Exposure to perfluoroalkyl acids and markers of kidney function among children and adolescents living near a chemical plant.

BACKGROUND: Serum levels of perfluorooctanoic acid (PFOA) have been associated with decreased renal function in cross-sectional analyses, but the direction of the association is unclear. OBJECTIVES: We examined the association of measured and model-predicted serum PFOA concentrations with estimated glomerular filtration rate (eGFR), a marker of kidney function, in a highly exposed population (median serum PFOA, 28.3 ng/mL). METHODS: We measured serum creatinine, PFOA, perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) and calculated eGFR in 9,660 children 1 to < 18 years of age at study enrollment. We predicted concurrent and historical serum PFOA concentrations using a validated environmental, exposure, and pharmacokinetic model based on individual residential histories, and used linear regression to estimate the association between eGFR and measured and predicted serum PFOA concentrations. We hypothesized that predicted serum PFOA levels would be less susceptible to reverse causation than measured levels. RESULTS: An interquartile range increase in measured serum PFOA concentrations [IQR ln(PFOA) = 1.63] was associated with a decrease in eGFR of 0.75 mL/min/1.73 m(2) (95% CI: -1.41, -0.10; p = 0.02). Measured serum levels of PFOS, PFNA, and PFHxS were also cross-sectionally associated with decreased eGFR. In contrast, predicted serum PFOA concentrations at the time of enrollment were not associated with eGFR (-0.10; 95% CI: -0.80, 0.60; p = 0.78). Additionally, predicted serum PFOA levels at birth and during the first ten years of life were not related to eGFR. CONCLUSIONS: Our findings suggest that the cross-sectional association between eGFR and serum PFOA observed in this and prior studies may be a consequence of, rather than a cause of, decreased kidney function

Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play

In response to queries about whether brain imaging technology has reached the point where it is useful for making a clinical diagnosis and for helping to guide treatment selection, the American Psychiatric Association (APA) has recently written a position paper on the Clinical Application of Brain Imaging in Psychiatry. The following perspective piece is based on our contribution to this APA position paper, which specifically emphasized the application of neuroimaging in mood disorders. We present an introductory overview of the challenges faced by researchers in developing valid and reliable biomarkers for psychiatric disorders, followed by a synopsis of the extant neuroimaging findings in mood disorders, and an evidence-based review of the current research on brain imaging biomarkers in adult mood disorders. Although there are a number of promising results, by the standards proposed below, we argue that there are currently no brain imaging biomarkers that are clinically useful for establishing diagnosis or predicting treatment outcome in mood disorders

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size). Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML

The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

Pregnancy-induced hypertension in North Carolina, 1988 and 1989.

INTRODUCTION: Pregnancy-induced hypertension (PIH) is a highly prevalent pregnancy complication with adverse effects on maternal and infant health. Epidemiologic research concerning its etiology is limited. METHODS: Birth records from North Carolina for the period 1988 through 1989 included an indication of the presence of PIH. The risk of PIH was examined in relation to several maternal characteristics and exposures, including reproductive history, demographic characteristics, and tobacco use during pregnancy. Risk ratio estimates, adjusted for confounders, were calculated contrasting PIH among exposed vs unexposed women. RESULTS: The overall risk of PIH was 43.1 per 1000 births, with multiple pregnancies, nulliparity, and advanced maternal age associated with markedly increased risks. Tobacco use was inversely associated with PIH, and Blacks and Whites were at virtually equal risk. CONCLUSIONS: Problems in diagnosis and classification impede research in this area, with birth certificates limited in quality and breadth of information. Nonetheless, several patterns emerged that are worthy of further epidemiologic evaluation using more sophisticated designs

Modeling the variability of shapes of a human placenta

While it is well-understood what a normal human placenta should look like, a deviation from the norm can take many possible shapes. In this paper we propose a mechanism for this variability based on the change in the structure of the vascular tree

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Parental occupation and childhood cancer: review of epidemiologic studies.

Parental occupational exposures might affect childhood cancer in the offspring through genetic changes in the ovum or sperm or through transplacental carcinogenesis. The 24 published epidemiologic studies of this association have all used case-control designs, with controls generally selected from birth certificates or from general population sampling. Occupational exposures were inferred from job titles on birth certificates or through interviews. A large number of occupation-cancer associations have been reported, many of which were not addressed or not confirmed in other studies. Several associations have been found with consistency: paternal exposures in hydrocarbon-associated occupations, the petroleum and chemical industries, and especially paint exposures have been associated with brain cancer; paint exposures have also been linked to leukemias. Maternal exposures have received much less attention, but studies have yielded strongly suggestive results linking a variety of occupational exposures to leukemia and brain cancer. The primary limitations in this literature are the inaccuracy inherent in assigning exposure based on job title alone and imprecision due to limited study size. Although no etiologic associations have been firmly established by these studies, the public health concerns and suggestive data warrant continued research

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

Pesticides and childhood cancers.

To evaluate the possible association between pesticides and the risk of childhood cancers, epidemiologic studies published between 1970 and 1996 were critically reviewed. Thirty-one studies investigated whether occupational or residential exposure to pesticides by either parents or children was related to increased risk of childhood cancer. In general, the reported relative risk estimates were modest. Risk estimates appeared to be stronger when pesticide exposure was measured in more detail. Frequent occupational exposure to pesticides or home pesticide use was more strongly associated with both childhood leukemia and brain cancer than either professional exterminations or the use of garden pesticides. Occupational pesticide exposure was also associated with increased risk of Wilms' tumor, Ewing's sarcoma, and germ cell tumors. Residence on a farm, a proxy for pesticide exposure, was associated with increased risk of a number of childhood cancers. Although increased risk of some childhood cancers in association with pesticide exposure is suggested by multiple studies, methodological limitations common to many studies restrict conclusions; these include indirect exposure classification, small sample size, and potential biases in control selection. Opportunities for methodologic improvement in future studies of pesticides and childhood cancers are described