Analysis of rehabilitation activities within skilled nursing and inpatient rehabilitation facilities after hip replacement for acute hip fracture.

OBJECTIVE: To characterize rehabilitation services in two types of postacute facilities in patients who underwent hip replacement following a hip fracture. DESIGN: Multisite prospective observational cohort from 6 freestanding skilled nursing facilities and 11 inpatient rehabilitation facilities. Patients (n = 218) with hip fracture who had either hemiarthroplasty or total hip arthroplasty followed by rehabilitation at skilled nursing facilities or inpatient rehabilitation facilities were enrolled. Using a point-of-care methodology, we recorded data from actual physical therapy and occupational therapy sessions completed including functional outcomes during the postacute admission. RESULTS: Onset time from surgical repair to rehabilitation admission was not significantly different between sites. Average skilled nursing facilities length of stay was 24.7 +/- 13.6 days, whereas inpatient rehabilitation facilities was 13.0 +/- 5.7 days (P < 0.01). Total hours of physical therapy and occupational therapy services per patient day were 1.2 in skilled nursing facilities and 2.0 in inpatient rehabilitation facilities. For weekdays only, these data changed to 1.6 in skilled nursing facilities and 2.6 hrs per patient in inpatient rehabilitation facilities (P < 0.01). Patients in inpatient rehabilitation facilities accrued more time for gait training and exercise in physical therapy, which was found to be 48% and 40% greater, respectively, through day 8. In occupational therapy, patients of inpatient rehabilitation facilities had more time allocated to lower body dressing and transfers. CONCLUSIONS: Significant differences in rehabilitation activities were observed, and intensity was notably different within the first 8 therapy days even though baseline demographics and medical complexity were comparable across facility types. Our data suggest that after more complex hip replacement surgery, hip fracture patients can tolerate more intensive therapy earlier within the rehabilitation program.

Ganglioside GM1 binding the N-terminus of amyloid precursor protein.

Secreted amyloid precursor protein (APPs) plays a role in several neuronal functions, including the promotion of synaptogenesis, neurite outgrowth and neuroprotection. Previous study has demonstrated that ganglioside GM1 inhibits the secretion of APPs; however the underlying mechanism remains unknown. Here we reported that GM1 can bind cellular full length APP and APPs secreted from APP(695) stably-transfected SH-SY5Y cells. To characterize the GM1-APP interaction further, we expressed and purified recombinant fragments of the N-terminal APP. Immunoprecipitation experiments revealed that GM1 was able to bind the recombinant APP(18-81) fragment. Moreover, the synthetic peptide APP(52-81) could inhibit the binding. Therefore, the binding site for GM1 appears to be located within residues 52-81 of APP. Furthermore, we found that only GM1, but not GD1a, GT1b and ceramide, binds APP-N-terminus, indicating that the specific binding depends on the sugar moiety of GM1. Fluorescent studies revealed a decrease in the intrinsic fluorescence intensity of the APP(52-81) peptide in phosphatidylcholine (PC)/GM1 vesicles. By using FTIR techniques, we found that the major secondary structure of the APP(52-81) peptide was altered in PC/GM1 vesicles. Our results demonstrate that GM1 binds the N-terminus of APP and induces a conformational change. These findings suggest that secreted APP is decreased by membrane GM1 binding to its precursor protein and provide a possible molecular mechanism to explain the involvement of GM1 in APP proteolysis and pathogenesis of Alzheimer's disease.

Control of T Cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis.

Autoimmunity is a complex trait disease where the environment influences susceptibility to disease by unclear mechanisms. T cell receptor clustering and signaling at the immune synapse, T cell proliferation, CTLA-4 endocytosis, T(H)1 differentiation, and autoimmunity are negatively regulated by beta1,6GlcNAc-branched N-glycans attached to cell surface glycoproteins. Beta1,6GlcNAc-branched N-glycan expression in T cells is dependent on metabolite supply to UDP-GlcNAc biosynthesis (hexosamine pathway) and in turn to Golgi N-acetylglucosaminyltransferases Mgat1, -2, -4, and -5. In Jurkat T cells, beta1,6GlcNAc-branching in N-glycans is stimulated by metabolites supplying the hexosamine pathway including glucose, GlcNAc, acetoacetate, glutamine, ammonia, or uridine but not by control metabolites mannosamine, galactose, mannose, succinate, or pyruvate. Hexosamine supplementation in vitro and in vivo also increases beta1,6GlcNAc-branched N-glycans in naïve mouse T cells and suppresses T cell receptor signaling, T cell proliferation, CTLA-4 endocytosis, T(H)1 differentiation, experimental autoimmune encephalomyelitis, and autoimmune diabetes in non-obese diabetic mice. Our results indicate that metabolite flux through the hexosamine and N-glycan pathways conditionally regulates autoimmunity by modulating multiple T cell functionalities downstream of beta1,6GlcNAc-branched N-glycans. This suggests metabolic therapy as a potential treatment for autoimmune disease.