Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.

Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF's impact on mitochondrial function persists, even in cells lacking septins. Furthermore, the impaired mitochondrial function leads to the degradation of HIF-1α, facilitated by increased cellular oxygen. FCF also induces AMPK activation, suppresses Erk1/2 phosphorylation, and reduces the expression of HER2, ß-catenin, and PD-L1. Endometrial cancer is characterized by metabolic disorders such as diabetes and aberrant HER2/Ras-Erk1/2/ß-catenin signaling. Thus, FCF may hold promise as a potential therapeutic in endometrial cancer.

A Systematic Review of Breast Implant-Associated Squamous Cell Carcinoma.

Breast augmentation is considered safe, but rare cases of breast implant-associated squamous cell carcinoma (BIA-SCC) have been reported. This study aimed to systematically review published cases of BIA-SCC, providing valuable clinical data. The review included 14 articles and 18 cases of BIA-SCC. An increasing trend in reported BIA-SCC cases was observed, with four cases in the 1990s and 14 cases since 2010. The mean age of affected patients was 56 years, and symptoms typically appeared around 21 years after breast augmentation. Silicone implants used in cosmetic procedures were most commonly associated with BIA-SCC. Implant removal was necessary in all cases, and some patients required a mastectomy. Treatment approaches varied, with the selective use of chemotherapy and/or radiotherapy. The estimated 6-month mortality rate was 11.1%, while the 12-month mortality rate was 23.8%. The estimated 6-month mortality rate should be cautiously interpreted due to the limited sample size. It appears lower than the rate reported by the American Society of Plastic Surgeons, without clear reasons for this discrepancy. This study highlights the importance of enhanced monitoring and information sharing to improve detection and management of BIA-SCC. Healthcare providers should maintain vigilance during the long-term follow-up of breast augmentation patients.

Maternal Choline Supplementation as a Potential Therapy for Down Syndrome: Assessment of Effects Throughout the Lifespan.

Maternal choline supplementation (MCS) has emerged as a promising therapy to lessen the cognitive and affective dysfunction associated with Down syndrome (DS). Choline is an essential nutrient, especially important during pregnancy due to its wide-ranging ontogenetic roles. Using the Ts65Dn mouse model of DS, our group has demonstrated that supplementing the maternal diet with additional choline (4-5 × standard levels) during pregnancy and lactation improves spatial cognition, attention, and emotion regulation in the adult offspring. The behavioral benefits were associated with a rescue of septohippocampal circuit atrophy. These results have been replicated across a series of independent studies, although the magnitude of the cognitive benefit has varied. We hypothesized that this was due, at least in part, to differences in the age of the subjects at the time of testing. Here, we present new data that compares the effects of MCS on the attentional function of adult Ts65Dn offspring, which began testing at two different ages (6 vs. 12 months of age). These data replicate and extend the results of our previous reports, showing a clear pattern indicating that MCS has beneficial effects in Ts65Dn offspring throughout life, but that the magnitude of the benefit (relative to non-supplemented offspring) diminishes with aging, possibly because of the onset of Alzheimer's disease-like neuropathology. In light of growing evidence that increased maternal choline intake during pregnancy is beneficial to the cognitive and affective functioning of all offspring (e.g., neurotypical and DS), the addition of this nutrient to a prenatal vitamin regimen would be predicted to have population-wide benefits and provide early intervention for fetuses with DS, notably including babies born to mothers unaware that they are carrying a fetus with DS.

Time to treatment initiation and outcomes in high-grade glioma patients in rehabilitation: a retrospective cohort study.

Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods: A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

Clinical Efficacy of Tumor Treating Fields for Newly Diagnosed Glioblastoma.

BACKGROUND/AIM: Whether adding tumor treating fields (TTF) to the Stupp protocol increases survival for glioblastoma (GBM) patients in routine clinical care remains unknown. PATIENTS AND METHODS: We retrospectively identified adult patients with newly diagnosed GBM (n=104) treated with the Stupp protocol or TTF at our Institution. RESULTS: Thirty-six percent (37/104) of patients received TTF in conjunction with the Stupp protocol and these patients had increased 6-month (p=0.006) and 1-year (p=0.170), but not 2-year survival rates compared to the 67-patients who received Stupp alone. The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (p=0.010). However, we did not observe any improvement in overall survival (OS) with a Cox model. CONCLUSION: While adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect was mild and may be largely due to selection bias.

Immune checkpoint inhibitors in older adults with melanoma or cutaneous malignancies: The Wilmot Cancer Institute experience.

OBJECTIVES: The purpose of this study was to explore the associations between age and frailty with immune-related adverse events (irAEs) among patients with cutaneous malignancies receiving immune checkpoint inhibitor (ICI) therapy. METHODS: A retrospective review of all patients receiving ipilimumab, nivolumab, or pembrolizumab for treatment of cutaneous malignancies at the Wilmot Cancer Institute between 1 Jan 2011 and 3 Apr 2017. RESULTS: A total of 120 patients (age <70 N = 68, age ≥70 N = 52; range, 26-93) were identified. 44.1%[95%CI:32-57%] of patients age <70 and 31.4%[95%CI:19-46%] of patients age ≥70 experienced ≥1 irAE on 1st line ICI therapy (P = 0.158). A total of 3 adults died of irAEs (2 age ≥70; 1 age <70). Patients ≥70 were more frequently treated with anti-PD-1 monotherapy than dual checkpoint blockade or ipilimumab (P < 0.01) in the first line setting. Among patients on first line anti-PD-1 monotherapy for cutaneous melanoma, 21 were age <70 and 20 were age ≥70, with similar observed rates of irAEs (52.4%[95%CI 29.8-74.3] and 63.2%[95%CI 38.4-83.7]). Indirect frailty markers in patients age ≥70 such as having fallen in the prior six months, ECOG PS ≥2 or Charlson comorbidity scores ≥11 experienced similar rates of response and toxicity. Among 9 patients with a PS = 3, 8 died, 6 due to progressive disease. No deaths due to irAEs occurred in this frail subgroup. CONCLUSION: Anti-PD-1 monotherapy for older adults with cutaneous malignancies have similar response and irAE rates when compared to those of younger patients. Deaths from disease progression were more frequent than those from toxicity in both age subgroups.

Use of an Online Diet Goal-Setting Tool: Relationships With Gestational Weight Gain.

OBJECTIVES: To describe (1) the use of a diet goal-setting tool in a self-directed online intervention aimed at promoting a healthy lifestyle, and (2) the association of tool use with gestational weight gain (GWG). DESIGN: Cross-sectional analysis of data from the intervention group in a randomized effectiveness trial. SETTING: An urban county in the northeastern US. PARTICIPANTS: A total of 898 healthy pregnant women aged 18-35 years with body mass indexes of (BMI) ≥18.5 and <35; 39.1% were low-income. MAIN OUTCOME MEASURES: Physical, sociodemographic, and psychosocial characteristics; use of tool features; and GWG. ANALYSIS: Frequencies, chi-square tests of independence, and regression analysis. RESULTS: Use of the online dietary tool was 45.1% completed the assessment, 35.3% set a goal, and 22.6% engaged in self-monitoring. Among women with normal BMI, setting ≥2 goals and engaging in self-monitoring were significantly (P < .05) associated with less GWG. Among women with higher BMI, setting ≥2 goals was significantly associated with greater GWG. CONCLUSIONS AND IMPLICATIONS: Although online diet goal setting is a potentially effective weight management tool for pregnant women with normal BMI, findings suggest that it may not be for higher-BMI women. Additional research is needed to explain this finding.

The effectiveness of an online intervention in preventing excessive gestational weight gain: the e-moms roc randomized controlled trial.

BACKGROUND: Excessive gestational weight gain (GWG) is common and contributes to the development of obesity in women and their offspring. Electronic or e-health interventions have the potential to reach large groups of women and prevent excessive GWG, but their effectiveness has not been demonstrated. The purpose of this study was to evaluate, in a real-world setting, the effectiveness of a self-directed, integrated online and mobile phone behavioral intervention in preventing excessive GWG. METHODS: This effectiveness trial was a double-blind, three-arm trial with a parallel group design. Two arms received the same e-health intervention during pregnancy with the third arm serving as the placebo control. The intervention was based on a previously efficacious non-digital intervention that was adapted to electronic format. It included three behavior change tools: a weight gain tracker, and separate diet and physical activity goal-setting and self-monitoring tools. Both treatment conditions received access to informational tools, event reminders, and a blogging feature. Healthy pregnant women age 18-35 years with body mass indexes (BMI) ≥18.5 and < 35, at ≤20 weeks gestation, and an e-mail address were eligible. The proportion of women with excessive total GWG, as defined by the Institute of Medicine (IOM), was the primary outcome. 1689 randomized women were analyzed in the intent-to-treat (ITT) analysis. The study was designed to have 87% power to detect a 10 percentage point reduction from a control rate of 55% with a sample of 1641 (p = 0.0167, two-sided). RESULTS: In the ITT sample, 48.1% (SD = 2.0%) gained excessively in the intervention group as did 46.2% (SD = 2.4%) in the placebo control group. These proportions were not significantly different (RR 1.09; 95% CI 0.98, 1.20, p = 0.12). The results were not altered in several sensitivity analyses. CONCLUSION: The addition of three behavior change tools to an informational placebo control did not result in a difference in the proportion of women with excessive total GWG compared to the placebo control in this effectiveness trial of an online, self-directed intervention. The similarity of intervention and control treatments and low usage of the behavior change tools in the intervention group are possible explanations. TRIAL REGISTRATION: NCT01331564 , ClinicalTrials.gov.

Association between consistent weight gain tracking and gestational weight gain: Secondary analysis of a randomized trial.

OBJECTIVE: The effective components of interventions for reducing excessive gestational weight gain (GWG) remain to be identified. This study investigated the sociodemographic, physical, psychosocial, and environmental correlates of online GWG tracking and its independent association with GWG outcomes. METHODS: Eight hundred ninety-eight women in the intervention arms of a randomized trial assessing the effectiveness of an integrated online and mobile phone behavioral intervention to decrease the prevalence of excessive GWG were included in this secondary analysis. Data were analyzed using χ2 analysis and modified Poisson and linear regression approaches. RESULTS: Only 16.5% of low-income (Medicaid-eligible) women consistently tracked GWG, as did 34.2% of not-low-income women. More highly educated, older, and white women were more likely to be consistent GWG trackers. Among not-low-income women, consistent GWG tracking was associated with 2.35 kg less GWG (95% CI: -3.23 to -1.46 kg; P < 0.0001) and a reduced risk of excessive GWG (RR 0.73; 95% CI: 0.59 to 0.89; P = 0.002). CONCLUSIONS: Electronic tracking of GWG is an effective component of electronic and mobile health interventions aiming to decrease the prevalence of excessive GWG in not-low-income women. Income group-specific motivators are needed to increase the prevalence of GWG tracking.

Does Usage of an eHealth Intervention Reduce the Risk of Excessive Gestational Weight Gain? Secondary Analysis From a Randomized Controlled Trial.

BACKGROUND: Excessive gestational weight gain (GWG) contributes to the development of obesity in mother and child. Internet-based interventions have the potential for delivering innovative and interactive options for prevention of excessive GWG to large numbers of people. OBJECTIVE: The objective of this study was to create a novel measure of Internet-based intervention usage patterns and examine whether usage of an Internet-based intervention is associated with reduced risk of excessive GWG. METHODS: The website featured blogs, local resources, articles, frequently asked questions (FAQs), and events that were available to women in both the intervention and control arm. Weekly reminders to use the website and to highlight new content were emailed to participants in both arms. Only intervention arm participants had access to the weight gain tracker and diet and physical activity goal-setting tools. A total of 1335 (898 intervention and 437 control) relatively diverse and healthy pregnant women were randomly assigned to the intervention arm or control arm. Usage patterns were examined for both intervention and control arm participants using latent class analysis. Regression analyses were used to estimate the association between usage patterns and three GWG outcomes: excessive total GWG, excessive GWG rate, and GWG. RESULTS: Five usage patterns best characterized the usage of the intervention by intervention arm participants. Three usage patterns best characterized control arm participants' usage. Control arm usage patterns were not associated with excessive GWG, whereas intervention arm usage patterns were associated with excessive GWG. CONCLUSIONS: The control and intervention arm usage pattern characterization is a unique methodological contribution to process evaluations for self-directed Internet-based interventions. In the intervention arm some usage patterns were associated with GWG outcomes. CLINICALTRIAL: ClinicalTrials.gov; Clinical Trials Number: NCT01331564; https://clinicaltrials.gov/ct2/show/NCT01331564 (Archived by WebCite at http://www.webcitation/6nI9LuX9w).

Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.

The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer's disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12-17months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD.

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs.

Weight-related self-efficacy in relation to maternal body weight from early pregnancy to 2 years post-partum.

Excessive gestational weight gain may lead to long-term increases in maternal body weight and associated health risks. The purpose of this study was to examine the relationship between maternal body weight and weight-related self-efficacy from early pregnancy to 2 years post-partum. Women with live, singleton term infants from a population-based cohort study were included (n = 595). Healthy eating self-efficacy and weight control self-efficacy were assessed prenatally and at 1 year and 2 years post-partum. Body weight was measured at early pregnancy, before delivery, and 6 weeks, 1 year and 2 years post-partum. Behavioural (smoking, breastfeeding) and sociodemographic (age, education, marital status, income) covariates were assessed by medical record review and baseline questionnaires. Multi-level linear regression models were used to examine the longitudinal associations of self-efficacy measures with body weight. Approximately half of the sample (57%) returned to early pregnancy weight at some point by 2 years post-partum, and 9% became overweight or obese at 2 years post-partum. Body weight over time was inversely related to healthy eating (ß = -0.57, P = 0.02) and weight control (ß = -0.99, P < 0.001) self-efficacy in the model controlling for both self-efficacy measures as well as time and behavioural and sociodemographic covariates. Weight-related self-efficacy may be an important target for interventions to reduce excessive gestational weight gain and post-partum weight gain.

The healthy start partnership: an approach to obesity prevention in young families.

This article investigates the impact of community-based interventions developed by the Healthy Start Partnership (HSP) to promote healthy body weights in families. Intercept surveys were conducted to monitor community exposure. A nonconcurrent, no treatment control design was used to assess population-level weight outcomes. Control (n = 219) and intervention (n = 276) cohorts of pregnant women were recruited and followed until 6 months postpartum. Data were collected through 2 self-administered questionnaires and medical record audits. Results indicate community residents were exposed to interventions. However, little evidence of positive effects of interventions on weight outcomes was found for mothers or infants.

Maternal weight change between 1 and 2 years postpartum: the importance of 1 year weight retention.

Pregnancy weight gain may lead to long-term increases in maternal BMI for some women. The objective of this study was to examine maternal body weight change 1y-2y postpartum, and to compare classifications of 2y weight retention with and without accounting for 1y-2y weight gain. Early pregnancy body weight (EPW, first trimester) was measured or imputed, and follow-up measures obtained before delivery, 1 year postpartum (1y) and 2 years postpartum (2y) in an observational cohort study of women seeking prenatal care in several counties in upstate New York (n = 413). Baseline height was measured; demographic and behavioral data were obtained from questionnaires and medical records. Associations of 1y-2y weight change (kg) and 1y-2y weight gain (≥2.25 kg) with anthropometric, socioeconomic, and behavioral variables were evaluated using linear and logistic regressions. While mean ± SE 1y-2y weight change was 0.009 ± 4.6 kg, 1y-2y weight gain (≥2.25 kg) was common (n = 108, 26%). Odds of weight gain 1y-2y were higher for overweight (OR(adj) = 2.63, CI(95%) = 1.43-4.82) and obese (OR(adj) = 2.93, CI(95%) = 1.62-5.27) women than for women with BMI <25. Two year weight retention (2y-EPW ≥2.25 kg) was misclassified in 38% (n = 37) of women when 1y-2y weight gain was ignored. One year weight retention (1YWR) (1y-EPW) was negatively related to 1y-2y weight change (ß(adj) ± SE = -0.28 ± 0.04, P < 0.001) and weight gain (≥2.25 kg) (OR(adj) = 0.91, CI(95%) = 0.87-0.95). Relations between 1y weight retention and 1y-2y weight change were attenuated for women with higher early pregnancy BMI. Weight change 1y-2y was predicted primarily by an inverse relation with 1y weight retention. The high frequency of weight gain has important implications for classification of postpartum weight retention.

Associations Between Mothers' and Their Children's Weights at 4 Years of Age.

OBJECTIVES: To examine the importance of maternal weight characteristics as predictors of overweight (BMI ≥85th percentile and <95th percentile) and obesity (BMI ≥ 95th percentile) in offspring at age 4 years. METHODS: Chi-square and logistic regression analyses were conducted on a sample of 321 mother/child pairs from an earlier observational cohort study on mothers' postpartum weight retention. RESULTS: Maternal early pregnancy BMI and infant birth weight were each positively and significantly (p <0.05) associated with increased risk of obesity in offspring at age 4 years. A significant interaction was found between these two variables in predicting children's risk of obesity. It was driven by the high proportion of obese children among obese women who had infants weighing < 3 kg at birth. Net gestational weight gain was not associated with obesity risk in children, but was positively associated with infant birth weight among normal weight and overweight women. CONCLUSIONS: Reducing maternal BMI in the preconception period among overweight and obese women and preventing excessive weight gain in pregnancy for all women appear to be appropriate strategies to address the childhood obesity epidemic.

Maternal weight gain during pregnancy and child weight at age 3 years.

OBJECTIVES: To determine the importance of pregnancy weight gain as a predictor of overweight (Body Mass Index [BMI] >85th percentile) in offspring at age 3 years and if its influence varies by maternal BMI. METHODS: Chi-square and logistic regression analyses were conducted on a sample of 208 mother-child pairs from an earlier observational cohort study on postpartum weight retention. RESULTS: In the final reduced regression model, maternal early pregnancy BMI was positively and significantly associated with overweight in offspring, as were birth weight above the sample median of 3,600 g and maternal smoking during pregnancy (P < or = 0.01). In addition, a significant interaction was found between maternal BMI and gestational weight gain (P = 0.03). The risk of offspring overweight that is associated with 5 excess pounds of net pregnancy weight gain increases with maternal BMI. CONCLUSIONS: Excess pregnancy weight gain is associated with increased risk of child overweight at age 3 years and its impact is greater among high and obese BMI women than it is in normal BMI women. Reducing maternal BMI in the preconception period in overweight women and preventing excessive weight gain in pregnancy for all women appear to be appropriate strategies to address the childhood obesity epidemic.

Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome.

This study assessed social behavior in a mouse model of Fragile X syndrome (FXS), the Fmr1 (tm1Cgr) or Fmr1 "knockout" (KO) mouse. Both the KO and wild-type (WT) mice preferred to be near a novel conspecific than to be alone. However, during the initial interaction with a novel conspecific, (1) a greater proportion of the KO mice exhibited high levels of grooming; and (2) the average duration of nose contact with the stimulus mouse was significantly shorter for the KO mice, both indicative of increased arousal and/or anxiety. Both groups exhibited a robust novelty preference when the novel animal was a "preferred" mouse. However, when the novel mouse was a "nonpreferred" animal, both groups showed a diminished novelty preference but this effect was more pronounced for the WT mice. This blunted negative reaction of the KO mice to a nonpreferred animal may indicate that they were less proficient than controls in distinguishing between positive and negative social interactions. These findings provide support for the use of this animal model to study the autistic features of FXS and autism spectrum disorders.

The relationship between food insecurity and obesity in rural childbearing women.

CONTEXT: While food insecurity and obesity have been shown to be positively associated in women, little is known about the direction of the causal relationship between these 2 constructs. PURPOSE: To clarify the direction of the causal relationship between food insecurity and obesity. METHODS: Chi-square and logistic regression analysis of data from a cohort of 622 healthy childbearing women living in a 10-county rural area of upstate New York and followed from early pregnancy until 2 years postpartum. FINDINGS: Obesity in early pregnancy was associated with increased risk of food insecurity at 2 years postpartum. Initial food insecurity was not associated with increased risk of obesity at 2 years postpartum. Women who were both obese and food insecure in early pregnancy were at greatest risk of major weight gain over the pregnancy and postpartum period. CONCLUSIONS: Obesity appears to lead to food insecurity rather than the converse. Obesity combined with food insecurity present the greatest risk for major weight gain in this sample of childbearing women.

Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure.

BACKGROUND: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure. OBJECTIVES: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning. RESULTS: Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb-exposed children. Succimer treatment of the Pb-exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen. CONCLUSIONS: These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb-exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals.