Blood Lead Levels of Children in Flint, Michigan: 2006-2016.

OBJECTIVE: We evaluated the increases in blood lead levels (BLLs) observed in young children in Flint, Michigan, during their exposure to corrosive Flint River water during the years 2014 and 2015 and compared their BLLs to those of Flint children measured during the years 2006-2013 and 2016. STUDY DESIGN: This was a retrospective study design using BLLs extracted from databases from 2006 to 2016. We analyzed a population sample of 15 817 BLLs from children aged ≤5 years with potential exposure to contaminated Flint River water. Percentages of BLLs ≥5.0 µg/dL and geometric mean (GM) BLLs were analyzed over time. RESULTS: A significant decline in the percentages of BLLs ≥5.0 µg/dL from 11.8% in 2006 to 3.2% in 2016 was observed (P < .001). GM ± SE BLLs decreased from 2.33 ± 0.04 µg/dL in 2006 to 1.15 ± 0.02 µg/dL in 2016 (P < .001). GM BLLs increased twice: from 1.75 ± 0.03 µg/dL to 1.87 ± 0.03 µg/dL (2010-2011) and from 1.19 ± 0.02 µg/dL to 1.30 ± 0.02 µg/dL (2014-2015). Overall, from 2006 to 2016, there was a 72.9% decrease in the percentage of children with BLLs ≥5.0 µg/dL and a 50.6% decrease in GM BLLs. CONCLUSION: These findings suggest that the 11 year trend of annual decreases in BLLs in children in Flint, Michigan, reversed to a degree consistent with random variation from 2010 to 2011, and again during the exposure to Flint River water in 2014-2015. Historically, public health efforts to reduce BLLs of young children in Flint have been effective over the 11-year period studied.

Blood Lead Concentrations of Children in the United States: A Comparison of States Using Two Very Large Databases.

OBJECTIVES: To determine whether there are substantial differences by state between 2 large datasets in the proportion of children with elevated blood lead levels (BLLs); to identify states in which the percentage of elevated BLLs is high in either or both datasets; and to compare the percentage of elevated BLLs in individual states with those of children living in Flint, Michigan, during the months when these children were exposed to lead-contaminated drinking water. STUDY DESIGN: Tables of BLLs for individual states from the Quest Diagnostics and the Centers for Disease Control and Prevention datasets for 2014-2015, containing more than 3 million BLLs of young children?

Lead Content of Sindoor, a Hindu Religious Powder and Cosmetic: New Jersey and India, 2014-2015.

OBJECTIVES: To assess the extent of lead content of sindoor, a powder used by Hindus for religious and cultural purposes, which has been linked to childhood lead poisoning when inadvertently ingested. METHODS: We purchased 95 samples of sindoor from 66 South Asian stores in New Jersey and 23 samples from India and analyzed samples with atomic absorption spectrophotometry methods for lead. RESULTS: Analysis determined that 79 (83.2%) sindoor samples purchased in the United States and 18 (78.3%) samples purchased in India contained 1.0 or more micrograms of lead per gram of powder. For US samples, geometric mean concentration was 5.4 micrograms per gram compared with 28.1 micrograms per gram for India samples. The maximum lead content detected in both US and India samples was more than 300 000 micrograms per gram. Of the examined US sindoor samples, 19% contained more than 20 micrograms per gram of lead (US Food and Drug Administration [FDA] limit); 43% of the India samples exceeded this limit. CONCLUSIONS: Results suggested continued need for lead monitoring in sindoor in the United States and in sindoor carried into the United States by travelers from India, despite FDA warnings.

Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading Enzyme and Nerve Growth Factor Expression in Mouse Pups.

Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life. This study was aimed to investigate the effects of lead exposure of pregnant mice on the expressions of insulin-degrading enzyme (IDE) and nerve growth factor (NGF) in the hippocampus of their offspring. Blood samples were collected from the tail vein, and after anesthetizing the pups, the brain was excised on postnatal day 21. Lead concentrations were determined by graphite furnace atomic absorption spectrophotometry, and the expressions of IDE and NGF were determined by immunohistochemistry and Western blotting. Results showed that the reduction in IDE and NGF expression in the hippocampus of pups might be associated with impairment of learning and memory and dementia induced by maternal lead exposure during pregnancy and lactation.

Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats.

We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca(2+) transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca(2+) absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca(2+) transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca(2+) transport rate as well as in expression of intestinal and renal Ca(2+) transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca(2+) transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca(2+) transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca(2+) and vitamin D deficiency.

Blood Lead Concentrations in Newark Children. Comment on Franklin, R.C.; Behmer Hansen, R.A.; Pierce, J.M.; Tsitouras, D.J.; Mazzola, C.A. Broken Promises to the People of Newark: A Historical Review of the Newark Uprising, the Newark Agreements, and Rutgers New Jersey Medical School's Commitments to Newark. Int. J. Environ. Res. Public Health 2021, 18, 2117.

The recently published article of RC Franklin et al [...].

Essential trace elements and progression and management of HIV infection.

This review was written to update the review that we published in Nutrition Research in 2007 by examining studies published in the last 11 years which describe the effects of trace mineral deficiencies and micronutrient supplementation on HIV infection and its progression. In addition, we included studies that explore the interactions between Highly Active Anti-Retroviral Therapy (HAART) and micronutrient nutrition, focusing on the essential trace minerals. This review summarizes the results described in relevant articles that were identified by literature searches conducted using the OVID Medline database. Four of the nine essential trace minerals, specifically chromium, iron, selenium, and zinc, can influence HIV progression and/or its treatment. Notably, copper-containing filters may prevent transmission of the HIV virus via breastfeeding. However, there is a lack of good evidence to date that fluoride, iodine, manganese, or molybdenum influence HIV infection. Recent studies reveal that HAART can alter serum trace mineral and vitamin concentrations, but the effects vary based on the medications used. Although they have contributed useful new data, the sample sizes for most of these studies were too small to draw definitive conclusions for introducing changes in the management of HIV infection. Larger studies are needed to better understand and define the roles of trace mineral and vitamin deficiencies and micronutrient supplementation in the management and treatment of HIV-infected patients.

Blood Lead Levels in Females of Childbearing Age in Flint, Michigan, and the Water Crisis.

OBJECTIVE: To compare blood lead levels in females of childbearing age, 12-50 years, living within and adjacent to Flint, Michigan, before, during, and after the Flint River water exposure and compare the levels to those that have been shown to cause fetal loss and preterm birth. METHODS: The switch in the community water source to the Flint River occurred on April 25, 2014, and was reverted to the original source on October 15, 2015. Using a retrospective cross-sectional study design using geocoded blood lead levels obtained from all females of childbearing age available from a single hospital database, we compared blood lead levels for the following 18-month time periods: April 25, 2012-October 15, 2013 (PRE), April 25, 2014-October 15, 2015 (DURING), and April 25, 2016-October 15, 2017 (POST). RESULTS: Results are reported as geometric mean (95% CI). Within Flint, PRE blood lead levels in females of childbearing age were 0.69 micrograms/dL (95% CI 0.63-0.75), DURING blood lead levels were 0.65 micrograms/dL (95% CI 0.60-0.71), and POST blood lead levels were 0.55 micrograms/dL (95% CI 0.54-0.56). DURING Flint River water exposure blood lead levels were not significantly different than the PRE Flint River water time period. POST Flint River water exposure blood lead levels were significantly lower than both PRE and DURING levels. Overall, lower blood lead levels were found outside the Flint boundary in all cohorts. CONCLUSION: Blood lead levels in Flint females of childbearing age did not increase during the Flint River water exposure and subsequent 18-month time period. Mean blood lead levels during the Flint River water exposure are not consistent with the markedly higher blood lead levels reported in the literature to be associated with fetal loss, low birth weight, or preterm birth.

Analysis of blood lead levels of young children in Flint, Michigan before and during the 18-month switch to Flint River water.

Background: The toxicity of lead, like any xenobiotic, is directly linked to the duration of exposure and toxin concentration in the body. The elevation in blood lead levels (BLLs) in young Flint, Michigan children noted in time-periods before, and during the 18-month exposure to Flint River water (FRW) from 25 April 2014 to 15 October 2015 is well-known internationally. The length of time BLLs were elevated is unknown, yet key in understanding the potential health impact of the event. The objective of this study was to evaluate whether BLLs in Flint children were increased during the entire 18-month FRW exposure compared to similar earlier time periods. Methods: We conducted a retrospective study analyzing BLLs from Flint children aged 5 years and under. The geometric mean (GM) BLLs and percentages of BLLs ≥5.0 µg/dL in Period I: 25 April 2006 to 15 October 2007 (earliest timeframe available for study) and Period II: 25 April 2012 to 15 October 2013 (timeframe immediately before the water switch), were compared to Period III, 25 April 2014 to 15 October 2015 (FRW exposure). Results: There were 5663 BLLs available for study. GM ± SE BLLs decreased from 2.19 ± 0.03 µg/dL in Period I to 1.47 ± 0.02 µg/dL in Period II [95% CI, 0.64, 0.79]; p<.001 and decreased further to 1.32 ± 0.02 µg/dL during the FRW Period III [95% CI, 0.79, 0.95]; p<.001. The percentage of BLLs ≥5.0 µg/dL decreased from Period I (10.6%) to Period II (3.3%) [95% CI, 5.7, 8.8]; p<.001 and from Period I to Period III (3.9%) [95% CI, 5.0, 8.2]; p=.002. The 0.6% increase from Period II to Period III was not statistically significant [95% CI, -1.9, 0.57]; p=.30. Conclusion: Analyses of GM and percentages ≥5.0 µg/dL of BLLs do not support the occurrence of a global increase in BLLs in young children of Flint during the entire 18-month period of FRW exposure.

Soil metal concentrations and vegetative assemblage structure in an urban brownfield.

Anthropogenic sources of toxic elements have had serious ecological and human health impacts. Analysis of the soil samples from a brownfield within Liberty State Park, Jersey City, NJ, USA, showed that arsenic, chromium, lead, zinc and vanadium exist at concentrations above those considered ambient for the area. Accumulation and translocation features were characterized for the dominant plant species of four vegetative assemblages. The trees Betula populifolia and Populus deltoides were found to be accumulating Zn in leaf tissue at extremely high levels. B. populifolia, P. deltoides and Rhus copallinum accumulated Cr primarily in the root tissue. A comparison of soil metal maps and vegetative assemblage maps indicates that areas of increasing total soil metal load were dominated by successional northern hardwoods while semi-emergent marshes consisting mostly of endemic species were restricted primarily to areas of low soil metal load.

Elevated blood lead concentrations and vitamin D deficiency in winter and summer in young urban children.

BACKGROUND: It is widely recognized that blood lead concentrations are higher in the summer than in winter. Although the effects of some environmental factors such as lead in dust on this phenomenon have been studied, relationships to sunlight-induced vitamin D synthesis have not been adequately investigated. Vitamin D status is influenced by the diet, sunlight exposure, age, skin pigmentation, and other factors, and may modify gastrointestinal lead absorption or release of lead stored in bones into the bloodstream. OBJECTIVE AND METHODS: We collected paired blood samples from 142 young, urban African-American and Hispanic children in the winter and summer to study the seasonal increase in blood lead and its relationships to vitamin D nutrition, age, and race. RESULTS: A winter/summer (W/S) increase in blood lead concentrations of 32.4% was found for children 1-3 years of age. There was a smaller W/S increase of 13.0% in children 4-8 years of age. None of the 51 Hispanic children had an elevated blood lead concentration (> or = 10 microg/dL) during the winter, and only one had an elevated summertime concentration. In contrast, elevated blood lead concentrations were frequent in the 91 African-American children, especially those 1-3 years of age. For the latter, the percentage with elevated blood lead levels increased from 12.2% in winter to 22.5% in summer. A 1.2% W/S increase in serum 25-hydroxy-vitamin D (serum 25-OH-D) concentrations was found for children 1-3 years of age. However, in children 4-8 years of age the W/S increase in serum 25-OH-D was much larger-33.6%. The percentages of children with low (< 16 microg/L) serum 25-OH-D concentrations were 12.0% in winter and 0.7% in summer and were consistently greater in African-American than in Hispanic children. The seasonal increases in blood lead and serum 25-OH-D in children 4-8 years of age were significantly associated. CONCLUSION: The higher summertime serum 25-OH-D concentrations for the 4- to 8-year-old children are likely caused by increased sunlight-induced vitamin D synthesis and may contribute to the seasonal increase in blood lead. Age and race are key factors that affect blood lead and vitamin D nutrition, as well as their interactions, in young urban children.

The thyroid and pregnancy: a novel risk factor for very preterm delivery.

The major cause of neonatal mortality and morbidity is preterm delivery in general (< 37 completed weeks), and especially very preterm delivery (< 32 completed weeks). The objective of this study is to determine if either thyroid hormonal dysfunction and/or the presence of thyroid autoantibodies in the mother are associated with an increased risk of preterm and/or very preterm delivery. Data were collected prospectively and analyzed as a nested-case control study. There were 953 delivered gravidas enrolled between 1996 and 2002. Samples were collected at entry to care and stored at -70 degrees C. Cases included all women with preterm delivery (n = 124). Controls (n = 124) were randomly selected from among the 829 women who delivered at term (> 37 completed weeks). All samples were assessed for thyroid stimulating hormone, thyroperoxidase antibody, and thyroglobulin antibody. Gravidas with high thyrotropin (TSH) levels had a greater than threefold increase in risk of very preterm delivery. In some analyses, gravidas who tested positive for thyroglobulin antibody at entry to prenatal care also had a better than twofold increased risk of very preterm delivery. There were no significant associations between TSH level or thyroglobulin antibody positivity and the risk of moderately preterm delivery.

Case of elevated blood lead in a South Asian family that has used Sindoor for food coloring.

After a routine blood testing, a local pediatrician discovered that a 13-month-old boy had an elevated blood lead level (BLL) of 57 microg/dL. Since the baby was mostly breast-fed, the pediatrician did a blood test on the mother, and the result showed a BLL of 85 microg/dL. As the mother denied any history of pica behavior, the pediatrician suspected a source of lead to which the entire family might have been exposed and tested the father's BLL. The results showed a BLL of 95 microg/dL, and the pediatrician informed the poison center. The subsequent epidemiological investigation revealed that the parents had used a product called Sindoor for food coloring. Laboratory analyses showed that the product contains more than 57.8% of acid-extractable lead by weight. Given the extremely high content of Pb in this product, Sindoor poses a serious risk of lead poisoning if it is used for food coloring.

Blood lead concentrations and pregnancy outcomes.

In this study, the authors related blood lead concentrations to Apgar scores, birth weight, gestational age, small-for-gestational age, and hypertension in pregnancy (HIP)/toxemia. Data and blood were collected 4 times during pregnancy from 705 women, aged 12-34 yr. Blood lead concentrations, measured by atomic absorption spectrophotometry, were related to reproductive outcomes, abstracted from medical records. Average blood lead concentrations were 1.2 microgram/dl (standard error = +/- 0.03). Maternal blood lead concentrations were related significantly to HIP/toxemia--before and after adjusting for age, calcium intake, and race/ethnicity (p < .03). Longitudinal regression analyses revealed that blood lead concentrations in women with HIP/toxemia changed by 0.02 microgram/dl for every 0.01 microgram/dl change in women without HIP/toxemia. Maternal blood lead concentration and its change were not significantly associated with other reproductive outcomes. Low levels of maternal blood lead concentrations were significantly associated with HIP/toxemia.

The effects of local vanadium treatment on angiogenesis and chondrogenesis during fracture healing.

This study quantified the effects of local intramedullary delivery of an organic vanadium salt, which may act as an insulin-mimetic on fracture healing. Using a BB Wistar rat femoral fracture model, local vanadyl acetylacetonate (VAC) was delivered to the fracture site and histomorphometry, mechanical testing, and immunohistochemistry were performed. Callus percent cartilage was 200% higher at day 7 (p < 0.05) and 88% higher at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Callus percent mineralized tissue was 37% higher at day 14 (p < 0.05) and 31% higher at day 21 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Maximum torque to failure was 104% and 154% higher at 4 weeks post-fracture (p < 0.05) for the healing femurs from the VAC-treated (1.5 and 3.0 mg/kg) animals. Animals treated with other VAC doses demonstrated increased mechanical parameters at 4 weeks (p < 0.05). Immunohistochemistry detected 62% more proliferating cells at days 7 (p < 0.05) and 94% more at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg VAC. Results showed 100% more vascular endothelial growth factor-C (VEGF-C) positive cells and 80% more blood vessels at day 7 (p < 0.05) within the callus subperiosteal region of VAC-treated animals (1.5 mg/kg) compared to controls. The results suggest that local VAC treatment affects chondrogenesis and angiogenesis within the first 7-10 days post-fracture, which leads to enhanced mineralized tissue formation and accelerated fracture repair as early as 3-4 weeks post-fracture.

Control of Alzheimer's amyloid beta toxicity by the high molecular weight immunophilin FKBP52 and copper homeostasis in Drosophila.

FK506 binding proteins (FKBPs), also called immunophilins, are prolyl-isomerases (PPIases) that participate in a wide variety of cellular functions including hormone signaling and protein folding. Recent studies indicate that proteins that contain PPIase activity can also alter the processing of Alzheimer's Amyloid Precursor Protein (APP). Originally identified in hematopoietic cells, FKBP52 is much more abundantly expressed in neurons, including the hippocampus, frontal cortex, and basal ganglia. Given the fact that the high molecular weight immunophilin FKBP52 is highly expressed in CNS regions susceptible to Alzheimer's, we investigated its role in Abeta toxicity. Towards this goal, we generated Abeta transgenic Drosophila that harbor gain of function or loss of function mutations of FKBP52. FKBP52 overexpression reduced the toxicity of Abeta and increased lifespan in Abeta flies, whereas loss of function of FKBP52 exacerbated these Abeta phenotypes. Interestingly, the Abeta pathology was enhanced by mutations in the copper transporters Atox1, which interacts with FKBP52, and Ctr1A and was suppressed in FKBP52 mutant flies raised on a copper chelator diet. Using mammalian cultures, we show that FKBP52 (-/-) cells have increased intracellular copper and higher levels of Abeta. This effect is reversed by reconstitution of FKBP52. Finally, we also found that FKBP52 formed stable complexes with APP through its FK506 interacting domain. Taken together, these studies identify a novel role for FKBP52 in modulating toxicity of Abeta peptides.

Soil metal concentrations and productivity of Betula populifolia (gray birch) as measured by field spectrometry and incremental annual growth in an abandoned urban Brownfield in New Jersey.

A forested brownfield within Liberty State Park, Jersey City, New Jersey, USA, has soils with arsenic, chromium, lead, zinc and vanadium at concentrations above those considered ambient for the area. Using both satellite imagery and field spectral measurements, this study examines plant productivity at the assemblage and individual specimen level. Longer term growth trends (basal area increase in tree cores) were also studied. Leaf chlorophyll content within the hardwood assemblage showed a threshold model for metal tolerance, decreasing significantly beyond a soil total metal load (TML) of 3.0. Biomass production (calculated with RG-Red/Green Ratio Index) in Betula populifolia (gray birch), the co-dominant tree species, had an inverse relationship with the Zn concentration in leaf tissue during the growing season. Growth of B. populifolia exhibited a significant relationship with TML. Assemblage level NDVI and individual tree NDVI also had significant decreases with increasing TML. Ecosystem function measured as plant production is impaired at a critical soil metal load.

Bone mineral density and content during weight cycling in female rats: effects of dietary amylase-resistant starch.

BACKGROUND: Although there is considerable evidence for a loss of bone mass with weight loss, the few human studies on the relationship between weight cycling and bone mass or density have differing results. Further, very few studies assessed the role of dietary composition on bone mass during weight cycling. The primary objective of this study was to determine if a diet high in amylase-resistant starch (RS2), which has been shown to increase absorption and balance of dietary minerals, can prevent or reduce loss of bone mass during weight cycling. METHODS: Female Sprague-Dawley (SD) rats (n = 84, age = 20 weeks) were randomly assigned to one of 6 treatment groups with 14 rats per group using a 2 x 3 experimental design with 2 diets and 3 weight cycling protocols. Rats were fed calcium-deficient diets without RS2 (controls) or diets high in RS2 (18% by weight) throughout the 21-week study. The weight cycling protocols were weight maintenance/gain with no weight cycling, 1 round of weight cycling, or 2 rounds of weight cycling. After the rats were euthanized bone mineral density (BMD) and bone mineral content (BMC) of femur were measured by dual energy X-ray absorptiometry, and concentrations of calcium, copper, iron, magnesium, manganese, and zinc in femur and lumbar vertebrae were determined by atomic absorption spectrophotometry. RESULTS: Rats undergoing weight cycling had lower femur BMC (p < 0.05) and marginally lower BMD (p = 0.09) than rats not undergoing weight cycling. In comparison to controls, rats fed RS2 had higher femur BMD (p < 0.01) and BMC (p < 0.05), as well as higher values for BMD and BMC measured at the distal end (p < 0.001 and p < 0.01) and femoral neck (p < 0.01 and p < 0.05). Consistent with these findings, RS2-fed rats also had higher femur calcium (p < 0.05) and magnesium (p < 0.0001) concentrations. They also had higher lumbar vertebrae calcium (p < 0.05) and magnesium (p < 0.05) concentrations. CONCLUSION: Weight cycling reduces bone mass. A diet high in RS2 can minimize loss of bone mass during weight cycling and may increase bone mass in the absence of weight cycling.