Montreal cognitive assessment (MoCA) is highly correlated with 1-year mortality in hip fracture patients.

Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates. INTRODUCTION: Hip fractures rank amongst the top 10 causes of disability and current mortality of hip fractures is high. Objectives were to determine 1) prevalence of cognitive impairment, 2) whether Montreal Cognitive Assessment (MoCA) score was an independent risk factor associated with mortality, 3) MoCA cut-off that result in high risk of mortality. METHODS: This was a cohort study between July 2019 to June 2020. Inclusion criteria were 1) hip fracture, 2) > = 65 years old, and 3) low-energy trauma. Patients undergo assessment for cognitive impairment with MoCA. Prevalence was assessed, MoCA cut-off point, and accuracy of statistical model was evaluated. Logistic regression modelling was used to assess association between mortality and MoCA. RESULTS: There were 260 patients recruited. Two hundred twenty-five patients had MoCA score < 22 signifying cognitive impairment, and 202 patients had MoCA score of < 19. 46 hip fracture patients died at 1-year follow-up. 45 of these patients had MoCA score < 19, and 1 patient had a MoCA > 22. Results showed statistical significance and good model effect (at least 0.8) with MoCA cut-off points between < 15 and < 19 (p < 0.05). After controlling confounding factors, statistical significance still existed in MoCA cut-off point at < 15 (odds ratio (95% CI) = 11.71 (1.14, 120.71); p = 0.04). CONCLUSION: Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality in hip fracture patients. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality at 1-year after a hip fracture. AUC with MoCA score < 15 was 0.948. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates.

Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2.

Cyclin A-Cdk2 complexes bind to Skp1 and Skp2 during S phase, but the function of Skp1 and Skp2 is unclear. Skp1, together with F-box proteins like Skp2, are part of ubiquitin-ligase E3 complexes that target many cell cycle regulators for ubiquitination-mediated proteolysis. In this study, we investigated the potential regulation of cyclin A-Cdk2 activity by Skp1 and Skp2. We found that Skp2 can inhibit the kinase activity of cyclin A-Cdk2 in vitro, both by direct inhibition of cyclin A-Cdk2 and by inhibition of the activation of Cdk2 by cyclin-dependent kinase (CDK)-activating kinase phosphorylation. Only the kinase activity of Cdk2, not of that of Cdc2 or Cdk5, is reduced by Skp2. Skp2 is phosphorylated by cyclin A-Cdk2 on residue Ser76, but nonphosphorylatable mutants of Skp2 can still inhibit the kinase activity of cyclin A-Cdk2 toward histone H1. The F box of Skp2 is required for binding to Skp1, and both the N-terminal and C-terminal regions of Skp2 are involved in binding to cyclin A-Cdk2. Furthermore, Skp2 and the CDK inhibitor p21(Cip1/WAF1) bind to cyclin A-Cdk2 in a mutually exclusive manner. Overexpression of Skp2, but not Skp1, in mammalian cells causes a G1/S cell cycle arrest.

Characterization of the cullin and F-box protein partner Skp1.

Skp1 interacts with cullins, F-box containing proteins, and forms a complex with cyclin A-Cdk2 in mammalian cells. Skp1 is also involved in diverse biological processes like degradation of key cell cycle regulators, glucose sensing, and kinetochore function. However, little is known about the structure and exact function of Skp1. Here we characterized the interaction between Skp1 and the F-box protein Skp2. We show that Skp1 can bind to Skp2 in vitro using recombinant proteins, and in vivo using the yeast two-hybrid system. Deletion analysis of Skp1 indicated that most of the Skp1 protein is required for binding to Skp2. In mammalian cell extracts, a large portion of Skp1 appears to associate with proteins other than Skp2. Biochemical analysis indicated that Skp1 is likely to be a flexible, non-spherical protein, and is capable of forming dimers.

Local recurrence of carcinoma of the tongue after glossectomy: patient prognosis.

We conducted a retrospective review of the prognosis for patients with local recurrence after surgical treatment of carcinoma of the tongue. Glossectomy for squamous cell carcinoma of the tongue was performed in 167 patients. Local recurrence developed in 32 patients including 21 with local recurrence alone, 10 with locoregional recurrence and one with locodistant recurrence. The incidence of local recurrence increased with tumor stage (from 16% of T1 tumors to 46% of T4 carcinomas). Eleven (34%) patients underwent surgical salvage for local recurrence, with only one (9%) patient surviving free of carcinoma at 43 months post-surgical salvage. All of the remaining 21 patients with local recurrence were treated palliatively and all died within one year. Patients who underwent surgical salvage had significantly higher survival rates compared to those treated palliatively. Close follow-up after glossectomy is important for early detection of local recurrence amenable to surgical salvage. However, the overall prognosis for patients with local recurrence was poor, with a three-year actuarial survival rate of only 3%. Therefore, prevention of local recurrence with adequate initial surgical treatment is essential.

The effect of tranexamic acid on growth and spread of an experimental tumor model.

In the spontaneously metastasizing murine P815 mastocytoma studied, exposure of the cell cultures to Tranexamic acid increased plasminogen activator activity (PAA) in the cytosol and in the primary solid tumors. These increased PAA levels were associated with an increased rate of metastasis to the liver.