Prediction models for the risk of gestational diabetes : a systematic review

Background Numerous prediction models for gestational diabetes mellitus (GDM) have been developed, but their methodological quality is unknown. The objective is to systematically review all studies describing first-trimester prediction models for GDM and to assess their methodological quality. Methods MEDLINE and EMBASE were searched until December 2014. Key words for GDM, first trimester of pregnancy, and prediction modeling studies were combined. Prediction models for GDM performed up to 14 weeks of gestation that only include routinely measured predictors were eligible. Data was extracted by the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). Data on risk predictors and performance measures were also extracted. Each study was scored for risk of bias. Results Our search yielded 7761 articles, of which 17 were eligible for review (14 development studies and 3 external validation studies). The definition and prevalence of GDM varied widely across studies. Maternal age and body mass index were the most common predictors. Discrimination was acceptable for all studies. Calibration was reported for four studies. Risk of bias for participant selection, predictor assessment, and outcome assessment was low in general. Moderate to high risk of bias was seen for the number of events, attrition, and analysis. Conclusions Most studies showed moderate to low methodological quality, and few prediction models for GDM have been externally validated. External validation is recommended to enhance generalizability and assess their true value in clinical practice

Altered serotonergic function may partially account for behavioral endophenotypes in steroid sulfatase-deficient mice

The X-linked gene STS encodes the steroid hormone-modulating enzyme steroid sulfatase. Loss-of-function of STS, and variation within the gene, have been associated with vulnerability to developing attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition characterized by inattention, severe impulsivity, hyperactivity, and motivational deficits. ADHD is commonly comorbid with a variety of disorders, including obsessive–compulsive disorder. The neurobiological role of steroid sulfatase, and therefore its potential role in ADHD and associated comorbidities, is currently poorly understood. The 39,XY*O mouse, which lacks the Sts gene, exhibits several behavioral abnormalities relevant to ADHD including inattention and hyperactivity. Here, we show that, unexpectedly, 39,XY*O mice achieve higher ratios than wild-type mice on a progressive ratio (PR) task thought to index motivation, but that there is no difference between the two groups on a behavioral task thought to index compulsivity (marble burying). High performance liquid chromatography analysis of monoamine levels in wild type and 39,XY*O brain tissue regions (the frontal cortex, striatum, thalamus, hippocampus, and cerebellum) revealed significantly higher levels of 5-hydroxytryptamine (5-HT) in the striatum and hippocampus of 39,XY*O mice. Significant correlations between hippocampal 5-HT levels and PR performance, and between striatal 5-HT levels and locomotor activity strongly implicate regionally-specific perturbations of the 5-HT system as a neurobiological candidate for behavioral differences between 40,XY and 39,XY*O mice. These data suggest that inactivating mutations and functional variants within STS might exert their influence on ADHD vulnerability, and disorder endophenotypes through modulation of the serotonergic system