Air Pollution-Related Neurotoxicity Across the Life Span.

Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress-based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.

Cumulative Risk Evaluation of Phthalates Under TSCA.

The U.S. Environmental Protection Agency (EPA) is currently conducting separate Toxic Substances Control Act (TSCA) risk evaluations for seven phthalates: dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), diisobutyl phthalate (DIBP), dicyclohexyl phthalate (DCHP), di-isodecyl phthalate (DIDP), and diisononyl phthalate (DINP). Phthalates are highly abundant plastic additives used primarily to soften materials and make them flexible, and biomonitoring shows widespread human exposure to a mixture of phthalates. Evidence supports biological additivity of phthalate mixture exposures, including the enhancement of toxicity affecting common biological targets. Risk estimates based on individual phthalate exposure may not be protective of public health. Thus, a cumulative risk approach is warranted. While EPA initially did not signal that it would incorporate cumulative risk assessment (CRA) as part of its current risk evaluation for the seven phthalates, the agency recently announced that it is reconsidering if CRA for phthalates would be appropriate. Based on our review of existing chemical mixtures risk assessment guidance, current TSCA scoping documents for the seven phthalates, and pertinent peer-reviewed literature, we delineate a CRA approach that EPA can easily implement for phthalates. The strategy for using CRA to inform TSCA risk evaluation for existing chemicals is based upon integrative physiology and a common adverse health outcome algorithm for identifying and grouping relevant nonchemical and chemical stressors. We recommend adjustments for how hazard indices (HIs) or margins of exposure (MOEs) based on CRA are interpreted for determining "unreasonable risk" under TSCA.

Making the invisible visible: Using a qualitative system dynamics model to map disparities in cumulative environmental stressors and children's neurodevelopment.

BACKGROUND: The combined effects of multiple environmental toxicants and social stressor exposures are widely recognized as important public health problems, likely contributing to health inequities. However, US policy makers at state and federal levels typically focus on one stressor exposure at a time and have failed to develop comprehensive strategies to reduce multiple co-occurring exposures, mitigate cumulative risks and prevent harm. This research aimed to move from considering disparate environmental stressors in isolation to mapping the links between environmental, economic, social and health outcomes as a dynamic complex system using children's exposure to neurodevelopmental toxicants as an illustrative example. Such a model can be used to support a broad range of child developmental and environmental health policy stakeholders in improving their understanding of cumulative effects of multiple chemical, physical, biological and social environmental stressors as a complex system through a collaborative learning process. METHODS: We used system dynamics (SD) group model building to develop a qualitative causal theory linking multiple interacting streams of social stressors and environmental neurotoxicants impacting children's neurodevelopment. A 2 1/2-day interactive system dynamics workshop involving experts across multiple disciplines was convened to develop the model followed by qualitative survey on system insights. RESULTS: The SD causal map covered seven interconnected themes: environmental exposures, social environment, health status, education, employment, housing and advocacy. Potential high leverage intervention points for reducing disparities in children's cumulative neurotoxicant exposures and effects were identified. Workshop participants developed deeper level of understanding about the complexity of cumulative environmental health risks, increased their agreement about underlying causes, and enhanced their capabilities for integrating diverse forms of knowledge about the complex multi-level problem of cumulative chemical and non-chemical exposures. CONCLUSION: Group model building using SD can lead to important insights to into the sociological, policy, and institutional mechanisms through which disparities in cumulative impacts are transmitted, resisted, and understood.

Both parents matter: a national-scale analysis of parental race/ethnicity, disparities in prenatal PM2.5 exposures and related impacts on birth outcomes.

BACKGROUND: Most U.S. studies that report racial/ethnic disparities in increased risk of low birth weight associated with air pollution exposures have been conducted in California or northeastern states and/or urban areas, limiting generalizability of study results. Few of these studies have examined maternal racial/ethnic groups other than Non-Hispanic Black, non-Hispanic White and Hispanic, nor have they included paternal race. We aimed to examine the independent effects of PM2.5 on birth weight among a nationally representative sample of U.S. singleton infants and how both maternal and paternal race/ethnicity modify relationships between prenatal PM2.5 exposures and birth outcomes. METHODS: We used data from the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B), a longitudinal nationally representative cohort of 10,700 U.S. children born in 2001, which we linked to U.S.EPA's Community Multi-scale Air Quality (CMAQ)-derived predicted daily PM2.5 concentrations at the centroid of each Census Bureau Zip Code Tabulation Area (ZCTA) for maternal residences. We examined relationships between term birthweight (TBW), term low birthweight rate (TLBW) and gestational PM2.5 pollutant using multivariate regression models. Effect modification of air pollution exposures on birth outcomes by maternal and paternal race was evaluated using stratified models. All analyses were conducted with sample weights to provide national-scale estimates. RESULTS: The majority of mothers were White (61%). Fourteen percent of mothers identified as Black, 21% as Hispanic, 3% Asian American and Pacific Islander (AAPI) and 1% American Indian and Alaskan Native (AIAN). Fathers were also racially/ethnically diverse with 55% identified as White Non-Hispanic, 10% as Black Non-Hispanic, 19% as Hispanic, 3% as AAPI and 1% as AIAN. Results from the chi-square and ANOVA tests of significance for racial/ethnic differences indicate disparities in prenatal exposures and birth outcomes by both maternal and paternal race/ethnicity. Prenatal PM2.5 was associated with reduced birthweights during second and third trimester and over the entire gestational period in adjusted regression models, although results did not reach statistical significance. In models stratified by maternal race and paternal race, one unit increase in PM2.5 was statistically significantly associated with lower birthweights among AAPI mothers, -5.6 g (95% CI:-10.3, -1.0 g) and AAPI fathers, -7.6 g (95% CI: -13.1, -2.1 g) during 3rd trimester and among births where father's race was not reported, -14.2 g (95% CI: -24.0, -4.4 g). CONCLUSIONS: These data suggest that paternal characteristics should be used, in addition to maternal characteristics, to describe the risks of adverse birth outcomes. Additionally, our study suggests that serious consideration should be given to investigating environmental and social mechanisms, such as air pollution exposures, as potential contributors to disparities in birth outcomes among AAPI populations.

The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice.

BACKGROUND: Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4-7 and 10-13 for 4 h/day. RESULTS: Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2. CONCLUSIONS: Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection.

Healthy Air, Healthy Brains: Advancing Air Pollution Policy to Protect Children's Health.

Evidence is growing on the adverse neurodevelopmental effects of exposure to combustion-related air pollution. Project TENDR (Targeting Environmental Neurodevelopmental Risks), a unique collaboration of leading scientists, health professionals, and children's and environmental health advocates, has identified combustion-related air pollutants as critical targets for action to protect healthy brain development. We present policy recommendations for maintaining and strengthening federal environmental health protections, advancing state and local actions, and supporting scientific research to inform effective strategies for reducing children's exposures to combustion-related air pollution. Such actions not only would improve children's neurological development but also would have the important co-benefit of climate change mitigation and further improvements in other health conditions.

The Impact of Inhaled Ambient Ultrafine Particulate Matter on Developing Brain: Potential Importance of Elemental Contaminants.

Epidemiological studies report associations between air pollution (AP) exposures and several neurodevelopmental disorders including autism, attention deficit disorder, and cognitive delays. Our studies in mice of postnatal (human third trimester brain equivalent) exposures to concentrated ambient ultrafine particles (CAPs) provide biological plausibility for these associations, producing numerous neuropathological and behavioral features of these disorders, including male-biased vulnerability. These findings raise questions about the specific components of AP that underlie its neurotoxicity, which our studies suggest could involve trace elements as candidate neurotoxicants. X-ray fluorescence analyses of CAP chamber filters confirm contamination of AP exposures by multiple elements, including iron (Fe) and sulfur (S). Correspondingly, laser ablation inductively coupled plasma mass spectrometry of brains of male mice indicates marked postexposure elevations of Fe and S and other elements. Elevations of brain Fe and S in particular are consistent with potential ferroptotic, oxidative stress, and altered antioxidant capacity-based mechanisms of CAPs-induced neurotoxicity, supported by observations of increased serum oxidized glutathione and increased neuronal cell death in nucleus accumbens with no corresponding significant increase in caspase-3, in male brains following postnatal CAP exposures. Understanding the role of trace element contaminants of particulate matter AP as a source of neurotoxicity is critical for public health protection.

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice.

BACKGROUND: Recent epidemiological studies indicate early-life exposure to pollution particulate is associated with adverse neurodevelopmental outcomes. The need is arising to evaluate the risks conferred by individual components and sources of air pollution to provide a framework for the regulation of the most relevant components for public health protection. Previous studies in rodent models have shown diesel particulate matter has neurotoxic potential and could be a health concern for neurodevelopment. The present study shows an evaluation of pathological and protracted behavioral alterations following neonatal exposure to aerosolized diesel exhaust particles (NIST SRM 1650b). The particular behavioral focus was on temporal control learning, a broad and fundamental cognitive domain in which reward delivery is contingent on a fixed interval schedule. For this purpose, C57BL/6 J mice were exposed to aerosolized NIST SRM 1650b, a well-characterized diesel particulate material, from postnatal days 4-7 and 10-13, for four hours per day. Pathological features, including glial fibrillary-acidic protein, myelin basic protein expression in the corpus callosum, and ventriculomegaly, as well as learning alterations were measured to determine the extent to which NIST SRM 1650b would induce developmental neurotoxicity. RESULTS: Twenty-four hours following exposure significant increases in glial-fibrillary acidic protein (GFAP) in the corpus callosum and cortex of exposed male mice were present. Additionally, the body weights of juvenile and early adult diesel particle exposed males were lower than controls, although the difference was not statistically significant. No treatment-related differences in males or females on overall locomotor activity or temporal learning during adulthood were observed in response to diesel particulate exposure. CONCLUSION: While some sex and regional-specific pathological alterations in GFAP immunoreactivity suggestive of an inflammatory reaction to SRM 1650b were observed, the lack of protracted behavioral and pathological deficits suggests further clarity is needed on the developmental effects of diesel emissions prior to enacting regulatory guidelines.

Effects of neonatal inhalation exposure to ultrafine carbon particles on pathology and behavioral outcomes in C57BL/6J mice.

BACKGROUND: Recent epidemiological studies indicate early-life exposure to air pollution is associated with adverse neurodevelopmental outcomes. Previous studies investigating neonatal exposure to ambient fine and ultrafine particles have shown sex specific inflammation-linked pathological changes and protracted learning deficits. A potential contributor to the adverse phenotypes from developmental exposure to particulate matter observed in previous studies may be elemental carbon, a well-known contributor to pollution particulate. The present study is an evaluation of pathological and protracted behavioral alterations in adulthood following subacute neonatal exposure to ultrafine elemental carbon. C57BL/6J mice were exposed to ultrafine elemental carbon at 50 µg/m3 from postnatal days 4-7 and 10-13 for 4 h/day. Behavioral outcomes measured were locomotor activity, novel object recognition (short-term memory), elevated plus maze (anxiety-like behavior), fixed interval (FI) schedule of food reward (learning, timing) and differential reinforcement of low rate (DRL) schedule of food reward (impulsivity, inability to inhibit responding). Neuropathology was assessed by measures of inflammation (glial fibrillary-acidic protein), myelin basic protein expression in the corpus callosum, and lateral ventricle area. RESULTS: Twenty-four hours following the final exposure day, no significant differences in anogenital distance, body weight or central nervous system pathological markers were observed in offspring of either sex. Nor were significant changes observed in novel object recognition, elevated plus maze performance, FI, or DRL schedule-controlled behavior in either females or males. CONCLUSION: The limited effect of neonatal exposure to ultrafine elemental carbon suggests this component of air pollution is not a substantial contributor to the behavioral alterations and neuropathology previously observed in response to ambient pollution particulate exposures. Rather, other more reactive constituent species, organic and/or inorganic, gas-phase components, or combinations of constituents may be involved. Defining these neurotoxic components is critical to the formulation of better animal models, more focused mechanistic assessments, and potential regulatory policies for air pollution.

Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer's disease mice.

BACKGROUND: A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer's disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed. RESULTS: No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104-4.7 × 105 particles/cm3; mass concentration, 29-132 µg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory. CONCLUSIONS: A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1-6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.

Endocrine active metals, prenatal stress and enhanced neurobehavioral disruption.

Metals, including lead (Pb), methylmercury (MeHg) and arsenic (As), are long-known developmental neurotoxicants. More recently, environmental context has been recognized to modulate metals toxicity, including nutritional state and stress exposure. Modulation of metal toxicity by stress exposure can occur through shared targeting of endocrine systems, such as the hypothalamic-pituitary-adrenal axis (HPA). Our previous rodent research has identified that prenatal stress (PS) modulates neurotoxicity of two endocrine active metals (EAMs), Pb and MeHg, by altering HPA and CNS systems disrupting behavior. Here, we review this research and further test the hypothesis that prenatal stress modulates metals neurotoxicity by expanding to test the effect of developmental As ±â€¯PS exposure. Serum corticosterone and behavior was assessed in offspring of dams exposed to As ±â€¯PS. PS increased female offspring serum corticosterone at birth, while developmental As exposure decreased adult serum corticosterone in both sexes. As + PS induced reductions in locomotor activity in females and reduced response rates on a Fixed Interval schedule of reinforcement in males, with the latter suggesting unique learning deficits only in the combined exposure. As-exposed males showed increased time in the open arms of an elevated plus maze and decreased novel object recognition whereas females did not. These data further confirm the hypothesis that combined exposure to chemical (EAMs) and non-chemical (PS) stressors results in enhanced neurobehavioral toxicity. Given that humans are exposed to multiple environmental risk factors that alter endocrine function in development, such models are critical for risk assessment and public health protection, particularly for children.

Elemental mercury neurotoxicity and clinical recovery of function: A review of findings, and implications for occupational health.

This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cases, the extent of such recoveries varied considerably by individual and endpoint. Factors accounting for the extensive inter-individual variation in toxicity and recovery were not specifically assessed such as age, gender, diet, environmental enrichment, chelation strategies and dose-rate. While the data indicate that psychomotor endpoints often show substantial and relatively rapid (i.e., 2-6 months) recovery and that neuropsychological endpoints display slower and less complete recovery, generalizations are difficult due to highly variable study designs, use of different endpoints measured between studies, different Hg exposures based on blood/urine concentrations and Hg dose-rates, the poor capacity for replicating findings due to the unpredictable/episodic nature of harmful exposures to elemental Hg, and the inconsistency of the initiation of studies after induced toxicities and the differing periods of follow up during recovery periods. Finally, there is strikingly limited animal model literature on the topic of recovery/reversibility of elemental Hg toxicity, a factor which significantly contributes to the overall marked uncertainties for predicting the rate and magnitude of recovery and the factors that affect it.

Enhanced cerebellar myelination with concomitant iron elevation and ultrastructural irregularities following prenatal exposure to ambient particulate matter in the mouse.

Accumulating evidence indicates the developing central nervous system (CNS) is a target of air pollution toxicity. Epidemiological reports increasingly demonstrate that exposure to the particulate matter (PM) fraction of air pollution during neurodevelopment is associated with an increased risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). These observations are supported by animal studies demonstrating prenatal exposure to concentrated ambient PM induces neuropathologies characteristic of ASD, including ventriculomegaly and aberrant corpus callosum (CC) myelination. Given the role of the CC and cerebellum in ASD etiology, this study tested whether prenatal exposure to concentrated ambient particles (CAPs) produced pathological features in offspring CC and cerebella consistent with ASD. Analysis of cerebellar myelin density revealed male-specific hypermyelination in CAPs-exposed offspring at postnatal days (PNDs) 11-15 without alteration of cerebellar area. Atomic absorption spectroscopy (AAS) revealed elevated iron (Fe) in the cerebellum of CAPs-exposed female offspring at PNDs 11-15, which connects with previously observed elevated Fe in the female CC. The presence of Fe inclusions, along with aluminum (Al) and silicon (Si) inclusions, were confirmed at nanoscale resolution in the CC along with ultrastructural myelin sheath damage. Furthermore, RNAseq and gene ontology (GO) enrichment analyses revealed cerebellar gene expression was significantly affected by sex and prenatal CAPs exposure with significant enrichment in inflammation and transmembrane transport processes that could underlie observed myelin and metal pathologies. Overall, this study highlights the ability of PM exposure to disrupt myelinogenesis and elucidates novel molecular targets of PM-induced developmental neurotoxicity.

Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that children aged 6-15 with detectable levels of pyrethroid metabolites in their urine were more than twice as likely to be diagnosed with ADHD. Our epidemiologic finding, combined with the recapitulation of ADHD behavior in pesticide-treated mice, provides a mechanistic basis to suggest that developmental pyrethroid exposure is a risk factor for ADHD.

The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice.

Exposures to ambient ultrafine particle (UFP) air pollution (AP) during the early postnatal period in mice (equivalent to human third trimester brain development) produce male-biased changes in brain structure, including ventriculomegaly, reduced brain myelination, alterations in neurotransmitters and glial activation, as well as impulsive-like behavioral characteristics, all of which are also features characteristic of male-biased neurodevelopmental disorders (NDDs). The purpose of this study was to ascertain the extent to which inhaled Cu, a common contaminant of AP that is also dysregulated across multiple NDDs, might contribute to these phenotypes. For this purpose, C57BL/6J mice were exposed from postnatal days 4-7 and 10-13 for 4 hr/day to inhaled copper oxide (CuxOy) nanoparticles at an environmentally relevant concentration averaging 171.9 ng/m3. Changes in brain metal homeostasis and neurotransmitter levels were determined following termination of exposure (postnatal day 14), while behavioral changes were assessed in adulthood. CuxOy inhalation modified cortical metal homeostasis and produced male-biased disruption of striatal neurotransmitters, with marked increases in dopaminergic function, as well as excitatory/inhibitory imbalance and reductions in serotonergic function. Impulsive-like behaviors in a fixed ratio (FR) waiting-for-reward schedule and a fixed interval (FI) schedule of food reward occurred in both sexes, but more prominently in males, effects which could not be attributed to altered locomotor activity or short-term memory. Inhaled Cu as from AP exposures, at environmentally relevant levels experienced during development, may contribute to impaired brain function, as shown by its ability to disrupt brain metal homeostasis and striatal neurotransmission. In addition, its ability to evoke impulsive-like behavior, particularly in male offspring, may be related to striatal dopaminergic dysfunction that is known to mediate such behaviors. As such, regulation of air Cu levels may be protective of public health.

Early-stage primary school children attending a school in the Malawian School Feeding Program (SFP) have better reversal learning and lean muscle mass growth than those attending a non-SFP school.

In developing countries, schoolchildren encounter a number of challenges, including failure to complete school, poor health and nutrition, and poor academic performance. Implementation of school feeding programs (SFPs) in less developed countries is increasing and yet there is mixed evidence regarding their positive effects on nutrition, education, and cognition at the population level. This study evaluated cognitive and anthropometric outcomes in entry-level primary school children in Malawi with the aim of generating evidence for the ongoing debate about SFPs in Malawi and other developing countries. A total of 226 schoolchildren aged 6-8 y in 2 rural Malawian public primary schools were followed for one school year. Children attending one school (SFP school) received a daily ration of corn-soy blend porridge, while those attending the other (non-SFP school) did not. Baseline and post-baseline outcomes included the Cambridge Neurological Test Automated Battery cognitive tests of paired associate learning, rapid visual information processing and intra-extra dimensional shift, and anthropometric measurements of weight, height, and mid-upper arm circumference (MUAC). At follow-up, the SFP subcohort had a greater reduction than the non-SFP subcohort in the number of intra-extra predimensional shift errors made (mean 18.5 and 24.9, respectively; P-interaction = 0.02) and also showed an increase in MUAC (from 16.3 to 17.0; P-interaction <0.0001). The results indicate that the SFP in Malawi is associated with an improvement in reversal learning and catch-up growth in lean muscle mass in children in the SFP school compared with children in the non-SFP school. These findings suggest that the Malawian SFP, if well managed and ration sizes are sustained, may have the potential to improve nutritional and cognitive indicators of the most disadvantaged children.

Multisystem physiological dysfunction is associated with depressive symptoms in a population-based sample of older adults.

OBJECTIVE: To evaluate the association between multisystem physiological dysfunction and depressive symptom severity in the US older adults. METHODS: We examined 2405 adults of age 60 years and older by using the data from the 2005-2008 National Health and Nutrition Examination Survey. We constructed a summary score of "physiological dysfunction," encompassing cardiovascular function, glucose regulation, liver function, and renal function. Overall depressive symptoms were obtained from the 9-item Patient Health Questionnaire depression scale, and factor analysis was used to derive affective and somatic symptom scores. We employed multiple linear regression models to estimate associations between physiological dysfunction scores and affective, somatic, and overall depressive symptoms, while adjusting for demographic, socioeconomic factors, and other potentially confounding factors. RESULTS: Greater multisystem physiological dysfunction scores were associated with an increased severity of overall, affective, and somatic depressive symptoms. These associations persisted after adjusting for all covariates: beta = 0.23 (95% confidence interval (CI) = 0.13, 0.32); beta = 0.08 (95% CI = 0.04, 0.11); beta = 0.12 (95% CI = 0.06, 0.18), respectively. CONCLUSIONS: Our results suggest that the multisystem physiological dysfunction is associated with late-life depressive symptoms. Additional longitudinal studies of links between allostatic load, psychosocial stress events throughout the life course, and late-life depressive symptoms may shed further light on this association.

Nutritional and cognitive status of entry-level primary school children in Zomba, rural Malawi.

Entry-level Malawian children (n = 226) aged 6-8 years from two public primary schools, one a participant in a national school feeding programme (FP), the other not, were investigated for differences in nutritional and cognitive status. Stunted growth (42%) and underweight (25%) were prevalent, with no significant differences between the schools, although the school attended was a significant predictor of mid-upper arm circumference. Previous attendance at a community-based childcare centre was significantly associated with lower body weight and height. There were no significant differences in memory, reversal learning and attention outcomes between the schools. These findings report no major significant difference in nutrition or cognitive statuses between the schools, and on this basis suggest that both schools were equally in need of FP participation. More inclusive interventions and broadening/review of FP participation criteria are recommended.