Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely compromises its effective clinical use. Whereas specific DPP-IV inhibitors have been developed, NEP 24.11 targets multiple sites in the GLP-1 sequence, which makes it difficult to block. To address this drawback, we have designed and synthesized conformationally constrained GLP-1 analogues by introducing multiple lactam bridges that stabilized both alpha-helices in the N- and C-terminal regions simultaneously. In addition to improving the receptor activation capability (up to 5-fold) by fixing the alpha-helical conformations required for optimal receptor interaction, the introduced lactam bridges provided outstanding shielding over NEP 24.11 (half-life of >96 h). These highly constrained peptides are the first examples of NEP 24.11-resistant GLP-1 analogues.

To determine the frequency of acute traumatic findings in computed tomographic (CT) chest abdomen pelvis (CAP) examinations in patients with acute traumatic head and/or cervical spine injury and no evidence suggesting bodily injury. Materials and Methods: After institutional review board approval with a waiver of informed consent was obtained, a HIPAA-compliant retrospective study was performed. A review of the electronic medical records and dictated reports identified patients who met the following criteria: CT-documented acute head and/or cervical spine trauma, CT CAP performed at least 20 minutes after initial brain and/or cervical spine CT, and no evidence of bodily injury at physical examination or on initial plain radiographs. The types of head and/or cervical injury, as well as mechanisms of injury in these patients, were analyzed. The frequency of acute traumatic injury in the CT CAP examinations was also determined, and 95% confidence intervals were calculated. Results: There were 115 patients who met the study criteria (average age, 67.3 years). Sixty-three (54.8%) patients were male. The average injury severity score was 9.3. No patients who met the criteria for this study were found to have an acute traumatic injury to the chest, abdomen, or pelvis. These 115 CT CAP examinations comprised 7.5% (115 of 1530) of all CT CAP examinations performed in the emergency department over the 15-month study period. Conclusion: CT CAP examinations rarely if ever reveal acute traumatic injury in patients who have experienced low-velocity trauma and have acute head and/or cervical spine trauma in the absence of evidence of bodily injury.

The relative attenuation ratio of oral contrast in the excluded stomach versus the gastric pouch can be a reliable tool in differentiating GG fistula from oral contrast reflux up the biliopancreatic limb on CT.

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