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Background: Exposure to arsenic (As) and its metabolites can affect normal growth in children, but the combine effects at simultaneous low-level exposures, remain uncertain. Hence, this study aims to analyze how the combined effects of As and its metabolites can impact growth indicators in 1,792 US children aged 6-12 years, from the NHANES., Methods: Levels of arsenic species in urine were measured using HPLC coupled with ICP-DRC-MS during the 2007-2020 NHANES cycles. The sum of iAs ([AsIII + AsV]), MMA, and DMA was used as a biomarker of internal iAs exposure (∑As), and methylation efficiency was assessed using the primary and secondary methylation indices (PMI, SMI). Linear regression and BKMR models were applied to identify adverse effects, nonlinear associations, interactions, and combined effects., Results: Median concentrations of MMA, DMA, iAs, and ∑As were 0.56 μg/L, 4.07 μg/L, 1.33 μg/L, and 6.40 μg/L, respectively. In the linear regression analyses, higher urinary concentrations of MMA were associated with reductions in several growth indicators. Specifically, each interquartile range (IQR) increase in MMA concentration was linked to decreases of -0.18 (95 % CI: -0.29, -0.06) in Body Mass Index (BMI) Z-score, -0.18 (95 % CI: -0.29, -0.06) in Weight Z-score, and -0.01 (95 % CI: -0.02, -0.01) in Waist circumference/Height ratio. Additionally, higher DMA concentrations were negatively associated with Height Z-score, with a reduction of -0.08 (95 % CI: -0.15, -0.01). In the BKMR analysis, DMA consistently emerged as the dominant contributor across multiple outcomes, showing the highest Posterior Inclusion Probabilities (PIPs) for indicators such as BMI Z-score and Waist circumference/Height ratio. While MMA exhibited notable PIPs in certain models, its influence was generally weaker than that of DMA., Conclusion: Childhood exposure to a mixture of arsenic species, even at low levels, appears to influence growth indicators and adversely affect physical development in children enrolled in NHANES., 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 © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study was to explore the association between symptoms of attention deficit hyperactivity disorder (ADHD) and oral health in a representative sample of the Spanish population aged 6-14 years. We also examined the contribution of several sociodemographic and behavioral determinants of children/adolescents and their family environment., Methods: A cross-sectional study involving 3,402 subjects aged between 6 and 14 years from the Spanish National Health Survey. The presence of ADHD symptoms was determined using the self-reported hyperactivity/inattention subscale of the Strength and Difficulties Questionnaire. Oral health was assessed using five indicators: caries, extraction, restorations, gingival bleeding, and the presence of teeth in poor condition (e.g., broken or misaligned). Logistic regressions were used to examine the association between the presence of ADHD symptoms and oral health indicators. These models were adjusted for sociodemographic factors, lifestyle variables, and oral hygiene behaviors relating to both the children and their parents., Results: Compared to children without ADHD symptoms, children with ADHD symptoms had a higher risk of caries (fully adjusted odds ratio: 2.16; 95% confidence interval: 1.66-2.82), extraction (1.42; 1.09-1.85), restoration (1.47; 1.19-1.82) and gingival bleeding (1.64; 1.11-2.41). The increased risk of caries was maintained when the analyses were restricted to middle/high social class families and children with low sugar intake, good oral hygiene behaviors and regular dental visits., Conclusions: Children with ADHD symptoms in Spain had worse oral health indicators than those without ADHD symptoms. Our results suggest that the association of ADHD symptoms with caries was independent of socioeconomic level, cariogenic diet, frequency of toothbrushing, and dental visits., (© 2024 S. Karger AG, Basel.)

Aims: We investigated the association between the frequency of visits to general practitioners (GPs) and the degree of disease control in patients with T2DM., Methods: This study included patients diagnosed with T2DM who visited their GPs between 2014 and 2018. A total of 89,674 patients, accounting for 1,203,035 visits, were included. Different clinical features such as glycated hemoglobin (HbA1c%), blood pressure (BP), and c-LDL levels were analyzed. Multifactorial control of T2DM was defined as HbA1c ≤ 7 %, BP ≤ 140/90 mmHg, and LDL cholesterol ≤ 100 mg/dL. Generalized Estimating Equations models were implemented in order to deal with repeated measures for the same patient., Results: The median age of the patients is 70 years, with 52.8 % being male. An increase in the number of visits per year significantly improves the likelihood of achieving multifactorial diabetes control. Patients with more than 3-visits per year (55.6 %) have a Relative Risks (RR) of 1.258 (95 % Confidence Interval: 1.120-1.414). Frequent visits are associated with better multifactorial control and better c-LDL management. Patients visiting more than 3-times annually tend to achieve better outcomes in multifactorial and c-LDL control., Conclusion: Increasing the frequency of primary care visits significantly enhances multifactorial and cholesterol control among T2DM patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no competing financial interest If there are other authors, they 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 © 2025. Published by Elsevier Ltd.)

Background: This study aims to investigate the differential miRNA expression profile between the visceral white adipose tissue and the skeletal muscle of people with obesity undergoing bariatric surgery., Methods: Skeletal muscle and visceral adipose tissue samples of 10 controls and 38 people with obesity (50% also with type 2 diabetes) undergoing bariatric surgery were collected. miRNA expression profiles were analyzed using Next-Generation Sequencing and subsequently validated using RT-PCR., Results: Approximately 69% of miRNAs showed similar expression in both tissues, however, 55 miRNAs were preferentially expressed in visceral adipose tissue and 53 in skeletal muscle. miR-122b-5p was uniquely identified in skeletal muscle, while miR-1-3p and miR-206 were upregulated in skeletal muscle. Conversely, miR-224-5p and miR-335-3p exhibited upregulation in visceral adipose tissue. Notably, distinctions related to the presence of type 2 diabetes were observed solely in the expression of miR-1-3p and miR-206 in visceral adipose tissue., Conclusions: This is the first study unveiling distinct miRNA expression profiles in paired samples of visceral adipose tissue and skeletal muscle in humans. The identification of obesity-specific miRNAs in these tissues opens up promising avenues for research into potential biomarkers for obesity diagnosis and treatment., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: In recent years, the implementation of electronic health records across all hospitals and primary care centres within the National Health System has significantly enhanced access to patients' clinical data. This study aims to estimate the prevalence of type 2 diabetes (T2DM) in primary care settings and to outline its associated cardiovascular risk factors (CVRF) and epidemiological characteristics., Methods: An observational cross-sectional study was conducted including 89,679 patients diagnosed with T2DM who attended the primary health care system from 2014 to 2018. Data was provided by the Primary Health Care System of the Principality of Asturias (SESPA)., Results: The estimated prevalence of diagnosed T2DM was 8.01% (95% Confidence Interval [CI]: 7.96-8.06) of the total population. Additionally, it was more prevalent in males compared to females (9.90% [95% CI: 9.81-9.99] vs. 6.50% [95% CI: 6.44-6.57]) and increased with age in both sexes. People with T2DM had an average age of 74 years, 52.3% were male, and the most frequently associated CVRF were: dyslipidaemia (47.90%) and hypertension (62.20%). Glycaemic control improved during the 2014-2018 period (31.69%), as did lipid control (23.66%). However, the improvement in blood pressure control (9.34%) was less pronounced for the same period. Regarding the multifactorial control of diabetes (measured by LDL-cholesterol, HbA1C and blood pressure) the overall degree of control improved by 11.55% between 2014 and 2018., Conclusion: In this 5-year retrospective population-based study, the utilisation of data from electronic medical records provides insights into the prevalence of T2DM in a large population, as well as real-time CVRFs. Leveraging this data facilitates the development of targeted health policies., (Copyright © 2024 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Metformin is a well-established drug for the treatment of type 2 diabetes; however, the mechanism of action has not been well described and many aspects of how it truly acts are still unknown. Moreover, regarding in vitro experiments, the glycaemic status when metformin is used is generally not considered, which, added to the suprapharmacological drug concentrations that are commonly employed in research, has resulted in gaps of its mechanism of action. The aim of this study was to determine how glucose and metformin concentrations influence cell culture. Considering that diabetic retinopathy is one of the most common complications of diabetes, a retinal pigment epithelial cell line was selected, and cell viability and proliferation rates were measured at different glucose and metformin concentrations. As expected, glucose concentration by itself positively influenced cell proliferation rates. When the metformin was considered, results were conditioned, as well, by metformin concentration. This conditioning resulted in cell death when high concentrations of metformin were used under physiological concentrations of glucose, while this did not happen when clinically relevant concentrations of metformin were used independently of glucose status. Our study shows the importance of in vitro cell growth conditions when drug effects such as metformin's are being analysed.

Type 1 diabetes is a chronic autoimmune disease which results in inefficient regulation of glucose homeostasis and can lead to different vascular comorbidities through life. In this study we aimed to analyse the circulating miRNA expression profile of patients with type 1 diabetes, and with no other associated pathology. For this, fasting plasma was obtained from 85 subjects. Next generation sequencing analysis was firstly performed to identify miRNAs that were differentially expressed between groups (20 patients vs. 10 controls). hsa-miR-1-3p, hsa-miR-200b-3p, hsa-miR-9-5p, and hsa-miR-1200 expression was also measured by Taqman RT-PCR to validate the observed changes (34 patients vs. 21 controls). Finally, through a bioinformatic approach, the main pathways affected by the target genes of these miRNAs were studied. Among the studied miRNAs, hsa-miR-1-3p expression was found significantly increased in patients with type 1 diabetes compared to controls, and positively correlated with glycated haemoglobin levels. Additionally, by using a bioinformatic approach, we could observe that changes in hsa-miR-1-3p directly affect genes involved in vascular development and cardiovascular pathologies. Our results suggest that, circulating hsa-miR-1-3p in plasma, together with glycaemic control, could be used as prognostic biomarkers in type 1 diabetes, helping to prevent the development of vascular complications in these patients., (© 2023. The Author(s).)

Background: Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4-5 years of age., Methods: We used urine metal concentrations as biomarkers of exposure in 328 children enrolled in the Spanish INMA-Asturias cohort. Anthropometric measurements (arm, head, and waist circumferences, standing height, and body mass index) and parental sociodemographic variables were collected through face-to-face interviews by trained study staff. Linear regressions were used to estimate the independent effects and were adjusted for each metal in the mixture. We applied Bayesian kernel machine regression to examine non-linear associations and potential interactions., Results: In linear regression, urinary levels of cadmium were associated with reduced arm circumference (β adjusted  = -0.44, 95% confidence interval [CI]: -0.73, -0.15), waist circumference (β adjusted  = -1.29, 95% CI: -2.10, -0.48), and standing height (β adjusted  = -1.09, 95% CI: -1.82, -0.35). Lead and cobalt concentrations were associated with reduced standing height (β adjusted  = -0.64, 95% CI: -1.20, -0.07) and smaller head circumference (β adjusted  = -0.29, 95% CI: -0.49, -0.09), respectively. However, molybdenum was positively associated with head circumference (β adjusted  = 0.22, 95% CI: 0.01, 0.43). BKMR analyses showed strong linear negative associations of cadmium with arm and head circumference and standing height. BKMR analyses also found lead and cobalt in the metal mixture were related to reduce standing height and head circumference, and consistently found molybdenum was related to increased head circumference., Conclusion: Our findings suggest that exposure to metal mixtures impacts growth indicators in children., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Lead (Pb), mercury (Hg) and fluoride (F) exposure during childhood is of concern owing to their toxicity. Also, evidence suggests that high and low exposure levels to manganese (Mn) and selenium (Se) during this vulnerable period are associated with an increased risk of adverse health effects. A reduced growth is associated with high Pb and F exposure; however, little is known about their impact on children's body size, and there is a lack of consensus on the effects of Hg, Mn, and Se exposure on children's anthropometric measures. This is particularly true for childhood metal co-exposures at levels relevant to the general population. We investigated the joint effects of exposure to a metal mixture (Pb, Mn, Hg, and Se in blood and F in plasma) on 6-11-year-old US children's anthropometry ( n = 1,634). Median F, Pb, Mn, Hg, and Se concentrations were 0.3 μmol/L, 0.5 μg/dL, 10.2 μg/L, 0.3 μg/L, and 178.0 μg/L, respectively. The joint effects of the five metals were modeled using Bayesian kernel machine and linear regressions. Pb and Mn showed opposite directions of associations with all outcome measured, where Pb was inversely associated with anthropometry. For body mass index and waist circumference, the effect estimates for Pb and Mn appeared stronger at high and low concentrations of the other metals of the mixture, respectively. Our findings suggest that metal co-exposures may influence children's body mass and linear growth indicators, and that such relations may differ by the exposure levels of the components of the metal mixture., Competing Interests: Declarations The authors declare they have no known competing financial interests of personal relationships that could have appeared to influence the work reported in this paper.

Smoking by women is associated with adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, low birth weight, infertility, and prolonged time to pregnancy. Anogenital distance (AGD) is a sensitive biomarker of prenatal androgen and antiandrogen exposure. We investigated the effect of smoking and passive smoke exposure during pregnancy on anogenital distance in offspring at 4 years in the INMA-Asturias cohort (Spain). Women were interviewed during pregnancy to collect information on tobacco consumption, and anogenital distance was measured in 381 children: Anoscrotal distance in boys and anofourchetal distance in girls. We also measured maternal urinary cotinine levels at 32 weeks of pregnancy. We constructed linear regression models to analyze the association between prenatal smoke exposure and anogenital distance and adjusted the models by relevant covariates. Reported prenatal smoke exposure was associated with statistically significant increased anogenital index (AGI), both at week 12 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) and at week 32 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) in male children, suggesting altered androgenic signaling.

This systematic review summarizes the current evidence related to the reliability of toenail total arsenic concentrations (thereafter "arsenic") as a biomarker of long-term exposure. Specifically, we reviewed literature on consistency of repeated measures over time, association with other biomarkers and metal concentrations, factors influencing concentrations, and associations with health effects. We identified 129 papers containing quantitative original data on arsenic in toenail samples covering populations from 29 different countries. We observed geographic differences in toenail arsenic concentrations, with highest median or mean concentrations in Asian countries. Arsenic-contaminated drinking water, occupational exposure or living in specific industrial areas were associated with an increased toenail arsenic content. The effects of other potential determinants and sources of arsenic exposure including diet, gender and age on the concentrations in toenails need further investigations. Toenail arsenic was correlated with the concentrations in hair and fingernails, and with urine arsenic mainly among highly exposed populations with a toenail mean or median ≥1 μg/g. Overall, there is a growing body of evidence suggesting that arsenic content from a single toenail sample may reflect long-term internal dose-exposure. Toenail arsenic can serve as a reliable measure of toxic inorganic arsenic exposure in chronic disease research, particularly promising for cancer and cardiovascular conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children., Methods: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex., Results: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß = -0.065, 95% CI: -0.096, -0.035, second tertile; ß = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß = -0.029, 95% CI: -0.059, -0.000, second tertile; ß = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile)., Conclusions: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Early-life exposure to inorganic arsenic (iAs) may adversely impact health later in life. To date, evidence of iAs adverse effects on children's neurodevelopment comes mainly from populations highly exposed to contaminated water with conflicting results. Little is known about those effects among populations with low iAs exposure from food intake. We investigated the cross-sectional association between exposure to iAs and neurodevelopment scores among children living in Spain whose main route of exposure was diet. Arsenic species concentrations in urine from 400 children was determined, and the sum of urinary iAs, dimethylarsinic acid, and monomethylarsonic acid was used to estimate iAs exposure. The McCarthy Scales of Children's Abilities was used to assess children's neuropsychological development at about 4-5 years of age. The median (interquartile range) of children's sum of urinary iAs, MMA, and DMA was 4.85 (2.74-7.54) μg/L, and in adjusted linear regression analyses the natural logarithm transformed concentrations showed an inverse association with children's motor functions (β, [95% confidence interval]; global scores (-2.29, [-3.95, -0.63])), gross scores (-1.92, [-3.52, -0.31]) and fine scores (-1.54, [-3.06, -0.03]). In stratified analyses by sex, negative associations were observed with the scores in the quantitative index (-2.59, [-5.36, 0.17]) and working memory function (-2.56, [-5.36, 0.24]) only in boys. Our study suggests that relatively low iAs exposure may impair children's neuropsychological development and that sex-related differences may be present in susceptibility to iAs related effects; however, our findings should be interpreted with caution given the possibility of residual confounding., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD., Methods: POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models., Results: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (β = -0.28, 95% confidence interval [CI]: -0.51, -0.04) and PBDE-153 (β = -0.61, 95% CI: -1.11, -0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females., Conclusions: Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity., (The Author(s). Published by S. Karger AG, Basel.)

Antimicrobial peptides form part of the first line of defense against pathogens for many organisms. Current treatments for fungal infections are limited by drug toxicity and pathogen resistance. Cm-p5 (SRSELIVHQRLF), a peptide derived from the marine mollusk Cenchritis muricatus peptide Cm-p1, has a significantly increased fungistatic activity against pathogenic Candida albicans (minimal inhibitory concentration, 10 µg/ml; EC50, 1.146 µg/ml) while exhibiting low toxic effects against a cultured mammalian cell line. Cm-p5 as characterized by circular dichroism and nuclear magnetic resonance revealed an α-helical structure in membrane-mimetic conditions and a tendency to random coil folding in aqueous solutions. Additional studies modeling Cm-p5 binding to a phosphatidylserine bilayer in silico and isothermal titration calorimetry using lipid monophases demonstrated that Cm-p5 has a high affinity for the phospholipids of fungal membranes (phosphatidylserine and phosphatidylethanolamine), only moderate interactions with a mammalian membrane phospholipid, low interaction with ergosterol, and no interaction with chitin. Adhesion of Cm-p5 to living C. albicans cells was confirmed by fluorescence microscopy with FITC-labeled peptide. In a systemic candidiasis model in mice, intraperitoneal administration of Cm-p5 was unable to control the fungal kidney burden, although its low amphiphaticity could be modified to generate new derivatives with improved fungicidal activity and stability., (© FASEB.)