Diet‐induced obesity increases the frequency of Pig‐a mutant erythrocytes in male C57BL/6J mice

Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens. To test this hypothesis, we examined two in vivo genotoxicity endpoints. Pig‐a mutant frequencies and micronucleus frequencies were determined in blood cells in two independent experiments in 30‐week old male mice reared on either a high‐fat diet (60% calories from fat) that exhibit an obese phenotype or a normal‐fat diet (10% calories from fat) that do not exhibit an obese phenotype. Mice were assayed again at 52 weeks of age in one of the experiments. N‐ethyl‐N‐nitrosourea (ENU) was used as a positive mutation control in one experiment. ENU induced a robust Pig‐a mutant and micronucleus response in both phenotypes. Obese, otherwise untreated mice, did not differ from non‐obese mice with respect to Pig‐a mutant frequencies in reticulocytes or micronucleus frequencies. However, such mice, had significantly higher and sustained Pig‐a mutant frequencies (increased 2.5‐3.7‐fold, p < 0.02) in erythrocytes as compared to non‐obese mice (based on measurements collected at 30 weeks or 30 and 52 weeks of age). This suggests that obesity, in the absence of exposure to an exogenous mutagen, is itself mutagenic. Environ. Mol. Mutagen. 57:668–677, 2016. © 2016 Wiley Periodicals, Inc.     

Evidence Base Update on the Treatment of Early Childhood Anxiety and Related Problems

The controlled evaluation of treatments for early childhood anxiety and related problems has been a relatively recent area of investigation, and accordingly, trials examining early childhood anxiety treatment have not been well represented in existing systematic reviews of youth anxiety treatments. This Evidence Base Update provides the first systematic review of evidence supporting interventions specifically for the treatment of early childhood anxiety and related problems. Thirty articles testing 38 treatments in samples with mean age < 7.9 years (N = 2,228 children) met inclusion criteria. We applied Southam-Gerow and Prinstein’s (2014) review criteria, which classifies families of treatments according to one of five levels of empirical support—Well-Established, Probably Efficacious, Possibly Efficacious, Experimental, and of Questionable Efficacy. We found family-based cognitive-behavioral therapy (CBT) to be a Well-Established treatment, and Group Parent CBT and Group Parent CBT + Group Child CBT to both be Probably Efficacious treatments. In contrast, play therapy and attachment-based therapy are still only Experimental treatments for early childhood anxiety, relaxation training has Questionable Efficacy, and there is no evidence to date to speak to the efficacy of individual child CBT and/or medication in younger anxious children. All 3 currently supported interventions for early childhood anxiety entail exposure-based CBT with significant parental involvement. This conclusion meaningfully differs from conclusions for treating anxiety in older childhood that highlight the well-established efficacy of individual child CBT and/or medication and that question whether parental involvement in treatment enhances outcomes.     

Supporting skill acquisition in cochlear implant surgery through virtual reality simulation

Objectives: To evaluate the effectiveness of a virtual reality (VR) temporal bone simulator in training cochlear implant surgery.

Methods: We compared the performance of 12 otolaryngology registrars conducting simulated cochlear implant surgery before (pre-test) and after (post-tests) receiving training on a VR temporal bone surgery simulator with automated performance feedback. The post-test tasks were two temporal bones, one that was a mirror image of the temporal bone used as a pre-test and the other, a novel temporal bone. Participant performances were assessed by an otologist with a validated cochlear implant competency assessment tool. Structural damage was derived from an automatically generated simulator metric and compared between time points.

Results: Wilcoxon signed-rank test showed that there was a significant improvement with a large effect size in the total performance scores between the pre-test (PT) and both the first and second post-tests (PT1, PT2) (PT-PT1: P?=?0.007, r?=?0.78, PT-PT2: P?=?0.005, r?=?0.82).

Conclusion: The results of the study indicate that VR simulation with automated guidance can effectively be used to train surgeons in training complex temporal bone surgeries such as cochlear implantation.     

Fluorophilia: Fluorophore-containing compounds adhere non-specifically to injured neurons

Ionic (free) zinc (Zn^2 +) is implicated in apoptotic neuronal degeneration and death. In our attempt to examine the effects of Zn^2 + in neurodegeneration following brain injury, we serendipitously discovered that injured neurons bind fluorescein moieties, either alone or as part of an indicator dye, in histologic sections. This phenomenon, that we have termed “fluorophilia”, is analogous to the ability of degenerating neuronal somata and axons to bind silver ions (argyrophilia — the basis of silver degeneration stains). To provide evidence that fluorophilia occurs in sections of brain tissue, we used a wide variety of indicators such as Fluoro-Jade (FJ), a slightly modified fluorescein sold as a marker for degenerating neurons; Newport Green, a fluorescein-containing Zn^2 + probe; Rhod-5N, a rhodamine-containing Ca^2 + probe; and plain fluorescein. All yielded remarkably similar staining of degenerating neurons in the traumatic brain-injured tissue with the absence of staining in our sham-injured brains. Staining of presumptive injured neurons by these agents was not modified when Zn^2 + in the brain section was removed by prior chelation with EDTA or TPEN, whereas staining by a non-fluorescein containing Zn^2 + probe, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ), was suppressed by prior chelation. Thus, certain fluorophore-containing compounds nonspecifically stain degenerating neuronal tissue in histologic sections and may not reflect the presence of Zn^2 +. This may be of concern to researchers using indicator dyes to detect metals in brain tissue sections. Further experiments may be advised to clarify whether Zn^2 +-binding dyes bind more specifically in intact neurons in culture or organotypic slices.     

Predicting Risk-Taking With and Without Substance Use: The Effects of Parental Monitoring, School Bonding, and Sports Participation

Risk-taking is statistically normative during adolescence, yet is associated with adverse outcomes including substance use. The present study draws the distinction between protective factors (effective for those identified as high risk takers) and promotive factors (effective for all) against substance use, focusing on parental monitoring, school bonding, and sports participation. A total of 36,514 8th and 10th grade participants in the national Monitoring the Future study were included. Although parental monitoring was associated with lower alcohol and marijuana use among all adolescents (i.e., promotive effect), these effects were strongest among the highest risk takers (i.e., protective effect) and females. School bonding was associated with lower levels of both alcohol and marijuana use among all groups of adolescents, but these promotive effects were weak. Sports participation was associated with higher levels of alcohol use among all males and among 8th grade females who did not identify as high risk takers. Despite being a risk factor for alcohol use, sports participation did demonstrate a promotive effect against marijuana use among 10th grade females only, and especially so for high risk-taking females (i.e., protective effect). Overall, these findings suggest that of the three mechanisms studied, parental monitoring emerged as the most promising entry point for substance use prevention and intervention across groups, particularly for females and high risk-taking adolescents.