Background: In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children’s Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age.Objective: The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age.Methods: In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches.Results: On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons).Conclusions: We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.
Aims In HIV-infected individuals, heavy drinking compromises survival. In HIV primary care, the efficacy of brief motivational interviewing (MI) to reduce drinking is unknown, alcohol-dependent patients may need greater intervention and resources are limited. Using interactive voice response (IVR) technology, HealthCall was designed to enhance MI via daily patient self-monitoring calls to an automated telephone system with personalized feedback. We tested the efficacy of MI-only and MI+HealthCall for drinking reduction among HIV primary care patients. Design Parallel random assignment to control (n = 88), MI-only (n = 82) or MI+HealthCall (n = 88). Counselors provided advice/education (control) or MI (MI-only or MI+HealthCall) at baseline. At 30 and 60 days (end-of-treatment), counselors briefly discussed drinking with patients, using HealthCall graphs with MI+HealthCall patients. Setting Large urban HIV primary care clinic. Participants Patients consuming ≥4 drinks at least once in prior 30 days. Measurements Using time-line follow-back, primary outcome was number of drinks per drinking day, last 30 days. Findings End-of-treatment number of drinks per drinking day (NumDD) means were 4.75, 3.94 and 3.58 in control, MI-only and MI+HealthCall, respectively (overall model χ2, d.f. = 9.11,2, P = 0.01). For contrasts of NumDD, P = 0.01 for MI+HealthCall versus control; P = 0.07 for MI-only versus control; and P = 0.24 for MI+HealthCall versus MI-only. Secondary analysis indicated no intervention effects on NumDD among non-alcohol-dependent patients. However, for contrasts of NumDD among alcohol-dependent patients, P < 0.01 for MI+HealthCall versus control; P = 0.09 for MI-only versus control; and P = 0.03 for MI+HealthCall versus MI-only. By 12-month follow-up, although NumDD remained lower among alcohol-dependent patients in MI+HealthCall than others, effects were no longer significant. Conclusions For alcohol-dependent HIV patients, enhancing MI with HealthCall may offer additional benefit, without extensive additional staff involvement.
Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs). Studies have suggested that these helicases unzip dsNAs in single–base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. We used optical tweezers to follow the unwinding of double-stranded RNA by the hepatitis C virus NS3 helicase. Single–base pair steps by NS3 were observed, along with nascent nucleotide release that was asynchronous with base pair opening. Asynchronous release of nascent nucleotides rationalizes various observations of its dsNA unwinding and may be used to coordinate the translocation speed of NS3 along the RNA during viral replication.
Genomic testing presents multiple logistical challenges for the community-based oncologist, including coordination of sample handling, long turnaround times, test reimbursement, access to targeted therapies, insufficient tissue, and patient harm from the repeat biopsies necessary if the tissue sample is insufficient. Opportunities exist for improvement in guideline adherence, possibly through new technologies such as "liquid biopsies," which obviates the need tissue biopsy samples in select settings.
Background Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. Objectives We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (FENO) values in children. Methods The Columbia Center for Children’s Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. FENO values were measured at ages 7 to 11 years. Results Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5–0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1–1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0–1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0–1.9; P = .04) and FENO values (β = 0.1; 95% CI, 0.02–0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1–2.0], P = .005; OR, 1.4 [95% CI, 1.0–1.9], P = .03; and OR, 1.5 [95% CI, 1.0–2.1], P = .04, respectively). Conclusions This is the first report of an association between postnatal urinary BPA concentrations and asthma in children.
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