10-LB: Dasiglucagon Ameliorates Postprandial Hypoglycemia after Roux-en-y Gastric Bypass

Introduction: Postprandial hypoglycemia is a frequent and debilitating complication following Roux-en-Y gastric bypass (RYGB) without effective treatments. In a proof-of-concept study, we investigated the effects of dasiglucagon, a novel, stable glucagon analog, on postprandial hypoglycemia after RYGB. Methods: Ten RYGB-operated individuals with confirmed symptomatic postprandial hypoglycemia (plasma glucose concentration (PG) &amp;lt;3.5 mmol×L-1) completed a randomized crossover study consisting of three study days each including a standardized liquid mixed meal test (25 kJ per kg body mass; 50% carbohydrates, 35% fat and 15% protein). A subcutaneous injection of either placebo, 80 or 200 µg dasiglucagon (D80µg and D200µg) was administered after the postprandial PG peak, ten minutes before the projected time point where PG returned to fasting levels, using a subject-specific linear regression model. Blood sampling and assessment of hypoglycemic symptoms (Edinburgh Hypoglycemia Symptom Scale) were performed at fixed time intervals. Data were analyzed using linear mixed models and Tuckey’s corrections model for multiple comparisons. Results: Compared with placebo, treatment with both D80µg and D200µg significantly increased nadir PG (placebo: 3.0±0.2 mmol×L-1; D80µg: 3.9±0.3 mmol×L-1; D200µg: 4.5±0.2 mmol×L-1; P=0.002 and P=0.0002) and PG incremental area under the curve (iAUC70-240min) after drug administration (placebo: 752±19 mmol×L-1×min; D80µg: 917±22 mmol×L-1×min; D200µg: 992±28 mmol×L-1×min; P&amp;lt;0.0001 and P&amp;lt;0.0001). Moreover, both doses reduced time spent in hypoglycemia (&amp;lt;3.9 mmol×L-1) (placebo: 62.0±8 min; D80µg: 27.5±12 min; D200µg: 14.0±9 min; P=0.05 and P=0.003). There were no significant changes in hypoglycemic symptoms between the three study days. Conclusion: Administration of dasiglucagon effectively ameliorates postprandial hypoglycemia representing a promising new therapeutic option for management of postprandial hypoglycemia after RYGB. Disclosure C.K. Nielsen: None. C. Oehrstroem: None. U. Kielgast: None. D.L. Hansen: None. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp &amp; Dohme Corp., Sanofi. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Norgine B.V., Novo Nordisk A/S. </jats:sec

Risk to fragmented DNA in dry, wet, and frozen states from computed tomography: a comparative theoretical study

Computed tomography represents the gold standard in forensic and palaeopathological diagnosis. However, the X-rays used may affect the DNA quality through fragmentation and loss of genetic information. Previous work showed that the effects of ionizing radiation on dry DNA are non-significant with P < 10−8, which cannot be detected by means of polymerase chain reaction methods. In the present paper, complete analytical model that characterizes radiation effects on fragmented DNA in dry, wet, and frozen states is described. Simulation of radiation tracks in water phantom cells was performed using the Geant4-DNA toolkit. Cell hits by electrons with energies between 5 and 20 keV were simulated, and the formation of radiolytic products was assessed at a temperature of 298 K. The diffusion coefficient and the mean square displacement of reactive species were calculated by Stokes–Einstein–Smoluchowski relations at 273 K. Finally, DNA fragment damage was estimated using the density distribution of fragments calculated from atomic force microscopy images. The lowest probability of radiation-induced DNA damage was observed for dry state, with a range from 2.5 × 10−9 to 7.8 × 10−12 at 298 K, followed by that for frozen state, with a range from 0.9 to 4 × 10−7 at 273 K. The highest probability of radiation-induced DNA damage was demonstrated for fragmented DNA in wet state with a range from 2 to 9 × 10−7 at 298 K. These results significantly improve the interpretation of CT imaging in future studies in forensic and palaeopathological science

Review of Terahertz Tomography Techniques

Terahertz and millimeter waves penetrate various dielectric materials, including plastics, ceramics, crystals, and concrete, allowing terahertz transmission and reflection images to be considered as a new imaging tool complementary to X-Ray or Infrared. Terahertz imaging is a well-established technique in various laboratory and industrial applications. However, these images are often two-dimensional. Three-dimensional, transmission-mode imaging is limited to thin samples, due to the absorption of the sample accumulated in the propagation direction. A tomographic imaging procedure can be used to acquire and to render three-dimensional images in the terahertz frequency range, as in the optical, infrared or X-ray regions of the electromagnetic spectrum. In this paper, after a brief introduction to two dimensional millimeter waves and terahertz imaging we establish the principles of tomography for Terahertz Computed tomography (CT), tomosynthesis (TS), synthetic aperture radar (SAR) and time-of-flight (TOF) terahertz tomography. For each technique, we present advantages, drawbacks and limitations for imaging the internal structure of an object.Development and Optimization of THz NDT on Aeronautics Composite Multi-layered Structur