Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Comparison of Two Genotyping Methods for Distinguishing Recrudescence from Reinfection in Antimalarial Drug Efficacy/Effectiveness Trials.

Genotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 (msp-1 and msp-2), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher's exact test; P = 0.887 and P = 0.768, respectively). There was a strong agreement between the two methods in predicting treatment outcomes and resolving the genetic complexity of malaria infections in this setting. These results support the use of this SNP assay as an alternative method for correcting antimalarial efficacy/effectiveness data.

Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm.

OBJECTIVE: A neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age. STUDY DESIGN: In a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child's medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders. RESULTS: An undesirably high SNAP-II (⩾30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports. In analyses that adjusted for potential confounders, Z-scores ⩽-1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category, and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4.6). CONCLUSION: Among very preterm newborns, physiologic derangements present in the first 12 postnatal hours are associated with dysfunctions in several neurodevelopmental domains at 10 years of age. We are unable to make inferences about causality.

Overexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration.

PURPOSE: To test the hypothesis that overexpression of genes coding for the anti-apoptotic proteins Bcl-2 or Bcl-XL in photoreceptor cells may prevent or delay photoreceptor degenerations. METHODS: Transgenic mice were generated in which the bcl-2 or bcl-XL transgenes were expressed in photoreceptor cells under the transcriptional control of a rhodopsin gene promoter. Bcl-2 or bcl-XL transgenic mice were crossed separately to a mouse strain carrying the rd/rd mutation and to another mouse line carrying a dominant rhodopsin gene mutation; both genetic defects result in photoreceptor degeneration. Photoreceptor cell death in mice expressing one of the bcl transgenes and carrying either the rd mutation homozygously or the rhodopsin mutation heterozygously was examined by histologic and electroretinographic measurements. Bcl-2 and bcl-XL transgenic mice also were tested for possible resistance to light-induced photoreceptor damage under two different experimental conditions. RESULTS: Bcl-2 or bcl-XL transgenes were expressed in photoreceptor cells of all lines of transgenic mice. In both the rd and the rhodopsin mutant mice, expression of either bcl-2 or bcl-XL transgenes did not prevent or measurably delay photoreceptor degeneration. Apoptosis-related nuclear DNA fragmentation, as assessed by in situ labeling with terminal deoxynucleotidyl transferase, was present in 13-day-old rd/rd mouse retinas with or without transgene expression. Twelve days after exposure to 2 hours of high-intensity light, bcl-2 transgenic mice retained approximately four rows of photoreceptor cells in the central retina as compared to none in littermate controls, whereas bcl-XL transgenic mice showed no increased resistance to light damage. Expression of the bcl-2 but not the bcl-XL transgene also was associated with a reduction in rhodopsin content. CONCLUSIONS: Overexpression of bcl-2 or bcl-XL transgenes does not rescue photoreceptor cells from apoptosis caused by the two genetic mutations tested. Resistance to light damage seen in the bcl-2 transgenic mice is likely from a reduction in rhodopsin content rather than an anti-cell death activity of Bcl-2. Cell death pathways not regulated by Bcl-2 may be operative in photoreceptor degeneration.

Protective effects of zinc in indomethacin-induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide.

BACKGROUND: Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals. AIM: To determine (i) the protective effects of zinc in indomethacin-induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity. METHODS: Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre-treated with zinc sulphate and in controls. RESULTS: Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre-treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre-treated with N-nitro-L-arginine methyl ester (L-NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre-treatment. CONCLUSIONS: Zinc provides protection against indomethacin-induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.

An investigation of attention and affect in children with autism and Down syndrome.

Longitudinal videotape recordings of six young children with autism and six age- and language-matched children with Down syndrome in structured play with their mothers at home were coded for the focus of the child's visual attention for four bimonthly visits and for facial affect for two of the four visits. The main finding was that the children with autism showed reduced expression of positive affect in a familiar social context. The autistic group attended to the mother's face and the researchers only about half as much as the Down syndrome group, but these differences did not reach statistical significance. Compared to the Down syndrome group, the autistic group displayed a smaller proportion of their total positive affect toward the mother's face and toward the researcher, but only the latter group difference reached statistical significance. Although limited by the small sample size, these findings suggest that autistic children's known deficits in attention and affective responsiveness to others persist even in structured interactions with a familiar partner in the home.

Intention and knowledge in preschoolers' conception of pretend.

Experiments 1 and 2 investigated 3- and 4-year-olds' understanding of the intended nature of pretend behaviors by testing their ability to distinguish between involuntary behaviors and the same behaviors emitted intentionally through acts of pretend. Four-year-olds' high rate of passing showed that (1) they understood intention as a mental cause of action and (2) they construed pretend behaviors mentalistically. Experiment 3 used the same contrastive procedure to examine Lillard's contention that 4-year-olds do not understand the knowledge conditions and hence the mental representational component of pretend actions. Whereas nearly all of the 5-year-olds understood that an agent who did not know of a specific animal could not be pretending to be that animal, 4-year-olds systematically associated ignorance with pretend. On the basis of the combined findings of the present experiments, and other research showing a mentalistic understanding of pretense by the age of 3 or 4, it was concluded that the specific reasoning requirements of Lillard's tasks resulted in an underestimation of children's appreciation of the mental features of pretend.

Neuropsychological frameworks for understanding autism.

Neuropsychological theories have traditionally attempted to provide a unifying account of the complex and diverse behavioral manifestations of autism in terms of their underlying psychological mechanisms and associated brain bases. This article reviews three competing neuropsychological theories of autism: the executive dysfunction hypothesis, the weak central coherence hypothesis, and the limbic system hypothesis. Each theory is evaluated critically with regard to the primary neuropsychological deficit hypothesized and the research findings that have been offered in support of it. In a concluding section, some of the metatheoretical assumptions informing attempts to identify a "core" neuropsychological impairment in autism are outlined and questioned, and new approaches to a neuropsychological understanding of autism are suggested.

Direct time integration of Maxwell's equations in two-dimensional dielectric waveguides for propagation and scattering of femtosecond electromagnetic solitons.

We present what are to our knowledge first-time calculations from vector nonlinear Maxwell's equations of femtosecond soliton propagation and scattering, including carrier waves, in two-dimensional dielectric waveguides. The time integration efficiently implements linear and nonlinear convolutions for the electric polarization, and the nonlinear convolution accounts for two quantum effects, the Kerr and Raman interactions. By retaining the optical carrier, the new method solves for fundamental quantities-optical electric and magnetic fields in space and time-rather than a nonphysical envelope function. It has the potential to provide an unprecedented two- and three-dimensional modeling capability for millimeter-scale integrated-optical circuits with submicrometer engineered inhomogeneities.