Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer.

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.

Long Non-coding RNAs in Myeloid Malignancies.

Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15-20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.

Sustainability via Active Garden Education: Translating Policy to Practice in Early Care and Education.

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.

Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

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.

Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.

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.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

Evaluating the quality and accessibility of physical activity resources in two southern cities.

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.