Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory.

Entorhinal cortex neuropathology begins very early in Alzheimer's disease (AD), a disorder characterized by severe memory disruption. Indeed, loss of entorhinal volume is predictive of AD and two of the hallmark neuroanatomical markers of AD, amyloid plaques and neurofibrillary tangles (NFTs), are particularly prevalent in the entorhinal area of AD-afflicted brains. Gene transfer techniques were used to create a model neurofibrillary tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the entorhinal cortex of adult rats. The objective of the present investigation was to determine whether adult onset, spatially restricted tauopathy could be sufficient to reproduce progressive deficits in mnemonic function. Spatial memory on a Y-maze was tested for approximately 3 months post-surgery. Upon completion of behavioral testing the brains were assessed for expression of human tau and evidence of tauopathy. Rats injected with the tau vector became persistently impaired on the task after about 6 weeks of postoperative testing, whereas the control rats injected with a green fluorescent protein vector performed at criterion levels during that period. Histological analysis confirmed the presence of hyperphosphorylated tau and NFTs in the entorhinal cortex and neighboring retrohippocampal areas as well as limited synaptic degeneration of the perforant path. Thus, highly restricted vector-induced tauopathy in retrohippocampal areas is sufficient for producing progressive impairment in mnemonic ability in rats, successfully mimicking a key aspect of tauopathies such as AD.

Self-efficacy and participation in physical and social activity among older adults in Spain and the United States.

PURPOSE: We explored Bandura's self-efficacy theory as applied to older adult (aged 63-92) participation in physical and social activity in a cross-cultural study. DESIGN AND METHODS: Older adults in Spain (n = 53) and the United States (n = 55) completed questions regarding self-efficacy, outcome expectancy, and participation in physical and social activities. RESULTS: Self-efficacy significantly predicted both physical and social activity in both Spain and the United States. Outcome expectancy did not significantly predict either activity, nor did education, gender, or overall health. Modified and new self-efficacy measures proved reliable in both samples. IMPLICATIONS: This study enhances understanding of how self-efficacy motivates participation in physical activity, as noted in previous studies, as well as provides a new understanding of what motivates participation in social activities. The high reliability of the new measures used in this study provides evidence for further use of these measures in other contexts. It is important to note that this study further supports the use of Bandura's theory of self-efficacy for cross-cultural applications.

Bilateral entorhinal cortex lesions impair acquisition of delayed spatial alternation in rats.

Entorhinal cortex lesions induce significant reorganization of several homotypic and heterotypic inputs to the hippocampus. This investigation determined whether surviving heterotypic inputs after bilateral entorhinal lesions would support the acquisition of a learned alternation task. Rats with entorhinal lesions or sham operations were trained to acquire a spatial alternation task. Although the sham-operated rats acquired the task within about 3 weeks postsurgery, rats with bilateral entorhinal lesions failed to learn the task after 12 consecutive weeks of training despite heterotypic sprouting of the cholinergic septodentate pathway and the expansion of the commissural/associational fiber plexus within the dentate gyrus. Thus, heterotypic sprouting failed to ameliorate significantly the effects of bilateral entorhinal lesions. Rather, entorhinal lesions produced a persistent impairment of spatial memory, characterized by a mixture of random error production and perseverative responding.

The effects of short-term and long-term pulmonary rehabilitation on functional capacity, perceived dyspnea, and quality of life.

STUDY OBJECTIVES: The purposes of this study were as follows: (1) to determine whether physical performance, quality of life, and dyspnea with activities of daily living improved following both short-term and long-term pulmonary rehabilitation (PR) across multiple hospital outpatient programs; (2) to examine the differences in these parameters between men and women; and (3) to determine what relationships existed between the psychosocial parameters and the results of the 6-min walk (6MW) test performance across programs. DESIGN: Non-experimental, prospective, and comparative. SETTING: Seven outpatient hospital PR programs from urban and rural settings across North Carolina. PARTICIPANTS: Three hundred nine women and 281 men who were 20 to 93 years of age (mean [+/- SD] age, 66.7 +/- 11.1 years) with chronic lung disease. INTERVENTIONS: All 6MW tests and health surveys were administered prior to and immediately following 12 and 24 weeks of supervised PR participation. Scores from the 6MW tests, the Ferrans and Powers quality of life index-pulmonary version III (QLI), the Medical Outcomes Study 36-item short form (SF-36), and the University of California at San Diego shortness of breath questionnaire (SOBQ) were compared at PR entry, at 12 weeks, and at 24 weeks for differences by gender with repeated-measures analysis of variance. The study entry and follow-up SF-36 physical and mental component summary scores, the QLI health/function and overall scores, and the SOBQ scores were also compared to the 6MW test scores with Pearson correlation coefficient analysis. RESULTS: The mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR (p < 0.05), and improvements were maintained by 24 weeks of PR participation (p < 0.05). Scores on the SOBQ improved after 12 weeks (p < 0.001) among the short-term participants, but not until after 24 weeks among the long-term participants (p = 0.009). The 6MW test performance improved after 12 weeks (p < 0.001) and again from 12 to 24 weeks (p = 0.002) in the long-term participants. No relevant correlational relationships were found between 6MW scores and the summary scores of the administered surveys (r = -0.43 to 0.36). CONCLUSIONS: Physical performance, as measured by the 6MW test, continued to improve with up to 24 weeks of PR participation. Quality-of-life measures and the perception of dyspnea improved after 12 weeks of PR participation, with improvements maintained by 24 weeks of PR participation. It is recommended that PR patients participate in supervised PR for at least 24 weeks to gain and maintain optimal health benefits.

Stroke prevention in atrial fibrillation: are we following the guidelines?

BACKGROUND: Warfarin therapy substantially reduces stroke in atrial fibrillation (AF), yet medical literature reports it is only prescribed in 15-60% of eligible patients. No current national benchmarks for warfarin use in AF patients exist, and it is unclear whether the reported poor compliance represents current rates within primary care practices. The primary study objective was to measure the rate of warfarin use in eligible, high-risk AF patients in a large southeastern group family practice. Secondary objectives were to report the demographics, stroke-risk profiles, contraindications, and reasons for discontinuation of warfarin therapy METHODS: A retrospective chart review was performed on all active patients with documented AF in a large southeastern group family practice/residency between July 1, 2000 and June 30, 2002. Data was abstracted on warfarin use, contraindications, stroke risk, and reasons for discontinuation. RESULTS: Four hundred ninety-one (491) patients were identified from the electronic billing system as potential study subjects. Two hundred eighty-three (283) patients met study criteria, with 210 patients considered to be at high-risk of stroke without contraindications to warfarin therapy. Ninety-four percent (198/210) of these patients were prescribed warfarin during the study period, and 87% (172/198) continued warfarin throughout the study period. CONCLUSION: Family physicians in this practice prescribe warfarin in AF more frequently than published rates demonstrating that high rates of physician adherence to standards are achievable in primary care. Most patients in this setting were considered high-risk for stroke.

Six-minute walk performance and quality of life comparisons in North Carolina cardiac rehabilitation programs.

OBJECTIVE: The purposes of this study were (1). to determine if six-minute walk (6MW) performance improved after short-term cardiac rehabilitation (CR) across multiple outpatient programs; (2). to examine differences in 6MW performance by patient age, sex, and race; and (3). to determine what relationships existed, if any, between 6MW performance and subscales of the Ferrans and Powers' Quality of Life Index-Cardiac Version III (QOLI). DESIGN: Study design was nonexperimental, prospective, and comparative. SETTING: Study setting included 14 outpatient CR programs from urban and rural settings across North Carolina. PATIENTS: Adults aged 40 to 89 years (N = 630; men = 424 [67%], women = 206 [33%]; mean age, 61 +/- 10.32 years) with medically or surgically treated coronary heart disease enrolled in outpatient CR. OUTCOME MEASURES: Study measures included scores on the QOLI and distance walked (feet) on the 6MW test. RESULTS: Six-minute walk tests and QOLI surveys were administered before and immediately after short-term CR participation. Six-minute walk distance increased for all patients in all age categories across programs after CR (P <.0001). As a group, women improved 6MW distance by 15% (1243.9 +/- 301.2 to 1435.3 +/- 298.1; P <.001). Men also improved 6MW distance by 15% (1463.3 +/- 339.5 to 1683.7 +/- 346.9; P <.001) and walked farther than women on both the initial and follow-up 6MW tests (P <.0001). By age, there were no differences in 6MW scores between men and women aged 40 to 49 years (n = 58) and 50 to 59 years (n = 140; P = 0.54). Both of these age groups had greater initial and discharge 6MW scores than those aged 70 to 79 years (n = 183) and 80 to 89 years (n = 22; P <.001). Those aged 60 to 69 years (n = 227) had lower 6MW scores than those aged 40 to 49 years (P = 0.001) and 50 to 59 years (P <.05), and greater scores than those aged 70 to 79 years (P <.05) and 80 to 89 years (P <.05). Those aged 70 to 79 years had greater initial and follow-up 6MW scores than those aged 80 to 89 years(P <.001). Overall improvements in 6MW performance were found in both white subjects (n = 575; P <.001) and African-Americans (n = 54; P <.001). There were no apparent relationships between 6MW performance and overall or Health and Function QOLI scores (r <.21). CONCLUSIONS: Participation in short-term outpatient CR improved 6MW performance in patients aged 40 to 89 years across 14 programs in North Carolina. No relationships were found between 6MW performance and any domain of the QOLI, including the Health and Function domain.