An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood.

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.

Diagnostic cutoff for pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve: A patient-level analysis.

OBJECTIVES AND BACKGROUND: Functional assessment of intermediate coronary stenosis during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR). CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a nondimensional index derived from fundamental fluid dynamic principles, based on a combination of intracoronary pressure, and flow measurements may improve the functional assessment of coronary lesion severity. METHODS: Patient-level data pertaining to 350 intracoronary pressure and flow measurements across coronary stenoses was assessed to evaluate CFR, FFR, HSR, HMR, and CDP. CDP was calculated as (ΔP)/(0.5 × ρ × APV(2)). The density of blood (ρ) was assumed to be 1.05 g/cm(3). The correlation of current diagnostic parameters (CFR, FFR, HSR, and HMR) with CDP was evaluated. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off point of CDP, corresponding to the clinically used cut-off values (FFR = 0.80 and CFR = 2.0). RESULTS: CDP correlated significantly with FFR (r = 0.81, P < 0.05) and had significant diagnostic efficiency (ROC-area under curve of 86%), specificity (72%) and sensitivity (85%) at FFR < 0.8. The corresponding cut-off value for CDP to detect FFR < 0.8 was at CDP>25.4. CDP also correlated significantly (r = 0.98, P < 0.05) with epicardial-specific parameter, HSR. CONCLUSIONS: CDP, a functional parameter based on both intracoronary pressure and flow measurements, has close agreement (area under ROC curve = 86%) with FFR, the frequently used method of evaluating stenosis severity.

Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. OBJECTIVE: To quantify the risk associated with genes and environment on familial clustering of EoE. METHODS: Family history was obtained from a hospital-based cohort of 914 EoE probands (n = 2192 first-degree "Nuclear-Family" relatives) and an international registry of monozygotic and dizygotic twins/triplets (n = 63 EoE "Twins" probands). Frequencies, recurrence risk ratios (RRRs), heritability, and twin concordance were estimated. Environmental exposures were preliminarily examined. RESULTS: Analysis of the Nuclear-Family-based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10 to 64, depending on the family relationship, and were higher in brothers (64.0; P = .04), fathers (42.9; P = .004), and males (50.7; P < .001) than in sisters, mothers, and females, respectively. The risk of EoE for other siblings was 2.4%. In the Nuclear-Family cohort, combined gene and common environment heritability was 72.0% ± 2.7% (P < .001). In the Twins cohort, genetic heritability was 14.5% ± 4.0% (P < .001), and common family environment contributed 81.0% ± 4% (P < .001) to phenotypic variance. Probandwise concordance in monozygotic co-twins was 57.9% ± 9.5% compared with 36.4% ± 9.3% in dizygotic co-twins (P = .11). Greater birth weight difference between twins (P = .01), breast-feeding (P = .15), and fall birth season (P = .02) were associated with twin discordance in disease status. CONCLUSIONS: EoE RRRs are increased 10- to 64-fold compared with the general population. EoE in relatives is 1.8% to 2.4%, depending on relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, the Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%).

Muscular activity of lower limb muscles associated with working on inclined surfaces.

This study investigated the effects of visual cues, muscular fatigue, task performance and experience of working on inclined surfaces on activity of postural muscles in the lower limbs associated with maintaining balance on three inclined surfaces - 0°, 14° and 26°. Normalised electromyographic (NEMG) data were collected in 44 professional roofers bilaterally from the rectus femoris, biceps femoris, tibialii anterior and gastrocnemii medial muscle groups. The 50th and 95th percentile NEMG amplitudes were used as EMG variables. Results showed that inclination angle and task performance caused a significant increase in the NEMG amplitudes of all postural muscles. Visual cues were significantly associated with a decrease in the 95th percentile EMG amplitude for the right gastrocnemius medial and tibialis anterior. Fatigue was related to a significant decrease in the NEMG amplitude for the rectus femoris. Experience of working on inclined surfaces did not have a significant effect on the NEMG amplitude.

Effect of myocardial contractility on hemodynamic end points under concomitant microvascular disease in a porcine model.

In this study, coronary diagnostic parameters, pressure drop coefficient (CDP: ratio of trans-stenotic pressure drop to distal dynamic pressure), and lesion flow coefficient (LFC: ratio of % area stenosis (%AS) to the CDP at throat region), were evaluated to distinguish levels of %AS under varying contractility conditions, in the presence of microvascular disease (MVD). In 10 pigs, %AS and MVD were created using angioplasty balloons and 90-µm microspheres, respectively. Simultaneous measurements of pressure drop, left ventricular pressure (p), and velocity were obtained. Contractility was calculated as (dp/dt)max, categorized into low contractility <900 mmHg/s and high contractility >900 mmHg/s, and in each group, compared between %AS <50 and >50 using analysis of variance. In the presence of MVD, between the %AS <50 and >50 groups, values of CDP (71 ± 1.4 and 121 ± 1.3) and LFC (0.10 ± 0.04 and 0.19 ± 0.04) were significantly different (P < 0.05), under low-contractility conditions. A similar %AS trend was observed under high-contractility conditions (CDP: 18 ± 1.4 and 91 ± 1.4; LFC: 0.08 ± 0.04 and 0.25 ± 0.04). Under MVD conditions, similar to fractional flow reserve, CDP and LFC were not influenced by contractility.

Implementation of a comprehensive intervention to reduce physical assaults and threats in the emergency department.

INTRODUCTION: The purpose of this study was to test the effectiveness of a comprehensive program to reduce the incidence of workplace violence (WPV) against ED providers by patients and visitors. METHODS: An intervention study was conducted with 3 intervention and 3 comparison emergency departments. Participants completed monthly surveys during an 18-month period to measure violent event rates before and after the WPV intervention implementation. Descriptive statistics were used to describe violent events. Analysis of variance was used to assess if the emergency departments participating in the WPV intervention experienced a significant reduction in violence rates compared with nonintervention emergency departments. RESULTS: On average, participants experienced more than 6 incidents of violence during the 18-month study period. Although the study hypothesis was not supported, 2 intervention sites had a significant decrease in violence. DISCUSSION: This study emphasizes the risk of WPV to ED workers and highlights the need for prevention programs. Future research needs to be conducted to test additional comprehensive WPV prevention interventions.

Environmental health and household demographics impacting biosand filter maintenance and diarrhea in Guatemala: an application of structural equation modeling.

In rural health development practice, engineers and scientists must recognize the complex interactions that influence individuals' contact with disease-causing pathogens and understand how household habits may impact the adoption and long-term sustainability of new technology. The goal of this study was to measure the effect of various environmental health factors and household demographics on the operation and maintenance of the Biosand filter (Centre for Affordable Water and Sanitation Technology, Calgary, Alberta, Canada) and diarrhea health burden in the region. In July and August 2010, randomized household surveys (n = 286) were completed in rural Guatemala detailing water access, sanitation availability, hygiene practice, socio-economic status, education level, filter operation and maintenance, and diarrhea health burden of the home. A hypothesized structural equation model was developed based on a review of published research and tested using the surveyed data. Model-derived parameter estimates indicated that: (a) proper personal hygiene practices significantly promote proper filter operation and maintenance; and (b) higher household education level, proper filter operation and maintenance, and improved water supply significantly reduce diarrhea health burden. Additionally, a high level of unexplained variance in diarrhea indicated the filter, though protective of health, is not the only factor influencing diarrhea.

Longitudinal assessment of hemodynamic endpoints in predicting arteriovenous fistula maturation.

Arteriovenous fistula (AVF) nonmaturation is currently a significant clinical problem; however, the mechanisms responsible for this have remained unanswered. Previous work by our group and others has suggested that anatomical configuration and the corresponding hemodynamic endpoints could have an important role in AVF remodeling. Thus, our goal was to assess the longitudinal (temporal) effect of wall shear stress (WSS) on remodeling process of AVFs with two different configurations. The hypothesis is that early assessment of hemodynamic endpoints such as temporal gradient of WSS will predict the maturation status of AVF at later time points. Two AVFs with curved (C-AVF) and straight (S-AVF) configurations were created between the femoral artery and vein of each pig. Three pigs were considered in this study and in total six AVFs (three C-AVF and three S-AVF) were created. The CT scan and ultrasound were utilized to numerically evaluate local WSS at 20 cross-sections along the venous segment of AVFs at 2D (D: days), 7D, and 28D postsurgery. These cross-sections were located at 1.5 mm increments from the anastomosis junction. Local WSS values at these cross-sections were correlated with their corresponding luminal area over time. The WSS in C-AVF decreased from 22.3 ± 4.8 dyn/cm(2) at 2D to 4.1 ± 5.1 dyn/cm(2) at 28D, while WSS increased in S-AVF from 13.0 ± 5.0 dyn/cm(2) at 2D to 36.7 ± 5.3 dyn/cm(2) at 28D. Corresponding to these changes in WSS levels, luminal area of C-AVF dilated (0.23 ± 0.14 cm(2) at 2D to 0.87 ± 0.14 cm(2) at 28D) with attendant increase in flow rate. However, S-AVF had minimal changes in area (0.26 ± 0.02 cm(2) at 2D to 0.27 ± 0.03 cm(2) at 28D) despite some increase in flow rate. Our results suggest that the temporal changes of WSS could have significant effects on AVF maturation. Reduction in WSS over time (regardless of initial values) may result in dilation (p < 0.05), while increase in WSS may be detrimental to maturation. Thus, creation of AVFs in a specific configuration which results in a decline in WSS over time may reduce AVF maturation failure.

Impact of low-level gestational exposure to organophosphate pesticides on neurobehavior in early infancy: a prospective study.

BACKGROUND: National data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy. METHODS: Among a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression. RESULTS: After adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy. CONCLUSIONS: In this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.

The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial.

BACKGROUND: Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other. METHODS: This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern. RESULTS: We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%). CONCLUSIONS: This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.

Prospective study of violence against ED workers.

BACKGROUND: Health care support occupations have an assault-injury rate nearly 10 times the general sector. Emergency departments (EDs) are at greatest risk of such events. OBJECTIVE: The objective was to describe the incidence of violence in ED health care workers (HCWs) over 9 months. Specific aims were to (1) identify demographic, occupational, and perpetrator factors related to violent events (VEs) and (2) identify predictors of acute stress in victims and predictors of loss of productivity. METHODS: A longitudinal, repeated-methods design was used to collect monthly survey data from ED HCWs at 6 hospitals. Surveys assessed number and type of VEs, and feelings of safety and confidence. Victims also completed specific VE surveys. Descriptive statistics and a repeated-measure linear regression model were used. RESULTS: Two hundred thirteen ED HCWs completed 1795 monthly surveys and 827 VEs were reported. Average VE rate per person per 9 months was 4.15. Six hundred one events were physical threats (PTs) (3.01 per person). Two hundred twenty six events were assaults (1.13 per person). Five hundred one VE surveys were completed, describing 341 PTs and 160 assaults. Men perpetrated 63% of PTs and 52% of assaults. Significant differences in VEs were reported between registered nurses (RNs) and medical doctors (MDs) (P = .0017) and patient care assistants (P < .05). The RNs felt less safe than the MDs (P = .0041). The MDs felt more confident than the RNs in dealing with violent patients (P = .013). The RNs were more likely to experience acute stress than the MDs (P < .001). Acute stress reduced productivity (P < .001). CONCLUSION: Emergency department HCWs are frequent victims of violence perpetrated by visitors and patients. This results in injuries, acute stress, and lost productivity. Acute stress has negative consequences on workers' ability to perform their duties.

Secretory phospholipase A2-IIa is a target gene of the HER/HER2-elicited pathway and a potential plasma biomarker for poor prognosis of prostate cancer.

BACKGROUND: Our previous study showed that prostate cancer cells overexpress and secrete secretory phospholipases A2 group IIa (sPLA2-IIa) and plasma sPLA2-IIa was elevated in prostate cancer patients. The current study further explored the underlying mechanism of sPLA2-IIa overexpression and the potential role of sPLA2-IIa as a prostate cancer biomarker. METHODS: Plasma and tissue specimens from prostate cancer patients were analyzed for sPLA2-IIa levels. Regulation of sPLA2-IIa expression by Heregulin-α was determined by Western blot and reporter assay. RESULTS: We found that Heregulin-α enhanced expression of the sPLA2-IIa gene via the HER2/HER3-elicited pathway. The EGFR/HER2 dual inhibitor Lapatinib and the NF-kB inhibitor Bortezomib inhibited sPLA2-IIa expression induced by Heregulin-α. Heregulin-α upregulated expression of the sPLA2-IIa gene at the transcriptional level. We further confirmed that plasma sPLA2-IIa secreted by mouse bearing human prostate cancer xenografts reached detectable plasma concentrations. A receiver operating characteristic (ROC) analysis of patient plasma specimens revealed that high levels of plasma sPLA2-IIa, with the optimum cutoff value of 2.0 ng/ml, were significantly associated with high Gleason score (8-10) relative to intermediate Gleason score (6-7) prostate cancers and advanced relative to indolent cancers. The area under the ROC curve (area under curve, AUC) was 0.73 and 0.74, respectively. CONCLUSION: We found that Heregulin-α, in addition to EGF, contributes to sPLA2-IIa overexpression in prostate cancer cells. Our findings support the notion that high levels of plasma sPLA2-IIa may serve as a poor prognostic biomarker capable of distinguishing aggressive from indolent prostate cancers, which may improve decision-making and optimize patient management.

Predicting allergic disease at age four using an atopy predisposition score at age two: the application of item response theory.

When defining allergic outcomes in epidemiology studies, results of the skin prick test (SPT) panel are often dichotomized as positive/negative or categorized based on the number of positive responses. Item response theory (IRT) models, however, may prove to be a better alternative with the ability to generate scores that account for both type and number of positive SPTs. IRT was applied to SPT responses administered to 537 children at age two to determine predictability of allergic disease at age four. The children received SPTs to 15 aeroallergens and two foods. Atopy predisposition scores were obtained from the IRT model using the posterior distribution of the latent trait, atopy. These scores were used to predict persistent wheeze, rhino-conjunctivitis, and eczema at age four. Results were compared to the dichotomized and categorical (positive to ≥2, positive to one, vs. negative to all allergens) SPT variables. At age two, 39% of children had at least one positive SPT. All three allergic disease outcomes were significantly associated with IRT atopy scores: persistent wheeze odds ratio (OR) = 1.7 (95% confidence interval (CI): 1.2, 2.3); rhino-conjunctivitis OR = 1.7 (95% CI: 1.2, 2.3); eczema OR = 1.6 (95% CI: 1.2, 2.3). In contrast, rhino-conjunctivitis was the only outcome significantly associated with the dichotomized SPT variable with an OR = 1.9 (95% CI: 1.2, 3.0). For the categorical SPT variable, all three allergic symptoms were significantly associated with positive to ≥2 allergens compared to negative to all, but no difference was observed between those with positive to one compared to negative to all. The IRT model proved to be an informative methodology to assess the predictability of early SPT responses and identify the allergens most associated with atopy predisposition.

NICU Network Neurobehavioral Scale profiles predict developmental outcomes in a low-risk sample.

BACKGROUND: Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. METHODS: NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. RESULTS: Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. CONCLUSIONS: Three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations.

A Markov model to estimate Salmonella morbidity, mortality, illness duration, and cost.

Approximately 690000-1790000 Salmonella cases, 20000 hospitalizations, and 400 deaths occur in the USA annually, costing approximately $2.6bn. Existing models estimate morbidity, mortality, and cost solely from incidence. They do not estimate illness duration or use time as an independent cost predictor. Existing models may underestimate physician visits, hospitalizations, deaths, and associated costs. We developed a Markov chain Monte Carlo model to estimate illness duration, physician/emergency room visits, inpatient hospitalizations, mortality, and resultant costs for a given Salmonella incidence. Interested parties include society, third-party payers, health providers, federal, state and local governments, businesses, and individual patients and their families. The marginal approach estimates individual disease behavior for every patient, explicitly estimates disease duration and calculates separate time-dependent costs. The aggregate approach is a Markov equivalent of the existing models; it assumes average disease behavior and cost for a given morbidity/mortality. Transition probabilities were drawn from a meta-analysis of 53 Salmonella studies. Both approaches were tested using the 1993 Salmonella typhimurium outbreak in Gideon, Missouri. This protocol can be applied to estimate morbidity, mortality and cost of specific outbreaks, provide better national Salmonella burden estimates, and estimate the benefits of reducing Salmonella risk.

Evaluation of exposure biomarkers in offshore workers exposed to low benzene and toluene concentrations.

PURPOSE: Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions. METHODS: BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study. RESULTS: The geometric mean exposure over the three work shifts were 0.02 ppm benzene, 0.05 ppm toluene, 0.03 ppm ethylbenzene, and 0.06 ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r = 0.69, p < 0.001) and urine (r = 0.64, p < 0.001), but not with urinary t,t-MA (r = 0.27, p = 0.20). Toluene in air was highly correlated with the internal dose of toluene in both blood (r = 0.70, p < 0.001) and urine (r = 0.73, p < 0.001). Co-exposures were present; however, an interaction of metabolism was not likely at these low benzene and toluene exposures. CONCLUSION: Urinary benzene, but not t,t-MA, was a reliable biomarker for benzene at low exposure levels. Urinary toluene was a useful biomarker for toluene exposure. Xylene and ethylbenzene air levels were low. Dermal exposure assessment needs to be performed in future studies among these workers.

Spirituality and religiosity in urban adolescents with asthma.

Predictors of multiple dimensions of spirituality/religiosity (S/R) and adolescents' preferences for having S/R (e.g., prayer) addressed in hypothetical medical settings were assessed in a sample of urban adolescents with asthma. Of the 151 adolescents (mean age = 15.8, 60% female, 85% African-American), 81% said that they were religious and spiritual, 58% attended religious services in the past month, and 49% prayed daily. In multivariable models, African-American race/ethnicity and having a religious preference were associated with higher levels of S/R (R (2) = 0.07-0.25, P < .05). Adolescents' preferences for including S/R in the medical setting increased with the severity of the clinical situation (P < .05).

Identification of maternally regulated fetal gene networks in the placenta with a novel embryo transfer system in mice.

The mechanisms for provisioning maternal resources to offspring in placental mammals involve complex interactions between maternally regulated and fetally regulated gene networks in the placenta, a tissue that is derived from the zygote and therefore of fetal origin. Here we describe a novel use of an embryo transfer system in mice to identify gene networks in the placenta that are regulated by the mother. Mouse embryos from the same strain of inbred mice were transferred into a surrogate mother either of the same strain or from a different strain, allowing maternal and fetal effects on the placenta to be separated. After correction for sex and litter size, maternal strain overrode fetal strain as the key determinant of fetal weight (P < 0.0001). Computational filtering of the placental transcriptome revealed a group of 81 genes whose expression was solely dependent on the maternal strain [P < 0.05, false discovery rate (FDR) < 0.10]. Network analysis of this group of genes yielded highest statistical significance for pathways involved in the regulation of cell growth (such as insulin-like growth factors) as well as those involved in regulating lipid metabolism [such as the low-density lipoprotein receptor-related protein 1 (LRP1), LDL, and HDL], both of which are known to play a role in fetal development. This novel technique may be generally applied to identify regulatory networks involved in maternal-fetal interaction and eventually help identify molecular targets in disorders of fetal growth.

Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model.

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.

Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules.

BACKGROUND: Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. METHODS: Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. RESULTS: We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. CONCLUSION: Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs.