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Codling moth (Cydia pomonella L.) is one of the most important apple pests which population is steadily growing. The aim of this study, conducted in Eastern Croatia, was to determine the efficiency of two biological preparations CpGV and kaolin clay compared with pyrethroids and control treatment. The preparations used in treatments were: 1) Cydia pomonella granulovirus (CpGV), 2) deltamethrin, beta cyfluthrin and alpha-cipemetrina, 3) kaolin, 4) control treatment, applying in two different methods of time control, on the three apple varieties 'Melrose', 'Jonagored' and 'Golden Delicious' clone B. The efficiency of the treatment 1 (CpGV) ranged from 78% to 95%, of treatment 2 (pyrethroids) from 96% to 97%, and treatment 3 (kaolin) - between 21.5 and 57%. There was significant negative correlation between yield and damage (r = -07.56). Two methods of determining time control did not differ significantly. Variety 'Melrose' had the highest number of fruits damage in all three years and 'Golden Delicious' clon B the lowest number which can be related to the codling moth caterpillar affinity to a certain variety. It is very important to make the best choice of preparations in control and at the same time be sure of their positive effect on the environment and human health. [ABSTRACT FROM AUTHOR]

Surface sterilization is the most important step in preparation of explants for micropropagation, because controlling fungal and bacterial contamination of woody plant from field sources is very difficult. Six sterilizing agents: sodium hypochlorite (NaOCl), calcium hypochlorite [Ca(ClO)2], sodium dichloroisocyanurate (DICA), mercuric (II) chloride (HgCl2), silver nitrate (AgNO3) and hydrogen peroxide (H2O2) were tested for sterilization of ‘Oblačinska’ sour cherry buds, by varying their concentration and time of exposure. The aim of this study was to establish best surface sterilization for in vitro propagation of ‘Oblačinska’ sour cherry. Aseptic cultures of ‘Oblačinska’ sour cherry were established from axillary buds which were placed in nutrient medium, supplemented with plants hormones 6-benzylaminopurine (BA), 1- naphthaleneacetic acid (NAA) and gibberellic acid (GA3). The results indicated that among these sterilizing agents silver nitrate (AgNO3) at concentration of 1% for 20 minutes was the best for controlling the infection, whereas sterilization with sodium dichloroisocyanurate (DICA) at concentration of 1% for 10 minutes was not satisfactory.

Fruit skin colour plays a major role in quality assessment of food, significantly determining consumer`s choice. Colour of sour cherries depends on anthocyanins which are phenolic compounds (flavonoids) present in high amounts in fruits. The aim of this study was to determine a possible relation between polyphenols (total phenolics and anthocyanins) and colour parameters of fruit skin of sour cherries. The plant material used in this study was twenty two sour cherry genotypes from an orchard of Agricultural Institute Osijek. Total phenolics and anthocyanins contents as well as colour parameters (L*, a*, b*, h and C) of fruit skin were determined. Variability between sour cherry genotypes in total phenolics and anthocyanins as well as in colour parameters was revealed. Total polyphenols content varied from 462.7 to 1049.0 mg GAE/100 g of fresh weight, while total anthocyanins ranged from 160.1 to 495.6 mg CGE/100 g of fresh weight. A significant positive correlation was found between polyphenols and anthocyanins content. Total phenolics content had a significant negative correlation with colour parameters b* and h, while anthocyanins content negatively correlated with colour parameters L*, b* and h. According to the obtained results, genotypes Maraska, Heimanns Konservenweichsel and Rexelle are the richest genotypes in polyphenols and anthocyanins content.

Type 1 diabetes has become prevalent among the adult population, who have increasingly gained access to sensing technology. This study delved into the impact of diet, nutritional status, and the use of a continuous glucose monitoring system (CGM) on glycemic regulation among adults diagnosed with T1D. Employing a prospective design, data were gathered from 151 participants aged 18-60 across multiple cycles. Participants utilized the FreeStyle Libre (FSL) Flash Glucose Monitoring (FGM) System and provided dietary details via questionnaires and diaries. The findings unveiled correlations between dietary patterns and glycemic control, with higher protein intake associated with improved glycated hemoglobin A1C values ( p = 0.019), yet elevated fat and protein consumption was linked to heightened rates of hyperglycemia. Conversely, no significant relationship was observed between dietary variables and hypoglycemia occurrence. Interestingly, subjects with more readings of glucose levels consumed fewer carbohydrates ( p = 0.004) and more proteins ( p = 0.000). Furthermore, physical activity and marital status correlated with glycemic stability, while higher education was associated with enhanced glycemic control ( p = 0.021). This study confirmed the importance of structured education on glycemic regulation and the importance of dietary patterns in glucose management. Also, the educational role of the FGM system in changing dietary habits was confirmed, which is one of the key factors for improving glycemic regulation in continuous glucose monitoring system users.

Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin-angiotensin-aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients.

Introduction: The aim of this study was to investigate serum levels of galectin-3 (Gal-3) and N-terminal pro-brain Natriuretic Peptide (NT-proBNP) in patients with stable obstructive coronary artery disease, as well as their potential to predict clinical outcomes., Methods: This was a single-center cross-sectional cohort study. 168 patients were divided into three groups: percutaneous coronary intervention (PCI) group (N 64), coronary artery bypass graft surgery (CABG) group (N 57), and group with no coronary stenosis (N 47). Gal-3 and NT-proBNP levels were measured and the Syntax score (Ss) was calculated., Results: The mean value of Gal-3 was 19.98 ng/ml and 9.51 ng/ml ( p  < 0.001) in the study group and control group, respectively. Highest value of Gal-3 was found in the group of subjects with three-vessel disease ( p  < 0.001). The mean value of NT-proBNP in the study group was 401.3 pg/ml, and in the control group 100.3 pg/ml ( p  = 0.159). The highest value of NT-proBNP was found in the group of subjects with three-vessel disease ( p  = 0.021). There was a statistically significant association between Gal-3, NT-proBNP and occurrence of adverse cardiovascular event ( p  = 0.0018; p  = 0.0019)., Conclusion: Gal-3 and NT-proBNP could be used as an additional tool for diagnosis and severity assessment of stable obstructive coronary artery disease. Furthermore, it could help identify high-risk patients who could experience major adverse cardiovascular events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bošnjak, Bedeković, Selthofer-Relatić, Roguljić, Mihaljević, Dukić and Bilić-Ćurčić.)

Organic anion transporting polypeptides (OATPs) facilitate the cellular uptake of a large number of compounds. Zebrafish Oatp1d1 matches the functional capabilities of human OATP orthologs, particularly in hormone and drug transport. It is highly expressed in the liver and later stages of embryonic development, indicating its critical role in zebrafish physiology and development. Data from previous in vitro analyses have shown a high affinity of zebrafish Oatp1d1 for pharmaceuticals and xenobiotics, providing the basis for further in vivo studies on its defence and developmental functions. Using CRISPR-Cas9 technology, we have generated an Oatp1d1 zebrafish mutant that has highly reduced Oatp1d1 expression in embryos and adult tissues compared to wild type (WT). The absence of Oatp1d1 was confirmed using custom-made antibodies. To evaluate its ecotoxicological relevance, mutant and WT embryos were exposed to increasing concentrations of diclofenac, an NSAID known for its wide and frequent use, environmental pseudo-persistence and ecological implications. WT embryos showed developmental delays and malformations such as spinal curvature, cardiac edema and blood pooling at higher diclofenac concentrations, whereas the Oatp1d1 mutant embryos showed marked resilience, with milder developmental defects and delayed toxic effects. These observations suggest that the absence of Oatp1d1 impedes the efficient entry of diclofenac into hepatocytes, thereby slowing its biotransformation into potentially more toxic metabolites. In addition, the changes in transcript expression of other uptake transporters revealed a highly probable and complex network of compensatory mechanisms. Therefore, the results of this study point to the importance of Oatp1d1-mediated transport of diclofenac, as demonstrated for the first time in vivo using an Oatp1 deficient zebrafish line. Finally, our data indicates that the compensatory role of other transporters with overlapping substrate preferences needs to be considered for a reliable understanding of the physiological and/or defensive role(s) of membrane transporters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Zebrafish Mate3 is one of six co-orthologs of human multidrug and toxin extrusion proteins. It is highly expressed in the kidneys, intestine, testes, and brain of males. Initial interaction studies showed its interaction with xenobiotic compounds, suggesting a role in the efflux of toxic compounds. In this study, we aimed to test various environmental contaminants for their interaction with zebrafish Mate3. We developed a stable zebrafish Mate3 cell line and optimized a high-throughput screening assay using DAPI and ASP + as fluorescent model substrates. To gain insight into the structure and function of the Mate3 protein and relate these to the results of the DAPI and ASP + transport measurements, we predicted its 3D structure using the AlphaFold2 algorithm. A 3D structure with high per residue confidence scores with 13 transmembrane segments (TMs) was obtained, with topology and mutual positioning characteristic of the Mate protein family in a shape open to the extracellular part. Molecular docking methods were used to identify DAPI and ASP + binding sites on the surface and in the center of the protein cavity. Because our kinetics experiments combined with molecular docking indicated that there may be additional active sites in zebrafish Mate3, additional cytotoxicity experiments were performed and highly potent Mate3 interactors were identified from a set of 55 different environmental contaminants. Our results suggest that some of the identified interactors may be of environmental concern, as their interaction with Mate3 could lead to an impairment of its normal efflux function, making fish more sensitive to harmful substances commonly released into the aquatic environment. Finally, the quality of zebrafish Mate3 structures predicted by the AlphaFold2 algorithm opens up the possibility of successfully using this tool for in silico research on transport preferences of other Mate proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Both insufficient and excessive iodine intake can lead to a broad range of disorders. A cross-sectional survey was conducted to assess iodine status in schoolchildren from Croatia., Design: 957 healthy 6 to 12-year-olds were enrolled (381 from northwestern region, 190 from eastern region, 215 from north Adriatic, and 171 from central Dalmatia region). Urinary iodine concentration (UIC) was measured in spot urine samples. Thyroid volume (Tvol) was recorded by ultrasound device. Standard anthropometric measures were taken, and body surface area (BSA) was determined. Tvol medians were calculated as a function of age, sex and BSA and compared with reference values., Results: Total sample size included 490 boys and 467 girls. Overall median UIC was 250.68 µg/L, with statistically significant variance in geographical regions (median UIC was 244.71 µg/L in northwestern, 208.02 µg/L in eastern, 216.07 µg/L in north Adriatic and 366.43 µg/L in central Dalmatia region). There were 10.08% of samples with UIC < 100 mcg/L while 38.24% of samples had UIC > 300 mcg/L. Age-matched Tvol medians in schoolchildren from all regions of Croatia were at the upper limits of reference values, but in north Adriatic and central Dalmatia exceeded the 97th percentile. BSA-matched Tvol was within the reference range in all regions., Conclusions: Our results demonstrate sufficient (more than adequate) iodine intake in schoolchildren of Croatia, and excessive iodine intake in central Dalmatia region. Total thyroid volumes in schoolchildren of Croatia were within the normal range, however borderline enlarged age-matched thyroid glands were observed in coastal areas., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease and higher mortality rates. Interestingly, recent findings suggest a reciprocal relationship between COVID-19 and diabetes, wherein COVID-19 may contribute to developing new-onset diabetes and worsen existing metabolic abnormalities. This narrative review aims to shed light on the intricate molecular mechanisms underlying the diabetogenic effects of COVID-19. Specifically, the review explores the potential role of various factors, including direct damage to β-cells, insulin resistance triggered by systemic inflammation, and disturbances in hormonal regulation, aiming to enhance our understanding of the COVID-19 impact on the development and progression of diabetes. By analysing these mechanisms, the aim is to enhance our understanding of the impact of COVID-19 on the development and progression of diabetes. The binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) receptors, which are present in key metabolic organs and tissues, may interfere with glucometabolic pathways, leading to hyperglycaemia, and potentially contribute to the development of new disease mechanisms. The virus's impact on β-cells through direct invasion or systemic inflammation may induce insulin resistance and disrupt glucose homeostasis. Furthermore, glucocorticoids, commonly used to treat COVID-19, may exacerbate hyperglycaemia and insulin resistance, potentially contributing to new-onset diabetes. The long-term effects of COVID-19 on glucose metabolism are still unknown, necessitating further research into the possibility of developing a novel type of diabetes. This article provides a comprehensive overview of the current understanding of the interaction between COVID-19 and diabetes, highlighting potential areas for future research and therapeutic interventions.

Background: This study aimed to investigate the possible role of serum galectin-3 (Gal-3) levels in the diagnosis and assessment of significant epicardial artery lesions in patients with suspected coronary artery disease (CAD)., Methods: This was a single-center cross sectional cohort study including 168 subjects with suspected CAD and indications for coronary angiography divided into three groups: percutaneous coronary intervention (PCI) group (N 64), coronary artery bypass graft surgery (CABG) group (N 57), and group with no coronary stenosis (N 47). Gal-3 levels were measured and the syntax score (Ss) was calculated., Results: The mean value of Gal-3 in the PCI and CABG group was 19.98 ng/ml, while in the control group, it was 9.51 ng/ml (p < 0.001). The highest value of Gal-3 was found in the group of subjects with three-vessel disease (p < 0.001). When subgroups were analyzed by Gal-3 levels (< 17.8 ng/ml low, 18.8-25.9 ng/ml intermediate, > 25 ng/ml high risk) there was a significant difference between at least two Gal-3 groups for the arithmetic mean of Syntax score (p < 0.001). The syntax I's arithmetic mean at low and intermediate-risk Gal-3 levels was significantly lower than at high-risk Gal-3 levels (p < 0.001)., Conclusion: Gal-3 could be used as an additional tool for diagnosis and severity assessment of atherosclerotic disease in patients with suspected CAD. Furthermore, it could help identify high-risk subjects in patients with stable CAD., (© 2023. The Author(s).)

The increasing use of the zebrafish model in biomedical and (eco)toxicological studies aimed at understanding the function of various proteins highlight the importance of optimizing existing methods to study gene and protein expression and localization in this model. In this context, zebrafish cryosections are still underutilized compared with whole-mount preparations. In this study, we used zebrafish embryos (24-120 hpf) to determine key factors for the preparation of high-quality zebrafish cryosections and to determine the optimal protocol for (immuno)fluorescence analyses of Na + /K + -ATPase and F-actin, across developmental stages from 1 to 5 dpf. The results showed that the highest quality zebrafish cryosections were obtained after the samples were fixed in 4% paraformaldehyde (PFA) for 1 h, incubated in 2.5% bovine gelatin/25% sucrose mixture, embedded in OCT, and then sectioned to 8 μm thickness at -20°C. Fluorescence microscopy analysis of phalloidin-labeled zebrafish skeletal muscle revealed that 1-h-4% PFA-fixed samples allowed optimal binding of phalloidin to F-actin. Further immunofluorescence analyses revealed detailed localization of F-actin and Na + /K + -ATPase in various tissues of the zebrafish and a stage-dependent increase in their respective expression in the somitic muscles and pronephros. Finally, staining of zebrafish cryosections and whole-mount samples revealed organ-specific and zone-dependent localizations of the Na + /K + -ATPase α1-subunit. RESEARCH HIGHLIGHTS: This study brings optimization of existing protocols for preparation and use of zebrafish embryos cryosections in (immuno)histological analyses. It reveals stage-dependent localization/expression of F-actin and Na + /K + -ATPase in zebrafish embryos., (© 2022 Wiley Periodicals LLC.)

Socks, being a necessary item of clothing, must be comfortable and maintain their quality throughout their life. Since the applicability of modal fibers and microfibers, as well as yarns produced using unconventional processes, in sock knitting has been insufficiently researched, this paper evaluated three groups of medium sized socks knitted in a plain single jersey pattern produced with the highest percentage of ring, rotor and air-jet spun modal or micro modal yarns of the same linear density in full plating with different textured polyamide 6.6 yarns compared to conventional cotton socks. The sock quality was evaluated through an investigation of the physical properties, wear resistance and dimensional stability, as well as the water vapor absorption, air permeability and thermal resistance using the thermal foot model before and after five repeated washing and drying cycles, according to the proposed methodology. The results showed that the fiber fineness, the structure of the differently spun yarns and the sock plain knits, the polyamide content and the implementation of the pretreatment of the socks had an influence on the obtained results. The socks made from modal and micro modal yarns differed in their properties. Compared to cotton socks, they have better comfort properties, a generally better pilling resistance and, after pretreatment, a comparable abrasion resistance.

Graves' disease is an autoimmune disease of the thyroid gland, characterized by increased production of thyroid hormones, which can affect many different organ systems in the body. Among other problems, it can cause disorders of the skeletal system, shortening the bone remodeling cycle and causing a decrease in bone density. The Wnt cascade signaling pathway and the β-catenin, as a part of the canonical Wnt pathway, also play roles in maintaining bone mass. Inhibition of the Wnt pathway can cause bone loss, and its stimulation can increase it. The Wnt signaling pathway influences the effectiveness of thyroid hormones by affecting receptors for thyroid hormones and deiodinase, while thyroid hormones can change levels of β-catenin within the cell cytoplasm. This indicates that the Wnt pathway and thyroid hormone levels, including hyperthyroidism, are linked and may act together to change bone density. In this review article, we attempt to explain the interplay between thyroid hormones and the Wnt pathway on bone density, with a focus on directions for further research and treatment options.

Graves' disease is an autoimmune disease characterized by excessive thyroid hormone production. One of the consequences of that state can be a decrease in bone mineral density (BMD). Graves' disease is often treated with antithyroid drugs (ATD) as first line therapy, which can lead to disease remission. Moreover, recent data show that improvement in BMD can be expected. However, vitamin D deficiency can coexist along with Graves' disease, which is also involved in the process of bone remodeling. It is still not known whether lower values of vitamin D can contribute to onset of Graves' disease and if its supplementation might be helpful in therapy for hyperthyroidism. In the past couple of decades, osteopenia and osteoporosis have become a major health burden not only in post-menopausal women but also as a result of other diseases, leading to extensive research into various pathophysiological mechanisms responsible for bone remodeling. The Wnt (wingless integrated) signaling pathway is a very important factor in bone homeostasis, especially the canonical pathway. Present data indicate that stimulation of the Wnt pathway leads to bone mass increase and, in contrast, its inhibition leads to bone mass decrease. Hence, inhibitors of the canonical Wnt pathway became the focus of interest, in particular sclerostin and dickkopf 1 (DKK1). Hyperthyroidism and osteopenia/osteoporosis are quite common today and can coexist together or as separate entities. In this article, we aimed to give an overview of possible associations and potential mutual pathophysiological mechanisms.

This study aimed to investigate the association of Wnt inhibitors with thyroid hormones, bone turnover markers, and bone mineral density (BMD) in patients with newly diagnosed Graves’ disease (GD) at the beginning of the antithyroid treatment and after a follow-up period of one year. The study included 37 patients with newly diagnosed GD who were treated with antithyroid drugs (ATD). At baseline and after one year, thyroid hormones and thyroid-stimulating hormone (TSH), serum concentrations of sclerostin, and Dickkopf-1 (DKK1) were measured by an enzyme-linked immunosorbent assay (ELISA). In addition, BMD was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover including osteocalcin (OC), beta-cross laps (β-CTX), and deoxypyridinoline (DPD) were determined. After one year of ATD therapy sclerostin levels were significantly decreased (p < 0.001), whereas DKK1 levels were significantly increased (p = 0.01). In addition, BMD of the lumbar spine, total hip, and femoral neck was significantly improved (p < 0.001), accompanied by an increase in OC, β-CTX, and DPD concentrations (p < 0.001). At baseline, sclerostin levels were positively associated with free triiodothyronine (FT3). Following ATD therapy, a positive correlation was observed between FT3 and DKK1 (p = 0.003), whereas a negative correlation was found between TSH and DKK1 (p = 0.04). Correlation analysis demonstrated no association of the sclerostin and DKK1 with other bone remodeling biomarkers OC, β-CTX, or DPD. Also, no significant correlation between sclerostin or DKK1 and T-score or BMD of the lumbar spine, hip, and femoral neck was observed at both time points. Conclusion: Observed differences in sclerostin and DKK1 serum following GD treatment indicate involvement of Wnt inhibitors in the etiopathogenesis of bone loss associated with hyperthyroidism. Furthermore, both sclerostin and DKK1 are involved in the reversal of changes in bone metabolism following ATD therapy, thus presenting potentially valuable bone remodeling markers worth further investigation.

The selection of drought-tolerant sour cherry genotypes is essential for developing sustainable fruit production in today's climate-change conditions. The phenotypic heterogenic population of sour cherry Oblačinska, with high and regular yield suitable for mechanical harvesting and industrial processing, is a traditional and predominant cultivar in northern Croatia (Pannonian region) and Serbia commercial orchards. In this context, 2-year old virus-free sour cherry plants of 4 isolated Oblačinska sour cherry ecotypes (OS, 18, D6, and BOR) produced by micropropagation were exposed to severe drought in a greenhouse under semi-controlled conditions to evaluate its photosynthetic intra-varietal variability. Relative water content (RWC), chlorophyll fluorescence (ChlF), and photosynthetic pigments were evaluated during the ten days of the experiment. As a visible symptom of stress, the withering of plants was followed by a diminution of RWC and photosynthetic pigments in the drought exposed leaves of sour cherry ecotypes compared to the control treatment. ChlF elucidated variability in the photosynthetic efficiency within studied sour cherry ecotypes, highlighting PI ABS , PI total , and ψE 0 as the most sensitive and thus the most informative JIP parameters for drought screening. Among the investigated ecotypes, BOR proved to be the most sensitive. The Oblačinska sour cherry ecotype OS showed the highest tolerance to drought conditions and, therefore, can be used as a source of tolerance in sour cherry breeding programs.

The aim of the study was to investigate the prevalence of thyroid dysfunction, positive thyroid peroxidase antibodies (TPOAb) and hypercholesterolemia in elderly and younger subjects, and the association of subclinical hypothyroidism with hypercholesterolemia. The study included 204 elderly (136 females and 68 males, age median 71, range 60-92 years), and 83 younger control subjects (63 females and 20 males, age median 45, range 19-55 years). Subjects with prior thyroid dysfunction were excluded. Serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), TPOAb, total cholesterol, height and weight were measured. Mann-Whitney, χ 2 -test and Student's t-test were used on statistical analysis. The prevalence of subclinical hypothyroidism (TSH >5 mU/L) in elderly was 7.4% vs . 3.6% in younger subjects, with the highest prevalence of 8.8% in elderly women vs . 4.8% in younger women, and 4.4% in elderly men. The prevalence of hypothyroidism and subclinical hyperthyroidism in elderly subjects was 0.5% and 1.5%, respectively. In women with subclinical hypothyroidism, the prevalence of TPOAb was 77% in elderly women and 67% in younger women (overall 19.9% in elderly and 14.3% in younger women). The mean FT3 level was lower in elderly women as compared with elderly men (p<0.01) and younger women (p<0.05). The mean cholesterol level was higher in elderly subjects in comparison with younger ones (p<0.01), and in elderly women vs . elderly men (p<0.01), but without difference between subclinical hypothyroidism and euthyroid subjects (6.0 mmol/L). In conclusion, subclinical hypothyroidism is the most prevalent thyroid dysfunction in elderly, with the highest prevalence in elderly women, and autoimmune thyroiditis is the most common etiology. Hypercholesterolemia was more related to older age, especially elderly females, but not influenced by subclinical hypothyroidism.

Microcystins (MCs) are the most studied cyanotoxins. The uptake of MCs in cells and tissues of mammals and fish species is mostly mediated by organic anion-transporting polypeptides (OATPs in humans and rodents; Oatps in other species), and the Oatp1d1 appears to be a major transporter for MCs in fish. In this study, six MC congeners of varying physicochemical properties (MC-LR, -RR, -YR, -LW, -LF, -LA) were tested by measuring their effect on the uptake of model Oatp1d1 fluorescent substrate Lucifer yellow (LY) in HEK293T cells transiently or stably overexpressing zebrafish Oatp1d1. MC-LW and -LF showed the strongest interaction resulting in an almost complete inhibition of LY transport with IC 50 values of 0.21 and 0.26 μM, while congeners -LR, -YR and -LA showed lower inhibitory effects. To discern between Oatp1d1 substrates and inhibitors, results were complemented by Michaelis-Menten kinetics and chemical analytical determinations of MCs uptake, along with molecular docking studies performed using the developed zebrafish Oatp1d1 homology model. Our study showed that Oatp1d1-mediated transport of MCs could be largely dependent on their basic physicochemical properties, with log P OW being the most obvious determinant. Finally, apart from determination of the chemical composition of cynobacterial blooms, a reliable risk assessment should take into account the interaction of identified MC congeners with Oatp1d1 as their primary transporter, and herewith we demonstrated that such a comprehensive approach could be based on the use of highly specific in vitro models, accompanied by chemical assessment and in silico molecular docking studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)