Perfluoroalkyl substances (PFAS) and lead (Pb) as "cardiovascular disruptors" in 9-11-year-old children living in Syracuse, New York, United States.

OBJECTIVE: Per- and polyfluoro-alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). METHODS: We assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9-11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). RESULTS: Significant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater "vascular reactivity" (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (ß = 0.21, p = 0.010). CONCLUSION: To our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as "cardiovascular disruptors" in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Airborne levels of cadmium are correlated with urinary cadmium concentrations among young children living in the New York state city of Syracuse, USA.

Air pollution is a serious public health issue with early childhood exposure being of high concern because of the greater risk that children might experience negative health outcomes. Industrial sources in and near communities are one potential path of exposure that children might face with greater levels of air pollution correlating with higher levels of toxicants detected in children. We compare estimated ambient air concentrations of Cadmium (Cd) to a cohort (n = 281) of 9 to 11-year old children during their early childhood years (0-5 years of age) in a mid-size city in Upstate New York. Levels of Cd air pollution are compared to children's urine-Cd levels. Urine has been shown to be a superior biomarker to blood for Cd exposure particularly for longer-term exposures. We find that participants who reside in households that faced greater Cd air pollution during the child's early years have higher urine-Cd levels. This association is stable and stronger than previously presented associations for blood-Cd. Findings support expanded use of air modelling data for risk screening to reduce the potential health burden that industrial pollution can have.

Association of Sleep Quality With Greater Left Ventricular Mass in Children Aged 9 to 11 Years.

OBJECTIVE: Research has consistently found associations between sleep characteristics and cardiovascular disease risk in children, adolescents, and adults. Although primarily investigated in clinical samples (e.g., in those with sleep disorders), greater left ventricular mass is associated with poor sleep quality in nonclinical adult populations as well; however, this has not been evaluated in children or adolescents. Our study aim was to consider the relationship between objectively measured sleep characteristics and left ventricular mass in children. METHODS: We assessed sleep and cardiac structure in a biracial sample of 9- to 11-year-old children (n = 176; 41% White, 59% Black; 50% female). Sleep was assessed with actigraphy for five nights. Cardiac dimensions were assessed using echocardiography. RESULTS: After adjusting for covariates, we found that poor sleep quality was associated with significantly greater left ventricular mass (ß = 0.13, t(167) = 2.14, p = .034, Cohen d = 0.16, for activity during sleep; ß = 0.15, t(167) = 2.43, p = .016, Cohen d = 0.18, for sleep fragmentation). Other cardiac dimensions (namely, relative wall thickness and right ventricular dimension) were also significantly associated with sleep characteristics. Notably, associations did not differ as a function of sex or race. CONCLUSIONS: The present findings are novel and unique because no prior reports have systematically documented the association between poor sleep quality with potentially detrimental cardiac remodeling in a nonclinical sample of children. However, the novelty and importance of these findings require additional research for confirmation.

Linking metal (Pb, Hg, Cd) industrial air pollution risk to blood metal levels and cardiovascular functioning and structure among children in Syracuse, NY.

BACKGROUND: Exposure to air pollution has been linked to individual health effects in occupational environments and communities proximate to air pollution sources. Use of estimated chemical concentrations from the Risk Screening Environmental Indicators (RSEI) model, derived from the Toxics Release Inventory, can help approximate some contributions to individual lifetime exposure to risk from air pollution and holds potential for linkages with specific health outcome data. OBJECTIVES: Our objectives were: (1) use regression modeling to test for associations between observed blood metal concentrations in children and RSEI total air concentrations of the same metals released from proximate manufacturing facilities; (2) determine the relative contribution of RSEI air pollution to blood metal concentrations; and (3) examine associations between chronic metal exposure and cardiovascular functioning and structure in study participants. METHODS: Using data synthesis methods and regression modeling we linked individual blood-based levels of lead, mercury, and cadmium(Pb, Hg, Cd) and cardiovascular functioning and structure to proximate industrial releases of the same metals captured by the Environmental Protection Agency's (EPA) RSEI geographic microdata. RESULTS: We found that RSEI-derived ground-level ambient air concentrations of Hg and Cd were a significant predictor of blood metal levels, when controlling for covariates and other exposure variables. In addition to associations with blood metal findings, RSEI concentrations also predicted cardiovascular dysfunction and risk including changes in left-ventricular mass, blood pressure, and heart rate. DISCUSSION: Right-to-know data, such as EPA's RSEI, can be linked to objective health outcomes, rather than simply serving as a non-specific risk estimate. These data can serve as a proxy for hazard exposure and should be used more widely to understand the dynamics of environmental exposure. Furthermore, since these data are both a product of and contribute to regulatory decision making, they could serve as an important link between disease risk and translation-orientated national environmental health policy.

Dietary contributions to increased background lead, mercury, and cadmium in 9-11 Year old children: Accounting for racial differences.

BACKGROUND: Initial interest in the adverse consequences of exposure to lead (Pb), mercury (Hg), and cadmium (Cd) focused on relatively high exposures through environmental or occupational sources; however, recent evidence suggests even low-level background exposure to non-essential metals might be detrimental, particularly for children's health and development. One potentially important source of increased background levels of non-essential toxic metals is diet. OBJECTIVES: We considered whether differences in diet are associated with levels of non-essential metals in blood and whether racial differences in metals are mediated by dietary differences. METHODS: We assessed blood levels of Pb, Hg, and Cd in a sample of 9-11 year-old children (N = 295) comprised of 42% European Americans (EAs), 58% African American (AAs), and 47% female. Diet was assessed using 24-h dietary recalls during phone interviews administered to parents on two consecutive days (Friday and Saturday). The Healthy Eating Index-2105 (HEI-2015) was calculated to assess diet quality. RESULTS: The current study identified significant dietary sources of non-essential metal exposure - namely total fruit for Pb, total protein for Hg, and greens and beans for Cd. Moreover, AAs were found to have significantly higher blood levels of Pb and Hg than EAs and these racial differences were significantly mediated by these dietary differences. DISCUSSION: This study is one of very few to consider total diet in children and exposure to the non-essential metals Pb, Hg, and Cd, and the first to demonstrate that racial differences in increased background blood levels of non-essential toxic metals can be accounted for by racial differences in diet. Given regional differences in food consumption patterns and specific farm and store sources for the foods, the generalizability of the current findings has yet to be determined; however, commonly consumed foods appear to be a significant source of low-level non-essential metals.

Neurogenesis within the hippocampus after chronic methylphenidate exposure.

Methylphenidate is a psychostimulant used to treat attention deficit hyperactivity disorder. Neurogenesis occurs throughout adulthood within the dentate gyrus of the hippocampus and can be altered by psychoactive medications; however, the impact of methylphenidate on neurogenesis is not fully understood. We investigated the effects of chronic low (1 mg/kg) and high (10 mg/kg) intraperitoneal doses of methylphenidate on neurogenesis in mouse hippocampus following 28 days and 56 days of treatment. Interestingly, methylphenidate, at both doses, increased neurogenesis. However, if methylphenidate treatment was not continued, the newly generated cells did not survive after 28 days. If treatment was continued, the newly generated neurons survived only in the mice receiving low-dose methylphenidate. To investigate the mechanism for this effect, we examined levels of proteins linked to cell proliferation in the hippocampus, including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), and beta-catenin. BDNF or GDNF levels were not significantly different between groups. However, hippocampal VEGF, TrkB, and beta-catenin were significantly increased in mice receiving low-dose methylphenidate for 28 days compared to controls. Interestingly, high-dose methylphenidate significantly decreased beta-catenin after 28 days and decreased VEGF, beta-catenin, and TrkB after 56 days compared to controls. Thus, low-dose methylphenidate appears to increase cell proliferation and cell survival in the hippocampus, and these effects may be mediated by increase in VEGF, TrkB, and beta-catenin. While high dose methylphenidate may initially increase neuronal proliferation, newly generated neurons are unable to survive long-term, possibly due to decrease in VEGF, TrkB and beta-catenin.

Variability in the spatial density of vacant properties contributes to background lead (Pb) exposure in children.

BACKGROUND: Heightened blood lead levels (BLL) are associated with cognitive deficiencies and adverse behavioral outcomes. Lead-contaminated house dust is the primary source of exposure in U.S. children, and evidence suggests that even background (low-level) exposure has negative consequences. Identifying sources of background exposure is of great public health significance because of the larger number of children that can be affected. METHODS: Blood lead was assessed in a bi-racial sample of children from Syracuse, NY, aged 9-11, using established biomonitoring methods. The spatial density of vacant properties was modelled from publicly available georeferenced datasets. Further, regression models were used to measure the impact of this spatial density variable on children's BLL. RESULTS: In a sample of 221 children, with a mean BLL of 1.06 µg/dL (SD = 0.68), results showed increases in spatial density of vacant properties predict increases in median blood-PB levels, b = 0.14 (0.06-0.21), p < .001. This association held true even after accounting for demographic covariates, and age of individual housing. Further analysis showed spatial autocorrelation of the residuals changed from a clustered pattern to a random pattern once the spatial density variable was introduced to the model. DISCUSSION: This study is the first to identify a background-lead exposure source using spatial density modelling. As vacant properties deteriorate, lead-contaminated dust likely disperses into the surrounding environment. High-density areas have an accumulation of lead hazards in environmental media, namely soil and dust, putting more children at risk of exposure.

A real-time PCR regimen for testing environmental samples for Salmonella enterica subsp. enterica serovars of concern to the poultry industry, with special focus on Salmonella Enteritidis.

A real-time PCR (qPCR) regimen, using up to six genetic targets, was developed to rapidly detect Salmonella and in particular identify Salmonella Enteritidis. The test regimen was first evaluated using a reference culture collection of Salmonella to confirm the appropriateness of the selected targets, which included up to three genetic markers for discrimination of Salmonella Enteritidis from other Salmonella serovars commonly found in poultry facilities. The qPCR procedure was then compared with culture methods used to detect Salmonella using a collection of enrichment broths previously generated from 239 environmental samples collected from a large number of hatchery facilities across Canada over several years. The qPCR regimen facilitated specific detection of Salmonella Enteritidis, and on a sample basis, it showed excellent agreement with the culture methods. Moreover, in many cases, qPCR detected Salmonella earlier in the culture process than did the culture method. Application of this method will significantly shorten test times and allow more timely identification of infected poultry premises, thereby improving present programmes aimed at controlling Salmonella Enteritidis at the environmental source.

Racial Differences in Aortic Stiffness in Children.

OBJECTIVE: To investigate racial differences in central blood pressure and vascular structure/function as subclinical markers of atherosclerotic cardiovascular disease in children. STUDY DESIGN: This cross-sectional study recruited 54 African American children (18 female, 36 male; age 10.5 ± 0.9 years) and 54 white children (27 female, 26 male; age 10.8 ± 0.9 years) from the Syracuse City community as part of the Environmental Exposures and Child Health Outcomes study. Participants underwent blood lipid and vascular testing on 2 separate days. Carotid artery intima-media thickness and aortic stiffness were measured by ultrasonography and carotid-femoral pulse wave velocity, respectively. Blood pressure was assessed at the brachial artery and estimated in the carotid artery using applanation tonometry. RESULTS: African American children had significantly higher pulse wave velocity (4.8 ± 0.8 m/s) compared with white children (4.2 ± 0.7 m/s; P < .05), which remained significant after adjustment for confounding variables including socioeconomic status. African American children had significantly higher intima-media thickness (African American 0.41 ± 0.06, white 0.39 ± 0.05 mm), and carotid systolic blood pressure (African American 106 ± 11, white 102 ± 8 mm Hg; P < .05) compared with white children, although these racial differences were no longer present after covariate adjustments for height. CONCLUSIONS: Racial differences in aortic stiffness are present in childhood. Our findings suggest that racial differences in subclinical cardiovascular disease occur earlier than previously recognized.

Background lead and mercury exposures: Psychological and behavioral problems in children.

BACKGROUND: The potential harm from exposure to nonessential metals, particularly mercury (Hg) and lead (Pb), has been the focus of research for years. Initial interest focused on relatively high exposures; however, recent evidence suggests that even background exposures might have adverse consequences for child development. Identifying the extent of these consequences is now a priority. METHODS: We assessed blood Pb and Hg levels in a biracial sample of 9-11 year-old children (N = 203). Neurodevelopment and psychological functioning assessments included hostility, disruptive behaviors, emotion regulation, and autism spectrum disorder behaviors. Parasympathetic (vagal) responses to acute stress were indexed by heart rate variability (HRV) at rest and during stress. RESULTS: With increasing Pb levels, children exhibit higher levels of hostile distrust and oppositional defiant behaviors, were more dissatisfied and uncertain about their emotions, and had difficulties with communication. These significant associations were found within a range of blood Pb levels from 0.19 to 3.25µg/dL, well below the "reference value" for children of >5µg/dL. Vagal reactivity interacted with Hg such that increasing Hg was associated with increasing autism spectrum behaviors for those children with sustained vagal tone during acute stress. CONCLUSIONS: This study is the first to demonstrate an association between very low-level Pb exposure and fundamental psychological mechanisms that might explain prior associations with more complex outcomes such as delinquency. Analyses of vagal reactivity yielded entirely novel associations suggesting that Hg may increase autism spectrum behaviors in children with sustained vagal tone during acute stress. The novelty of these later findings requires additional research for confirmation and the cross-sectional nature of the data caution against assumptions of causality without further research.

Resurgence of Vaccine-Preventable Diseases in the United States: Anesthetic and Critical Care Implications.

Vaccine-preventable diseases (VPDs) such as measles and pertussis are becoming more common in the United States. This disturbing trend is driven by several factors, including the antivaccination movement, waning efficacy of certain vaccines, pathogen adaptation, and travel of individuals to and from areas where disease is endemic. The anesthesia-related manifestations of many VPDs involve airway complications, cardiovascular and respiratory compromise, and unusual neurologic and neuromuscular symptoms. In this article, we will review the presentation and management of 9 VPDs most relevant to anesthesiologists, intensivists, and other hospital-based clinicians: measles, mumps, rubella, pertussis, diphtheria, influenza, meningococcal disease, varicella, and poliomyelitis. Because many of the pathogens causing these diseases are spread by respiratory droplets and aerosols, appropriate transmission precautions, personal protective equipment, and immunizations necessary to protect clinicians and prevent nosocomial outbreaks are described.

Effects of sertraline on behavioral indices of crayfish Orconectes virilis.

Sertraline, a selective serotonin re-uptake inhibitor, is a widely prescribed antidepressant in North America. Though sertraline is continuously released from wastewater treatment plant discharge to surface water, effects of aqueous exposure of sertraline on behavioral responses of aquatic animals are largely unknown. Our study explored the effects of aqueous exposures of sertraline on antagonistic bouts and predator response behavior of virile crayfish (Orconectes virilis). Crayfish were either exposed or not exposed to waterborne sertraline and then size-matched for paired antagonistic bouts to determine if sertraline affects the aggression of each crayfish. We investigated the effect of sertraline on responses to visual predator cues and determined whether sertraline acts as an olfactory cue. Our results demonstrate that crayfish exposed to sertraline are more aggressive when paired with control crayfish but, when sertraline crayfish are paired, there is no change in aggression. Attraction response to sertraline in behavioral mazes was also observed, which may represent a maladaptive behavior, and in an ecological context may result in crayfish moving to areas with elevated levels of sertraline. However, aqueous exposure to sertraline had no effect on predator responses of crayfish. Future research is warranted to determine whether such medicine released in wastewater treatment plant effluents produces long-term ecologically important consequences for aquatic animals residing in urbanized aquatic ecosystems.

Extracurricular activities and the development of social skills in children with intellectual and specific learning disabilities.

BACKGROUND: Children with intellectual disability and specific learning disabilities often lack age-appropriate social skills, which disrupts their social functioning. Because of the limited effectiveness of classroom mainstreaming and social skills training for these children, it is important to explore alternative opportunities for social skill acquisition. Participation in social activities is positively related to children's social adjustment, but little is known about the benefits of activity participation for children with intellectual and specific learning disabilities. METHODS: This study investigated the association between frequency and type of social activity participation and the social competence of 8-11-year-old children with intellectual disability (n = 40) and specific learning disabilities (n = 53), in comparison with typically developing peers (n = 24). RESULTS: More time involved in unstructured activities, but not structured activities, was associated with higher levels of social competence for all children. This association was strongest for children with intellectual disability, suggesting that participation in unstructured social activities was most beneficial for these children. CONCLUSION: Future research on the quality of involvement is necessary to further understand specific aspects of unstructured activities that might facilitate social development.

Polybrominated diphenyl ether (PBDE) exposure in children: possible associations with cardiovascular and psychological functions.

BACKGROUND: Polybrominated diphenyl ethers (PBDE) have been used widely in consumer products and are currently found at detectable levels in the blood of humans and animals across the globe. In stark contrast to this widespread exposure to PBDEs, there is relatively little research on potential adverse health effects of exposure of children to these chemicals. OBJECTIVES: We performed this cross-sectional study to determine if blood PBDE levels (for 4 congeners) are associated with cardiovascular stress responses and psychological states in children. METHODS: Levels of 4 PBDE congeners (BDE-28, -47, -99, and -100) in whole blood were measured in children (N=43). These levels were analyzed in relation to cardiovascular disease risk factors, including cardiovascular responses to acute stress and relevant psychological variables, namely, hostility and depression. RESULTS: Higher levels of blood PBDEs were associated with significantly greater sympathetic activation during acute psychological stress and greater anger, as evidenced by significant associations with 3 different measures of this psychological variable. CONCLUSIONS: This study suggests an association between PBDE exposure and children's cardiovascular responses to stress as well as parental and self-reported anger in the child. These variables are particularly important as they may be of potential relevance to the future development of cardiovascular disease (CVD). Although intriguing, there is a need for further investigation and replication with a larger sample of children.

Low-level mercury in children: associations with sleep duration and cytokines TNF-α and IL-6.

There is a sizeable literature suggesting that mercury (Hg) exposure affects cytokine levels in humans. In addition to their signaling role in the immune system, some cytokines are also integrally associated with sleep behavior. In this cross-sectional study of 9-11 year old children (N=100), we measured total blood Hg in whole blood, serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), and objectively measured sleep and activity using actigraphy. Increasing blood Hg was associated with significantly shorter sleep duration and lower levels of TNF-α. IL-6 was not associated with sleep or blood Hg. This study is the first to document an association between total blood Hg and sleep (albeit a small effect), and the first to consider the associations of total blood Hg with cytokines TNF-α and IL-6 in a pediatric sample. Further research using alternative designs (e.g., time-series) is necessary to determine if there is a causal pathway linking low-level Hg exposure to sleep restriction and reduced cytokines.

Inactivation of infectious bursal disease and Newcastle disease viruses at temperatures below 0 C using chemical disinfectants.

This study evaluated the effectiveness of bleach, Surface Decontamination Foam (SDF), and Virkon in inactivating infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) at temperatures below 0 C. To simulate the influence of organic load on the effectiveness of disinfectants, as would be encountered in disinfecting farm vehicles and equipment, the viruses were suspended in preparations containing light or heavy levels of organic matter. A small volume of the viral suspension was applied to the upper surface of stainless steel carrier disks and these were then air dried. The dried virus inoculum was covered with disinfectant to which propylene glycol had been added to prevent freezing. The disks were incubated at various temperatures for periods up to 24 hr. With NDV, at -10 C all three disinfectants in both organic preparations achieved a 5 log 10 reduction within 5 min. Results with SDF were similar at -25 and -10 C. To achieve comparable reduction with Virkon and bleach at -25 C, contact periods up to 2 or 24 hr, respectively, were required. With IBDV, to achieve a 5 log 10 to reduction by treatment with Virkon or SDF at -20 C, contact periods of 2 or 24 hr, respectively, were required in both organic preparations. It was concluded that at temperatures as low as -20 to -25 C, SDF was the most effective disinfectant for killing NDV and Virkon was most effective for killing IBDV. The finding that a contact period of up to 2 hr was required to kill IBDV, whereas NDV was killed within 5 min, attests to the greater stability of the former virus.

Chromatographic and electrophoretic strategies for the chiral separation and quantification of d- and l-threo methylphenidate in biological matrices.

Commercially available methylphenidate (MPH) exists as a racemic mixture composed of the d- and l-threo enantiomers. Various pharmacokinetic studies of MPH have shown a greater pharmacological potency of the d-threo enantiomer. Furthermore, it was deduced that the stereoselective cleavage of MPH to produce ritalinic acid (RA) by human carboxylesterase results in a higher oral bioavailability of the d-threo enantiomer. As a requirement for pharmaceutical regulation authorities, efforts have been made to determine the differential biological distribution of d- and l-threo MPH and RA enantiomers. In support of these efforts, numerous analytical procedures have been developed for the chiral separation and quantification of MPH enantiomers in a variety of biological matrices. The available methodologies accomplish the enantioseparation and quantification of MPH using gas chromatography, liquid chromatography or capillary electrophoretic techniques coupled with a variety of detectors. The current review discusses the technical procedures involved, and the sensitivity and selectivity of these assays.

Evaluation of postprocedure cognitive function using 3 distinct standard sedation regimens for endoscopic procedures.

The primary purpose of this investigation was to evaluate postprocedure cognitive function associated with 3 distinct standard sedation regimens used for endoscopic procedures. A secondary aim was to identify complications requiring provider interventions. Subjects scheduled for colonoscopies were approached for enrollment the day of their procedure. A convenience sample of 96 subjects was randomly assigned. Cognitive function was recorded on the day of surgery using the Mini-Mental State Examination (MMSE) and 24 and 48 hours postoperatively using the Telephone Interview of Cognitive Status (TICS). The propofol plus fentanyl group had a mean TICS score of 34.53 at 24 hours compared with 34.96 at 48 hours (P = .017). The midazolam plus fentanyl group had a mean TICS score of 34.76 at 24 hours compared with 36.26 at 48 hours (P = .004). The propofol-alone group had a mean TICS score of 35.09 at 24 hours compared with 35.98 at 48 hours (P = .924). The results of this investigation indicate that the sedation regimen of propofol alone has the least impact on postprocedure cognitive function. Additionally, the number of jaw lift interventions was significantly higher in both groups who received fentanyl.