The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

Key factors in the success of DART implementation were the adoption of a programmatic approach, strong institutional commitment, and a primary focus on clinic-based response. We have demonstrated that large-scale routine screening for distress in a cancer center is achievable and has the potential to enhance the cancer care experience for both patients and staff.

Costford SR, Chaudhry SN, Crawford SA, Salkhordeh M, Harper ME. Long-term high-fat feeding induces greater fat storage in mice lacking UCP3. Am J Physiol Endocrinol Metab 295: E1018-E1024, 2008. First published August 19, 2008 doi:10.1152/ajpendo.00779.2007.-Uncoupling protein-3 (UCP3) is a mitochondrial inner-membrane protein highly expressed in skeletal muscle. While UCP3's function is still unknown, it has been hypothesized to act as a fatty acid (FA) anion exporter, protecting mitochondria against lipid peroxidation and/or facilitating FA oxidation. The aim of this study was to determine the effects of long-term feeding of a 45% fat diet on whole body indicators of muscle metabolism in congenic C57BL/6 mice that were either lacking UCP3 (Ucp3 Ϫ/Ϫ ) or had a transgenically induced approximately twofold increase in UCP3 levels (UCP3tg). Mice were fed the high-fat (HF) diet for a period of either 4 or 8 mo immediately following weaning. After long-term HF feeding, UCP3tg mice weighed an average of 15% less than wild-type mice (P Ͻ 0.05) and were 20% less metabolically efficient than both wild-type and Ucp3 Ϫ/Ϫ mice (P Ͻ 0.01). Additionally, wild-type mice had 21% lower, whereas UCP3tg mice had 36% lower, levels of adiposity compared with Ucp3 Ϫ/Ϫ mice (P Ͻ 0.05 and P Ͻ 0.001, respectively), indicating a protective effect of UCP3 against fat gain. No differences in whole body oxygen consumption were detected following long-term HF feeding. Glucose and insulin tolerance tests revealed that both the UCP3tg and Ucp3 Ϫ/Ϫ mice were more glucose tolerant and insulin sensitive compared with wild-type mice after short-term HF feeding, but this protection was not maintained in the long term. Findings indicate that UCP3 is involved in protection from fat gain induced by long-term HF feeding, but not in protection from insulin resistance. uncoupling protein-3; obesity; insulin resistance; type 2 diabetes mellitus; skeletal muscle BECAUSE OF ITS HIGH SEQUENCE HOMOLOGY to the original uncoupling protein [uncoupling protein-1 (UCP1)] expressed in brown adipose tissue (BAT), UCP3 was first hypothesized to dissipate the proton gradient across the mitochondrial inner membrane in skeletal muscle, thereby uncoupling oxidative phosphorylation and releasing energy as heat. Since its discovery in 1997, several studies have shown that UCP3 is likely not responsible for basal proton leak in muscle (1, 6). In fact, the adenine nucleotide translocator is probably responsible for the majority of proton leak in this tissue (5). The novel uncoupling proteins (UCPs 2-5) have been studied over the last decade; however, their physiological functions are still unclear. UCP3 is expressed highly selectively in skeletal muscle, BAT, and at low levels in the heart (3, 35). Early studies of UCP3 overexpression in experimental systems ranging from yeast to mice were confounded by supraphysiological levels of expression (9,14,16,31,39). These high levels of protein expressed on the mitochondrial inner membrane induced artifactual proton leak (14, 31)...

Our multidisciplinary program with in-hospital psychosocial resources resulted in very few persons being excluded from receiving surgical treatment. However, less than half of those referred underwent surgery as most persons self-removed from our program for unknown reasons. Further investigation is required to determine which patient, administrative, and system factors play a role in the patients' decision to not undergo bariatric surgical treatment.

In the short to moderate term, in situ fenestration appears to be a reasonable and effective method to extend the proximal landing zone for revascularization of the left subclavian artery. However, longer follow-up is needed to fully assess the long-term durability of this procedure. Based on studies of material properties, an energy-based fenestration technique (radiofrequency or laser) is recommended, along with the avoidance of cutting balloons for dilation of the fenestration.

A past history of an anxiety or substance use disorder may play a role in patients not completing the assessment component of the bariatric surgery process. Additional psychosocial support, such as cognitive behavioral therapy or targeted psychoeducation, may help improve patient completion of the pre-surgery assessment phase.

Fenestrated endovascular aneurysm repair (FEVAR) is a minimally invasive method of abdominal aortic aneurysm (AAA) repair utilized in patients with complex vessel anatomies. Stent grafts (SG) used in this process contain fenestrations within the device that need to be aligned with the visceral arteries upon successful SG deployment. Proper alignment is crucial to maintain blood flow to these arteries and avoid surgical complications. During fenestrated SG deployment, rotation of the SG can occur during the unsheathing process. This leads to misalignment of the vessels, and the fenestrations and is associated with poor clinical outcomes. The aim of this study was to develop a computational model of the FEVAR process to predict SG rotation. Six patient-specific cases are presented and compared with surgical case data. Realistic material properties, frictional effects, deployment methods, and boundary conditions are included in the model. A mean simulation error of 2 deg (range 1-4 deg) was observed. This model was then used to conduct a parameter study of frictional properties to see if rotation could be minimized. This study showed that increasing or decreasing the coefficients of friction (COF) between the sheath and the vessel walls would decrease the amount of rotation observed. Our model accurately predicts the amount of SG rotation observed during FEVAR and can be used as a preoperative planning tool within the surgical workflow.

Aims/hypothesis Obesity is an important risk factor for the development of type 2 diabetes, but not all obese individuals develop this complication. The clinical signs of type 2 diabetes can often be reversed with weight loss; however, it is unknown whether the skeletal muscle oxidative stress associated with type 2 diabetes remains after weight loss. We hypothesised that chronic exposure to high glucose and insulin would re-elicit impaired metabolism in primary myotubes from patients with a history of type 2 diabetes. Methods Obese participants with or without type 2 diabetes completed a standardised weight loss protocol, following which all participants were euglycaemic and had similar indices of insulin sensitivity. Satellite cells were isolated from muscle biopsies and differentiated under low or high glucose and insulin conditions (HGI).