Probable Delirium as a Risk Factor for Adverse Surgical Outcomes in Geriatric Patients With Acute Hip Fracture: Preoperative Assessment Using a Short Screening Tool.

Hip fractures in geriatric patients are associated with substantial morbidity and mortality including postoperative delirium. Few data are available regarding preoperative identification of patients at risk of postoperative delirium before surgical repair of hip fracture. We used the Ultrabrief Two-Item Bedside Test, a proxy for delirium, to identify patients who are likely to have adverse outcomes postoperatively. This prospective pilot study included patients 65 years and older with an acute hip fracture. The questionnaire was administered preoperatively, and patients were followed up for 30 days postoperatively. We enrolled 30 patients, with a mean age of 78 years. The 12 patients with an abnormal test result had a significantly lower body mass index, a trend in descriptive statistics for pulmonary disease, and a higher ASA physical status. In addition, hospital stay following fracture repair was longer for patients with an abnormal test result, although not significantly (mean [SD]=8.8 [4.2] days vs 6.4 [2.0] days, median=8 vs 6 days, log-rank P=.052). A 2-item questionnaire could help identify patients who have sustained hip fracture who are likely to have a longer hospitalization. Future studies are needed to confirm these findings and determine whether interventions can reduce risk.

The Use of Alfaxalone in Quaker Parrots (Myiopsitta monachus).

Alfaxalone is a neurosteroid anesthetic that acts on gamma-aminobutyric acid alpha-receptors. The objective of this study was to evaluate the clinical safety and efficacy of alfaxalone (Alfaxan CD). Due to observed hyperexcitability in the subject animals when alfaxalone was the only drug used during the initial trials, premedication with midazolam was also evaluated during the final study. Ten adult Quaker parrots (Myiopsitta monachus) were assigned to 3 groups: 1) low-dose alfaxalone 10 mg/kg (LD), 2) high-dose alfaxalone 25 mg/kg (HD), and 3) alfaxalone 10 mg/ kg with midazolam 1 mg/kg premedication (AM), administered intramuscularly. Induction time, sedation quality, duration of action, and vital parameters, including heart rate, respiratory rate, and temperature, were recorded. All protocols achieved adequate sedation; however, muscle tremors and hyperexcitation were variable. The LD group had a significantly longer mean ± SD induction time (13.5 ± 4.5 minutes) as compared to the HD (6.0 ± 1.3 minutes, P = .002) and AM (6.5 ± 2.9 minutes, P = .006) groups, while recovery time was significantly longer in the HD group (86.2 ± 13.4 minutes) than the LD group (44.4 ± 10.8 minutes, P < .001). Midazolam premedication resulted in reduction of both muscle tremors and hyperexcitation associated with alfaxalone administration, but the recovery time was significantly longer (103.5 ± 15.1 minutes, P < .001) than for the LD group. Alfaxalone as a sole agent resulted in muscle tremors and hyperexcitation during induction, which was attenuated by premedication with midazolam. Further investigation is warranted to characterize the effects of alfaxalone and drugs used to premedicate Quaker parrots.

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function.

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes.