Wayne State University

About: Wayne State University is a education organization based out in Detroit, Michigan, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 42801 authors who have published 82738 publications receiving 3083713 citations. The organization is also known as: WSU & Wayne University.

Prenatal Alcohol Exposure and Childhood Behavior at Age 6 to 7 Years: I. Dose-Response Effect

Abstract: Objective. Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age. Methods. Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but 2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children9s behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and Internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included perinatal factors of maternal age, education, cigarette, cocaine, and other substances of abuse and the gestational age of the baby. Postnatal factors studied included maternal psychopathology, continuing alcohol and drug use, family structure, socioeconomic status, children9s whole blood lead level, and exposure to violence. Data were collected only from black women as there was inadequate representation of other racial groups. Statistical Analyses. Statistical analyses were performed using the SPSS statistical package. Frequency distribution, cross-tabulation, odds ratio, and χ 2 tests were used for analyzing categorical data. Continuous data were analyzed using t tests, analyses of variance (ANOVAs) with posthoc tests, and regression analysis. Results. Testing was available for 501 parent–children dyads. Almost one fourth of the women denied alcohol use during pregnancy. Low levels of alcohol use were reported in 63.8% and moderate/heavy use in 13% of pregnancies. Increasing prenatal alcohol exposure was associated with lower birth weight and gestational age, higher lead levels, higher maternal age, and lower education level, prenatal exposure to cocaine and smoking, custody changes, lower socioeconomic status, and paternal drinking and drug use at the time of pregnancy. Children with any prenatal alcohol exposure were more likely to have higher CBCL scores on Externalizing (Aggressive and Delinquent) and Internalizing (Anxious/Depressed and Withdrawn) syndrome scales and the Total Problem Score. The odds ratio of scoring in the clinical range for Delinquent behavior was 3.2 (1.3–7.6) in children with any prenatal exposure to alcohol compared with nonexposed controls. The threshold dose was evaluated with the 3 prenatal alcohol exposure groups. One-way ANOVA revealed a significant between group difference for Externalizing (Aggressive and Delinquent) and the Total Problem Score. Posthoc tests revealed the between group differences to be significant (no and low-exposure group) for Aggressive and Externalizing behavior suggesting that the adverse effects of prenatal alcohol exposure on child behavior at age 6 to 7 years are evident even at low levels of exposure. For Delinquent and Total Problem behavior, the difference was significant between the no and moderate-heavy exposure group, suggesting a higher threshold for these behaviors. Prenatal alcohol exposure remained a significant predictor of behavior after adjusting for covariates. Although maternal psychopathology was the most important predictor of behavior, gender was also a significant predictor, with boys having higher scores on Externalizing (Delinquent) and Attention Problems. The amount of variance uniquely accounted for by prenatal alcohol exposure ranged between 0.6% to 1.7%. Conclusions. Maternal alcohol consumption even at low levels was adversely related to child behavior; a dose-response relationship was also identified. The effect was observed at average levels of exposure of as low as 1 drink per week. Although effects on mean scores for Externalizing and Aggressive behaviors were observed at low levels of prenatal alcohol exposure, effects on Delinquent behavior and Total Problem Scores were observed at moderate/heavy levels of exposure. Children with any prenatal alcohol exposure were 3.2 times as likely to have Delinquent behavior scores in the clinical range compared with nonexposed children. The relationship between prenatal alcohol exposure and adverse childhood behavior outcome persisted after controlling for other factors associated with adverse behavioral outcomes. Clinicians are often asked by pregnant women if small amounts of alcohol intake are acceptable during pregnancy. These data suggest that no alcohol during pregnancy remains the best medical advice.

Galectin-3: A novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family

Abstract: Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.

Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals

Abstract: A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcγRIIB receptor complex that activated β-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor κB. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals.