Innovative Self-Regulation Strategies to Reduce Weight Gain in Young Adults: The Study of Novel Approaches to Weight Gain Prevention (SNAP) Randomized Clinical Trial

Weight gain occurs commonly in young adults and has adverse effects on health. Reducing weight gain in young adults would have significant public health impact

Dietary outcomes within the study of novel approaches to weight gain prevention (SNAP) randomized controlled trial

Abstract Background Young adults (YA) are at high-risk for unhealthy dietary behaviors and weight gain. The Study of Novel Approaches to Weight Gain Prevention (SNAP) Trial demonstrated that two self-regulation approaches were effective in reducing weight gain over 2 years compared with control. The goal of this analysis was to examine effects of intervention on dietary outcomes and the association of diet changes with weight change. Methods Participants were 599 YA, age 18–35 years, BMI 21.0–30.0 kg/m2 (27.4 ± 4.4 years; 25.4 ± 2.6 kg/m2; 22% men; 73% non-Hispanic White), who were recruited in Providence, RI and Chapel Hill, NC and randomized to self-regulation with Small Changes (SC), self-regulation with Large Changes (LC) or Control (C). SC and LC emphasized frequent self-weighing to cue behavior changes (small daily changes vs. periodic large changes) and targeted high-risk dietary behaviors. Diet and weight were assessed at baseline, 4 months and 2 years. Results LC and SC had greater decreases in energy intake than C at 4 months but not 2 years. LC had the greatest changes in percent calories from fat at 4 months, but differences were attenuated at 2 years. No differences in diet quality were observed. Across conditions, increased total energy consumption, fast food, meals away from home, and binge drinking, and decreased dietary quality and breakfast consumption were all associated with weight gain at 2 years. Conclusions This study suggests the need to strengthen interventions to produce longer term changes in dietary intake and helps to identify specific behaviors associated with weight gain over time in young adults. Trial registration Clinicaltrials.gov # NCT01183689 , registered August 18, 2010

A Case of mistaken identity: Rhabdomyosarcoma development from endothelial progenitor cells

Rhabdomyosarcoma (RMS) histologically resembles developing skeletal muscle and is thought to solely originate from a differentiation block in muscle progenitors. We demonstrate that RMS can arise from endothelial progenitor cells following reprogramming and myogenic transdifferentiation. These results highlight how tumors with identical morphological features can arise from different cell types and offer insight into RMS formation in non-myogenic tissue

The perfect PTEN – transcriptional regulation by PTEN dictates sarcoma identity

Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis

Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis

Pulmonary endothelial cell apoptosis is a transient, yet defining pathogenic event integral to the onset of many pulmonary vascular diseases such as pulmonary hypertension (PH). However, there is a paucity of information concerning the molecular pathway(s) that control pulmonary arterial endothelial cell apoptosis. Here, we introduce a molecular axis that when functionally active seems to induce pulmonary arterial endothelial cell apoptosis in vitro and PH in vivo. In response to apoptotic stimuli, human pulmonary arterial endothelial cells exhibited robust induction of a programmed cell death 4 (PDCD4)/caspase-3/apoptotic pathway that was reversible by direct PDCD4 silencing. Indirectly, this pathway was also repressed by delivery of a microRNA-21 mimic. In vivo, genetic deletion of microRNA-21 in mice (miR-21−/− mice) resulted in functional activation of the PDCD4/caspase-3 axis in the pulmonary tissues, leading to the onset of progressive PH. Conversely, microRNA-21–overexpressing mice (CAG-microRNA-21 mice) exhibited reduced PDCD4 expression in pulmonary tissues and were partially resistant to PH in response to chronic hypoxia plus SU 5416 injury. Furthermore, direct PDCD4 knockout in mice (PDCD4−/− mice) potently blocked pulmonary caspase-3 activation and the development of chronic hypoxia plus SU 5416 PH, confirming its importance in disease onset. Broadly, these findings support the existence of a microRNA-21–responsive PDCD4/caspase-3 pathway in the pulmonary tissues that when active serves to promote endothelial apoptosis in vitro and PH in vivo