HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy – Study design and characteristics of participants

Background: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. Methods: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. Results: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and 90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. Conclusions: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.We acknowledge funding for HBM4EU from the European Union’s Horizon 2020 research and innovation program under grant agreement #733032 and the national governments of the participating countries. This publication reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the in formation it contains.info:eu-repo/semantics/publishedVersio

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy - Study design and characteristics of participants

Background: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. Methods: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. Results: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and 90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. Conclusions: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.We acknowledge funding for HBM4EU from the European Union’s Horizon 2020 research and innovation program under grant agreement #733032 and the national governments of the participating countries. This publication reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the information it contains.S

Study of photocatalytic degradation of selected anticancer compounds and analysis of their transformation products with mass spectrometry

The first aim of the present thesis was the study of the photolytic and photocatalytic degradation of three anticancer compounds (etoposide, irinotecan, methotrexate) using UV radiation and TiO2 Degussa P25 as a catalyst. The thesis was begun with the study of the hydrolysis of the compounds at different pH values and continued with the study of the photolysis at the corresponding values. Next step was the study of the adsorption at different pH values and catalyst concentrations. Finally, the photocatalysis was studied under different pH values, catalyst concentrations and initial concentrations of the compounds. The monitoring of the concentration levels of the compounds was performed by UPLC. At the same time, the degree of mineralization of the selected anticancer compounds and their transformation products was evaluated through the measurement of the dissolved organic carbon. Furthermore, the spectral characterization of the radiation source and the photon flux of the system were performed. In the second part of the thesis, the detection and the identification of the basic transformation products formed during the photocatalytic degradation of etoposide and the photolytic and photocatalytic degradation of irinotecan were performed by using LC-MS/MS and in some cases by LC-TOF-MS. Finally, the toxicity changes of the treated aqueous solutions of etoposide, irinotecan and their transformation products of each experimental procedure were monitored.Σκοπός της διατριβής ήταν αρχικά η μελέτη της φωτολυτικής και φωτοκαταλυτικής διάσπασης τριών αντικαρκινικών ενώσεων (ετοποσίδη, ιρινοτεκάνη, μεθοτρεξάτη) χρησιμοποιώντας ακτινοβολία UV και ΤiO2 Degussa P25 ως καταλύτη. Η έρευνα ξεκίνησε με τη μελέτη της υδρολυτικής διάσπασης των ενώσεων υπό διαφορετικές τιμές pΗ και συνεχίστηκε με τη μελέτη της φωτόλυσης στις αντίστοιχες τιμές. Έπειτα, προχώρησε στη μελέτη της προσρόφησης της εκάστοτε ένωσης στην επιφάνεια του καταλύτη υπό διαφορετικές τιμές pΗ και συγκεντρώσεις καταλύτη. Τέλος, ολοκληρώθηκε με τη μελέτη της φωτοκατάλυσης υπό διαφορετικές τιμές pΗ, συγκεντρώσεις καταλύτη και αρχικές συγκεντρώσεις των ενώσεων. Η παρακολούθηση της διάσπασης των ενώσεων πραγματοποιήθηκε με τη βοήθεια του UPLC. Παράλληλα, σε όλα τα πειράματα έγινε εκτίμηση του βαθμού ανοργανοποίησης των επιλεγμένων αντικαρκινικών ενώσεων και των παραγόμενων προϊόντων μετασχηματισμού μέσω του διαλυτού οργανικού άνθρακα. Ακόμη, πραγματοποιήθηκε ο φασματικός χαρακτηρισμός της πηγής ακτινοβολίας και ο υπολογισμός της ροής των φωτονίων του συστήματος επεξεργασίας. Στο δεύτερο μέρος της διατριβής πραγματοποιήθηκε η ανίχνευση και η ταυτοποίηση των προϊόντων μετασχηματισμού της ετοποσίδης κατά τη φωτοκατάλυση και της ιρινοτεκάνης κατά τη φωτόλυση και τη φωτοκατάλυση με τη βοήθεια του LC-MS/MS και σε κάποιες περιπτώσεις του LC-TOF-MS. Τέλος, έγινε παρακολούθηση της μεταβολής της τοξικότητας των ενώσεων και των παραγόμενων προϊόντων τους

Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A

The total synthesis of the structure assigned to the natural product phaeosphaeride A <b>1a</b> was accomplished. The key steps involve the addition of vinyllithium reagent <b>7</b> to the acetonide-protected aldehyde <b>8</b> to access the carbon backbone of <b>1a</b>, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of <b>1a</b> were synthesized and tested for biological activity. Preliminary results showed that (6<i>R</i>,7<i>R</i>,8<i>R</i>)-<b>1a</b> and (6<i>S</i>,7<i>S</i>,8<i>S</i>)-<b>1a</b> inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells

Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A

The total synthesis of the structure assigned to the natural product phaeosphaeride A <b>1a</b> was accomplished. The key steps involve the addition of vinyllithium reagent <b>7</b> to the acetonide-protected aldehyde <b>8</b> to access the carbon backbone of <b>1a</b>, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of <b>1a</b> were synthesized and tested for biological activity. Preliminary results showed that (6<i>R</i>,7<i>R</i>,8<i>R</i>)-<b>1a</b> and (6<i>S</i>,7<i>S</i>,8<i>S</i>)-<b>1a</b> inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells