Three-dimensional object geometry of mitochondria-associated signal: 3-D analysis pipeline for two-photon image stacks of cerebrovascular endothelial mitochondria.

Increasing evidence indicates the role of mitochondrial and vascular dysfunction in aging and aging-associated pathologies; however, the exact mechanisms and chronological processes remain enigmatic. High-energy demand organs, such as the brain, depend on the health of their mitochondria and vasculature for the maintenance of normal functions, therefore representing vulnerable targets for aging. This methodology article describes an analysis pipeline for three-dimensional (3-D) mitochondria-associated signal geometry of two-photon image stacks of brain vasculature. The analysis methods allow the quantification of mitochondria-associated signals obtained in real time in their physiological environment. In addition, signal geometry results will allow the extrapolation of fission and fusion events under normal conditions, during aging, or in the presence of different pathological conditions, therefore contributing to our understanding of the role mitochondria play in a variety of aging-associated diseases with vascular etiology.NEW & NOTEWORTHY Analysis pipeline for 3-D mitochondria-associated signal geometry of two-photon image stacks of brain vasculature.

Lead in Air, Soil, and Blood: Pb Poisoning in a Changing World.

(1) Background: Leaded petrol became a worldwide vehicle fuel during the 20th century. While leaded petrol was totally banned on 30 August 2021, its lead (Pb) dust legacy remains in the environment as soil Pb. The health impacts of Pb are well known and risks occur when exposures are above zero. The inextricable links between air Pb, soil Pb, and blood Pb are not widely A. Exposure risks continue even after banning leaded petrol and must be explored. (2) Methods: This article evaluates selected examples of temporal measurements of atmospheric Pb and human Pb exposure and the effect of soil Pb on blood Pb. Several search engines were used to find articles on temporal changes in air Pb and human Pb exposures. New Orleans studies provided empirical data on the association between soil Pb and blood Pb. (3) Results: Vehicle Pb emission trends are closely associated with air Pb and blood Pb. Air Pb deposited in soil becomes a reservoir of Pb dust that is known to be remobilized into the atmosphere. (4) Conclusions: The dust from leaded petrol continues to pose major exposure risks to humans. Exogenous sources of Pb in soil and its remobilization into air along with endogenous bone Pb establish the baseline exposure of children and adults. Reducing human exposure to Pb requires novel policies to decrease exogenous contact from the reservoir of Pb in soil and curtailing remobilization of soil Pb into the atmosphere. Mitigating exposure to soil Pb must therefore play a central role in advancing primary prevention.

Exploring the Effect of Mechanical Anisotropy of Protein Structures in the Unfoldase Mechanism of AAA+ Molecular Machines.

Essential cellular processes of microtubule disassembly and protein degradation, which span lengths from tens of µm to nm, are mediated by specialized molecular machines with similar hexameric structure and function. Our molecular simulations at atomistic and coarse-grained scales show that both the microtubule-severing protein spastin and the caseinolytic protease ClpY, accomplish spectacular unfolding of their diverse substrates, a microtubule lattice and dihydrofolate reductase (DHFR), by taking advantage of mechanical anisotropy in these proteins. Unfolding of wild-type DHFR requires disruption of mechanically strong ß-sheet interfaces near each terminal, which yields branched pathways associated with unzipping along soft directions and shearing along strong directions. By contrast, unfolding of circular permutant DHFR variants involves single pathways due to softer mechanical interfaces near terminals, but translocation hindrance can arise from mechanical resistance of partially unfolded intermediates stabilized by ß-sheets. For spastin, optimal severing action initiated by pulling on a tubulin subunit is achieved through specific orientation of the machine versus the substrate (microtubule lattice). Moreover, changes in the strength of the interactions between spastin and a microtubule filament, which can be driven by the tubulin code, lead to drastically different outcomes for the integrity of the hexameric structure of the machine.

Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival.

Hypertrophic/dilated cardiomyopathy, often a prequel to heart failure, is accompanied by maladaptive transcriptional changes that contribute to arrythmias and contractile misfunction. Transgenic mice constitutively expressing high levels of calcineurin are known to develop extreme heart hypertrophy, which progresses to dilated cardiomyopathy, and to die several weeks after birth. Here, we characterized aberrant transcriptional and epigenetic pathways in this mouse model and established a pharmacological approach to treat established cardiomyopathy. We found that H3K4me3 (trimethyl histone 3 lysine 4) and H3K9me3 (trimethyl histone 3 lysine 9) Jumonji histone demethylases are markedly increased at the protein level and show enhanced enzymatic activity in diseased hearts. These epigenetic regulators continued to increase with time, further affecting cardiac gene expression. Our findings parallel the lower H3K4me3 and H3K9me3 levels seen in human patients. Inhibition of Jumonji demethylase activities in vivo results in lower histone demethylase enzymatic function in the heart and higher histone methylation levels and leads to partial reduction of heart size, reversal of maladaptive transcriptional programs, improved heart function, and prolonged survival. At the molecular level, target genes of transcription factor myocyte enhancer factor 2 are specifically regulated in response to pharmacological or genetic inhibition of Jumonji demethylases. Similar transcriptional reversal of disease-associated genes is seen in a second disease model based on cardiac mechanical overload. Our findings validate pharmacological inhibitors of Jumonji demethylases as potential therapeutics for the treatment of cardiomyopathies across disease models and provide evidence of the reversal of maladaptive transcriptional reprogramming leading to partial restoration of cardiac function. In addition, this study defines pathways of therapeutic resistance upregulated with disease progression.

The development of uncertainty monitoring during kindergarten: Change and longitudinal relations with executive function and vocabulary in children from low-income backgrounds.

Children's ability to monitor subjective feelings of uncertainty (i.e., engage in uncertainty monitoring) is a central metacognitive skill. In the current study, we examined the development of uncertainty monitoring as well as its relations with vocabulary and executive function development in children (N = 137, 52% female) from predominately White and Latinx/Hispanic backgrounds when they were 4-6 years old and enrolled in a Head Start preschool and kindergarten between 2018 and 2019. We found that children's uncertainty monitoring improved during the kindergarten year. Children's executive function and vocabulary in preschool and vocabulary growth from preschool to kindergarten predicted uncertainty monitoring at the end of kindergarten, which sheds new light on potential mechanisms supporting children's metacognitive development.

Agreement ℜ of Four Analytical Methods Applied to Pb in Soils from the Small City of St. John's, Newfoundland, Canada.

In the small city of St. John's, NL (2020 population ~114,000), 100% of the soils of the pre-1926 properties exceeded the Canadian soil Pb standard, 140 mg/kg. The Pb was traced to high-Pb coal ash used for heating and disposed on the soils outside. Analytical instruments became available in the late 1960s and 1970s and were first used for blood Pb and clinical studies and repurposed for measuring environmental Pb. The environmental research part of this study compared four common soil Pb analysis methods on the same set (N = 96) of St. John's soil samples. The methods: The US EPA method 3050B, portable X-ray fluorescence spectrometry (pXRF), The Chaney-Mielke leachate extraction (1 M nitric acid), and the relative bioaccessibility leaching procedure (US EPA method 1340). Correlation is not the same as agreement ℜ. There is strong agreement (Berry-Mielke's Universal ℜ) among the four soil Pb analytical methods. Accordingly, precaution is normally advisable to protect children from the high-Pb garden soils and play areas. A public health reality check by Health Canada surveillance of St. John's children (N = 257) noted remarkably low blood Pb. The low blood Pb of St. John's' children is contrary to the soil Pb results. Known urban processes causing the rise of environmental Pb and children's Pb exposure includes particle size, aerosol emission by traffic congestion, and quantities of leaded petrol during the 20th century. Smaller cities had minor traffic congestion and limited combustion particles from leaded petrol. From the perspective of the 20th century era of urban Pb pollution, St. John's, NL, children have blood Pb characteristics of a small city.

Perceptual Access Reasoning (PAR) in Developing a Representational Theory of Mind.

An important part of children's social and cognitive development is their understanding that people are psychological beings with internal, mental states including desire, intention, perception, and belief. A full understanding of people as psychological beings requires a representational theory of mind (ToM), which is an understanding that mental states can faithfully represent reality, or misrepresent reality. For the last 35 years, researchers have relied on false-belief tasks as the gold standard to test children's understanding that beliefs can misrepresent reality. In false-belief tasks, children are asked to reason about the behavior of agents who have false beliefs about situations. Although a large body of evidence indicates that most children pass false-belief tasks by the end of the preschool years, the evidence we present in this monograph suggests that most children do not understand false beliefs or, surprisingly, even true beliefs until middle childhood. We argue that young children pass false-belief tasks without understanding false beliefs by using perceptual access reasoning (PAR). With PAR, children understand that seeing leads to knowing in the moment, but not that knowing also arises from thinking or persists as memory and belief after the situation changes. By the same token, PAR leads children to fail true-belief tasks. PAR theory can account for performance on other traditional tests of representational ToM and related tasks, and can account for the factors that have been found to correlate with or affect both true- and false-belief performance. The theory provides a new laboratory measure which we label the belief understanding scale (BUS). This scale can distinguish between a child who is operating with PAR versus a child who is understanding beliefs. This scale provides a method needed to allow the study of the development of representational ToM. In this monograph, we report the outcome of the tests that we have conducted of predictions generated by PAR theory. The findings demonstrated signature PAR limitations in reasoning about the mind during the ages when children are hypothesized to be using PAR. In Chapter II, secondary analyses of the published true-belief literature revealed that children failed several types of true-belief tasks. Chapters III through IX describe new empirical data collected across multiple studies between 2003 and 2014 from 580 children aged 4-7 years, as well as from a small sample of 14 adults. Participants were recruited from the Phoenix, Arizona metropolitan area. All participants were native English-speakers. Children were recruited from university-sponsored and community preschools and daycare centers, and from hospital maternity wards. Adults were university students who participated to partially fulfill course requirements for research participation. Sociometric data were collected only in Chapter IX, and are fully reported there. In Chapter III, minor alterations in task procedures produced wide variations in children's performance in 3-option false-belief tasks. In Chapter IV, we report findings which show that the developmental lag between children's understanding ignorance and understanding false belief is longer than the lag reported in previous studies. In Chapter V, children did not distinguish between agents who have false beliefs versus agents who have no beliefs. In Chapter VI, findings showed that children found it no easier to reason about true beliefs than to reason about false beliefs. In Chapter VII, when children were asked to justify their correct answers in false-belief tasks, they did not reference agents' false beliefs. Similarly, in Chapter VIII, when children were asked to explain agents' actions in false-belief tasks, they did not reference agents' false beliefs. In Chapter IX, children who were identified as using PAR differed from children who understood beliefs along three dimensions-in levels of social development, inhibitory control, and kindergarten adjustment. Although the findings need replication and additional studies of alternative interpretations, the collection of results reported in this monograph challenges the prevailing view that representational ToM is in place by the end of the preschool years. Furthermore, the pattern of findings is consistent with the proposal that PAR is the developmental precursor of representational ToM. The current findings also raise questions about claims that infants and toddlers demonstrate ToM-related abilities, and that representational ToM is innate.

The Head-Toes-Knees-Shoulders Revised: Links to Academic Outcomes and Measures of EF in Young Children.

The measurement of self-regulation in young children has been a topic of great interest as researchers and practitioners work to help ensure that children have the skills they need to succeed as they start school. The present study examined how a revised version of a commonly used measure of behavioral self-regulation, the Head-Toes-Knees-Shoulders task (HTKS) called the HTKS-R, and measures of executive function (EF) was related to academic outcomes between preschool and kindergarten (ages 4-6years) in a diverse sample of children from families with low income participating in Head Start in the United States. Participants included 318 children (53% female; 76% White; and 20% Latino/Hispanic) from 64 classrooms in 18 Head Start preschools who were followed over four time points between the fall of preschool and the spring of kindergarten. Results indicated that children with higher HTKS-R scores had significantly higher math and literacy scores at all-time points between preschool and kindergarten. The HTKS-R was also a more consistent predictor of math and literacy than individual EF measures assessing inhibitory control, working memory, and task shifting. Parallel process growth models indicated that children who had high initial scores on the HTKS-R also had relatively higher initial scores on math and literacy. In addition, growth in children's scores on the HTKS-R across the preschool and kindergarten years was related to growth in both children's math and literacy scores over the same period independent of their starting points on either measure. For the HTKS-R and math, children's initial scores were negatively associated with growth over the preschool and kindergarten years indicating that lower skilled children at the start of preschool started to catch up to their more skilled peers by the end of kindergarten.

Breastfeeding, Early Self-Regulation, and Academic Achievement in Kindergarten Among Disadvantaged Children.

OBJECTIVES: The importance of breastfeeding exposure and children's development of self-regulation, independently, are well established. Each of these domains also has been linked to better cognitive development and academic achievement in children. However, little is known about how breastfeeding affects development of early self-regulation skills or whether self-regulation mediates the relationship between breastfeeding and academic achievement, particularly for disadvantaged children. This study examined breastfeeding exposure, self-regulation, and academic achievement in kindergarten among a population of children who previously attended Head Start. METHODS: Children were recruited from Head Start classrooms in the Pacific Northwest. Breastfeeding exposure was assessed via parent report. Children's self-regulation (Day Night Stroop, Dimensional Change Card Sort, Head-Knees-Toes-Shoulders-Revised) and academic achievement [Letter-Word Identification and Applied Problems subtests of Woodcock Johnson Tests of Achievement (English) or the Batería III Woodcock-Muñoz (Spanish)] were directly assessed in fall and spring of kindergarten. Regressions were performed using Stata v14.1 and included breastfeeding exposure as the primary independent variable, controlling for child age, sex, and language spoken. RESULTS: Of the 246 children, 56% were reported as White, 34% Latino/a, 4% African American, and 6% other; 83% were ever exposed to breastfeeding. Breastfeeding exposure was predictive of both fall kindergarten academic achievement (emergent math/literacy scores) and self-regulation (p < 0.05) and related to higher math performance in the spring of kindergarten, which was associated with stronger self-regulation in the fall (p = 0.04). CONCLUSIONS: These findings extend our understanding of the positive effects of breastfeeding exposure on children's development and support breastfeeding promotion, particularly for children at risk of academic difficulty.

Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability.

The trillions of microbes that make up the gut microbiome are an important contributor to health and disease. With respect to xenobiotics, particularly orally administered compounds, the gut microbiome interacts directly with drugs to break them down into metabolic products. In addition, microbial products such as bile acids interact with nuclear receptors on host drug-metabolizing enzyme machinery, thus indirectly influencing drug disposition and pharmacokinetics. Gut microbes also influence drugs that undergo enterohepatic recycling by reversing host enzyme metabolic processes and increasing exposure to toxic metabolites as exemplified by the chemotherapy agent irinotecan and non-steroidal anti-inflammatory drugs. Recent data with immune checkpoint inhibitors demonstrate the impact of the gut microbiome on drug pharmacodynamics. We summarize the clinical importance of gut microbe interaction with digoxin, irinotecan, immune checkpoint inhibitors, levodopa, and non-steroidal anti-inflammatory drugs. Understanding the complex interactions of the gut microbiome with xenobiotics is challenging; and highly sensitive methods such as untargeted metabolomics with molecular networking along with other in silico methods and animal and human in vivo studies will uncover mechanisms and pathways. Incorporating the contribution of the gut microbiome to drug disposition, pharmacokinetics, and pharmacodynamics is vital in this era of precision medicine.

Soil Lead (Pb) in New Orleans: A Spatiotemporal and Racial Analysis.

Spatialized racial injustices drive morbidity and mortality inequalities. While many factors contribute to environmental injustices, Pb is particularly insidious, and is associated with cardio-vascular, kidney, and immune dysfunctions and is a leading cause of premature death worldwide. Here, we present a revised analysis from the New Orleans dataset of soil lead (SPb) and children's blood Pb (BPb), which was systematically assembled for 2000-2005 and 2011-2016. We show the spatial-temporal inequities in SPb, children's BPb, racial composition, and household income in New Orleans. Comparing medians for the inner city with outlying areas, soil Pb is 7.5 or 9.3 times greater, children's blood Pb is ~2 times higher, and household income is lower. Between 2000-2005 and 2011-2016, a BPb decline occurred. Long-standing environmental and socioeconomic Pb exposure injustices have positioned Black populations at extreme risk of adverse health consequences. Given the overlapping health outcomes of Pb exposure with co-morbidities for conditions such as COVID-19, we suggest that further investigation be conducted on Pb exposure and pandemic-related mortality rates, particularly among Black populations. Mapping and remediating invisible environmental Pb provides a path forward for preventing future populations from developing a myriad of Pb-related health issues.

Children's Self-Regulation in Norway and the United States: The Role of Mother's Education and Child Gender Across Cultural Contexts.

Self-regulation develops rapidly during the years before formal schooling, and it helps lay the foundation for children's later social, academic, and educational outcomes. However, children's self-regulation may be influenced by cultural contexts, sociodemographic factors, and characteristics of the child. The present study investigates whether children's levels of self-regulation, as measured by the Head-Toes-Knees-Shoulders (HTKS) task, are the same in samples from Norway (M age = 5.79; N = 243, 49.4% girls) and the United States (U.S.) (M age = 5.65; N = 264, 50.8% girls) and whether the role of mother's education level and child gender on children's self-regulation differ across the two samples. Results showed that Norwegian and U.S. children had similar levels of self-regulation. Mother's education level significantly predicted children's self-regulation in the U.S. sample but not in the Norwegian sample, and this difference across samples was significant. Girls had a significantly higher level of self-regulation than boys in the Norwegian sample, but there were no gender differences in the U.S. sample. However, the effect of child gender on self-regulation did not differ significantly across the two samples. Results highlight the importance of cross-cultural studies of self-regulation.

Spatial-temporal association of soil Pb and children's blood Pb in the Detroit Tri-County Area of Michigan (USA).

Lead is a well-known toxicant associated with numerous chronic diseases. Curtailing industrial emissions, leaded paint, lead in food, and banning highway use of leaded gasoline effectively decreased children's exposure. In New Orleans, irrespective of Hurricane Katrina flooding, lead declined concurrently in topsoil and children's blood. We postulate that topsoil lead and blood lead decreases are associated and common in U.S. cities. This study tests that concept. A small 2002 soil lead survey of 8 Detroit Tri-County Area census tracts was repeated in October 2019. Between 2002 and 2019, Detroit median soil lead decreased from 183 to 92 mg/kg (or 5.4 mg/kg/yr.) and declined in Pontiac from 93 to 68 mg/kg (or 1.4 mg/kg/yr.). Median soil lead remained ~10 mg/kg in outlying communities. Median soil lead (in mg/kg) in communities at < 21 km compared to ≥ 21 km from central Detroit, respectively, decreased from 183 to 33 (P-value 10-12) in 2002 and from 92 to 35 (P-value 10-07) in 2019. Children's lead exposures were highest in Detroit (population 0.7 million in 2010) and lower by more than half in Pontiac (population 60 thousand in 2010). Between 2002 and 2018, children with blood lead ≥4.5 µg/dL in Detroit declined from 44% to 5%, and in Pontiac from 17% to 2%. The most vulnerable children live in the most lead contaminated communities. To meet the goal of primary prevention for children, along with other efforts, this study supports landscaping with low lead soil to reduce exposure in lead contaminated communities.

Alterations of peripheral gene expression in response to lipopolysaccharide-induced synovitis as a model for inflammation in horses.

While the use of lipopolysaccharide (LPS) to induce inflammation has been well described in the horse, the object of this study was to evaluate the effect of repeated intra-articular LPS injections and determine whether this method may be of use to assess changes in gene expression related to inflammation. Six mixed breed horses were utilized for this study, with three horses aged 10-17 years (older group) and three horses aged 3 years (younger group). One milliliter of phosphate-buffered saline containing 3 µg of LPS from Escherichia coli O111:B4 was aseptically injected into either the radiocarpal or front fetlock joint a total of four times, with at least two weeks between each injection and a different joint injected each time. Serum for protein concentration quantification and whole blood for expression analysis of 20 different genes were collected before each injection, as well as at multiple times post-injection. Statistical analysis was performed using analysis of variance (one-way and two-way) (P < 0.05). All horses experienced minimal or non-weight bearing lameness at 4-6 hours post-LPS injection, which generally improved by 24 h and resolved by 48 h. Multiple genes exhibited significantly differential expression when compared to both the pre-injection and sham injection time points, including CD14, TLR4, MMP1, MMP9, IL-1ß, IL1RN, IL-10, ALOX5AP, IL-8, TNFα, CCL8, IGF1, and PTGS2. Additionally, multiple genes exhibited increased expression in horses where the radiocarpal joint was injected when compared to the fetlock joint, as well as in younger horses compared to older horses. Serum concentrations of serum amyloid A (SAA) were negative prior to injection while all horses demonstrated an increase by 9 h post-injection, which often remained until at least 144 h. Attempts to measure in vivo serum cytokine levels using a multiplex assay were not successful and believed to be due to the lower limits of detection for the assays. The measurement of mRNA expression of pro- and anti-inflammatory genes provide sensitive and rapid information regarding the inflammatory response to an acute, localized stimulus, although care must be taken when selecting target joints or age groups of horses as the transcriptional response may vary based on these choices.

Disruption of the Plasmodium falciparum Life Cycle through Transcriptional Reprogramming by Inhibitors of Jumonji Demethylases.

Little is known about the role of the three Jumonji C (JmjC) enzymes in Plasmodium falciparum (Pf). Here, we show that JIB-04 and other established inhibitors of mammalian JmjC histone demethylases kill asexual blood stage parasites and are even more potent at blocking gametocyte development and gamete formation. In late stage parasites, JIB-04 increased levels of trimethylated lysine residues on histones, suggesting the inhibition of P. falciparum Jumonji demethylase activity. These epigenetic defects coincide with deregulation of invasion, cell motor, and sexual development gene programs, including gene targets coregulated by the PfAP2-I transcription factor and chromatin-binding factor, PfBDP1. Mechanistically, we demonstrate that PfJmj3 converts 2-oxoglutarate to succinate in an iron-dependent manner consistent with mammalian Jumonji enzymes, and this catalytic activity is inhibited by JIB-04 and other Jumonji inhibitors. Our pharmacological studies of Jumonji activity in the malaria parasite provide evidence that inhibition of these enzymatic activities is detrimental to the parasite.

Red Light, Purple Light! Results of an Intervention to Promote School Readiness for Children From Low-Income Backgrounds.

Considerable research has examined interventions that facilitate school readiness skills in young children. One intervention, Red Light, Purple Light Circle Time Games (RLPL; Tominey and McClelland, 2011; Schmitt et al., 2015), includes music and movement games that aim to foster self-regulation skills. The present study (N = 157) focused on children from families with low-income and compared the RLPL intervention (SR) to a revised version of RLPL that included literacy and math content (SR+) and a Business-As-Usual (BAU) control group. In both versions of the intervention, teachers were trained to administer the self-regulation intervention in preschool classrooms with coaching support. Although not statistically significant, children receiving either version of the intervention gained more in self-regulation on the Head-Toes-Knees-Shoulders (HTKS) over the preschool year compared to the BAU group (ß = 0.09, p = 0.082, Cohen's d = 0.31). Effect sizes were similar to previous studies (Schmitt et al., 2015; Duncan et al., 2018) and translated to a 21% difference in self-regulation over and above the BAU group at post-test. Furthermore, children participating in either version of the intervention gained significantly more in math across the school year compared to children in the BAU group (ß = 0.14; p = 0.003, Cohen's d = 0.38), which translated to a 24% difference in math over and above the BAU group at post-test. Results were somewhat stronger for the SR+ version, although effect sizes across intervention conditions were comparable. There were no statistically significant differences across groups for literacy skills. Results extend previous research and suggest that the RLPL intervention, which includes an explicit focus on self-regulation through music and movement games, may improve children's self-regulation and math scores over the preschool year.

The concurrent decline of soil lead and children's blood lead in New Orleans.

Lead (Pb) is extremely toxic and a major cause of chronic diseases worldwide. Pb is associated with health disparities, particularly within low-income populations. In biological systems, Pb mimics calcium and, among other effects, interrupts cell signaling. Furthermore, Pb exposure results in epigenetic changes that affect multigenerational gene expression. Exposure to Pb has decreased through primary prevention, including removal of Pb solder from canned food, regulating lead-based paint, and especially eliminating Pb additives in gasoline. While researchers observe a continuous decline in children's blood lead (BPb), reservoirs of exposure persist in topsoil, which stores the legacy dust from leaded gasoline and other sources. Our surveys of metropolitan New Orleans reveal that median topsoil Pb in communities (n = 274) decreased 44% from 99 mg/kg to 54 mg/kg (P value of 2.09 × 10-08), with a median depletion rate of ∼2.4 mg⋅kg⋅y-1 over 15 y. From 2000 through 2005 to 2011 through 2016, children's BPb declined from 3.6 µg/dL to 1.2 µg/dL or 64% (P value of 2.02 × 10-85), a decrease of ∼0.2 µg⋅dL⋅y-1 during a median of 12 y. Here, we explore the decline of children's BPb by examining a metabolism of cities framework of inputs, transformations, storages, and outputs. Our findings indicate that decreasing Pb in topsoil is an important factor in the continuous decline of children's BPb. Similar reductions are expected in other major US cities. The most contaminated urban communities, usually inhabited by vulnerable populations, require further reductions of topsoil Pb to fulfill primary prevention for the nation's children.

Curtailing Lead Aerosols: Effects of Primary Prevention on Declining Soil Lead and Children's Blood Lead in Metropolitan New Orleans.

After decades of accumulation of lead aerosols in cities from additives in gasoline, in 1975 catalytic converters (which are ruined by lead) became mandatory on all new cars. By 1 January 1986 the rapid phase-down banned most lead additives. The study objective is to review temporal changes of environmental lead and children's blood lead in communities of metropolitan New Orleans. In 2001, a soil lead survey of 287 census tracts of metropolitan New Orleans was completed. In August-September 2005 Hurricanes Katrina and Rita storm surges flooded parts of the city with sediment-loaded water. In April-June 2006, 46/287 (16%) of the original census tracts were selected for resurvey. A third survey of 44/46 (15%) census tracts was completed in 2017. The census tract median soil lead and children's median blood lead decreased across surveys in both flooded and unflooded areas. By curtailing a major urban source of lead aerosols, children's lead exposure diminished, lead loading of soil decreased, and topsoil lead declined. Curtailing lead aerosols is essential for primary prevention. For the sake of children's and ultimately societal health and welfare, the long-term habitability of cities requires terminating all remaining lead aerosols and cleanup of legacy-lead that persists in older inner-city communities.

Sub-lethal exposure to lead is associated with heightened aggression in an urban songbird.

Many urban areas have elevated soil lead concentrations due to prior large-scale use of lead in products such as paint and automobile gasoline. This presents a potential problem for the growing numbers of wildlife living in urbanized areas as lead exposure is known to affect multiple physiological systems, including the nervous system, in vertebrate species. In humans and laboratory animals, low-level lead exposure is associated with neurological impairment, but less is known about how lead may affect the behavior of urban wildlife. We focused on the Northern Mockingbird Mimus polyglottos, a common, omnivorous North American songbird, to gain insights into how lead may affect the physiology and behavior of urban wildlife. We predicted that birds living in neighborhoods with high soil lead concentrations would (a) exhibit elevated lead concentrations in their blood and feathers, (b) exhibit lower body condition, (c) exhibit less diverse and consistent vocal repertoires, and (d) behave more aggressively during simulated conspecific territorial intrusions compared to birds living in neighborhoods with lower soil lead concentrations. Controlling for other habitat differences, we found that birds from areas of high soil lead had elevated lead concentrations in blood and feathers, but found no differences in body condition or vocal repertoires. However, birds from high lead areas responded more aggressively during simulated intrusions. These findings indicate that sub-lethal lead exposure may be common among wildlife living in urban areas, and that this exposure is associated with increased aggression. Better understanding of the extent of the relationship between lead exposure and aggression and the consequences this could have for survival and reproduction of wild animals are clear priorities for future work in this and other urban ecosystems.

Introspection Plays an Early Role in Children's Explicit Theory of Mind Development.

This study assessed children's (N = 236) ability to introspect the mental states of seeing and knowing relative to their ability to attribute each state to others. Children could introspect seeing 10 months before they could introspect knowing. Two- and 3-year-olds correctly reported their own seeing states, whereas 3- and 4-year-olds correctly reported their own knowing states. For each mental state, there was a 7-month difference before children could correctly attribute that state to another. These findings indicate that knowing is more difficult to introspect than seeing and that the ability to introspect each mental state emerges prior to the ability to correctly attribute them to others. Theoretical implications for self-other differences in theory-of-mind development are considered.