The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson’s Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options.

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In order to understand the molecular mechanisms of longevity regulation, we recently performed a screen designed to enrich for genes common to several longevity interventions. Using this approach, we identified the Drosophila melanogaster gene takeout. takeout is upregulated in a variety of long-lived flies, and extends life span when overexpressed. Here, we investigate the mechanisms of takeout-dependent longevity. takeout overexpression specifically in the fat body is sufficient to increase fly longevity and is additive to the longevity effects of dietary restriction. takeout long-lived flies do not show phenotypes often associated with increased longevity, such as enhanced stress resistance or major metabolic abnormalities. However, males exhibit greatly diminished courtship behavior, leading to a reduction in fertility. Interestingly, takeout contains a binding domain for Juvenile Hormone, a fly hormone that plays a role in the regulation of developmental transitions. Importantly, the longevity and courtship phenotypes of takeout overexpressing flies are reversed by treatment with the Juvenile Hormone analog methoprene. These data suggest that takeout is a key player in the tradeoff-switch between fertility and longevity. takeout may control fertility via modulation of courtship behavior. This regulation may occur through Juvenile Hormone binding to takeout and a subsequent reduction in Juvenile Hormone signaling activity.

Therapeutic, IV.

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No abstract

Therapeutic, IV.

Introduction: Fenestrated endovascular aneurysm repair (FEVAR) is the highest radiation dose procedure performed by vascular surgeons. We sought to characterize the radiation dose to patients and staff during FEVAR procedures with different premanufactured devices. Methods: A single-center prospective study of FEVARs was performed over 24 months. Three FEVAR devices were included: off-the-shelf (OTS; t-Branch, p-Branch), Zenith Fenestrated (ZFen), and investigational custom-made devices (CMDs). Radiation doses to the surgeon, trainee, anesthesiologist, and scrub/circulating nurses were measured using a personal dosimetry system (DoseAware, Philips Healthcare, Amsterdam, The Netherlands). Procedure type, patient body mass index (BMI), reference air kerma (RAK), and kerma area product (KAP) were recorded. RAK and KAP were corrected for BMI based on an exponential fit of fluoroscopy dose rate and the dose per radiographic frame. Operator dose was corrected for BMI by the ratio of corrected to actual KAP. A one-sided Wilcox rank-sum test was used to compare personnel radiation doses, RAKs, and KAPs between procedure types. Statistical significance was set at P # .05. Results: There were 80 FEVARs performed by a single surgeon on a Philips Allura XperFD20 fluoroscopy system equipped with Clarity technology. Average BMI was 27 kg/m 2. Sixty CMDs (36 four-, 21 three-, and 3 two-vessel fenestrations), 11 ZFens (8 three-and 3 two-vessel fenestrations), and 9 OTS devices (4 p-Branch, 5 t-Branch) were included. ZFens had significantly lower patient (1800 mGy vs 2950 mGy; P ¼ .004), operator (120 mSv vs 370 mSv; P ¼ .004), assistant (60 mSv vs 210 mSv; P ¼ .003), circulator (10 mSv vs 30 mSv; P ¼ .049), and scrub nurse dose (10 mSv vs 40 mSv; P ¼ .02) compared with CMDs. OTS devices had significantly lower operator (220 mSv vs 370 mSv; P ¼ .04), assistant (110 mSv vs 210 mSv; P ¼ .02), and circulator doses (4 mSv vs 30 mSv; P ¼ .001) compared with CMDs. Four-vessel fenestrated devices had significantly higher patient dose (3020 mGy) compared with three-vessel FEVARs (2670 mGy; P ¼ .03) and two-vessel FEVARs (1600 mGy; P ¼ .0007), and significantly higher operator dose (440 mSv) compared with three-vessel FEVARs (170 mSv; P ¼ .0005). Patient dose was lowest with ZFens. Operating room personnel dose was lower with ZFens and OTS devices compared with CMDs. Fourvessel fenestrations required significantly more radiation compared with those involving three-vessel fenestrations; however, the dose increase was only 12% and should not preclude operators from extending coverage, if anatomically required. Conclusions: Overall, patient and personnel radiation doses during FEVAR with all devices were within acceptable limits and lower in our series than previously reported.