general population is continuously exposed to phthalates via various consumer products. Epidemiological research relating phthalate exposure to thyroid function during non-developmental periods is limited. This study aimed to investigate the associations between specific serum phthalate metabolites and indicators of thyroid function in adults. We measured 10 serum phthalate metabolites and thyroid hormones - total triiodothymnine (TT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) - in a subsample of 207 adults from the GraMo cohort. This subsample was made up of men and women (in equal proportions) of middle age (49 +/- 17 years) and from Southern Spain (province of Granada). Data on age, sex, body mass index, residence area, tobacco use, alcohol consumption and attained education were obtained from a questionnaire. Phthalate metabolites were log-transformed and categorized into tertiles. Cross-sectional associations of each metabolite with thyroid hormones were analyzed using multivariable-adjusted linear regression models. The mixture effect of metabolite phthalates was assessed using weighted quantile sum regression. After multivariable-adjustment, the following phthalate metabolites were significantly associated with TT3 in a dose-response manner: MMP (beta = 0.90: 95% confidence interval 0.68,1.12), MEP (beta = 0.67: 0.44, 0.90), MiBP (beta = 0.49: 0.21, 0.77), MiDP (beta = 0.27: 0.03, 0.52), MBzP (beta = 0.51: 0.28, 0.73), MEHP (beta = -0.59: -0.82, -0.35) and MiNP (beta = -0.43: -0.71, -0.14), when comparing highest vs. lowest exposed. The sum of all metabolites was also linked to FT4 levels. No significant associations were observed for TSH except for MiNP. Although phthalate metabolites with different molecular weight showed opposite associations, overall metabolite concentrations seem to associate with increased TT3 and FT4 serum levels. The cross-sectional nature of this analysis limits causal inference.Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20155Instituto de Salud Carlos III European Commission PI20/01568 PI16/0185

The efficacy of three-dimensional conformal radiation therapy on pain and quality of life in patients with painful bone metastases: a prospective study

AF, JE, and AM conceived and designed the study; all authors acquired the data; AF, JE, JP, and FM analyzed and interpreted the data; all authors drafted the manuscript; all authors critically revised the manuscript for important intellectual content; all authors gave approval of the version to be submitted; all authors agree to be accountable for all aspects of the work.Aim To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM). Methods This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours. The patients were followed up for eight weeks. Results The median age was 66.30 years. The most common primary cancer was lung cancer (31.1%). The most often prescribed scheme was 8 Gy in one fraction (70%). The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation. Overall, reduced pain and drug score were reported at two weeks of PRT in 68 (51.5%) and 37 (28%) of patients, respectively. Conclusions PRT is an effective treatment option for patients with painful BoM.Fundación Progreso y Salud and fundación Publica Andaluza para la investigación Biosanitaria Andalucía Oriental (FIBAO

Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment

This work was supported by research grants from CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Junta de Andalucia, European Regional Development Fund-FEDER (PI16/01858, PI16/01812, PI20/01568 and PI-13/02406) and Generalitat Valenciana. Dr. G Cakmak is awarded a grant by The Scientific and Technological Research Council of Turkey (TUBITAK-2219). Dr. JP Arrebola is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain).These results would not have been achieved without the selfless collaboration of the staff from Santa Ana and San Cecilio Hospitals and the participants who took part in the study.Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.CIBER de Epidemiologia y Salud Publica (CIBERESP)Instituto de Salud Carlos III, Junta de AndaluciaEuropean Commission PI16/01858 PI16/01812 PI20/01568 PI-13/02406Generalitat ValencianaEuropean CommissionTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) TUBITAK-2219Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-2015