OCPs have low knowledge regarding exercise counseling, but believe that discussing exercise is a multidisciplinary task and expressed a desire for further training. Interventions will require a multi-pronged approach including education for OCPs and guidance on assessment for exercise safety.

Spatial chromatin organization is emerging as an important mechanism to regulate the expression of genes. However, very little is known about genome architecture at high-resolution in vivo. Here, we mapped the three-dimensional organization of the human Hox clusters with chromosome conformation capture (3C) technology. We show that computational modeling of 3C data sets can identify candidate regulatory proteins of chromatin architecture and gene expression. Hox genes encode evolutionarily conserved master regulators of development which strict control has fascinated biologists for over 25 years. Proper transcriptional silencing is key to Hox function since premature expression can lead to developmental defects or human disease. We now show that the HoxA cluster is organized into multiple chromatin loops that are dependent on transcription activity. Long-range contacts were found in all four silent clusters but looping patterns were specific to each cluster. In contrast to the Drosophila homeotic bithorax complex (BX-C), we found that Polycomb proteins are only modestly required for human cluster looping and silencing. However, computational three-dimensional Hox cluster modeling identified the insulator-binding protein CTCF as a likely candidate mediating DNA loops in all clusters. Our data suggest that Hox cluster looping may represent an evolutionarily conserved structural mechanism of transcription regulation.

An interdisciplinary rehabilitation program may be beneficial to patients with head and neck cancer after treatment, but its effects should be evaluated in a controlled trial.

Background. People with metastatic cancers experience poor quality of life (QoL), fatigue, and decreased physical function. Exercise improves these symptoms in the curative setting, but the efficacy and safety of exercise in the metastatic setting is uncertain.Methods. Prospective, randomized trials of moderate/high-intensity aerobic exercise or resistance training vs. control in patients with advanced/metastatic solid cancers were identified from prior reviews and updated using a search of PubMed. The mean and SD for validated outcome measures (QoL, physical function, and fatigue) were extracted for intervention and control groups at baseline and postintervention. The Mann-Whitney test was used to evaluate the effect of exercise on the pooled change between baseline and postintervention. Safety was evaluated qualitatively.Results. Sixteen trials were analyzed. Among patients with scores at the mean or 2SD above, exercise was not associated with significant or clinical difference in QoL or fatigue. In patients with baseline scores 2SD below mean, exercise was associated with nonsignificant difference meeting minimal clinical important difference in QoL (À2.8 vs. 4.6, P ¼ 0.28). For function, patients at the mean had nonstatistically significant, but clinically meaningful difference in the six-minute walk test (6-MWT) (14.7 vs. 29.0 m, P ¼ 0.44). In patients 2 SD below the mean, there was a clinically meaningful difference in two patient-reported functional subscales (0.1 vs. 5.3, P ¼ 0.076 and 0.44 vs. 8.5, P ¼ 0.465) and a clinically meaningful improvement in the 6-MWT (À7.5 vs. 27.0 m, P ¼ 0.34), although none of these associations met statistical significance. There were no differences in falls, fractures, or pain.Discussion. Exercise is associated with clinically meaningful improvements in QoL, function, and 6-MWT in some patients with metastatic cancer. Despite poor reporting of safety, there was no signal of increased harm from exercise in this setting.