Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study.

BACKGROUND: Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. METHODS AND RESULTS: This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. CONCLUSIONS: Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.

Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers.

BRCA1 mutations substantially elevate the risks of breast and ovarian cancer. Various modifiers, including environmental factors, can influence cancer risk. Lead, a known carcinogen, has been associated with various cancers, but its impact on BRCA1 carriers remains unexplored. A cohort of 989 BRCA1 mutation carriers underwent genetic testing at the Pomeranian Medical University, Poland. Blood lead levels were measured using inductively coupled plasma mass spectrometry. Each subject was assigned to a category based on their tertile of blood lead. Cox regression analysis was used to assess cancer risk associations. Elevated blood lead levels (>13.6 µg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23-9.00; p = 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01; p = 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.

Association between breakfast skipping and blood levels of lead and cadmium in children and adolescents aged 6-17 years: Results from the National Health and Nutrition Examination Survey 2013-2018.

INTRODUCTION: Previous research suggests that fasting increases lead absorption in the gastrointestinal tract, and that regularly eating meals may reduce blood lead. However, there is insufficient evidence linking breakfast status and blood-metal levels in children. We assessed the cross-sectional association between breakfast consumption status and children and adolescent's blood levels of lead and cadmium. We also explored blood hemoglobin, serum ferritin, and age group as potential effect modifiers of these associations. METHODS: This analysis included children and adolescents aged 6-17 years who participated in the National Health and Nutrition Examination Survey (NHANES) cycles 2013-2018 with complete data on breakfast consumption status (consumers vs. skippers), blood metals, and covariates (N=3722). Blood metal variables were log-transformed. Crude and covariate-adjusted, survey-weighted linear regression models were conducted for each blood metal outcome. Potential effect modification was explored using stratification. RESULTS: Overall fewer participants reported skipping breakfast (n=719) than eating breakfast (n=3003). Mean (SE) concentrations of blood lead and cadmium (µg/L) were 0.63 (0.01) µg/dL and 0.13 (0.00) µg/L, respectively. Children and adolescents who skipped breakfast were more likely to be female (51.2%), older (mean 12.2 years, SE = 0.1), have a higher body mass index (mean 22.8 kg/m2, SE = 0.2), and a lower income-poverty ratio (mean 1.7, SE = 0.1) than breakfast consumers. No associations between breakfast consumption and any of the blood metals were found. When stratified by age (≤ 10, 11-13, and 14-17 years), children aged 11-13 years who consumed breakfast had lower log-transformed blood lead levels [ß = -0.14 µg/L; 95% CI: (-0.25, -0.03)] compared to children of the same age who skipped breakfast. CONCLUSION: Children 11-13 years-old who were breakfast consumers had lower blood lead levels compared to children of the same age who skipped breakfast. Our results support that encouraging breakfast consumption among school-age children may contribute to lower blood lead levels.

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Associations between maternal exposure to multiple metals and metalloids and blood pressure in preschool children: A mixture-based approach.

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.

Relationship between blood lead (Pb) concentration with risk of diabetes mellitus in women living in mining area.

Diabetes is a global health concern with significant implications for individuals and societies. Diabetes results from a complex interaction between genes and environmental factors, including metal exposure. Lead or plumbum (Pb) is a heavy metal pollutant and is predicted to be associated with the morbidity of diabetes. The aim of this study was to assess the relationship between blood Pb level and possible risk factors (body mass index insulin resistance, carbohydrate intake, sugar intake, and physical activity) with fasting blood sugar (FBS) level in women living in the mining area. A cross-sectional study was conducted in a mining area of Indonesia located in Pemali District, Bangka Belitung Regency, involving women aged 30-49, selected through purposive sampling. Logistic regression was used to assess the relationship between the risk factors and FBS level, while the Spearman correlation was used to analyze the correlations between the risk factors and FBS level. Our data indicated that blood Pb concentration and other risk factors (carbohydrate intake, sugar intake and physical activity) were neither associated nor correlated with FBS level. However, as predicted, insulin resistance was associated with FBS level with OR: 9.66; 95%CI: 1.13-82.29; p=0.038. In addition, the Homeostatic Model Assessment Insulin Resistance (HOMA-IR) score was also correlated with FBS level (r=0.316, p=0.002). This study highlights the level of Pb is not associated with the risk of diabetes in women living in mining area.

Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries.

Lead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.

Mapping Blood Lead Levels in China during 1980-2040 with Machine Learning.

Lead poisoning is globally concerning, yet limited testing hinders effective interventions in most countries. We aimed to create annual maps of county-specific blood lead levels in China from 1980 to 2040 using a machine learning model. Blood lead data from China were sourced from 1180 surveys published between 1980 and 2022. Additionally, regional statistical figures for 15 natural and socioeconomic variables were obtained or estimated as predictors. A machine learning model, using the random forest algorithm and 2973 generated samples, was created to predict county-specific blood lead levels in China from 1980 to 2040. Geometric mean blood lead levels in children (i.e., age 14 and under) decreased significantly from 104.4 µg/L in 1993 to an anticipated 40.3 µg/L by 2040. The number exceeding 100 µg/L declined dramatically, yet South Central China remains a hotspot. Lead exposure is similar among different groups, but overall adults and adolescents (i.e., age over 14), females, and rural residents exhibit slightly lower exposure compared to that of children, males, and urban residents, respectively. Our predictions indicated that despite the general reduction, one-fourth of Chinese counties rebounded during 2015-2020. This slower decline might be due to emerging lead sources like smelting and coal combustion; however, the primary factor driving the decline should be the reduction of a persistent source, legacy gasoline-derived lead. Our approach innovatively maps lead exposure without comprehensive surveys.

Current situation of lead (Pb) exposure in raptors and waterfowl in Japan and difference in sensitivity to in vitro lead exposure among avian species.

Although lead (Pb) poisoning in wild birds has been considered a serious problem in Japan for over 30 years, there is little information about Pb exposure and its sources throughout Japan except for Hokkaido. Furthermore, to identify and effectively prioritize the conservation needs of highly vulnerable species, differences in sensitivity to Pb exposure among avian species need to be determined. Therefore, we investigated the current situation of Pb exposure in raptors (13 species, N = 82), waterfowl (eight species, N = 44) and crows (one species, N = 6) using concentration and isotope analysis. We employed blood or tissue samples collected in various Japanese facilities mainly in 2022 or 2023. We also carried out a comparative study of blood δ-ALAD sensitivity to in vitro Pb exposure using blood of nine avian species. Pb concentrations in the blood or tissues displayed increased levels (>0.1 µg/g blood) in two raptors (2.4%), ten waterfowl (23%) and one crow (17%). Among them, poisoning levels (>0.6 µg/g blood) were found in one black kite and one common teal. The sources of Pb isotope ratios in ten blood samples with high Pb levels were determined as deriving from shot pellets (N = 9) or rifle bullets (N = 1). In the δ-ALAD study, red-crowned crane showed the highest sensitivity among the nine tested avian species and was followed in order by five Accipitriformes species (including white-tailed and Steller's sea eagle), Blakiston's fish owl, Muscovy duck and chicken, suggesting a genetically driven variance in susceptibility. Further studies on contamination conditions and exposure sources are urgently needed to inform strict regulations on the usage of Pb ammunition. Furthermore, detailed examinations of δ-ALAD sensitivity, interspecific differences, and other factors involved in the variability in sensitivity to Pb are required to identify and prioritize highly sensitive species.

Effect of Environmental and Socioeconomic Factors on Increased Early Childhood Blood Lead Levels: A Case Study in Chicago.

This study analyzes the prevalence of elevated blood lead levels (BLLs) in children across Chicagoland zip codes from 2019 to 2021, linking them to socioeconomic, environmental, and racial factors. Wilcoxon tests and generalized additive model (GAM) regressions identified economic hardship, reflected in per capita income and unemployment rates, as a significant contributor to increased lead poisoning (LP) rates. Additionally, LP rates correlate with the average age of buildings, particularly post the 1978 lead paint ban, illustrating policy impacts on health outcomes. The study further explores the novel area of land surface temperature (LST) effects on LP, finding that higher nighttime LST, indicative of urban heat island effects, correlates with increased LP. This finding gains additional significance in the context of anthropogenic climate change. When these factors are combined with the ongoing expansion of urban territories, a significant risk exists of escalating LP rates on a global scale. Racial disparity analysis revealed that Black and Hispanic/Latino populations face higher LP rates, primarily due to unemployment and older housing. The study underscores the necessity for targeted public health strategies to address these disparities, emphasizing the need for interventions that cater to the unique challenges of these at-risk communities.

Lead exposure by E-waste disposal and recycling in Agbogbloshie, Ghana.

BACKGROUND: Agbogbloshie in Ghana is the world's biggest dumpsite for the informal recycling of electronic waste (e-waste). E-waste is dismantled by rudimentary methods without personal or environmental protection. Workers and occupants are exposed to lead. There are no data so far about the extent and the consequences. We therefore analyzed blood lead levels (BLL) and creatinine levels (CL). METHODS: Full blood samples and basic data (i.e. age, job, length of stay) were collected from dumpsite volunteers. BLL were measured by atomic absorption spectrometry; CL were assessed using the standard clinical laboratory procedures of Aachen Technical University. European BLL reference values were used as Ghana lacks its own. Statistical analysis was by non-parametric tests (Mann-Whitney U test), with p < 0.05. RESULTS: Participants of both sexes (n = 327; 12-68 years; median age 23 years) were assessed. Most workers were aged <30 years. The collective's BLL was in pathological range for 77.7%; 14% had a BLL >10.0 µg/dl with symptoms consistent with high lead exposure including severe (6.5%) and intermediate (39%) renal disorder. BLL above 15.0 µg/dl were found in 5.9% of all workers which is the German threshold for those working with lead. Elevated CL in a pathological range were found in 254 participants. This is problematic as 75% of the lead entering the body is excreted via urine. CONCLUSION: Most of our volunteers had pathological BLL and CL. Preventive strategies are necessary to reduce health risks, particularly for vulnerable populations (i.e. children, pregnant women).

Navigating the complexity of spinal cord injuries with retained foreign bodies and the diagnostic challenge of lead toxicity-a case reportaaa.

INTRODUCTION: Retained shrapnel from gunshots is a common occurrence; however, retained shrapnel within the spinal canal is exceedingly uncommon. Guidelines for removal and treatment of these cases are a difficult topic, as surgical removal is not necessarily without consequence, and retention can lead to possible further injury or a secondary disease process of plumbism, which can be difficult to diagnose in this population. CASE PRESENTATION: This case report provides a unique example of a young patient with retained shrapnel from a gunshot. This patient suffered an initial spinal cord injury due to a gunshot and secondarily presented with abdominal pain, fatigue, elevated blood lead levels, and was diagnosed with plumbism. This was addressed with operative removal of shrapnel and posterior instrumented spinal fusion, resulting in decreased lead levels and symptom resolution postoperatively. DISCUSSION: Lead toxicity risk in patients with retained shrapnel, particularly in the spine, warrants vigilant monitoring. While management guidelines lack consensus, symptomatic lead toxicity may necessitate intervention. Residual neurological deficits complicate evaluation, emphasizing individualized management decisions.

Biomonitoring of lead in blood of children living in a former mining area in Lower Saxony, Germany.

Environmental exposure to lead substantially decreased over the past decades. However, soil of former mining areas still contains high lead levels. We therefore performed a biomonitoring study among children living in two former mining communities in Lower Saxony, Germany. In these communities, soil contains lead levels of 1000 to 30,000 mg/kg. Overall, 75 children (6-10 years of age) attending the two primary schools of the study area took part in the study. Parents completed a short questionnaire on sociodemographics, and children provided capillary whole blood samples. We analysed lead using inductively coupled plasma tandem mass spectrometer. We compared the results to current German (20 µg/l for boys, 15 µg/l for girls) and US (35 µg/l) reference values. Potential associations between questionnaire information and lead results were tested using lead as continuous outcome and using lead dichotomized at the reference values. Finally, we analysed spatial patterns of elevated biomonitoring results. Of all children, 48% exceeded the German reference values for lead (5% expected) and 8% the US reference value (2.5% expected). Children 6-8 years of age were more likely to exceed German reference values (63%) than 9-10 year old children were (32%; pFisher = 0.01). No other questionnaire information was statistically significantly associated with biomonitoring results. Additionally, we did not find any indication of spatial clustering. In conclusion, we observed elevated blood lead levels in primary school children living in a former mining area. In the next step, exposure pathways need to be identified to implement effective public health measures.

Development of a novel fluorescent protein-based probe for efficient detection of Pb2+ in serum inspired by the metalloregulatory protein PbrR691.

BACKGROUND: The accurate and rapid detection of blood lead concentration is of paramount importance for assessing human lead exposure levels. Fluorescent protein-based probes, known for their high detection capabilities and low toxicity, are extensively used in analytical sciences. However, there is currently a shortage of such probes designed for ultrasensitive detection of Pb2+, and no reported probes exist for the quantitative detection of Pb2+ in blood samples. This study aims to fill this critical void by developing and evaluating a novel fluorescent protein-based probe that promises accurate and rapid lead quantification in blood. RESULTS: A simple and small-molecule fluorescent protein-based probe was successfully constructed herein using a peptide PbrBD designed for Pb2+ recognition coupled to a single fluorescent protein, sfGFP. The probe retains a three-coordinate configuration to identify Pb2+ and has a high affinity for it with a Kd' of 1.48 ± 0.05 × 10-17 M. It effectively transfers the conformational changes of the peptide to the chromophore upon Pb2+ binding, leading to fast fluorescence quenching and a sensitive response to Pb2+. The probe offers a broad dynamic response range of approximately 37-fold and a linear detection range from 0.25 nM to 3500 nM. More importantly, the probe can resist interference of metal ions in living organisms, enabling quantitative analysis of Pb2+ in the picomolar to millimolar range in serum samples with a recovery percentage of 96.64%-108.74 %. SIGNIFICANCE: This innovative probe, the first to employ a single fluorescent protein-based probe for ultrasensitive and precise analysis of Pb2+ in animal and human serum, heralds a significant advancement in environmental monitoring and public health surveillance. Furthermore, as a genetically encoded fluorescent probe, this probe also holds potential for the in vivo localization and concentration monitoring of Pb2+.

A comprehensive analysis of children's blood lead levels in Latin America and the Caribbean over the last eight years: Progress and recommendations.

In 2017 we published a review on blood lead levels (BLL) in children from Latin America and the Caribbean (LAC) for data available up to 14th of March 2014 and recommended the identification and control of "lead hot spots". In the present study, an evaluation of progress toward reducing BLL in the region was carried out. A systematic review of the latest literature on lead exposure in the LAC region held on the PubMed, Web of Science and LILACS databases (January 2014 to March 2022) was conducted using the PRISMA methodology. Only original papers published in peer-reviewed English, Spanish, or Portuguese journals were eligible. A total of 558 papers were retrieved, 77 of which met the selection criteria and 31 (40.25 %) were carried out in Mexico. The prevalence of children with BLL above 10 µg. dL-1 was 22.08 % in the previous review versus 6.78 % in the current study. In the present review, the prevalence of children with BLL above 5 µg. dL-1 was 29.62 %, and only one study reported a BLL prevalence rate between 3.3 and 5 µg. dL-1. The highest BLLs were associated with well-known sources or occupational exposures. The number of countries (n = 13) that published data on BLL in children was lower compared to the previous review (n = 16). Most studies were conducted in areas with known lead exposure sources, similar to the earlier review. The percentage of children at risk of lead poisoning in the region remains unknown because few studies have published data on environmental exposure levels and most samples were relatively small. The recommendation to identify and control sources of lead exposure was maintained, while further suggestions for establishing a systematic public health surveillance system for lead were proposed to help reduce the knowledge gap and inform public health policy-making in LAC.

Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Estimated Childhood Lead Exposure From Drinking Water in Chicago.

Importance: There is no level of lead in drinking water considered to be safe, yet lead service lines are still commonly used in water systems across the US. Objective: To identify the extent of lead-contaminated drinking water in Chicago, Illinois, and model its impact on children younger than 6 years. Design, Setting, and Participants: For this cross-sectional study, a retrospective assessment was performed of lead exposure based on household tests collected from January 2016 to September 2023. Tests were obtained from households in Chicago that registered for a free self-administered testing service for lead exposure. Machine learning and microsimulation were used to estimate citywide childhood lead exposure. Exposure: Lead-contaminated drinking water, measured in parts per billion. Main Outcomes and Measures: Number of children younger than 6 years exposed to lead-contaminated water. Results: A total of 38 385 household lead tests were collected. An estimated 68% (95% uncertainty interval, 66%-69%) of children younger than 6 years were exposed to lead-contaminated water, corresponding to 129 000 children (95% uncertainty interval, 128 000-131 000 children). Ten-percentage-point increases in block-level Black and Hispanic populations were associated with 3% (95% CI, 2%-3%) and 6% (95% CI, 5%-7%) decreases in odds of being tested for lead and 4% (95% CI, 3%-6%) and 11% (95% CI, 10%-13%) increases in having lead-contaminated drinking water, respectively. Conclusions and Relevance: These findings indicate that childhood lead exposure is widespread in Chicago, and racial inequities are present in both testing rates and exposure levels. Machine learning may assist in preliminary screening for lead exposure, and efforts to remediate the effects of environmental racism should involve improving outreach for and access to lead testing services.

Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells.

PURPOSE: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process. METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined. RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs. CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.

Are lead, cadmium and mercury risk factors for resistant hypertension?

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AIMS: To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. METHODS: Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. RESULTS: 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7-5.2) vs. rHT 3.6 (IQR 2.8-6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07-0.80) vs. rHT 0.30 (IQR 0.07-0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8-12.9) vs. rHT 7.3 (IQR 4.6-13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84-14.10, p=0.086) for Pb, OR = 1.80 (0.39-8.24, p=0.451), for Cd and OR = 2.31 (0.59-9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8-200.2), p=0.072). CONCLUSION: A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.