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Papers by Alex Gomez

International Journal of Molecular Sciences

Melatonin plays multiple physiological roles in the human body. Evaluation of melatonin productio... more Melatonin plays multiple physiological roles in the human body. Evaluation of melatonin production by the determination of urinary 6-sulfatoxymelatonin in 24-h samples has important drawbacks which hinder the successful evaluation of melatonin production in large cohorts. Here, we evaluated the potential of nail analysis for estimating melatonin production. Firstly, mass spectrometry methodology for the determination of melatonin in nails was optimized and successfully validated. The method was found to be linear in the range 6.5–830 fg/mg with intraday and interday accuracy in the range 100–104 %, precision below 15 % and a LOD of 3.5 fg/mg. Secondly, nail melatonin concentrations from 84 volunteers (age 5–96) were determined. The expected correlation between melatonin and age was obtained (correlation coefficient −0.615; p < 0.001). Additionally, we showed that fingernails are preferable to toenails to determine nail melatonin content. Finally, fingernails collected for 180 day...

Nature Communications

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with postt... more Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction.

International Journal of Environmental Research and Public Health

Precarious employment has been highlighted as a social determinant of health, given, among others... more Precarious employment has been highlighted as a social determinant of health, given, among others, to its alleged association with chronic stress. However, few studies have been conducted analyzing such association, using both perceived stress indicators and biological markers. Accordingly, the present study analyzed the association of multidimensional (6 dimensions) precarious employment scale with perceived stress and 23 markers of adrenal and gonadal hormone production, including cortisol. The sample consisted of 255 salaried workers from Barcelona (125 men, 130 women) aged 25–60. OLS regression models stratified by sex were conducted. Results demonstrated that precarious employment increased the probabilities of having perceived stress in both sexes. In addition, the production of adrenal hormones among men is associated with precarious wages and among women with precarious contracts (“Temporariness”, “Disempowerment”, and “Rights” dimensions). Therefore, precarious employment c...

Pharmaceutics

The evolution of resistance by the malaria parasite to artemisinin, the key component of the comb... more The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 µM DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the patho...

Biomedicine & Pharmacotherapy

There has been a renewed interest in the potential use of psychedelics for the treatment of psych... more There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids. Plasma samples of 23 individuals were collected both before and after ayahuasca consumption. Samples were analysed through targeted metabolomics and further integrated with subjective ratings of the ayahuasca experience (i.e., using the 5-Dimension Altered States of Consciousness Rating Scale [ASC]), and plasma ayahuasca-alkaloids using integrated network analysis. Metabolic pathways enrichment analysis using diffusion algorithms for specific KEGG modules was performed on the metabolic output. Compared to baseline, the consumption of ayahuasca increased N-acyl-ethanolamine endocannabinoids, decreased 2-acyl-glycerol endocannabinoids, and altered several large-neutral amino acids (LNAAs). Integrated network results indicated that most of the LNAAs were inversely associated with 9 out of the 11 subscales of the ASC, except for tryptophan which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with the ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in several pathways involved in neurotransmission such as serotonin and dopamine synthesis. In conclusion, a crosstalk between the circulating LNAAs and the subjective effects is suggested, which is independent of the alkaloid concentrations and provides insights into the specific metabolic fingerprint and mechanism of action underlying ayahuasca experiences.

International Journal of Molecular Sciences, 2022

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within ... more Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the...

JAMA, 2021

Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortalit... more Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. OBJECTIVE To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks' gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020). INTERVENTIONS Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols. MAIN OUTCOMES AND MEASURES The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity). RESULTS Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], −7.9 [95% CI, −13.6 to −2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, −6.3 [95% CI, −11.8 to −0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, −7.6 [95% CI, −13.4 to −1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, −6.8 [95% CI, −12.6 to −0.3]; P = .02). CONCLUSIONS AND RELEVANCE In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients.

Analytica Chimica Acta, 2022

Metabolomics (both targeted and untargeted) has become the gold standard in biomarker discovery. ... more Metabolomics (both targeted and untargeted) has become the gold standard in biomarker discovery. Whereas targeted approaches only provide information for the selected markers, thus hampering the determination of out-of-the-box markers, the common bottleneck of untargeted metabolomics is the identification of detected biomarkers. In this study, we developed a strategy based on derivatization and LC-MS/MS detection in a precursor ion scan for the untargeted determination of a specific part of the metabolome (carbonyl-containing metabolites). The usefulness of this guided metabolomics approach has been demonstrated by elucidating carbonyl-containing biomarkers of COVID-19 severity. First, the LC-MS/MS behavior of 63 model compounds after O-benzylhydroxylamine derivatization was studied. A precursor ion scan of m/z 91 was selected as a suitable approach for the untargeted detection of carbonyl-containing metabolites. The method was able to detect ≈300 potential carbonyl-containing molecules in plasma, including mono-/di-/tricarbonylic compounds with satisfactory intra-day and inter-day repeatability and RSDs commonly <15%. Additionally, the semiquantitative nature of the precursor ion scan method was confirmed by comparison with a fully validated targeted method. The application of the guided metabolomics method to COVID-19 plasma samples revealed the presence of four potential COVID-19 severity biomarkers. Based on their LC-MS/MS behavior, these biomarkers were elucidated as 2-hydroxybutyrate, 2,3-dihydroxybutyrate, 2-oxobutyrate and 2-hydroxy-3-methylbutyrate. Their structures were confirmed by comparison with reference materials. The alterations of these biomarkers with COVID-19 severity were confirmed by a target analysis of a larger set of samples. Our results confirm that guided metabolomics is an alternative approach for the untargeted detection of selected families of metabolites; this approach can accelerate their elucidation and provide new perspectives for the establishment of health/disease biomarkers.

Frontiers in Public Health, 2021

The PRESSED project aims to explain the links between a multidimensional measure of precarious em... more The PRESSED project aims to explain the links between a multidimensional measure of precarious employment and stress and health. Studies on social epidemiology have found a clear positive association between precarious employment and health, but the pathways and mechanisms to explain such a relationship are not well-understood. This project aims to fill this gap from an interdisciplinary perspective, integrating the social and biomedical standpoints to comprehensively address the complex web of consequences of precarious employment and its effects on workers' stress, health and well-being, including health inequalities. The project objectives are: (1) to analyze the association between multidimensional precarious employment and chronic stress among salaried workers in Barcelona, measured both subjectively and using biological indicators; (2) to improve our understanding of the pathways and mechanisms linking precarious employment with stress, health and well-being; and (3) to an...

Nature Communications, 2021

Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to ... more Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3β/β-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.

ISEE Conference Abstracts, 2018

Background: Night shift work has been associated with increased risk for breast and prostate canc... more Background: Night shift work has been associated with increased risk for breast and prostate cancer. The effect of circadian disruption on steroid hormone production and metabolism is a possible un...

Talanta, 2021

Formalin-fixed paraffin-embedded (FFPE) tissues play an irreplaceable role in cancer research. Al... more Formalin-fixed paraffin-embedded (FFPE) tissues play an irreplaceable role in cancer research. Although extensive research has been conducted for the detection of DNA, RNA and proteins in FFPE samples, literature dealing with the FFPE determination of small molecules is scarce. In this study, we aimed to explore the potential of targeted metabolomics in FFPE specimens. For that purpose, we developed a LC-MS/MS method for the quantification of acidic metabolites in FFPE samples. The method involves trimming tissue slices from FFPE blocks, deparaffinization, lysis of the tissue, o-benzyl hydroxylamine derivatization and LC-MS/MS detection. Deparaffinization and lysis steps were optimized to maximize the analytes extraction and to minimize the effect of the ubiquitous presence of some metabolites in the paraffin. Two validation approaches were applied: (i) using blank paraffin as matrix and (ii) using actual human FFPE tissue samples by standard additions. The method quantified 40 metabolites with appropriate accuracy (commonly 80-120%) and precision (CV 2-19%) in both validation approaches. LLOQs ranging 0.88-2001 pg mg − 1 with low-moderate matrix effects (commonly 85-115%) were obtained. FFPE samples from 15 patients with colorectal cancer were analyzed and metabolites concentrations in tumor vs matched normal FFPE tissues were compared. Results show that tumor tissues have a well-established fingerprint including an increase in ketogenesis, a decrease in lipogenesis and an imbalance in the tricarboxylic acid cycle.

Journal of Clinical Medicine, 2020

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine u... more Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.0...

Journal of Pharmaceutical and Biomedical Analysis, 2021

Carboxylic acid containing compounds (R-COOH) are involved in a large number of biological proces... more Carboxylic acid containing compounds (R-COOH) are involved in a large number of biological processes and they are relevant for several pathological processes such as neurodegeneration or cancer. Comprehensive methodologies for the quantitative determination of R-COOH in biological samples are required. In this study we have developed a LC-MS/MS method for the quantification of 20 endogenous R-COOH belonging to different pathways such as kynurenine metabolism, serotoninergic pathway, glycolysis, tricarboxylic acid cycle, dopaminergic pathway, short chain fatty acids and glycine metabolism. The approach included derivatization with o-benzylhydroxylamine (reaction time 1 h), liquid-liquid extraction with ethyl acetate and LC-MS/MS detection (run time 10 min). The method was optimized and validated in 5 different matrices (urine, plasma, saliva, brain and liver) following two different approaches: (i) using surrogate matrices and (ii) using actual human samples by standard additions. A suitable linearity was obtained in the endogenous range of the analytes. Adequate intra and inter-assay accuracies (80-120%) and intra- and inter-assay precisions (<20%) were achieved for almost all analytes in all studied matrices. The method was applied in several scenarios to confirm (i) human urinary changes produced in glycolysis after exercise, (ii) metabolic changes produced in rat brain and plasma by methamphetamine administration and (iii) metabolic alterations in human plasma caused by vitamin B6 deficiency. Additionally, the application of the method allowed for establishing previously unreported alterations in R-COOH metabolites under these conditions. Due to the comprehensive analyte and matrix coverage and the wide applicability of the developed methodology, it can be considered as a suitable tool for the study of R-COOH status in health and disease by targeted metabolomics.

Antioxidants, 2021

Ceramides are a class of sphingolipids which have recently been shown to be better cardiovascular... more Ceramides are a class of sphingolipids which have recently been shown to be better cardiovascular disease (CVD) risk predictors than traditional CVD risk biomarkers. Tyrosol (TYR) is a dietary phenolic compound known to possess cardioprotective effects per se or through its in vivo active metabolite hydroxytyrosol. The purpose of this study was to evaluate the effects of the co-administration of white wine (WW) and TYR on circulating levels of ceramides and other lipids in humans at high CVD risk. Volunteers underwent a randomized controlled crossover clinical trial (4-week duration per intervention) with three different interventions: control, WW, and WW enriched with a capsule of TYR (WW + TYR). Endothelial function cardiovascular biomarkers and plasma lipidomic profile were assessed before and after each intervention. It was found that the WW + TYR intervention resulted in lower levels of three ceramide ratios, associated with an improvement of endothelial function (Cer C16:0/Cer...

Scandinavian Journal of Work, Environment & Health, 2021

Objective Data from real world settings on circadian disruption and subsequent hormone-related ch... more Objective Data from real world settings on circadian disruption and subsequent hormone-related changes may explain the higher risk of hormone-dependent cancers among night shift workers.The present study examines the melatonin and sex steroid hormone levels among night shift workers. Methods We included 44 male, rotating shift workers from a car factory in Spain, sampled both at the end of a 3-week night shift (22:00–06:00 hrs) and a 3-week early morning shift (06:00–14:00 hrs). Participants collected all urine voids over 24-hours during each shift. Urinary concentrations of sex steroid hormones (estrogens, androgens and progestogens) and 6-sulfatoxymelatonin (aMT6s, major melatonin metabolite) were determined. Individual cosinor analysis was used to derive the acrophase (peak time) and area under the curve (total production). Linear mixed models examined intraindividual associations between night shift work and log-transformed 24-hour peak time and total production of hormones compared to early morning shift work. Results The acrophase was delayed during the night shift for aMT6s [geometric mean difference (GMD) 7.53 hrs, 95% confidence interval (CI) 4.46–10.60], androgens (eg, testosterone: GMD 6.83 hrs, 95% CI 0.34–13.32) and progestogens (eg, 17-hydroxyprogesterone: GMD 4.54 hrs, 95% CI 2.92–6.16) compared to the early morning shift. We found a higher production of adrenal androgen 11-oxoandrosterone/11-oxoetiocholanolone [geometric mean ratio (GMR) 1.43, 95% CI 1.12–1.81], and a lower production of adrenal progestogen 16-cysteinylprogesterone (GMR 0.79, 95% CI 0.67–0.93) during the night shift compared to the early morning shift levels. Conclusions Night shift work was associated with melatonin and sex hormone-related changes in timing and total production, providing insight into the mechanistic path for its association with hormone-dependent cancer.

Journal of Inherited Metabolic Disease, 2021

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hyd... more Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long‐term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease‐states. In total, 25 patients (68%) presented with hyperhomocysteinemia (HHcy; tHcy > 15 μmol/L) during the observation period. HHcy was more frequent in AIP patients with recurrent disease receiving heme arginate, than in nonrecurrent (median tHcy: 21.6 μmol/L; range: 10‐129 vs median tHcy: 14.5 μmol/L; range 6‐77). Long‐term serial analyses showed a high within‐person tHcy variation, especially among the recurrent patients (coefficient of variation: 16.4%‐78.8%). HHcy was frequently associated with low blood concentrations of pyridoxal‐5′‐phosphate and folate, while cobalamin concentration and the allele distribution of the methylene‐tetrahydrofolate‐reductase gene were normal. Strikingly, 6 out of the 9 recurrent patients who were later included in a regime of givosiran, a small‐interfering RNA that effectively reduced recurrent attacks, showed further increased tHcy (median tHcy in 9 patients: 105 μmol/L; range 16‐212). Screening of amino acids in plasma by liquid‐chromatography showed co‐increased levels of methionine (median 71 μmol/L; range 23‐616; normal <40), suggestive of acquired deficiency of cystathionine‐β‐synthase. The kynunerine/tryptophan ratio in plasma was, however, normal, indicating a regular metabolism of tryptophan by heme‐dependent enzymes. In conclusion, even if HHcy was observed in AIP patients receiving heme arginate, givosiran induced an aggravation of the dysregulation, causing a co‐increase of tHcy and methionine resembling classic homocystinuria.

International Journal of Molecular Sciences, 2021

The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic path... more The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesi...

Food Chemistry, 2021

ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several compounds in ... more ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several compounds in milk. The in vitro and in vivo interactions between tryptophan-related compounds and ABCG2 were investigated. The tryptophan metabolome was determined by liquid chromatography-tandem mass spectrometry in milk and plasma from wild-type and Abcg2 − /− mice as well as dairy cows carrying the ABCG2 Y581S polymorphism (Y/S) and noncarrier animals (Y/Y). The milk-to-plasma ratios of tryptophan, kynurenic acid, kynurenine, anthranilic acid, and xanthurenic acid were higher in wild-type mice than in Abcg2 − /− mice. The ratio was 2-fold higher in Y/S than in Y/Y cows for kynurenine. In vitro transport assays confirmed that some of these compounds were in vitro substrates of the transporter and validated the differences observed between the two variants of the bovine protein. These findings show that the secretion of metabolites belonging to the kynurenine pathway into milk is mediated by ABCG2.

European Journal of Public Health, 2020

Background Precarious employment is an emerging social determinant of health and health inequalit... more Background Precarious employment is an emerging social determinant of health and health inequalities. It is known that it has an impact on health and could be a potential stressor. This study aims to examine the association between precarious employment and stress measured in two different ways: subjectively (questionnaire) and objectively (cortisol and its metabolites concentrations in hair, considered biomarkers of chronic stress). Methods Cross-sectional study in a sample of 256 workers of Barcelona, Spain, aged 25-60. We conducted a survey including questions on multidimensional precarious employment assessed by EPRES (Precarious Employment Scale), and perceived stress (measured through the Perceived Stress Scale (PSS)). We also collected hair samples to measure cortisol and metabolites concentrations. The associations between precarious employment and stress were assessed using lineal regression models, stratified by sex and adjusted for age and BMI. Results Preliminary analyse...