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Background While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition. Methods We developed a juvenile rodent CRT model that reproduces neurocognitive deficits. Next, we utilized the model to test whether exercise ameliorates these deficits. Fischer rats (31 days old) were irradiated with a fractionated dose of 4 Gy × 5 days, trained and tested at 6, 9, and 12 months post-CRT using 5-choice serial reaction time task. After testing, fixed rat brains were imaged using diffusion tensor imaging and immunohistochemistry. Results CRT caused early and lasting impairments in task acquisition, accuracy, and latency to correct response, as well as causing stunting of growth and changes in brain volume and diffusion. Exercising after irradiation improved acquisition, behavioral control, and processing speed, mitigated the stunting of brain size, and increased brain fiber numbers compared with sedentary CRT values. Further, exercise partially restored global connectome organization, including assortativity and characteristic path length, and while it did not improve the specific regional connections that were lowered by CRT, it appeared to remodel these connections by increasing connectivity between alternate regional pairs. Conclusions Our data strongly suggest that exercise may be useful in combination with interventions aimed at improving cognitive outcome following pediatric CRT.

Background: OXPHOS mediates resistance to BRAF and MEK inhibitors in melanoma. Recently, we showed that MBMs have higher expression of OXPHOS genes than patient-matched extracranial metastases (ECMs). The induction of, and dependence upon, OXPHOS in MBMs was confirmed in mouse xenograft models. Notably, our studies demonstrated that OXPHOS varies among MBMs. In order to improve our understanding of the High-OXPHOS phenotype, we report here the molecular, immune, metabolic, and radiomic features that correlate with OXPHOS levels in MBMs. Methods: We applied an OXPHOS gene signature to RNA-sequencing (RNA-seq) data from surgically resected MBMs (n=88). Clustering by these genes identified MBMs with significant enrichment (High-OXPHOS; n=21) and depletion (Low-OXPHOS; n=25) of OXPHOS genes. The EdgeR/limma/voom pipeline was used to perform differential gene expression (DGE) analysis between High- and Low-OXPHOS MBMs. Pathway analyses were performed via Ensemble of Gene Set Enrichment Analyses (EGSEA). The ESTIMATE and MCP-Counter R packages were used to assess immune infiltrates from voom-transformed counts. Quantitative analysis of P-S6 and P-PRAS40 was performed by immunohistochemistry (IHC). Tumor phenotypes were segmented on conventional magnetic resonance (MR) images, and radiomic features were extracted using an in-house radiome-sequencing pipeline. Radiomic features were utilized to predict High- vs. Low-OXPHOS status. To evaluate the robustness of the estimates, Leave One Out cross-validation (LOOCV) was conducted on the patient set. Direct metabolite analysis was performed via liquid chromatography mass spectrometry (LC-MS) of Low-OXPHOS A375 and High-OXPHOS, MEKi-resistant A375-R1 brain xenografts. Results: RNA-seq analysis identified that High-OXPHOS MBMs are characterized by significant enrichment of PGC1α (FDR q-val=0.0002) and mTOR (FDR q-val=0.001) signaling and significant depletion of ImmuneScores, T cells, cytotoxic lymphocytes, B lineage cells, and NK cells (p Conclusions: Significant differences in mTOR (enriched) and immune (depleted) signaling were identified in High-OXPHOS clinical MBMs, and enrichment of glutamine signaling was observed in High-OXPHOS MBM xenografts. Further, our results demonstrated that changes in MR radiomic features can noninvasively discriminate between High- and Low-OXPHOS MBMs. Additional studies are ongoing to evaluate the clinical, prognostic, and predictive values of OXPHOS status in melanoma. Citation Format: Grant M. Fischer, Aikaterini Kotrotsou, Sara Ahmed, Pilar O’Neal, Iman Sahnoune, Y.N. Vashisht Gopal, Courtney Hudgens, Barbara Knighton, Rivka Colen, Michael T. Tetzlaff, Michael A. Davies. Molecular, immunologic, metabolic, and radiomic associations of oxidative phosphorylation (OXPHOS) in melanoma brain metastases (MBMs) [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A05.

Background We describe the development of sustainability via active garden education (SAGE), an early care and education (ECE) garden-based curriculum developed from a 5-year community partnership to link national health policy guidelines with ECE accreditation standards. Methods National health guidelines and ECE accreditation standards were reviewed, and community advisory board members, ECE staff, and parents provided feedback and support throughout the development of the curriculum. The SAGE curriculum components were guided by the Ecologic Model of Physical Activity and Social Cognitive Theory. Strengths-weaknesses-opportunities-threat analyses were used to refine and revise the curriculum to overcome challenges to implementation. Results Twelve 1-hour, developmentally appropriate, modularized lessons were created using the garden as a metaphor for human development. Lessons featured songs, simple games, pretend play, modeling, and garden activities. Parents were engaged via weekly newsletters with information about activities in the classroom, strategies to improve health habits at home, and free community resources. Conclusion SAGE partnered scientific theory and rigor with community ingenuity and innovation to create a clear translation of policy guidelines to easily implementable practice in a fun and engaging manner.

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules.

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association.

Purpose. Access and quality of physical activity resources (PARs) influence physical activity (PA) participation. This study examined the type, size, accessibility, features, amenities, and incivilities of PARs in two cities. Design. Researchers identified all PARs within an 800-meter radius of the homes of participants from a larger study. Each PAR was evaluated by a trained assessor. Setting. PARs were evaluated in Houston and Austin, Texas. Patients. The final sample included 1326 PARs in Houston and 297 in Austin, Texas. Measures. The 2010 Physical Activity Resource Assessment (PARA), a direct-observation audit tool, was used to assess the type, size, accessibility, features, amenities, and incivilities of a PAR. Analysis. Both t-tests and analyses of variance were used to determine differences in features, amenities, and incivilities by city, type, and accessibility. Results. Houston PARs had greater amenities (t[421] = 4.445; p < .001) and fewer incivilities (t[371] = −6.89; p < .001) than Austin PARs. Combination resources had the highest score for features (M = 9.94; standard deviation [SD] = 5.62); fitness clubs had the highest score for amenities (M = 17.06; SD = 5.27); and trails had the most incivilities (M = 4.23; SD = 4.88). Free PARs had greater features (F[3, 1509] = 16.87; p < .001), amenities (F[3, 1500] = 3.13; p = .025), and incivilities (F[3, 1540] = 21.97; p < .001) than pay for use PARs. Conclusion. Improvements to quality and maintenance of existing free PARs may be an economical strategy to increase PA.