Mindfulness-based intervention for depression and insulin resistance in adolescents: Protocol for BREATHE, a multisite, pilot and feasibility randomized controlled trial.

BACKGROUND: Elevated depression symptoms have been associated with higher insulin resistance in adolescents, and consequently, greater risk for type 2 diabetes (T2D). Mindfulness-based intervention (MBI) may be suited for adolescents at risk for T2D given its potential to decrease depression and improve stress-related behavior/physiology underpinning insulin resistance. To prepare for a future multisite efficacy randomized controlled trial, a rigorous, multisite, pilot and feasibility study is needed to test this approach. The current paper describes the design and protocol for a multisite, pilot and feasibility randomized controlled trial of six-week MBI, cognitive-behavioral therapy (CBT), and health education (HealthEd) group interventions, to assess multisite fidelity, feasibility, and acceptability. METHODS: Participants are N = 120 adolescents ages 12-17, with body mass index (BMI) ≥85th percentile, elevated depression symptoms (20-item Center for Epidemiologic Studies-Depression Scale total score > 20), and family history of diabetes. Enrollment occurs across four United States (US) sites, two in Colorado, one in Washington, D·C., and one in Maryland. Group interventions are delivered virtually by trained psychologists and co-facilitators. Assessments occur at baseline, six-week follow-up, and one-year follow-up. RESULTS: Primary outcomes are intervention implementation fidelity, based upon expert ratings of audio-recorded sessions (≥80% adherence/competence), and recruitment feasibility, based upon percentage enrollment of eligible youth (≥80%). Secondary outcomes are intervention training fidelity/feasibility/acceptability, recruitment timeframe, and retention/assessment feasibility. CONCLUSION: Findings will inform optimization of training, recruitment, intervention delivery, retention, and assessment protocols for a multisite, efficacy randomized controlled trial evaluating MBI for decreasing depression and improving insulin resistance in adolescents at risk for developing T2D.

Online Monitoring of the Concentrations of Amorphous and Crystalline Mesoscopic Species Present in Solution.

Despite the growing evidence for the existence of amorphous mesoscopic species in a solution and their crucial roles in crystallization, there has been the lack of a suitable method to measure the time-resolved concentrations of amorphous and crystalline mesospecies in a lab-scale stirred reactor. This has limited experimental investigations to understand the kinetics of amorphous and crystalline mesospecies formation in stirred solutions and made it challenging to measure the crystal nucleation rate directly. Here, we used depolarized light sheet microscopy to achieve time-resolved measurements of amorphous and crystalline mesospecies concentrations in solutions at varying temperatures. After demonstrating that the concentration measurement method is reasonably accurate, precise, and sensitive, we utilized this method to examine mesospecies formation both in a mixture of two miscible liquids and in an undersaturated solution of dl-valine, thus revealing the importance of a temperature change in the formation of metastable and amorphous mesospecies as well as the reproducibility of the measurements. Moreover, we used the presented method to monitor both mesospecies formation and crystal nucleation in dl-valine solutions at four different levels of supersaturation, while achieving the direct measurement of the crystal nucleation rates in stirred solutions. Our results show that, as expected, the inherent variability in nucleation originating from its stochastic nature reduces with increasing supersaturation, and the dependence of the measured nucleation rate on supersaturation is in reasonable agreement with that predicted by the classical nucleation theory.

Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies.

UNLABELLED: AKT (a serine/threonine-specific protein kinase) regulates many cellular processes contributing to cytotoxic drug resistance. This study's primary objective examined the relationship between GSK2141795, an oral, pan-AKT inhibitor, and (18)F-FDG PET markers of glucose metabolism in tumor tissue to determine whether (18)F-FDG PET could be used to guide personalized dosing of GSK2141795. Biomarker analysis of biopsies was also undertaken. METHODS: Twelve patients were enrolled in 3 cohorts; all underwent dynamic (18)F-FDG PET scans and serial pharmacokinetic sampling at baseline, week 2, and week 4 with tumor biopsies before treatment and at week 4. Response was evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup criteria. Biopsy samples were analyzed for mutations and protein expression. RESULTS: GSK2141795 did not significantly influence blood glucose levels. No dose-response relationship was observed between GSK2141795 pharmacokinetics and (18)F-FDG PET pharmacodynamic measures; however, an exposure-response relationship was seen between maximum drug concentrations and maximal decrease in (18)F-FDG uptake in the best-responding tumor. This relationship also held for pharmacokinetic parameters of exposure and 1,5-anhydroglucitol (a systemic measure of glucose metabolism). Phospho-AKT upregulation at week 4 in biopsies confirmed AKT inhibition by GSK2141795. Single-agent activity was observed with a clinical benefit rate of 27% (3/11) and 30% (3/10) CA125 response in the study's platinum-resistant ovarian patients. AKT pathway activation by PIK3CA/PIK3R1 mutation did not correlate with clinical activity, whereas RAS/RAF pathway mutations did segregate with resistance to AKT inhibition. CONCLUSION: GSK2141795 demonstrated an exposure-response relationship with decreased (18)F-FDG uptake and is active and tolerable. This study's design integrating (18)F-FDG PET, pharmacokinetics, and biomarker analyses demonstrates the potential for clinical development for personalized treatment.

Telomere-based cancer treatment: emerging targeted therapies.

Chemotherapy and radiation therapy are standard care in cancer treatment; however, both have numerous adverse side effects because they affect healthy as well as cancerous cells. The side effects, including decreased white blood cell count, nausea, hair loss, and fatigue, can be severe enough that patients may decide to forgo treatment. Targeted therapies are treatments that focus on specific molecules in cancerous cells and avoid disruption of healthy cells. Telomeres, the ends of chromosomes, are possible targets. In healthy cells, telomeres become shorter with each cell division, limiting the number of divisions that a normal cell can undergo. Many cancer cells have telomerase activity, which rebuilds telomeres after each cell division and confers immortality to cancer cells. Telomerase is an enzyme normally present to a significant degree only in the cells of developing fetuses. Treatments that target the telomerase enzyme itself or the chromosomal telomeres are being developed and tested in early clinical trials. This article focuses on several approaches to telomere-targeted therapy.