Osteocalcin protects islet identity in low-density lipoprotein receptor knockout mice on high-fat diet.

Metabolic syndrome (MetS) is an increasing global health threat and strong risk factor for type 2 diabetes (T2D). MetS causes both hyperinsulinemia and islet size overexpansion, and pancreatic ß-cell failure impacts insulin and proinsulin secretion, mitochondrial density, and cellular identity loss. The low-density lipoprotein receptor knockout (LDLr-/-) model combined with high-fat diet (HFD) has been used to study alterations in multiple organs, but little is known about the changes to ß-cell identity resulting from MetS. Osteocalcin (OC), an insulin-sensitizing protein secreted by bone, shows promising impact on ß-cell identity and function. LDLr-/- mice at 12 months were fed chow or HFD for 3 months ± 4.5 ng/h OC. Islets were examined by immunofluorescence for alterations in nuclear Nkx6.1 and PDX1 presence, insulin-glucagon colocalization, islet size and %ß-cell and islet area by insulin and synaptophysin, and mitochondria fluorescence intensity by Tomm20. Bone mineral density (BMD) and %fat changes were examined by Piximus Dexa scanning. HFD-fed mice showed fasting hyperglycemia by 15 months, increased weight gain, %fat, and fasting serum insulin and proinsulin; concurrent OC treatment mitigated weight increase and showed lower proinsulin-to-insulin ratio, and higher BMD. HFD increased %ß and %islet area, while simultaneous OC-treatment with HFD was comparable to chow-fed mice. Significant reductions in nuclear PDX1 and Nkx6.1 expression, increased insulin-glucagon colocalization, and reduction in ß-cell mitochondria fluorescence intensity were noted with HFD, but largely prevented with OC administration. OC supplementation here suggests a benefit to ß-cell identity in LDLr-/- mice and offers intriguing clinical implications for countering metabolic syndrome.

The Callander laryngoscope blade modification is associated with a decreased risk of dental contact.

PURPOSE: Dental damage may occur with laryngoscopy. The purpose of this study was twofold: to determine whether preoperative examination could predict the risk of contacting the teeth with the laryngoscope and to evaluate the effectiveness of a modified Macintosh blade on reducing dental contact. METHODS: Four hundred and eighty-three patients scheduled for elective surgery requiring general anesthesia with endotracheal tube placement were studied prospectively. Features that might predict difficult intubation were assessed preoperatively. Laryngoscopy was performed twice on each patient, once with a regular Macintosh 3 blade and once with a blade in which the flange was partially removed (Callander modification). The distance between the flange of the blade and the upper incisors at glottic exposure was measured. We calculated correlations between individual airway characteristics and the chance of hitting the upper teeth with the regular Macintosh 3 blade and compared the frequencies of contacting the teeth between the two blades. RESULTS: The chance of hitting the upper teeth when using the regular Macintosh 3 blade increased significantly with non-parametric scores for Mallampati classification, mandibular subluxation, head and neck movement, interincisor gap, and condition of the upper teeth. (P < 0.01) The frequency of direct contact varied significantly between the two blades: 20.3% vs 4.1% for Macintosh 3 and modified blades, respectively (P < 0.05). Laryngeal views were improved with the modified blade. CONCLUSION: Airway characteristics correlate with the risk of hitting the upper teeth during laryngoscopy. The modified Macintosh blade reduces the risk of contacting the teeth.