Binge alcohol exposure once a week in early pregnancy predicts temperament and sleeping problems in the infant

Background

Prenatal alcohol exposure can cause several cognitive and behavioral difficulties. Few studies have investigated the associations with infant temperament or sleeping patterns. Our aim was to study potential associations between early prenatal binge exposure and infant temperament and sleeping pattern.

Methods

In a population based longitudinal study, representative of pregnant women in Oslo, questionnaires were answered at 17 and 30 weeks of pregnancy and 6 months after term. Two factors, difficult temperament and sleeping problems, were identified using Principal Component Analysis and dichotomized at the least optimal 14-15%. Logistic regression analyses identified predictive factors.

Results

Maternal binge drinking (≥ 5 drinks per occasion) once a week during pregnancy week 0-6 significantly predicted both difficult temperament (Odds Ratio OR 3.3**; 95% Confidence interval CI 1.4-7.9) and sleeping problems (OR 5.3**; 95% CI 2.1-13.7) in the infant, after adjusting for other confounding factors. Including binge drinking more often than once a week, further increased the OR of sleeping problems (6.0***; 2.7-13.7). Prenatal maternal depressive symptoms also predicted both outcomes. Reduced birth weight predicted difficult temperament. Maternal satisfaction with life reduced the probability of sleeping problems. Maternal smoking, and work stress, during pregnancy had no predictive power. The results were not explained by binge drinking later during pregnancy or higher consumption per occasion.

Conclusions

Binge drinking once a week during pregnancy week 0-6 had stronger predictive power of difficult temperament and sleeping problems during infancy, than other covariates. The findings support advising women to avoid binge drinking when planning pregnancy.     

Back-neck pain and symptoms of anxiety and depression: a population-based twin study

BACKGROUND: Clinical and epidemiological studies have shown an association between anxiety and depression and pain in the back and neck. The nature of this relationship is not clear. This study aimed to investigate the extent to which common genetic and environmental aetiological factors contribute to the covariance between symptoms of anxiety and depression and back-neck pain. METHODS: Measures of back-neck pain and symptoms of anxiety and depression were part of a self-report questionnaire sent in 1992 to twins born in Norway between 1967 and 1974 (3996 pairs). Structural equation modelling was applied to determine to what extent back-neck pain and symptoms of anxiety and depression share genetic and environmental liability factors. RESULTS: The phenotypic correlation between symptoms of anxiety and depression and back-neck pain was 0.31. Individual differences in both anxiety and depression and back-neck pain were best accounted for by additive genetic and individual environmental factors. Heritability estimates were 0.53 and 0.30 respectively. For back-neck pain, however, a model specifying only shared- and individual environmental effects could not be rejected. Bivariate analyses revealed that the correlation between back-neck pain and symptoms of anxiety and depression was best explained by additive genetic and individual environmental factors. Genetic factors affecting both phenotypes accounted for 60% of the covariation. There were no significant sex differences. CONCLUSION: The results support previous findings of a moderate association between back-neck pain and symptoms of anxiety and depression, and suggest that this association is primarily due to common genetic effects.     

Genetic and Environmental Causes of Variation in Trait Resilience in Young People

The aim of this multi-informant twin study was to determine the relative role of genetic and environmental factors in explaining variation in trait resilience in adolescents. Participants were consenting families (N = 2,638 twins in 1,394 families), from seven national cohorts (age 12–18 years, both sexes) of monozygotic and dizygotic twins reared together. Questionnaire data on the adolescents’ Ego-resilience (ER89) was collected from mothers, fathers and twins, and analysed by means of multivariate genetic modelling. Variance in trait resilience was best represented in an ADE common pathways model with sex limitation. Variance in the latent psychometric resilience factor was largely explained by additive genetic factors (77% in boys, 70% in girls), with the remaining variance (23 and 30%) attributable to non-shared environmental factors. Additive genetic sources explained more than 50% of the informant specific variation in mothers and fathers scores. In twins, additive and non-additive genetic factors together explained 40% and non-shared environmental factor the remaining 60% of variation. In the mothers’ scores, the additive genetic effect was larger for boys than for girls. The non-additive genetic factor found in the twins’ self ratings was larger in boys than in girls. The remaining sex differences in the specific factors were small. Trait resilience is largely genetically determined. Estimates based on several informants rather than single informants approaches are recommended.     

Ricin transport into cells: studies of endocytosis and intracellular transport

The plant toxin ricin binds to both glycoproteins and glycolipids with terminal galactose, and the toxin will therefore be endocytosed by the different mechanisms operating in a given cell. After endocytosis the toxin is transported to the Golgi apparatus by a process that differs from the Rab9-dependent transport of mannose-6-phosphate receptors. Retrograde toxin transport from the Golgi apparatus to the endoplasmic reticulum (ER) seems to be a requirement for subsequent toxin translocation to the cytosol where the toxin inhibits protein synthesis enzymatically. By using ricin we have characterized different types of endocytosis and the transport steps used by this toxin.     

A genetic study of the acute anxious response to carbon dioxide stimulation in man

People with panic disorder-agoraphobia and their relatives often react anxiously to CO(2)-enriched gas mixtures. Available data are not suited to disentangle genetic from common environmental causes of familial aggregation of CO(2) reactivity, nor provide quantitative estimations of the sources of trait variation. Three-hundred-forty-six twin pairs belonging to the general population-based Norwegian NIPH Mental Health Study underwent self-assessments of anxiety and of DSM-IV panic symptoms after inhalation of a 35%CO(2)-65%O(2) mixture. Two thresholds were employed - at sample's 75th and 90th percentiles of responses - to define provoked panic attacks and to calculate polychoric correlations. Variance components were estimated by structural equation modelling (SEM). For definitions of responses based on the sum of all 13 panic symptoms, SEM could not discriminate between shared environmental versus genetic causes of familial resemblance for provoked attacks. For definitions of responses based on global anxiety, or on the sums of those symptoms (dyspnea, dizziness, palpitations) with highest variance post-CO(2), the best-fitting models indicated additive genetic factors as the sole causes for within-family resemblance. Best-fit heritability estimates ranged from 0.42 to 0.57. Genetic and idiosyncratic environmental factors explain most of individual differences in reactivity to hypercapnia. Within-family similarities for this trait are largely explained by genetic determinants.     

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

Introduction  

The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function.     

Is social anxiety disorder in childhood associated with developmental deficit/delay?

Children with social anxiety disorder (SAD) have been reported to display reduced social skills. Less attention has been paid to whether neurodevelopmental deficits/delays (NDD’s) in language and motor function may contribute to their impaired social skills. The present study aimed to assess the extent of language and motor impairment in children with SAD. A population-based screened sample consisting of 150 children (11–12 years) was assessed with a diagnostic interview (Kiddie-SADS), the Wechsler Abbreviated Scale of Intelligence (WASI) and the Motor Assessment Battery for Children (MABC). Test results were compared across five diagnostic groups: SAD (n = 29); ADHD (n = 23); SAD and ADHD (n = 6); “other disorder” (n = 44) and “no disorder” (n = 48). Delays in language and motor development as reported by mother were also investigated. Verbal IQ and motor skills were reduced and maternally reported delay was more frequent in the SAD group compared to the “other disorder” and “no disorder” group.     

Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death

Background

B cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common paediatric cancer. BCP-ALL blasts typically retain wild type p53, and are therefore assumed to rely on indirect measures to suppress transformation-induced p53 activity. We have recently demonstrated that the second messenger cyclic adenosine monophosphate (cAMP) through activation of protein kinase A (PKA) has the ability to inhibit DNA damage-induced p53 accumulation and thereby promote survival of the leukaemic blasts.Development of BCP-ALL in the bone marrow (BM) is supported by resident BM-derived mesenchymal stromal cells (MSCs). MSCs are known to produce prostaglandin E₂ (PGE₂) which upon binding to its receptors is able to elicit a cAMP response in target cells. We hypothesized that PGE₂ produced by stromal cells in the BM microenvironment could stimulate cAMP production and PKA activation in BCP-ALL cells, thereby suppressing p53 accumulation and promoting survival of the malignant cells.

Methods

Primary BCP-ALL cells isolated from BM aspirates at diagnosis were cocultivated with BM-derived MSCs, and effects on DNA damage-induced p53 accumulation and cell death were monitored by SDS-PAGE/immunoblotting and flow cytometry-based methods, respectively. Effects of intervention of signalling along the PGE₂-cAMP-PKA axis were assessed by inhibition of PGE₂ production or PKA activity. Statistical significance was tested by Wilcoxon signed-rank test or paired samples t test.

Results

We demonstrate that BM-derived MSCs produce PGE₂ and protect primary BCP-ALL cells from p53 accumulation and apoptotic cell death. The MSC-mediated protection of DNA damage-mediated cell death is reversible upon inhibition of PGE₂ synthesis or PKA activity. Furthermore our results indicate differences in the sensitivity to variations in p53 levels between common cytogenetic subgroups of BCP-ALL.

Conclusions

Our findings support our hypothesis that BM-derived PGE₂, through activation of cAMP-PKA signalling in BCP-ALL blasts, can inhibit the tumour suppressive activity of wild type p53, thereby promoting leukaemogenesis and protecting against therapy-induced leukaemic cell death. These novel findings identify the PGE₂-cAMP-PKA signalling pathway as a possible target for pharmacological intervention with potential relevance for treatment of BCP-ALL.