Insure Me Cancer Free: An Intervention Utilizing a Dynamic Communication Model

The purpose of this study was to examine the impact of a pilot insurance company-based intervention guided by a Dynamic Communication Model to increase breast and colorectal cancer screening in Appalachian WV, a medically-underserved population with low screening rates. Our team and key informants developed letters and a website to promote cancer screening, and these were mailed to patients needing screening (breast: n = 232; colorectal: n = 324). After 6 months, a sample of women (n = 22) and men (n = 27) continuing to need screening received telephonic case management counseling. Screening rates were assessed at baseline, 6 months, and 12 months. A final telephone interview was conducted at 12 months with a subset of participants. Key informants (n = 21) provided feedback on the letter/website, resulting in improved readability, organization, and informational content. The letter/website had minimal impact on screening (breast: n = 8; colon: n = 5). The final telephone interview of plan members (n = 12) found they liked the personalized approach and appreciated learning more about cancer, and that you need to “catch it early for good treatment.” All understood the counseling and believed the information was correct. Nearly all intended to get screened. Following counseling, screening numbers increased (total breast: n = 39; total colon: n = 18). Our theoretically-driven, case management counseling intervention was well received and has the potential to increase cancer screening rates, particularly in a rural, medically-underserved populations

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain

Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel

Gene-targeted deletion of the potassium channel Kv1.3 (Kv1.3-/-) results in ‘Super-smeller’ mice with a sensory phenotype that includes an increased olfactory ability linked to changes in olfactory circuitry, increased abundance of olfactory cilia, and increased expression of odorant receptors and the G-protein, Golf. Kv1.3-/- mice also have a metabolic phenotype including lower body weight and decreased adiposity, increased total energy expenditure (TEE), increased locomotor activity, and resistance to both diet- and genetic-induced obesity. We explored two cellular aspects to elucidate the mechanism by which loss of Kv1.3 channel in the olfactory bulb (OB) may enhance glucose utilization and metabolic rate. First, using in situ hybridization we find that Kv1.3 and the insulin-dependent glucose transporter type 4 (GLUT4) is co-localized to the mitral cell layer of the OB. Disruption of Kv1.3 conduction via construction of a pore mutation (W386F Kv1.3) was sufficient to independently translocate GLUT4 to the plasma membrane in HEK 293 cells. Because olfactory sensory perception and the maintenance of action potential firing frequency by mitral cells of the OB is highly energy demanding and Kv1.3 is also expressed in mitochondria, we next explored the structure of this organelle in mitral cells. We challenged wildtype (WT) and Kv1.3-/- male mice with a moderately high-fat diet (MHF, 31.8 % kcal fat) for 4 months and then examined OB ultrastructure using transmission microscopy. In WT mice, mitochondria were significantly enlarged following diet-induced obesity (DIO) and there were fewer mitochondria, likely due to mitophagy. Interestingly, mitochondria were significantly smaller in Kv1.3-/- mice compared with that of WT mice. Similar to their metabolic resistance to DIO, the Kv1.3-/- mice had unchanged mitochondria in terms of cross sectional area and abundance following a challenge with modified diet. We are very interested to understand how targeted disruption of the Kv1.3 channel in the olfactory bulb can modify TEE. Our study demonstrates that Kv1.3 regulates mitochondrial structure and alters glucose utilization; two important metabolic changes that could drive whole system changes in metabolism initiated at the olfactory bulb