Effects of a mediterranean diet intervention on maternal stress, well-being, and sleep quality throughout gestation -The IMPACT-BCN Trial

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.The project was partially funded by a grant from “la Caixa” Foundation (LCF/PR/GN18/10310003 and LCF/BQ/DR19/11740018); Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); AGAUR under grant 2017 SGR nº 1531; Instituto de Salud Carlos III (PI22/00684, INT21/00027, CM21/00058). S. Castro-Barquero has received support from Margarita Salas fellowship, University of Barcelona. L.Youssef was supported by the grant FJC2021-048123-I, funded by MCIN/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU”/PRTR. L. Benitez was supported by a research grant from the Instituto de Salud Carlos III (CM21/00058). M. Larroya has received support from Hospital Clínic Barcelona (Contracte Clínic de Recerca Emili Letang-Josep Font). F. Crovetto has received support from Centro de Investigaciones Biomédicas en Red sobre Enfermedades Raras (CIBERER)

Gender differences in the indirect effect of psychosocial work environment in the association of precarious employment and chronic stress: A cross-sectional mediation analysis

Gender differences in the association between precarious employment and chronic stress have been found but the mechanisms underlying this relationship have not been explored. The main objective of this study was to evaluate the mediating effects of psychosocial risk factors at work (i.e., demands, control, and support) and work-life conflicts in the relationship between precarious employment and chronic stress as measured through the production of steroid hormones (both adrenal and gonadal) for men and women separately. Cross-sectional data were derived from a sample of workers from Barcelona (n = 125-255 men; 130 women). A set of 23 markers were determined from hair samples to evaluate the production of both adrenal and gonadal steroids. Decomposition analyses were applied to estimate the indirect effects of psychosocial risk factors and work-life conflict using linear regression models. Gender differences in the association between precarious employment and steroids production were confirmed. Psychosocial risk factors and work-life conflicts had indirect effects only among women (βCortisol = 0.18; 95% CI: 0.04-0.32; βCortisol/Cortisone 0.19; 95% CI: 0.08-0.31; β%Cortisol 0.12; 95% CI: 0.05-0.20). Gender differences suggest that the physiological response to precarious employment could be determined by the social construction of gender identities, as well as by positions and roles in the labour market and family. Future studies should delve further into these differences to improve employment and working policies, thus mitigating gender inequalities in the labour market to prevent work-related stress

GC/MS in recent years has defined the normal and clinically disordered steroidome: will it soon be surpassed by LC/Tandem MS in this role?

Gas chromatography/mass spectrometry (GC/MS) has been used for steroid analysis since the 1960s. The advent of protective derivatization, capillary columns, and inexpensive electron ionization bench-top single quadrupole soon made it the method of choice for studying disorders of steroid synthesis and metabolism. However, the lengthy sample workup prevented GC/MS from becoming routine for steroid hormone measurement, which was dominated by radioimmunoassay. It was the emergence of liquid chromatography/tandem MS (LC/MS/MS) that sparked a renewed interest in GC/MS for the multicomponent analysis of steroids. GC/MS is excellent at providing an integrated picture of a person's steroid metabolome, or steroidome, as we term it. We review the recent work on newly described disorders and discuss the technical advances such as GC coupling to triple quadrupole and ion trap analyzers, two-dimensional GC/MS, and alternative ionization and detection systems such as atmospheric pressure chemical ionization (APCI) and time of flight. We believe that no novel GC/MS-based technique has the power of GC(electron ionization)/MS/MS as a "discovery tool," although APCI might provide ultimate sensitivity, which might be required in tissue steroidomics. Finally, we discuss the role of LC/MS/MS in steroidomics. This remains a challenge but offers shorter analysis times and advantages in the detection and discovery of steroids with a known structure. We describe recent advances in LC/MS steroidomics of hydrolyzed and intact steroid conjugates and suggest the technique is catching up with GC/MS in this area. However, in the end, both techniques will likely remain complementary and both should be available in advanced analytical laboratories

Effect of a mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: A prespecified analysis of the IMPACT BCN randomized clinical trial

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, setting, and participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks' gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main outcomes and measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (β, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (β, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (β, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years. Trial registration: ClinicalTrials.gov Identifier: NCT03166332

Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models

Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.Work in the laboratory of P.J.F.-M. was funded by the IMDEA Food Institute, the Ramón Areces Foundation (CIVP18A3891), the AECC (SIRTBIO, LABAE18008FERN), the MICINN (SAF2017-85766-R and PRPPID2020-114077RB-I00) co-funded by the European Regional Development Fund, and a Ramon y Cajal Fellowship (MICINN, RYC-2017-22335). J.L.L.-A. was funded by the Spanish Ministry of Science and Innovation (MICINN) (PTA2017‐14689‐I). Work in FreshAge laboratory was funded by: Instituto de Salud Carlos III CB16/10/00435 (CIBERFES), (PID2019-110906RB-I00/AEI/10.13039/501100011033) from the Spanish Ministry of Innovation and Science; FGCSIC/PSLINTERREG/FEDER; PROMETEO/2019/097 de “Consellería de Sanitat de la Generalitat Valenciana” and EU Funded H2020- DIABFRAIL-LATAM (Ref: 825546). Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana). Support from Ramón Areces Fundation and Soria Melguizo Foundation is also acknowledged. E.G.-D. was a recipient of a predoctoral grant financed by the Spanish Ministry (FPU18/05350). Work in the laboratory of IdP was funded by the MICINN (RTI2018-100872-J-I00) and PlaGenT excellence research program of the Valencian regional government (CIDENGENT/2019/044). Work in the laboratory of M.-I.G. was funded by PROMETEU/2018/135 from “Consellería, de Sanitat de la Generalitat Valenciana” and part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). F.M. is grateful to the Austrian Science Fund FWF (SFB-LIPOTOX F3007 & F3012, W1226, P29203, P29262, P27893, and P31727); the Austrian Federal Ministry of Education, Science and Research and the University of Graz for grants Unkonventionelle Forschung-InterFast and ysleep (BMWFW-80.109/0001-WF/V/3b/2015) and the field of excellence program BioHealth. We acknowledge support from NAWI Graz, the BioTechMed-Graz agship project EPIAge. T.E. acknowledges support from Austrian Science Fund FWF (P 33957 and TAI 602 1000). Work in the laboratory of R.H.H. was financially supported by a VIDI grant from ZonMw (no. 91715305). J.S.D. was supported by Ohio University. D.F.-S. acknowledges Ministerio de Universidades in Spain for his Margarita Salas postdoctoral grant (Ref. MGS/2021/15). The CGC group is funded by NIH Office of Research Infrastructure Programs (P40 OD010440)

Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity

Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.Work at the laboratory of P.J.F.M. is funded by the Ramón Areces Foundation, (CIVP18A3891), Asociación Española contra el Cáncer-AECC (SIRTBIO—LABAE18008FERN), a Ramon y Cajal Award from the Spanish Ministry of Science, Innovation and Universities (MICINN) (RYC-2017-22335), RETOS projects Program of MICINN (SAF2017-85766-R) and the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016). Work at the laboratory of ARM was funded by the MICINN (PID2019-110183RB-C21), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM) and the Ramón Areces Foundation. Work at the laboratory of A.D.R. Funded by the Comunidad de Madrid—Talento Grant 2018-T1/BMD-11966 and the MICINN PID-2019-106893RA-100. Work at the laboratory of L.D. is funded by projects from the Health Research Fund (ISCIII FIS PI14/01374 and FISPI17/00508) and from a Manuel de Oya research fellowship from the Beer and Health Foundation. Work at the laboratory of A.E. is funded by a Ramon y Cajal Award from MICINN (RYC-2013-13546) and RETOS projects Program of the MICINN, co-funded by the European Regional Development Fund (ERDF) (SAF2015-67538-R). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and the “laCaixa” Foundation

Association between precarious employment and chronic stress: Effect of gender, stress measurement and precariousness dimensions-A cross-sectional study

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 could be embodied by workers, altering their perceived well-being and physiological characteristics. Differences between men and women in the physiological effect of precarious employment could express not just the biochemical differences inherent to biological sex, but also the social construction of gender identities, positions and roles in society and family, as well as gender inequalities in the labour market.This research was funded by the Spanish Ministry of Science and Innovation under grant agreement N° CSO2017-89719-R (AEI/FEDER, UE). FMR is funded by National Research and Innovation Agency (ANII) of Uruguay under the code POS_EXT_2018_1_153741

Improving liquid chromatography-tandem mass spectrometry determination of polycarboxylic acids in human urine by chemical derivatization. Comparison of o-benzyl hydroxylamine and 2-picolyl amine

Due to its high sensitivity and specificity, liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) could be considered as the gold-standard in targeted metabolomics. Although LC-MS/MS allows for the direct detection of a large number of molecules, the proper quantification of highly polar compounds such as poly-carboxylic acids in complex matrices like urine is still a challenge. Chemical derivatization offers a suitable way to improve chromatographic behavior and sensitivity for these compounds. Several derivatizing agents have been proposed for the LC-MS/MS determination of carboxylic acids but studies dealing with their comparison in challenging scenarios are scarce. Here we present the evaluation of two different derivatization agents; o-benzylhydroxyl amine (oBHA) and 2-picolyl amine (2-PA); for the quantification of the (poly)-carboxylic acids belonging to the tricarboxylic acid cycle in urine. The suitability of both derivatizating agents was compared by validation of the two approaches. Derivatization with oBHA showed important advantages against 2-PA derivatization such as (i) providing better sensitivity, (ii) more stable derivatives and (iii) allowing for the proper validation of a larger number of analytes. Moreover, while 2-PA derivatization failed in the determination of the target analytes in some stored urine samples, oBHA derivatization successfully allowed for their appropriate determination in the same samples. A comparison between the concentrations obtained using oBHA derivatization and those provided by an external laboratory using UV and GC-MS detection revealed a satisfactory agreement between both results. Additionally, the concentrations obtained by the oBHA method for a set of 38 urines are in agreement with those previously reported in the literature. As a conclusion, our results show that the use of oBHA is preferred against 2-PA for the detection and quantification of (poly)-carboxylic acids in urine