Does enamelin have pleiotropic effects on organs other than the teeth? Lessons from a phenotyping screen of two enamelin‐mutant mouse lines

We analyzed two mutant mouse lines, ATE1 and ATE2, that carry point mutations in the enamelin gene which result in premature stop codons in exon 8 and exon 7, respectively. Both mutant lines show amelogenesis imperfecta. To establish the effect of mutations within the enamelin gene on different organs, we performed a systematic, standardized phenotypic analysis of both mutant lines in the German Mouse Clinic. In addition to the initially characterized tooth phenotype that is present in both mutant lines, we detected effects of enamelin mutations on bone and energy metabolism, as well as on clinical chemical and hematological parameters. These data raise the hypothesis that enamelin defects have pleiotropic effects on organs other than the teeth.     

Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Sienaert P, Lambrichts L, Dols A, De Fruyt J.
Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment‐resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.     

Urinary detection of conjugated and unconjugated anabolic steroids by dilute‐and‐shoot liquid chromatography‐high resolution mass spectrometry

Anabolic androgenic steroids (AAS) are an important class of doping agents. The metabolism of these substances is generally very extensive and includes phase‐I and phase‐II pathways. In this work, a comprehensive detection of these metabolites is described using a 2‐fold dilution of urine and subsequent analysis by liquid chromatography‐high resolution mass spectrometry (LC‐HRMS). The method was applied to study 32 different metabolites, excreted free or conjugated (glucuronide or sulfate), which permit the detection of misuse of at least 21 anabolic steroids. The method has been fully validated for 21 target compounds (8 glucuronide, 1 sulfate and 12 free steroids) and 18 out of 21 compounds had detection limits in the range of 1–10 ng mL^?1 in urine. For the conjugated compounds, for which no reference standards are available, metabolites were synthesized in vitro or excretion studies were investigated. The detection limits for these compounds ranged between 0.5 and 18 ng mL^?1 in urine. The simple and straightforward methodology complements the traditional methods based on hydrolysis, liquid‐liquid extraction, derivatization and analysis by gas chromatography–mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS). Copyright © 2014 John Wiley & Sons, Ltd.     

Risk Selection into Consumer‐Directed Health Plans: An Analysis of Family Choices within Large Employers

Objective

To identify the degree of selection into consumer-directed health plans (CDHPs) versus traditional plans over time, and factors that influence choice and temper risk selection.

Data Sources/Study Setting

Sixteen large employers offering both CDHP and traditional plans during the 2004–2007 period, more than 200,000 families.

Study Design

We model CDHP choice with logistic regression; predictors include risk scores, in addition to family, choice setting, and plan characteristics. Additional models stratify by account type or single enrollee versus family.

Data Collection/Extraction Methods

Risk scores, family characteristics, and enrollment decisions are derived from medical claims and enrollment files. Interviews with human resources executives provide additional data.

Principal Findings

CDHP risk scores were 74 percent of traditional plan scores in the first year, and this difference declined over time. Employer contributions to accounts and employee premium savings fostered CDHP enrollment and reduced risk selection. Having to make an active choice of plan increased CDHP enrollment but also increased risk selection. Risk selection was greater for singles than families and did not differ between HRA and HSA-based CDHPs.

Conclusions

Risk selection was not severe and it was well managed. Employers have effective methods to encourage CDHP enrollment and temper selection against traditional plans.     

Bone Response to High-Intensity Interval Training versus Moderate-Intensity Continuous Training in Adolescents with Obesity

IntroductionSince adolescents with obesity are prone to bone fragility during weight loss, the aim was to compare the impact of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on bone density, geometry, and strength.MethodsSixty-one adolescents were randomly assigned to 2 cycling trainings (HIIT and MICT) and a control (CTR, without training) group. Anthropometry, dual-energy X-ray absorptiometry with hip structural analysis and the trabecular bone score (TBS) were assessed before and after the 16-week intervention.ResultsBody mass index (BMI) and fat mass (FM) percentage decreased at T1 versus T0 in both training groups (p < 0.001 for HIIT, p = 0.01 for MICT), though to a larger extent in HIIT (p < 0.05). Total body bone mineral density (BMD) and bone mineral content (BMC) increased in both training groups (p < 0.001), but to a greater extent in HIIT for BMC (p < 0.05). Lumbar spine BMD and BMC increased in both training groups (p < 0.001 for HIIT, p < 0.01 for MICT), with a time × group interaction between HIIT and CTR (p < 0.05) only. TBS increased in both training groups (p < 0.01 for HIIT, p < 0.05 for MICT). Hip BMD and BMC increased in both HIIT (p < 0.001 and p < 0.01) and MICT (p < 0.01 and p < 0.05). At the narrow neck (NN), endocortical diameter, width (p < 0.01), cross-sectional moment of inertia, and section modulus (Z) (p < 0.05) increased only in the HIIT group, such as BMD and Z (p < 0.05) at the intertrochanteric region (IT) and average cortical thickness (p < 0.001) and width (p < 0.05) at the femoral shaft. At the NN and IT, the buckling ratio decreased only in the HIIT group (p < 0.05), predicting higher resistance to fracture.ConclusionsIn addition to inducing greater BMI and FM percentage decreases in comparison to MICT, HIIT improves multisite bone density, geometry, and strength, which heighten the justification for HIIT as part of weight loss interventions in adolescents with obesity.