Ravn Blackburn (battleback3)

Medulloblastoma (MB) is the most common childhood malignant brain tumor, accounting for approximately 20% of all pediatric central nervous system tumors. Current standard treatments involving surgical interventions followed by craniospinal irradiation and adjuvant chemotherapy have severe motor and cognitive defects. Therefore, individualized treatment regimens with reduced toxicity designed according to the presence of specific oncogenic 'driver' genes are urgently demanded. To this end, recent genetic and epigenetic findings have advanced the classification of MB into the international consensus of four distinct MB molecular subgroups (WNT, SHH, Group 3, and Group 4) based on their respective molecular and histopathological characteristics. More recent studies have indicated that up to seven molecular subgroups exist in childhood MB. Moreover, studies on the inter- and intra-tumoral features of the four subgroups revealed that each subgroup contains variant subtypes. These results have greatly helped risk stratification of MB patients at diagnosis and significantly improved clinical treatment options. Herein, we highlight the recent advances and challenges associated with MB classification, and the development of therapeutic treatments targeting novel subgroup-specific molecular and epigenetic factors, especially those in the SHH-driven MB tumors. Vitamin A (retinol) is important for normal growth, vision and reproduction. It has a role in the immune response and the development of metabolic syndrome. Most of the retinol present in the body is stored as retinyl esters within lipid droplets in hepatic stellate cells (HSCs). In case of liver damage, HSCs release large amounts of stored retinol, which is partially converted to retinoic acid (RA). This surge of RA can mediate the immune response and enhance the regeneration of the liver. If the damage persists activated HSCs change into myofibroblast-like cells producing extracellular matrix, which increases the chance of tumorigenesis to occur. RA has been shown to decrease proliferation and metastasis of hepatocellular carcinoma. The levels of RA and RA signaling are influenced by the possibility to esterify retinol towards retinyl esters. This suggests a complex regulation between different retinoids, with an important regulatory role for HSCs. BACKGROUND MRI assessment of aortic pulse wave velocity (PWV) helps predict the risk of vascular events, but the recommended phase contrast sampling rate is faster than what is utilized in most clinical sequences. There are many existing MRI databases obtained for assessment of cardiac output using lower temporal frequency sampling where information might be obtained about aortic stiffness (PWV). In this work, we sought to evaluate whether the Group Delay (GD) method can generate a reproducible measure of stiffness and describe expected age-related stiffening of the aortic arch using lower sampling rates in standard clinical sequences. METHODS Phase contrast (PC) MRI was obtained on the ascending and descending aortic arch in a heterogeneous adult cohort (n = 23; 9 women) spanning over a wide range of ages (ages 24-89, mean 49.4 ± 18.4). Data was collected with standard cardiac MRI protocols for cardiac output evaluation (repetition time = 7.8 ms, views-per-segment = 4, encoding velocity = 200 cm/s). Pulse wave transit times (TT) were computed using the GD method, two other validated automated approaches (cross correlation TT Algorithm by Gaddum and Segment by Medviso), and the manual tangent method. Pressure waveforms from tonometry and flow waveforms from PC MRI were used to assess wave reflections. RESULTS Group Delay and TT-Algorithm showed significant and high retest reproducibility (r = 0.86 for both) as well as high PWV correlation with age (r = 0.93, P-value  less then  0.00005 and r = 0.96, P-value  less then  0.0000