Metabolic dysregulation and cancer risk program (MeDOC): a transdisciplinary approach to Obesity-Associated cancers.

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Obesity Cancer Risk (MeDOC) Program is a trans-NCI research program supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk, as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC Program.

Epilepsy in adults with intellectual disabilities: prevalence, associations and service implications.

STATEMENT OF THE PROBLEM: The prevalence of epilepsy in people with an intellectual disability (ID) is apparently higher than in the general population. The outlook for individuals with both epilepsy and ID depends on the presence of any associated conditions. However, there have been few epidemiological studies of the prevalence of epilepsy and associated problems within a representative adult ID population to inform the development of policy. METHOD: This was a population-based prevalence study using the Leicestershire Learning Disability Register. Prevalence was estimated from the number of individuals with reported epilepsy identified from structured home interviews with carers. Associations with epilepsy were investigated for a range of defined physical, mental and skill attributes. Logistic regression was done with and without adjustment for age, sex and level of understanding to identify specific and holistic links respectively. RESULTS: The prevalence of epilepsy was 26%. Among those with epilepsy, 68% experienced seizures despite anti-epileptic medication. Epilepsy showed a significant association with low levels of understanding. Specific morbid associations included wetting (adjusted odds ratio 2.7), soiling (2.2), walking (2.5), daily living skills (1.6), poor speech (2.2), lack of empathy (1.5), mood swings (1.5), being uncooperative (1.6), seeking attention (1.7) and disturbing others at night (1.9). Holistic associations included a wider range of physical and mental problems and global skills deficits. CONCLUSIONS: The high prevalence, associated morbidities and global skills deficits make epilepsy care for adults with ID important and complex. Specialist epilepsy services for this population need a multidisciplinary skills mix.

IL-1 beta transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors.

Monocyte extravasation initiates reorganization of the cytoskeleton (CSK) and adhesion-dependent cytokine gene transcription. The actin CSK is thought to be crucial for compartmentalization and translation of mRNA, many of which contain AU-rich (ARE) instability motifs in the 3' untranslated region. We investigated regulation of adhesion-induced IL-1 beta expression by the monocyte CSK. In serum-free adherent monocytes, the induced IL-1 beta mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL-1 beta transcripts were unstable, coextracted with actin filaments and were associated with only transient activation of the mitogen-activated protein kinases (MAPK). Under both conditions of adherence, the ARE-binding protein AUF1/hnRNP D was readily extracted in the cytosolic fraction. Electro-injection with AUF1/hnRNP D modified the actin CSK and, surprisingly, stabilized IL-1 beta transcripts. These data suggest that the control of mRNA degradation is linked with changes in the CSK. Mitogen-activated protein kinase activation or alterations in the availability of mRNA degradation factors may mediate these effects.