Battery Of Biomarkers Research Articles

Health effects of a glyphosate-based herbicide on Elliptio complanata: multi-biomarker approach

The active ingredient (a.i.) glyphosate is frequently detected in waterways at relatively high concentrations, posing a risk to aquatic organisms including freshwater mussels, North America's most endangered animal group. This research aims to evaluate for the first time the effect of a glyphosate-based herbicide on a freshwater mussel (Unionid) using a battery of biomarkers. The mussel Elliptio complanata was exposed for 21 days to Credit® Xtreme (at 0, 50, 100, and 150 µg/L a.i. of glyphosate). An integrated biomarker response (IBRv2) was used to visualize the overall impact of each glyphosate-based herbicide concentration on mussels’ health conditions. The biomarker results showed that glyphosate (used at 100 µg/L and 150 µg/L) induced lipid peroxidation in the gills and digestive gland and inhibited acetylcholinesterase in the foot and gills, indicating oxidative damage and neurotoxicity. Other biomarkers were influenced at the lowest concentration of glyphosate tested (50 µg/L): lipids (decrease), triglycerides (increase) and, to a lesser extent, vitellogenin (decrease). For the latter biomarkers, the sexes were not affected similarly, and they were only sensitive at 50 µg/L, only females showed a trend toward a decrease for vitellogenin and a decrease for lipids. Using IBRv2, we found a clear discrimination between concentrations, and the index values increased with glyphosate concentration, attesting to the deterioration in biomarker-defined mussel health when exposed to Credit® Xtreme at realistic glyphosate concentrations in agricultural rivers. This study shows that glyphosate-based herbicides can alter neurological function, induce oxidative damage, and selectively modify the E. complanata metabolism at relatively low concentrations.

Biomarkers of Frailty in Patients with Advanced Chronic Liver Disease Undergoing a Multifactorial Intervention Consisting of Home Exercise, Branched-Chain Amino Acids, and Probiotics.

Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by 1H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism.

A multi-comprehensive approach to assess the responses of the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1919) to a simulation of a diesel-oil mixture spill

Oil spills are a major cause of pollution impacting marine ecosystems. In this work, the effects of short-term exposure to three different concentrations of a hydrocarbon mixture (HC) that simulated the action of such an event were investigated on Mytilus galloprovincialis specimens. Physiological effects were measured using a battery of biomarkers consisting of cellular activity (phagocytosis), immune-related enzymes, chaperonins (HSP70 and HSC70), and histomorphological alterations. Different concentrations of HC led to a significant decrease in phagocytosis, especially following high concentrations. Immune-related enzymes evaluated in hemolymph and digestive gland extract showed up-regulation, suggesting the activation of antioxidant, detoxicant, and inflammatory responses. Morphological alterations of digestive gland tubules were observed after exposure to the HC. HSP70 and HSC70 activity was up regulated following the treatments, indicating their involvement in maintaining organism homeostasis. In addition, the diversity and composition of hemolymph and digestive gland microbiota exposed to HC were analyzed by automated ribosomal intergenic spacer analysis (ARISA) and a Next Generation Sequencing (NGS) approach to evaluate the connection with hydrocarbon contamination. Metagenomic analysis revealed significant differences in the hemolymph and digestive gland microbiota composition between mussels exposed and unexposed to HC. Exposure to increasing HC concentrations had a positive effect on microbial diversity with clear adaptative responses, an increase in the relative abundance of several known degrading bacterial genera, including Alcanivorax, Roseovarius, Pseudomonas, Vibrio, Oleibacter. These results show the utility of a multi-comprehensive approach to evaluating functional adaptation in terms of immunological dysfunctions and microbiota alteration in the sentinel organism M. galloprovincialis.

Accumulation, biochemical responses and changes in the redox proteome promoted by Ag and Cd in the burrowing bivalve Scrobicularia plana

Silver (Ag) and cadmium (Cd) are non-essential metals that, as a result of natural processes and human activities, reach the aquatic environment where they interact with biota inducing potential toxic effects. To determine the biological effects of these metals on the endobenthic bivalve Scrobicularia plana, specimens were exposed to Ag and Cd at two concentrations, 5 and 50 μg∙L-1, for 7 days in a controlled microcosm system. The levels of the metals were measured in the seawater, sediments and clam tissues. The possible toxic biological effects of Ag and Cd were studied using a battery of biochemical biomarkers that are responsive to oxidative stress: superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) activities, and metallothioneins (MTs) and lipid peroxidation (LPO) levels. Since both metals have been linked to oxidative stress, redox modifications to proteins were studied by differential isotopic labelling of the oxidised and reduced forms of cysteines (Cys). An accumulation of metals was observed in the digestive gland and gills following exposure, together with the activation of enzyme activities (SOD for the Cd exposure; SOD, CAT, GST, and GR for the Ag exposure). The MT and LPO levels (after individual exposure to Ag and Cd) increased, which suggests the existence of antioxidant and detoxification processes to mitigate the toxic oxidative effects of both metals. The redox proteomic analysis identified 771 Cys-containing peptides (out of 514 proteins), of which 195 and 226 changed after exposure to Ag and Cd, respectively. Bioinformatics analysis showed that exposure to metal affects relevant functional pathways and biological processes in S. plana, such as: “cellular respiration” (Ag), “metabolism of amino acids” and “synthesis and degradation of proteins” (Ag and Cd), “carbohydrate metabolism” and “oxidative stress” (Cd). The proteomic approach implemented here is a powerful complement to conventional biochemical biomarkers, since it evaluates changes at the protein level in a high-throughput unbiased manner, thus providing a general appraisal of the biological responses altered by exposure to the contaminants.

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)1. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. 1 Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)[1]. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P<0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. [1] Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6): 485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

Assessing the Effects of a Diet of BPA Analogue-Exposed Microalgae in the Clam Ruditapes philippinarum.

In our previous study, we demonstrated that the microalgae Phaeodactylum tricornutum can bioaccumulate bisphenol A analogues. Since this microalgae species is part of the diet of marine filter-feeding organisms, such as bivalves, in this study we tested the hypothesis that a diet based on exposed microalgae can exert negative effects on the clam Ruditapes philippinarum. Microalgae were exposed for 7 days to 300 ng/L of bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS), alone or as a mixture (MIX), to allow bioaccumulation. Microalgae were then supplied as food to bivalves. After 7 and 14 days of diet, the effects of exposed microalgae were evaluated on a battery of biomarkers measured in haemolymph/haemocytes, gills and digestive glands of clams. In addition, bioaccumulation of the three bisphenols was investigated in clams by UHPLC-HRMS. The results obtained demonstrated that total haemocyte count (THC) increased in clams following ingestion for 7 days of BPAF- and BPF-exposed microalgae, while BPS-exposed microalgae significantly reduced THC after 14 days of diet. MIX- and BPS-exposed microalgae increased haemocyte proliferation. The diet of exposed microalgae affected acid and alkaline phosphatase activity in clams, with an opposite response between haemolymph and haemocytes. Regarding antioxidants, an increase in catalase activity was observed in clams after ingestion of BPA analogue-exposed microalgae. The results also demonstrated marked oxidative stress in gills, the first tissue playing an important role in the feeding process. Oxidative damage was recorded in both the gills and digestive glands of clams fed BPA analogue-exposed microalgae. Alterations in epigenetic-involved enzyme activity were also found, demonstrating for the first time that BPA analogue-exposed food can alter epigenetic mechanisms in marine invertebrates. No bioaccumulation of BPA analogues was detected in clam soft tissues. Overall, this study demonstrated that a diet of BPA analogue-exposed microalgae can induce significant alterations of some important biological responses of R. philippinarum. To our knowledge, this is the first study demonstrating the effects of ingestion of BPA analogue-exposed microalgae in the clam R. philippinarum, suggesting a potential ecotoxicological risk for the marine food chain, at least at the first levels.

Biomarkers at the Individual and Biochemical Level: Effects of Pure and Formulated Lambda-Cyhalothrin in Boana pulchella Tadpoles (Duméril and Bibron, 1841).

We compared the effects of lambda-cyhalothrin as the pure active ingredient and as a formulated product (Zero®), on the larval stage of the autochthonous species Boana pulchella. We evaluated ecotoxicological endpoints, behavioral and developmental alterations, and the biochemical detoxifying, neurotoxic, and oxidative stress responses, covering a wide concentration range from environmental to high application levels. Both pyrethroid preparations displayed similar ecotoxicity (median lethal concentration of ~0.5 mg/L), with the lethal effect of Zero® being more pronounced than that of the active ingredient. Sublethal behavioral alterations in natatory activity were observed at 1000 times lower concentrations, indicating the ecological hazard of tadpole exposure to this pyrethroid at environmentally relevant concentrations. Biochemical endpoints in B. pulchella larvae showed significant responses to lambda-cyhalothrin in the ng/L range; these responses were different for the pure or the formulated product, and they were variable at higher concentrations. Principal components analysis confirmed the prevalence of biochemical responses as early endpoints at the lowest lambda-cyhalothrin concentrations; the Integrated Biomarker Response Index proportionally increased with pyrethroid concentration in a similar way for the pure and the formulated products. We conclude that lambda-cyhalothrin is of concern from an environmental perspective, with particular emphasis on autochthonous anuran development. The battery of biochemical biomarkers included in our study showed a consistent integrated biomarker response, indicating that this is a potent tool for monitoring impacts on amphibians. Environ Toxicol Chem 2024;00:1-11. © 2024 SETAC.

Integration of a battery of biomarkers to evaluate the health status of field-collected frogs of Leptodactylus luctator living in ecosystems with different anthropogenic disturbances

Amphibians are the most threatened group of vertebrates because they have certain biological and ecological characteristics that make them sensitive to environmental changes. The aim of this study was to evaluate the health status of field-collected adult frogs of Leptodactylus luctator (Amphibia, Anura) living in sites with different anthropogenic disturbances (florihorticulture, petrochemical industry and sewage discharges) and a reference site without any detectable influence of such activities. To this end, a battery of 21 biomarkers (hematological, biochemical and individual biomarkers) was studied using a multivariate approach that allows us to evaluate the relationship between them and provide information on their usefulness. The frogs at the florihorticulture, petrochemical and sewage discharges sites exhibited several biomarkers far from homeostasis. In addition, we identified 11 of 21 biomarkers that were useful indicators of the health status of the frogs and allowed discrimination between study sites in the following order: lymphocytes (98 %), neutrophils (45 %), hemoglobin (42 %), monocytes (41 %), fat body index (35 %), eosinophils (35 %), hepatosomatic index (33 %), mean corpuscular hemoglobin (32 %), thrombocytes (27 %), catalase in liver (26 %), and GST in liver (26 %). The results suggest that hematological biomarkers contribute the most to site separation, whereas biochemical biomarkers contribute the least. The integral interpretation of the results also allowed us to diagnose the different health status of L. luctator: The frogs from the petrochemical industry were the most negatively affected, followed by the frogs from the sewages discharges and finally the frogs from the florihorticulture and reference sites. This is the first field study with anurans in which so many biomarkers were examined.

Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care

Finding effective and scalable solutions to address diagnostic delays and disparities in autism is a public health imperative. Approaches that integrate eye-tracking biomarkers into tiered community-based models of autism evaluation hold promise for addressing this problem. To determine whether a battery of eye-tracking biomarkers can reliably differentiate young children with and without autism in a community-referred sample collected during clinical evaluation in the primary care setting and to evaluate whether combining eye-tracking biomarkers with primary care practitioner (PCP) diagnosis and diagnostic certainty is associated with diagnostic outcome. Early Autism Evaluation (EAE) Hub system PCPs referred a consecutive sample of children to this prospective diagnostic study for blinded eye-tracking index test and follow-up expert evaluation from June 7, 2019, to September 23, 2022. Participants included 146 children (aged 14-48 months) consecutively referred by 7 EAE Hubs. Of 154 children enrolled, 146 provided usable data for at least 1 eye-tracking measure. The primary outcomes were sensitivity and specificity of a composite eye-tracking (ie, index) test, which was a consolidated measure based on significant eye-tracking indices, compared with reference standard expert clinical autism diagnosis. Secondary outcome measures were sensitivity and specificity of an integrated approach using an index test and PCP diagnosis and certainty. Among 146 children (mean [SD] age, 2.6 [0.6] years; 104 [71%] male; 21 [14%] Hispanic or Latine and 96 [66%] non-Latine White; 102 [70%] with a reference standard autism diagnosis), 113 (77%) had concordant autism outcomes between the index (composite biomarker) and reference outcomes, with 77.5% sensitivity (95% CI, 68.4%-84.5%) and 77.3% specificity (95% CI, 63.0%-87.2%). When index diagnosis was based on the combination of a composite biomarker, PCP diagnosis, and diagnostic certainty, outcomes were concordant with reference standard for 114 of 127 cases (90%) with a sensitivity of 90.7% (95% CI, 83.3%-95.0%) and a specificity of 86.7% (95% CI, 70.3%-94.7%). In this prospective diagnostic study, a composite eye-tracking biomarker was associated with a best-estimate clinical diagnosis of autism, and an integrated diagnostic model including PCP diagnosis and diagnostic certainty demonstrated improved sensitivity and specificity. These findings suggest that equipping PCPs with a multimethod diagnostic approach has the potential to substantially improve access to timely, accurate diagnosis in local communities.

Multi-biomarker approach to evaluate the toxicity of chlorpyrifos (active ingredient and a commercial formulation) on different stages of Biomphalaria straminea

Biomphalaria straminea is a freshwater gastropod native to South America and used in toxicological assessments. Our aim was to estimate 48 h-LC50 and sub-chronic effects after the exposure to low concentrations of chlorpyrifos as commercial formulation (CF) and active ingredient (AI) on B. straminea adult, embryos and juveniles. Concentrations between 1 and 5000 μg L−1 were chosen for acute exposures and 0.1 and 1 μg L−1 for the sub-chronic one. After 14 days biochemical parameters, viability and sub-populations of hemocytes, reproductive parameters, embryotoxicity and offspring' survival were studied. Egg masses laid between day 12 and 14 were separated to continue the exposure and the embryos were examined daily. Offspring' survival and morphological changes were registered for 14 days after hatching. 48 h-LC50, NOEC and LOEC were similar between CF and AI, however the CF caused more sub-lethal effects. CF but not the AI decreased carboxylesterases, catalase and the proportion of hyalinocytes with respect to the total hemocytes, and increased superoxide dismutase and the % of granulocytes with pseudopods. Also CF caused embryotoxicity probably due to the increase of embryos' membrane permeability. Acetylcholinesterase, superoxide dismutase, hemocytes sub-populations, the time and rate of hatching and juveniles' survival were the most sensitive biomarkers. We emphasize the importance of the assessment of a battery of biomarkers as a useful tool for toxicity studies including reproduction parameters and immunological responses. Also, we highlight the relevance of incorporating the evaluation of formulations in order to not underestimate the effects of pesticides on the environment.

Antioxidant and Hepatoprotective Effects of L-Glu and NAC against CCl4-induced Oxidative Damage in Rats. Biochemical and Histopathological Evaluation

Background: The imbalance between free radical formation and antioxidant defence leads to the development of oxidative stress. The search for substances that would mitigate or prevent the effects of oxidative stress remains relevant. Objective: Our goal was to compare the antioxidant and mitigation effects of L-glutamic acid (LGlu) and N-acetylcysteine (NAC) alone or in combination using a battery of biomarkers of oxidative stress such as reduced glutathione (GSH) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST) and lipid peroxidation, determined as a content of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS). Histopathological examination of the liver was also performed. Methods: Experimental rats were divided into five experimental groups. Exp.1: was treated with CCl4 only, Exp. 2: was treated with CCl4/L-Glu, Exp. 3: was treated with CCl4/Glu/NAC. Exp. 4: was treated with CCl4/NAC, Control 5: served as the control rats. Results: These findings suggest that the CCl4 leads to oxidative stress by depleting the antioxidant enzyme activities and increasing peroxidation products. The studied biochemical parameters were altered by the introduction of CCl4, which was normalised (to one degree or another) by L-Glu, LGlu/ NAC and NAC treatment. Conclusion: The most remarkable protective effect was observed in groups of rats that were treated with L-Glu only. This conclusion was confirmed by histopathological findings which showed less severe hepatocellular necrosis, fibrosis and inflammation in CCl4/L- Glu and CCl4/L-Glu/NAC treated group, compared to the CCl4 group.

Potentially modifiable risk and protective factors affecting mental and emotional wellness in pregnancy.

Impaired mental and emotional wellness often co-occurs with prenatal substance use, and both affect infant socio-emotional, cognitive, language, motor, and adaptive behavioral outcomes. Guided by the modified biopsychosocial framework, this study examined the role of common substance exposures during pregnancy (i.e., alcohol and cannabis), socio-cultural factors (social support during pregnancy, adverse childhood experiences), and reproductive health factors on maternal mental health (MMH). Data were obtained from a prospective cohort study-Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-2), and included 202 pregnant persons. Alcohol and cannabis exposures were assessed through repeated prospective interviews and a comprehensive battery of drug and ethanol biomarkers. MMH outcomes were evaluated during the third trimester through the Perceived Stress Scale, Edinburgh Depression Scale, Generalized Anxiety Disorders-7, and Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders. Univariate and multivariable linear regression models evaluated significant predictors of MMH. Results of multivariable analysis indicate that both maternal adverse childhood experiences and alcohol exposure, even at low-to-moderate levels, during pregnancy were associated with poorer scores for most MMH measures, while higher level of social support and Spanish as the primary language at home (as a proxy of enculturation) had protective effects (all p's < 0.05). These findings highlight the importance of assessing substance use, including periconceptional alcohol exposure, and mental health in pregnant persons as closely related risk factors which cannot be addressed in isolation. Our findings also emphasize a strong protective effect of socio-cultural factors on maternal mental and emotional wellbeing-a strong precursor to maternal-infant bonding and infant neurodevelopment.

Comparative responses and effects of exposure to metallic and nanoparticle zinc in the mussel Mytilus galloprovincialis

Zinc (Zn) nanoparticles (NPs) are widely used in various industrial and commercial applications. Their intensive use in sunscreens, for instance, renders priority to understanding their effects on marine life, to which may be added the intensive use of Zn-based paints and anodes to protect submerged structures. We studied the effects of Zn nanoparticles and ions in the mussel Mytilus galloprovincialis exposed to 1, 10 and 100 μg/L of both zinc forms for up to 28 days. Effects were determined by analysing a battery of biomarkers, from oxidative stress (total antioxidant capacity and catalase activity) to acetylcholinesterase (AChE) activity. The results revealed that mussels responded only marginally differently to ionic and Zn nanoparticles, but also that their response was concentration- and time-dependent, suggesting distinct metabolic modes of action. These variations occurred almost exclusively at the highest concentration tested and were more pronounced as the exposure period increased. An integrated biomarker index (IBR) approach was used encompassing also previous findings (lipid peroxidation and metal accumulation in tissue), which further confirmed that these filter-feeding organisms are considerable targets for zinc exposure in the two forms tested and should be included in studies evaluating the overall toxicological impact of various forms of Zn in the marine environment.

Life stage-specific effects of tire particle leachates on the cosmopolitan planktonic copepod Acartia tonsa

Tire wear particles (TWP) are a major source of microplastics in the aquatic environment and the ecological impacts of their leachates are of major environmental concern. Among marine biota, copepods are the most abundant animals in the ocean and a main link between primary producers and higher trophic levels in the marine food webs. In this study, we determined the acute lethal and sublethal effects of tire particle leachates on different life stages of the cosmopolitan planktonic copepod Acartia tonsa. Median lethal concentration (LC50, 48 h) ranged from 0.4 to 0.6 g L−1 depending on the life stages, being nauplii and copepodites more sensitive to tire particle leachates than adults. The median effective concentration (EC50, 48 h) for hatching was higher than 1 g L−1, indicating a relatively low sensitivity of hatching to tire particle leachates. However, metamorphosis (from nauplius VI to copepodite I) was notably reduced by tire particle leachates with an EC50 (48 h) of 0.23 g L−1 and the absence of metamorphosis at 1 g L−1, suggesting a strong developmental delay or endocrine disruption. Leachates also caused a significant decrease (10–22%) in the body length of nauplii and copepodites after exposure to TWP leachates (0.25 and 0.5 g L−1). We tested a battery of enzymatic biomarkers in A. tonsa adult stages, but a sublethal concentration of 50 mg L−1 of tire particle leachates did not cause a statistically significant effect on the measured enzymatic activities. Our results show that tire particle leachates can negatively impact the development, metamorphosis, and survival of planktonic copepods. More field data on concentrations of TWPs and the fate and persistence of their leached additives is needed for a better assessment of the risk of tire particle pollution on marine food webs.

Integrated biomarker responses: a further improvement of IBR and IBRv2 indexes to preserve data variability in statistical analyses.

In biomonitoring and laboratory studies, it is typical to measure a battery of molecular, biochemical, and cytogenetic biomarkers to evaluate the effects of xenobiotics in biota. However, summarizing the results of several biomarkers to inform laypersons and environmental agencies is still a challenge for researchers and environmental specialists. To address this issue, researchers have developed indexes such as the Integrated Biomarker Responses (IBR) and Integrated Biomarker Response version 2 (IBRv2) to summarize all biomarkers responses into a single value. Unfortunately, these indexes do not preserve the original biological variability, which hampers subsequent statistical analyses. In this study, we created new versions of IBR and IBRv2, which preserve individual data variability and can be used in typical statistical analyses. The new Integrated Biomarker Responses individual (IBRi), Integrated Biomarker Responses version 2 individual (IBRv2i) and Weighted Integrated Biomarker Responses version 2 individual (Weighted IBRv2i) indexes correlated with the original IBR and IBRv2 indexes and were able to detect differences among experimental groups in a simulated and case studies. Using the IBRi, IBRv2i, or Weighted IBRv2i indexes is advantageous because they maintain the data variability of the experimental groups and can be analyzed using hypothesis testing statistics like any other parameter. Additionally, this approach can help translate technical scientific terminology into a more accessible language suitable for environmental governmental agencies and decision-makers.

Differential Spectrum of Albumin Glycation, Oxidation, and Truncation in Type 2 and Type 1 Diabetes: Clinical and Biological Implications.

Background: Albumin, the most abundant and physiologically vital serum protein, accumulates a range of chemical modifications, as consequence of encounters with large number of reactive molecules whose concentrations increase in serum under pathological conditions. Methods: In a "proof of concept" study, mass spectrometric analysis was utilized to quantitate albumin post-translational modifications (glycation, oxidation, and truncation; individual isoforms and total) in four informative subject groups [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity and healthy; all with estimated glomerular filtration rate ≥60 mL/(min·m2)]. Besides glycated albumin (GA/mass spectrometry), glycated serum protein (GSP/nitro blue tetrazolium colorimetry), and glycated hemoglobin (HbA1c/high-performance liquid chromatography) were also measured. Results: A wide spectrum of albumin molecular modifications was identified in diabetes, with significant differences between T2DM and T1DM. Albumin glycation: GA correlated more strongly with HbA1c in T1DM, compared to T2DM. Higher albumin glycation isoforms (human serum albumin +3G/2G) were more stable and discriminative markers of mean glycemia. Albumin oxidation: T2DM, in comparison with T1DM, showed enhanced oxidative and dual (glycation plus oxidation) modifications, representing extreme molecular pathology. Albumin truncation: There was dramatic reduction ("deficiency") of truncated albumin isoforms in T2DM, and significant reduction in T1DM. Albumin truncation negatively correlated with severity of albumin glycation (mean glycemia) and albumin oxidation (cysteinylation). Possible mechanisms of insulin resistance, with associated increased free fatty acids binding to albumin, in stimulating albumin oxidation and inhibiting albumin glycation ("metabolic cross talks") are reviewed. Conclusions: Albumin molecular modifications in diabetes, together with significant differences between T2DM and T1DM, suggest possible role for insulin resistance in their genesis and consequent cell, tissue, and vascular dysfunction/damage. Albumin molecular fingerprinting can provide valuable insights into pathogenesis, diagnosis, monitoring, and future therapies for diabetes. Identification of biomarker battery ("albuminomics," "diabetomics") driven diverse "healthy," prediabetes, obesity, and T2DM phenotypes represents additional novel step toward precision medicine in diabetes and related disorders.

Integrated assessment of biological responses to pollution in wild mussels (Mytilus edulis) from subarctic and arctic areas in the Norwegian sea

North Atlantic and Arctic Oceans contain large amount of undiscovered oil and gas reserves. Therefore threat of oil spills and its hazardous ecological consequences are of great importance to the marine environment. Although mussels (Mytilus sp.) respond clearly to contaminants, biomarkers have shown variability linked to biological and environmental changes. In order to help avoiding misinterpretation of biological responses the aim of this study was to reveal the effect of natural variability in the responsiveness to pollution of a battery of cell and tissue-level biomarkers in mussels. Mussels were collected in relatively non-impacted and potentially impacted sites at ports and the vicinity of a waste water treatment plant in Trondheim and Tromsø in autumn of 2016. Although the battery of biomarkers used herein proved to be useful to discriminate impacted and non-impacted mussel populations, some confounding factors altering the biological responses were identified. Geographical/latitudinal factors seemed to be critical regarding the reproductive cycle, reserve material storage and the prevalence of parasites such as Gymnophallus cf. Bursicola trematodes. Mussels from the reference site in Tromsø displayed general stress responses at different levels, which could be influenced by the pathogenic effect of the Gymnophallus cf. Bursicola trematode and by a more advanced gametogenic developmental stage compared to the mussels from Trondheim, which could lead to misinterpretation of the reasons behind the measured stress levels in those mussels. Despite these confounding effects, the use of integrative tools such as IBR index helped to discriminate mussel populations from chemically impacted and non-impacted sites. Overall, this work serves as an anchor point both as a reference of the baseline level values of the analyzed endpoints in the studied geographical area and time of the year, and as an indication of the potential extent of the environmental confounding factors in monitoring programs causing stress on the analyzed mussel populations.

Study of the ageing and the sorption of polyaromatic hydrocarbons as influencing factors on the effects of microplastics on blue mussel

The mussels are species with high socio-economic weights and are often used as bioindicators of biological and chemical contamination. In the field and aquaculture, they can intake microplastics during filter-feeding, and the microplastics can have a negative impact on their health, even at low concentrations. The effects of microplastics have yet to be fully examined on the blue mussel (Mytilus edulis), considering the factors of ageing and sorption of some polyaromatic hydrocarbons (PAHs), ubiquitous environmental contaminants. In this work, 5 different exposure conditions were studied: pristine microplastics, microplastics aged for 1000 days under UV radiation, microplastics sorbing PAHs, as well as microplastics both aged and sorbing PAHs, in parallel to controls. The microplastic changes after ageing were studied with spectroscopic and chromatographic methods. Then, 8-day laboratory exposures of mussels at 10 µg/L of microplastics were performed. The oxidative stress, as well as neurotoxic and immunological responses of M. edulis, were measured using a battery of biomarkers (catalase/CAT, superoxide dismutase/SOD, glutathione S-transferases/GST, acetylcholinesterase/AChE) in 3 different organs (digestive gland, gills and mantle), and acid phosphatase in hemolymph. Then, a study of lipid impairments on the digestive gland was performed through the use of lipidomic tools. No significant difference of oxidative stress activity was observed for all the tissues of mussels exposed to pristine microplastics at 10 µg/L, compared to controls. The ageing and the PAH soption onto microplastics were influencing factors of the oxydative stress in mussels with increased CAT activities in the digestive glands and decreased SOD activities in the mantles. The neurotoxicity was highlighted by higher AChE activities measured in the mantle of mussels exposed to all the microplastic treatments, compared to controls. Concerning lipidomics, no compound was determined as a biomarker of microplastic exposure. The study demonstrated a low toxicity of microplastics at environmental relevant concentration with a 8-day exposure and using the chosen biomarkers. However, some microplastic changes seemed to lead to specific effects on mussels.

Evidence for an association between allostatic load and multisensory integration in middle-aged and older adults

Multisensory integration, the ability of the brain to integrate information from different sensory modalities, is critical for responding to environmental stimuli. While older adults show changes in multisensory integration with age, the impact of allostatic load (AL) (i.e., the effect of exposure to chronic stress, which can accelerate ageing) on multisensory perception remains understudied. We explored the relationship between multisensory integration and AL in 1,358 adults aged 50+ from The Irish Longitudinal Study on Ageing by performing a Sound Induced Flash Illusion (SIFI) task at multiple audio-visual temporal asynchronies. The AL score was created using a battery of biomarkers representing the activity of four major physiological systems: immunological, cardiovascular, metabolic, and renal. The number of biomarkers for which a participant was categorised in the highest risk quartile using sex-specific cutoffs was used to produce an overall AL score. We accounted for medication use when calculating our AL score. We analysed the accuracy of illusion trials on a SIFI task using generalised logistic mixed effects regression models adjusted for a number of covariates. Observation of cross-sectional and longitudinal results revealed that lower accuracy in integration (i.e., higher SIFI susceptibility with larger temporal asynchronies) was associated with higher AL. This confirmed the distinct patterns of multisensory integration in ageing.