High-Performance Broadband Bistatic Piezoelectric Composite Array for Application in Ship Wake Detection.

In the far-field wake of a ship, the intensity of the scattering of bubbles is relatively weak. In addition, the wake is relatively thin, and the hole phenomenon is prominent. Thus, it is difficult to detect the wake at a long distance. On this basis, this paper studies a broadband 1-3 high-performance composite transceiver sub-array for the improved detection of a ship's far wake flow field. The content includes frequency characteristics, transmission performance, power tolerance, the beam width of the transmitting array, and the frequency characteristics, reception performance, and beam width of the receiving array. The frequency bandwidth of the transmission array developed in this paper can reach a value of 180 kHz (the center frequency is 390 kHz). The maximum sound source level can reach a value of 228 dB. In the same frequency band, the sensitivity of the receiving array can reach a value of 184 dB, and the fluctuation is less than 5 dB. Compared with the narrowband 1-3 composite array of the same size, the acoustic performance of this sub-array has obvious advantages. Finally, to improve the effective sound path (before the first interface reflection of the sound wave) of the emitted sound wave in the ship's far-field wake, combined with the speed of the moving carrier and the wide-band detection method of the ship's wake, the configuration method of the detection array for the width and direction of the ship's far-field wake is proposed. The results of this research have an important reference value for the research on broadband 1-3 high-performance composite arrays and their application in the far-field wake detection of ships.

Finite Element Calculation with Experimental Verification for a Free-Flooded Transducer Based on Fluid Cavity Structure.

A free-flooded transducer that couples the vibration of a longitudinal vibration transducer and the fluid cavity of an aluminum ring was investigated. Given the transducer is based on a fluid cavity structure and has no air cavity, it can resist high hydrostatic pressure when working underwater, which is suitable for application in the deep sea. At first, the structure and working principle of the transducer were introduced. Then, the axisymmetric finite element model of the transducer was established; and the transmitting voltage response, admittance, and radiation directivity of the transducer were simulated using the finite element method. According to the size of the finite element model, a prototype of the transducer was designed and fabricated, and the electro-acoustic performance of the prototype was measured in an anechoic water tank. The experimental results were consistent with the simulation results and showed a good performance of the transducer. Finally, the improvement of the radiation directivity of the transducer by the optimal design of the free-flooded aluminum ring was obtained using the finite element method and verified by experiments.

Comparing rehabilitation services and outcomes between older and younger people with spinal cord injury.

OBJECTIVE: To compare patient and injury characteristics, rehabilitation services, and outcomes between people incurring traumatic spinal cord injury (SCI) at younger and older ages. DESIGN: Multisite prospective observational cohort study. SETTING: Six acute rehabilitation facilities. PARTICIPANTS: Patients (N=866) aged ≥ 16 years admitted to participating centers for their initial rehabilitation after SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Motor FIM scores at discharge and 1 year postinjury, discharge location, and postacute clinical pathways. RESULTS: Patients were divided into 4 age-at-injury groups: 16 to 29, 30 to 44, 45 to 60, and >60 years of age. Older adults (>60 y) incurring SCI were more likely to be married, retired/unemployed, on Medicare, and to have attained more education. Their injuries mostly resulted from falls and were incomplete in nature. The oldest group had the highest severity of illness, lowest admission and discharge motor FIM scores, and longer rehabilitation stay. They received relatively less rehabilitation than younger groups. They spent proportionately more time in occupational therapy working on preparatory activities and less time on self-care activities during inpatient rehabilitation. In the aged >60 years group, 80% went home at discharge; 17.2% were discharged to a nursing home. Younger groups were less likely to go to a nursing home. Admission motor FIM was the most significant predictor of motor FIM at discharge and 1-year anniversary across age groups. But the age groups differed significantly in patient and treatment factors that explained their respective outcomes. CONCLUSIONS: Older injured individuals experienced a different clinical pathway from younger patients. The present study suggests the need for development of a rehabilitation program tailored specifically to older adults.

Rehospitalization in the first year of traumatic spinal cord injury after discharge from medical rehabilitation.

OBJECTIVE: To determine rates of rehospitalization among discharged rehabilitation patients with traumatic spinal cord injury (SCI) in the first 12 months postinjury, and to identify factors associated with rehospitalization. DESIGN: Prospective observational cohort study. SETTING: Six geographically dispersed rehabilitation centers in the U.S. PARTICIPANTS: Consecutively enrolled individuals with new traumatic SCI (N=951), who were discharged from participating rehabilitation centers and participated in a 1-year follow-up survey. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Occurrence of postrehabilitation rehospitalization within 1 year of injury, length of rehospitalization stays, and causes of rehospitalizations. RESULTS: More than one third (36.2%) of participants were rehospitalized at least once in the 12-month follow-up period; 12.5% were rehospitalized at least twice. The average number of rehospitalizations among those rehospitalized at least once was 1.37 times, with an average length of stay (LOS) of 15.5 days across all rehospitalization episodes. The 3 most common health conditions associated with rehospitalization were those related to the genitourinary system (eg, urinary tract infection), respiratory system (eg, pneumonia), and skin and subcutaneous tissue (eg, pressure ulcer). Being a woman (95% confidence interval [CI], 1.034-2.279), having Medicaid as the main payer (95% CI, 1.303-2.936), and more severe case mix were associated with increased odds of rehospitalization. Those who had more intensive physical therapy (95% CI, .960-.981) had lower odds of rehospitalization. Some center-to-center variation in rehospitalization rates remained unexplained after case mix and practice differences were considered. The 6 SCI rehabilitation centers varied nearly 2-fold in rates at which their former SCI patients were rehospitalized--from 27.8% to 50%. Center-to-center variation diminished when patient case mix was considered. CONCLUSIONS: Compared with earlier studies, rehospitalization rates among individuals with SCI in the first postinjury year remain high and vary by level and completeness of injury. Rehospitalization risk was associated with younger age, being a woman, unemployment and retirement, and Medicaid coverage. Those who had more intensive physical therapy had lower odds of rehospitalization. Future studies should examine center-to-center variations in rehospitalization rates and availability of patient education and community resources.

Role of body weight in therapy participation and rehabilitation outcomes among individuals with traumatic spinal cord injury.

OBJECTIVE: To examine the association between body weight, therapy participation, and functional outcomes among people with spinal cord injury (SCI). DESIGN: Multisite prospective observational cohort study. SETTING: Six acute rehabilitation facilities. PARTICIPANTS: Patients (N=1017) aged ≥ 12 years admitted for their initial rehabilitation after SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Motor FIM at inpatient rehabilitation discharge and 1 year postinjury. RESULTS: Underweight and overweight/obese patients consisted of 2 different clusters of SCI patients. Underweight patients were more likely to be younger, black, less educated, single, have Medicaid as a primary payer, and more likely to have had a cervical level injury because of violence and vehicular-related events than their overweight and obese counterparts. We found few significant differences in hours of therapy during inpatient rehabilitation across weight groups. Among patients with C5-8 ASIA Impairment Scale (AIS) grades A, B, and C injuries, underweight patients received fewer hours of physical therapy per week than patients with a healthy weight (P=.028). Obese patients with paraplegia AIS grades A, B, and C received more hours of occupational therapy during their rehabilitation stay (P<.001) than other weight groups. A higher percentage of underweight patients had pressure ulcers during inpatient rehabilitation in C5-8 AIS grades A, B, and C and paraplegia AIS grades A, B, and C groups. Only in the paraplegia AIS grades A, B, and C group did we find a significant association between weight groups and discharge motor FIM score. Regression models showed that among C1-4 AIS grades A, B, and C patients, the overweight group had better 1-year follow-up motor FIM scores than other weight groups. CONCLUSIONS: Patients who had an unhealthy body weight, that is, being underweight or obese, often have therapy participation and profiles different from those deemed healthy, or just overweight. For patients with paraplegia AIS grades A, B, and C, being overweight or obese was associated with diminished motor FIM outcomes at discharge from rehabilitation. The relation between body weight status, therapy participation, and outcomes are not consistent among study group participants.

Efficient rehabilitation care for joint replacement patients: skilled nursing facility or inpatient rehabilitation facility?

OBJECTIVE: There has been lengthy debate as to which setting, skilled nursing facility (SNF) or inpatient rehabilitation facility (IRF), is more efficient in treating joint replacement patients. This study aims to determine the efficiency of rehabilitation care provided by SNF and IRF to joint replacement patients with respect to both payment and length of stay (LOS). METHODS: This study used a prospective multisite observational cohort design. Tobit models were used to examine the association between setting of care and efficiency. The study enrolled 948 knee replacement patients and 618 hip replacement patients from 11 IRFs and 7 SNFs between February 2006 and February 2007. Output was measured by motor functional independence measure (FIM) score at discharge. Efficiency was measured in 3 ways: payment efficiency, LOS efficiency, and stochastic frontier analysis efficiency. RESULTS: IRF patients incurred higher expenditures per case but also achieved larger motor FIM gains in shorter LOS than did SNF patients. Setting of care was not a strong predictor of overall efficiency of rehabilitation care. Great variation in characteristics existed within IRFs or SNFs and severity groups. Medium-volume facilities among both SNFs and IRFs were most efficient. Early rehabilitation was consistently predictive of efficient treatment. CONCLUSIONS: The advantage of either setting is not clear-cut. Definition of efficiency depends in part on preference between cost and time. SNFs are more payment efficient; IRFs are more LOS efficient. Variation within SNFs and IRFs blurred setting differences; a simple comparison between SNF and IRF may not be appropriate.

Physical therapy activities in stroke, knee arthroplasty, and traumatic brain injury rehabilitation: their variation, similarities, and association with functional outcomes.

BACKGROUND: The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. OBJECTIVE: The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. DESIGN: This was a prospective observational cohort study. METHODS: The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. RESULTS: All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. LIMITATIONS: The study focused primarily on physical therapy without concurrently considering other therapies such as occupational therapy, speech-language pathology, nursing care, and case management or the potential interaction of these inputs. This analysis did not consider the interventions that physical therapists used when patients participated in discrete physical therapy activities. CONCLUSIONS: All 3 patient groups spent a considerable portion of their physical therapy time in gait training relative to other activities. Both gait training and community mobility are higher-level activities that were positively associated with outcomes, although all 3 groups spent little time in community mobility activities. Further research studies, such as randomized clinical trials and predictive validity studies, are needed to investigate whether higher-level or more-integrated therapy activities are associated with better patient outcomes.

Patterns of rehabilitation after hip arthroplasty and the association with outcomes: an episode of care view.

OBJECTIVES: To examine the patterns of rehabilitation after elective and nonelective hip arthroplasty and its association with outcomes over an episode of postacute care. DESIGN: Data were obtained from a multisite prospective observational cohort study and its companion follow-up study. Patterns of care were measured by the combination of settings of care where hip arthroplasty patients received rehabilitation therapy. Main outcome measure was motor portion of the functional independence measure. RESULTS: Approximately 90% of hip arthroplasty patients received rehabilitation care from more than one setting. Eight patterns of care were identified in the follow-up period. Patterns of subsequent care were driven more by initial setting than by etiology. Nonelective hip arthroplasty patients had lower motor functional independence measure scores and used more rehabilitation services than did elective hip arthroplasty patients. Patterns of care were modest factors (accounted for only 7% of variance) in predicting patient motor functional independence measure over an episode of postacute care. CONCLUSIONS: Etiology of hip arthroplasty is associated with amounts of rehabilitation care used and outcomes. After the initial postacute rehabilitation setting, patients continued to receive considerable amounts of therapy in various settings. It is important to look beyond a single setting of care to an entire episode of care when examining clinical outcomes.

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.

Racial disparities in stroke functional outcomes upon discharge from inpatient rehabilitation facilities.

PURPOSE: Analyse racial disparities in clinical outcomes after stroke in inpatient rehabilitation facilities (IRF). METHODS: Analyses based on data from a multi-center prospective observational cohort study on inpatient stroke rehabilitation in six IRFs from across the United States. Multivariate models examined racial disparities in functional outcomes upon discharge, taking into account patient characteristics and detailed information on processes of care. RESULTS: In the moderate stroke group (N = 397), functional scores on admission were not significantly different between African-Americans and whites. In the severe stroke group (N = 335), whites showed significantly lower functional scores at admission [Functional Independence Measurement, (FIM)], mean scores, 44 versus 49 for African-Americans, p < 0.001). Multivariate analyses predicting discharge motor FIM score found no significant differences between African-American and white stroke patients (p = 0.2194 and p = 0.3547 in the moderate and severe stroke group, respectively). CONCLUSION: Controlling for patient characteristics, therapy intensity and processes of care results in non-significant differences between African-Americans and whites in motor FIM scores upon discharge. The absence of significant differences in recovery while patients were on the rehabilitation unit suggests that racial disparities in long-term functional recovery after stroke are likely to have originated before or after the inpatient rehabilitation stay.

T cell receptor signaling co-regulates multiple Golgi genes to enhance N-glycan branching.

T cell receptor (TCR) signaling enhances beta1,6GlcNAc-branching in N-glycans, a phenotype that promotes growth arrest and inhibits autoimmunity by increasing surface retention of cytotoxic T lymphocyte antigen-4 (CTLA-4) via interactions with galectins. N-Acetylglucosaminyltransferase V (MGAT5) mediates beta1,6GlcNAc-branching by transferring N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to N-glycan substrates produced by the sequential action of Golgi alpha1,2-mannosidase I (MIa,b,c), MGAT1, alpha1,2-mannosidase II (MII, IIx), and MGAT2. Here we report that TCR signaling enhances mRNA levels of MIa,b,c and MII,IIx in parallel with MGAT5, whereas limiting levels of MGAT1 and MGAT2. Blocking the increase in MI or MII enzyme activity induced by TCR signaling with deoxymannojirimycin or swainsonine, respectively, limits beta1,6GlcNAc-branching, suggesting that enhanced MI and MII activity are both required for this phenotype. MGAT1 and MGAT2 have an approximately 250- and approximately 20-fold higher affinity for UDP-GlcNAc than MGAT5, respectively, and increasing MGAT1 expression paradoxically inhibits beta1,6GlcNAc branching by limiting UDP-GlcNAc supply to MGAT5, suggesting that restricted changes in MGAT1 and MGAT2 mRNA levels in TCR-stimulated cells serves to enhance availability of UDP-GlcNAc to MGAT5. Together, these data suggest that TCR signaling differentially regulates multiple N-glycan-processing enzymes at the mRNA level to cooperatively promote beta1,6GlcNAc branching, and by extension, CTLA-4 surface expression, T cell growth arrest, and self-tolerance.

Looking upstream: factors shaping the demand for postacute joint replacement rehabilitation.

Since 1993, the numbers of hip and knee replacements in the United States have increased 2-fold to 3-fold while lengths of stay in acute care have decreased by about half, leading to a significant growth in the use of postacute rehabilitative care for patients with a joint replacement. To document these trends, this article uses secondary analysis of acute hospital discharge survey data and evaluates projections to 2030. This article uses a market approach to identify 3 sets of factors that influence the use of joint replacements: (1) increasing patient demand, (2) increasing supply of practitioners, and (3) the role of fiscal intermediaries. The article reviews underlying epidemiologic trends, growing numbers of orthopedic surgeons performing the procedure, technologic innovations, changing indications for the procedure, changing payer mix, and the effects of payer attempts to contain joint replacement costs. An unintended effect of Medicare payment policy has been to shift costs from acute care to downstream postacute care. Medicare and private health plan reimbursement policies need to take into account this broader perspective and not examine joint replacement care and payment in isolated care settings. Future research and health policy needs to consider the interdependent features of the health care system by linking changes in postacute care with upstream changes both in society at large and in the organization, delivery, and financing of acute care associated with joint replacement.

Joint replacement rehabilitation outcomes on discharge from skilled nursing facilities and inpatient rehabilitation facilities.

OBJECTIVE: To compare functional outcomes at discharge across postacute settings. DESIGN: Prospective observational cohort study. SETTING: Eleven inpatient rehabilitation facilities (IRFs), 8 freestanding skilled nursing facilities (SNFs), and 1 hospital-based SNF from across the United States. PARTICIPANTS: Consecutively enrolled patients (N=2152): patients with knee replacement (n=1401) and patients with hip replacement (n=751). INTERVENTIONS: None; examination of existing practice patterns. MAIN OUTCOME MEASURE: FIM discharge motor score. RESULTS: Freestanding SNF patients entered with higher motor FIM scores and left with higher scores than did IRF patients. IRF patients, however, achieved larger motor FIM gains and achieved them in a shorter time. In multivariate models controlling for patient differences and onset days, IRFs were associated with better discharge motor outcomes, but the overall setting effect was not large. The largest motor FIM differences were between medium-volume IRFs and low-volume freestanding SNFs: 4.6 motor FIM points for patients with knee replacement and 7.3 motor FIM points for patients with hip replacement. Other differences between settings were much smaller. Multivariate models explained between a third and a half of the variance in outcome. CONCLUSIONS: As a group, IRFs had better motor FIM outcomes than did SNFs, but the size of the IRF advantage was not large. Other important facility and practice characteristics also were associated with discharge outcomes after joint replacement rehabilitation. Earlier and more intensive rehabilitation was associated with better outcomes. The volume of joint replacement patients seen by a facility also plays a part: medium-volume facilities among both SNFs and IRFs had better outcomes.

Use of rehabilitation and other health care services by patients with joint replacement after discharge from skilled nursing and inpatient rehabilitation facilities.

OBJECTIVE: To compare use of rehabilitation and other health services among patients with knee and hip replacement after discharge from a skilled nursing facility (SNF) or an inpatient rehabilitation facility (IRF). DESIGN: Follow-up interview study at 7.5 months after discharge. SETTING: Five freestanding SNFs, 1 hospital-based SNF, and 6 IRFs from across the United States. PARTICIPANTS: Patients (N=856): patients with knee replacement (n=561) and patients with hip replacement (n=295). INTERVENTIONS: No interventions. MAIN OUTCOME MEASURES: Number of home and outpatient therapy visits, physician visits, emergency room visits, rehospitalizations, and medical complications. RESULTS: After discharge from postacute care, the vast majority of patients received home rehabilitation, outpatient rehabilitation, or both. Patients with knee replacement received an average of 19 home and/or outpatient rehabilitation visits; patients with hip replacement received almost 15 visits. There were no statistically significant differences in rates of emergency room use and rehospitalization except that patients with hip replacement discharged from IRFs had higher rates of rehospitalization than those discharged from freestanding SNFs (15.8% vs 3.1%). Multivariate analyses did not find any SNF/IRF effects. CONCLUSIONS: Patients with joint replacement from both SNFs and IRFs receive considerable amounts of follow-up rehabilitation care. Study uncovered no setting effects related to rehospitalization or medical complications. Looking only at care rendered in the initial postacute setting provides an incomplete picture of all care received and how it may affect follow-up outcomes.

Long-term outcomes of joint replacement rehabilitation patients discharged from skilled nursing and inpatient rehabilitation facilities.

OBJECTIVE: To examine functional and health status outcomes of patients with joint replacement discharged from a skilled nursing facility (SNF) or an inpatient rehabilitation facility (IRF). DESIGN: Postdischarge follow-up interview study at 7.5 months after admission. SETTING: Five freestanding SNFs, 1 hospital-based SNF, and 6 IRFs. PARTICIPANTS: Patients (N=856): 561 with knee replacement and 295 with hip replacement. INTERVENTIONS: None. MAIN OUTCOME MEASURES: FIM and Short-Form 12-Item Health Survey (SF-12). RESULTS: Among patients with knee and hip replacement, IRF patients made larger motor FIM gains from admission and discharge to follow-up. IRF patients, however, were admitted with lower FIM scores and also had more to gain (especially given the ceiling effects within the FIM at follow-up). When adjusted for case mix, IRF patients made larger motor FIM gains and had higher SF-12-related scores among patients with hip replacement but not among patients with knee replacement. Multivariate regressions found modest setting effects that favored IRFs, and the setting effects explained only a modest portion of the variance in motor FIM outcomes. CONCLUSIONS: At follow-up, patients with joint replacement discharged from IRFs had better motor FIM outcomes than those discharged from freestanding SNFs and the hospital-based SNF. Settings did not differ materially in terms of SF-12 outcomes. Findings do not favor one setting decisively over another. A sole focus on initial postacute placement overlooks the larger trajectory of postacute care that needs to be managed to achieve superior outcomes.

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.

Hospital service offerings: does Catholic ownership matter?

Controlling for market and organizational characteristics, Catholic hospitals in 2001 offered more stigmatized and compassionate care services than investor-owned hospitals, and more stigmatized services than public hospitals. There were no differences between Catholic hospitals and other nonprofit hospitals, however, in the number of compassionate, stigmatized, and access services offered. This may reflect growing isomorphism in the nonprofit hospital sector.

Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene.

Active immunization with fibrillar beta-amyloid peptide (Abeta(42)) as well as passive transfer of anti-Abeta antibodies significantly reduces Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid precursor protein (APP)-transgenic mice. Although the mechanism(s) of clearance of Abeta from the brain following active or passive immunization remains to be determined, it is clear that anti-Abeta antibodies are critical for clearance. DNA immunization provides an attractive alternative to direct peptide and adjuvant approaches for inducing a humoral response to Abeta. We constructed a DNA minigene with Abeta fused to mouse interleukin-4 (pAbeta(42)-IL-4) as a molecular adjuvant to generate anti-Abeta antibodies and enhance the Th2-type of immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti-Abeta antibodies. Fine epitope analysis with overlapping peptides of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The DNA minigene-induced anti-Abeta antibodies bound to Abeta plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy.

Dityrosine cross-linked Abeta peptides: fibrillar beta-structure in Abeta(1-40) is conducive to formation of dityrosine cross-links but a dityrosine cross-link in Abeta(8-14) does not induce beta-structure.

Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosine cross-link formation is strongly influenced by the aggregation state of Abeta; more dityrosine is formed when copper-H(2)O(2) or horseradish peroxidase-catalyzed oxidation is applied to fibrillar Abeta vs soluble Abeta. Once formed, dityrosine cross-links are susceptible to further oxidative processes and it appears that cross-links formed in soluble Abeta react through these pathways more readily than those formed in fibrillar Abeta. Because preorganization of fibrils affects the efficiency of dityrosine formation, we examined the effect of dityrosine formation upon local peptide conformation by assessing the solution structure of a small dityrosine dimer derived from Abeta(8-14). Two-dimensional (1)H NMR studies of the short dityrosine dimer offer no evidence of structure. Thus, the fibrillar structure of Abeta enhances formation of dityrosine cross-links, but dityrosine cross-links do not seem to enhance local secondary structure.