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This study evaluates the effectiveness of two strategies--communication and condom skills training--for increasing condom-protected sex in a sample of 510 high-risk women ages 17 to 61. Baseline and 3- and 6-month postintervention interview data were gathered in three cities participating in a randomized trial of a six-session, group skill-building intervention. This analysis was conducted for the entire sample and for six subgroups categorized by age, single or multiple partners, and history of childhood sexual abuse. The dependent variable was the odds ratio of protected sex acts at each follow-up. Structural equation modeling was used to estimate effects for two intervention pathways. The pathway through condom skills increased the odds of protected sex for the intervention group (chi 2 difference = 35, df = 2, p < .05) as well as for all subgroups. The pathways through communication were significant for the intervention group (chi 2 difference = 23, df = 3, p < .05) but fully effective only for participants under 30 and participants who reported childhood sexual abuse. The effectiveness of both pathways diminished at 6 months. WINGS demonstrates that condom skills training can increase protected sex for a heterogeneous group of women. Further research needs to examine how such skill training translates into use of condoms by male partners. To increase the duration of intervention effects, booster sessions may need to be incorporated. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study assessed the effectiveness of a sexually transmitted disease (STD)/HIV behavior change intervention in increasing women's use of the female condom. METHODS: A total of 604 women at high risk for STDs and HIV in New York City, Baltimore, Md, and Seattle, Wash, enrolled in a randomized controlled trial of a small-group, skills-training intervention that included information and skills training in the use of the female condom. RESULTS: In a logistic regression, the strongest predictors of use were exposure to the intervention (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 2.8, 10.7), intention to use the female condom in the future (OR = 4.5; 95% CI = 2.4, 8.5), having asked a partner to use a condom in the past 30 days (OR = 2.3; 95% CI = 1.3, 3.9), and confidence in asking a partner to use a condom (OR = 1.9; 95% CI = 1.1, 3.5). CONCLUSIONS: Clinicians counseling women in the use of the female condom need to provide information, demonstrate its correct use with their clients, and provide an opportunity for their clients to practice skills themselves. [ABSTRACT FROM AUTHOR]

Over the past three decades, the influence and importance of social support has been well documented and the findings have suggested a beneficial effect on stress-related situations, mental and physical health, and social functioning. More recently, small group/skills training behavioral interventions have demonstrated success in changing behaviors which affect the transmission of sexually transmitted diseases, including HIV among populations at risk for these diseases. Studies of support groups to date have been conducted exclusively in research settings where women are offered financial incentives for participation. Little is known about the willingness of women to participate in ongoing support groups after successfully completing a skills training intervention. The present study examines the factors that may influence participation among women in a weekly support group after completing a structured, six session HIV/ STD intervention. Both quantitative and qualitative data are collected from 265 women in the intervention arm of a multi-site randomized controlled behavioral intervention trial. Results reveal that less than a quarter (22%) of women participated in at least one support group. Participation varied significantly by site, ranging from 34% to 15% (p = .008). Participation was also strongly linked to recent use of domestic violence services. Qualitative data indicated that although monetary incentives play some role in the woman's decision to participate, other factors are also important. These include program outreach, support group size, salience of the group content, consistency of group leadership from the intervention to the support group, and use of peer leaders along with professional facilitators. Implications for design of post-intervention support groups programs are discussed. [ABSTRACT FROM AUTHOR]

The withdrawal of water for irrigation in the dryer regions of Mexico already accounts for some 91% of potential availability. Further expansion of irrigated acreage, therefore, must rely more on increased water use efficiency rather than increased supply from engineering works. A prime instrument to bring about such an improvement could be an appropriate water pricing structure. The first three sections of the paper present the conceptual issues involved, as well as the empirical findings which show that irrigation farmers pay, on average, less than 10% of actual water costs. Water use efficiencies are shown to be less than 50% but are markedly higher in irrigation districts with volumetric compared to those with fixed water charges. The fourth section develops some representative pricing structures that are designed to account for both efficiency and income distributional goals, while the last one addresses some of the likely implementation problems. [ABSTRACT FROM AUTHOR]

Aims: Drought is one of the most destructive abiotic factors for agricultural production, causing considerable yield losses. Quinoa (Chenopodium quinoa Willd.) is cultivated worldwide in different environmental conditions due to its nutritional characteristics and ability to grow in harsh environments. This study aims to select drought stress tolerant rhizosphere bacteria from the Bolivian altiplano to evaluate their quinoa growth-promoting capacity, including in vitro germination, seedling growth under drought stress in greenhouse conditions and field studies., Methods and Results: Rhizosphere soil from the southern highlands of Bolivia was collected to isolate 164 drought-stress tolerant bacteria. From these, 28 strains were shown to produce indole acetic acid, and/or to possess nitrogen-fixing or phosphate solubilizing capacity under in vitro conditions. Furthermore, all strains were evaluated for improvement of in vitro quinoa seed germination. Based on these properties, nine bacterial strains were formulated in three different matrixes and evaluated for quinoa seedling growth promotion during drought stress in a 3-month greenhouse experiment. Three strains were shown to significantly (P < 0.05) increase root length of the quinoa seedlings. One strain was selected and shown to significantly (P < 0.05) increase leaf number in a field trial under semi-arid conditions in the southern altiplano in Bolivia. DNA sequencing and phylogenetic analyses of the 16S locus putatively identified the three strains with growth-promoting potential under drought stress as members of the genera Bacillus, Pseudomonas, and Serratia., Conclusion: Microorganisms from the arid Bolivian altiplano constitute a potential biological source of bioinoculants to improve quinoa productivity and provide sustainable mitigation of climate change effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

The excited states of unstable ^{20}O were investigated via γ-ray spectroscopy following the ^{19}O(d,p)^{20}O reaction at 8  AMeV. By exploiting the Doppler shift attenuation method, the lifetimes of the 2&#95;{2}^{+} and 3&#95;{1}^{+} states were firmly established. From the γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2&#95;{2}^{+} and 3&#95;{1}^{+} states, the B(E2) and B(M1) were determined. Various chiral effective field theory Hamiltonians, describing the nuclear properties beyond ground states, along with a standard USDB interaction, were compared with the experimentally obtained data. Such a comparison for a large set of γ-ray transition probabilities with the valence space in medium similarity renormalization group ab initio calculations was performed for the first time in a nucleus far from stability. It was shown that the ab initio approaches using chiral effective field theory forces are challenged by detailed high-precision spectroscopic properties of nuclei. The reduced transition probabilities were found to be a very constraining test of the performance of the ab initio models.

The aim of this work was to determine whether wearable inertial measurement units (IMUs) could detect gait improvements across different disability groups of people with Multiple Sclerosis (pwMS) by the six-minute walk test (6MWT) during a rehabilitation stay in a specialized rehabilitation center. Forty-six pwMS and 20 healthy controls (HC) were included in the study. They performed the 6MWT with two inertial measurement units (IMUs) placed on the feet. Thirty-two of the pwMS were retested at the end of the stay. PwMS were divided in a mild-disability and a moderate-disability group. The 6MWT was divided in six sections of 1 min each for technical analysis, and linear mixed models were used for statistical analyses. The comparison between the two disability groups and HC highlighted significant differences for each gait parameter (all p < 0.001). The crossing effect between the test-retest and the two disability groups showed greater improvement for the moderate-disability group. Finally, the gait parameter with the higher effect size, allowing the best differentiation between the disability groups, was the foot flat ratio (R 2  = 0.53). Gait analyses from wearable sensors identified different evolutions of gait patterns during the 6MWT in pwMS with different physical disability. The measured effect of a short-time rehabilitation on gait with 6MWT was higher for pwMS with higher degree of disability. Using IMUs in a clinical setting allowed to identify significant changes in inter-stride gait patterns. Wearable sensors and key parameters have the potential as useful clinical tools for focusing on gait in pwMS., (© 2022. The Author(s).)

Purpose: Diagnosis of inherited ataxia and related diseases represents a real challenge given the tremendous heterogeneity and clinical overlap of the various causes. We evaluated the efficacy of molecular diagnosis of these diseases by sequencing a large cohort of undiagnosed families., Methods: We analyzed 366 unrelated consecutive patients with undiagnosed ataxia or related disorders by clinical exome-capture sequencing. In silico analysis was performed with an in-house pipeline that combines variant ranking and copy-number variant (CNV) searches. Variants were interpreted according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines., Results: We established the molecular diagnosis in 46% of the cases. We identified 35 mildly affected patients with causative variants in genes that are classically associated with severe presentations. These cases were explained by the occurrence of hypomorphic variants, but also rarely suspected mechanisms such as C-terminal truncations and translation reinitiation., Conclusion: A significant fraction of the clinical heterogeneity and phenotypic overlap is explained by hypomorphic variants that are difficult to identify and not readily predicted. The hypomorphic C-terminal truncation and translation reinitiation mechanisms that we identified may only apply to few genes, as it relies on specific domain organization and alterations. We identified PEX10 and FASTKD2 as candidates for translation reinitiation accounting for mild disease presentation., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Patients with coronavirus disease 2019 (COVID-19) are prone to pulmonary artery hypertension (PAH) and right ventricular pressure overload due to severe bilateral infiltrates, high ventilation pressures, persistent hypoxemia, pulmonary fibrosis, and/or pulmonary embolism. In patients on extracorporeal membrane oxygenation (ECMO), this potentially leads to increased recirculation. In the current report, the authors present a case in which continuous inhaled nitric oxide (iNO)-enriched ventilation was effective in terms of PAH and recirculation reduction in a COVID-19 patient on veno-venous ECMO., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Refeeding syndrome is a life-threatening, physiological process that occurs when patients with severe malnutrition are too rapidly rehabilitated, leading to the development of electrolyte abnormalities. Hypophosphatemia, a hallmark of the disease, has most commonly been studied, because it is recognized to result in cardiac arrhythmias, seizures, cardiac failure, respiratory failure, rhabdomyolysis, coma, and even death. Although many studies have found caloric intake to be a main causal factor in refeeding syndrome, few have explored other factors, such as geographic location. Border cities, such as El Paso, Texas, have a unique, diverse population. The purpose of this study was to establish the incidence of refeeding syndrome concentrated within a border city., Methods: We performed a retrospective chart review that focused on the incidence of refeeding syndrome in pediatric patients with eating disorders, ages 10 to 19 years, admitted to El Paso Children's Hospital, the only tertiary teaching hospital in the area, associated with Texas Tech University Health Science Center, located along the US-Mexico border, in El Paso, Texas., Results: Twenty-six subjects with a diagnosis of eating disorder were admitted to El Paso Children's Hospital for treatment between 2012 and 2019. Five subjects developed refeeding syndrome, recognized in our study as hypokalemia or hypomagnesemia, during their treatment., Conclusions: Among hospitalized adolescents admitted to El Paso Children's Hospital, 19% developed refeeding syndrome. This incidence was higher in our population than had been previously reported. Further research is needed to better establish a protocol for the treatment of patients with eating disorders.

Aim: Use of systematic reviews (SRs) as first-level evidence for guideline recommendations hinges on review quality. In particular, US guidelines for adherence-related recommendations in the treatment of human immunodeficiency virus (HIV) are not based on available SRs of adherence-outcome relationships; it is unclear why. No published studies report on the quality of SRs on HIV adherence and outcomes, which may be driving the lack of use. We describe the quality of this body of literature., Methods: Literature searches were conducted in Ovid MEDLINE, EMBASE, CINAHL, PubMed Central, the Cochrane Library, Science Citation Index, Web of Science, ScIELO Citation Index, and Ovid Emcare. Screening and quality assessments were performed in duplicate using AMSTAR 2. Funding sources and impact factors of publishing journals were also extracted, and correlations between quality rankings and numbers of critical weaknesses versus impact factors were assessed using Spearman's rank correlation coefficient., Results: Nine SRs of 1141 records met eligibility criteria. Overall confidence in the results was critically low for most (78%) SRs. Underperformance was found across all AMSTAR 2 domains. Impact factor (a surrogate or journal reputation) did not correlate with quality., Conclusions: SRs do not necessarily comprise top-level evidence despite the availability of quality appraisal tools and reporting guidance, which could explain the lack of SR evidence in US HIV medication adherence-related guideline recommendations. All parties to evidence synthesis publication should require quality assessment of studies., (© 2021 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Type V collagen (ColV) is a component of the endothelial basement membrane zone. During angiogenesis, extracellular matrix remodelling results in the release of active protein fragments that display pro- or anti-angiogenic properties. The latter often exert their activity through their heparin-binding site. We previously characterized a ColVα1-derived fragment called HEPV that contains a high affinity-binding site for heparin and heparan sulphate chains. Here we show that HEPV binds to FGF2 through its heparin-binding site. Using in vitro and in vivo angiogenesis assays, we show that HEPV but not the HEPV mutant at the heparin-binding site, inhibits FGF2-dependant angiogenesis. On the opposite, HEPV does not bind to VEGFA and has no effect on VEGFA-mediated angiogenesis. In 3D collagen gels, the addition of HEPV abrogates endothelial cell invasion and sprouting induced by FGF2. Interestingly, in vivo experiments reveal that HEPV anti-angiogenic activity is associated with the appearance of endothelial to mesenchymal transition (EndMT) markers. Together, these findings indicate that the ColVα1-derived fragment HEPV functions as an anti-angiogenic factor that represses FGF2-mediated angiogenesis through the regulation of endothelial cell plasticity. Previous observations showing that ColV overexpression negatively regulates pathological angiogenesis were left unexplained. Our data provide insights into the possible molecular mechanisms., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To evaluate whether cystic fibrosis transmembrane conductance regulator (CFTR) variants are more common among individuals tested for primary ciliary dyskinesia (PCD) compared with controls., Study Design: Data were studied from 1021 individuals with commercial genetic testing for suspected PCD and 91 777 controls with genetic testing at the same company (Invitae) for symptoms/diseases unrelated to PCD or CFTR testing. The prevalence of CFTR variants was compared between controls and each of 3 groups of individuals tested for PCD (PCD-positive, -uncertain, and -negative molecular diagnosis)., Results: The prevalence of 1 pathogenic CFTR variant was similar among the individual groups. When combining the PCD-uncertain and PCR-negative molecular diagnosis groups, there was a higher prevalence of single pathogenic CFTR variants compared with controls (P = .03). Importantly, >1% of individuals who had negative genetic testing results for PCD had 2 pathogenic CFTR variants (8 of 723), and the incidence of cystic fibrosis (CF) (2 pathogenic variants) is roughly 1 in 3000 individuals of Caucasian ethnicity (∼0.03%). This incidence was also greater than that of 2 pathogenic CFTR variants in the control population (0.09% [84 of 91 777]; P = 9.60 × 10 -16 ). These variants correlate with mild CFTR-related disease., Conclusions: Our results suggest that a single pathogenic CFTR variant is not likely to be a PCD-mimetic, but ongoing studies are needed in individuals in whom PCD is suspected and genetic testing results are uncertain or negative. Furthermore, CF may be misdiagnosed as PCD, reflecting phenotypic overlap. Among individuals evaluated for PCD, CF should be considered in the differential even in the CF newborn screening era., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface. Among the six FATP/SLC27A family members, melanomas significantly overexpress FATP1/SLC27A1. Melanocyte-specific FATP1 expression cooperates with BRAF V600E in transgenic zebrafish to accelerate melanoma development, an effect that is similarly seen in mouse xenograft studies. Pharmacologic blockade of FATPs with the small-molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. These data demonstrate that stromal adipocytes can drive melanoma progression through FATP lipid transporters and represent a new target aimed at interrupting adipocyte-melanoma cross-talk. Significance: We demonstrate that stromal adipocytes are donors of lipids that mediate melanoma progression. Adipocyte-derived lipids are taken up by FATP proteins that are aberrantly expressed in melanoma. Inhibition of FATPs decreases melanoma lipid uptake, invasion, and growth. We provide a mechanism for how stromal adipocytes drive tumor progression and demonstrate a novel microenvironmental therapeutic target. Cancer Discov; 8(8); 1006-25. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 899 ., (©2018 American Association for Cancer Research.)

Background: Contemporary studies assessing the frequency, characteristics, and outcomes of serious infections (SIs) in patients presenting a ST-elevation myocardial infarction are scarce., Methods: Prospective cohort of consecutive patients undergoing primary percutaneous coronary intervention (pPCI). Serious infection was defined as the presence of infection that prolonged hospitalization. Community-acquired infection (CAI) was defined by SI diagnosed in the first 72 hours of hospitalization, whereas hospital-acquired infections (HAI) were those diagnosed after 72 hours of hospital admission., Results: From December 2009 to November 2012, 1,486 patients were included in the analysis. Serious infection was present in 58 (3.9%) individuals; 30 (2%) patients had CAI and 28 (1.9%) patients had HAI. Respiratory tract infection was responsible for 82% of the SI. Patients with SI were older, had more comorbidities, and had worse angiographic results of the pPCI procedure when compared with those without SIs. After multivariable adjustment, SI was associated with an approximately 10-fold risk of 30-day death. Patients with CAI had more often a history of smoking, Killip III/IV on hospital admission, worse pPCI, and angiographic results than did patients with HAI. However, no differences were seen in 30-day major cardiovascular outcomes between patients with CAI and HAI., Conclusion: In a contemporary cohort of unselected ST-elevation myocardial infarction patients representative of the daily practice, SI was uncommon but associated with worse pPCI results and high risk of mortality. The occurrences of CAI or HAI were similar, but CAI patients presented distinctly worse angiographic outcomes than did patients with HAI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite the large body of evidence suggesting that effective public health infrastructure is vital to improving the health status of populations, many universities in developing countries offer minimal opportunities for graduate training in public health. In Nepal, for example, only two institutions currently offer a graduate public health degree. Both institutions confer only a general Masters in Public Health (MPH), and together produce 30 graduates per year. The objective of this assessment was to identify challenges in graduate public health education in Nepal, and explore ways to address these challenges., Methods: The assessment included in-person school visits and data collection through semi-structured in-depth interviews with primary stakeholders of Nepal's public health academic sector. The 72 participants included faculty, students, alumni, and leaders of institutions that offered MPH programs, and the leadership of one government-funded institution that is currently developing an MPH program. Data were analyzed through content analysis to identify major themes., Results: Six themes characterizing the challenges of expanding and improving graduate public health training were identified: 1) a shortage of trained public health faculty, with consequent reliance on the internet to compensate for inadequate teaching resources; 2) teaching/learning cultures and bureaucratic traditions that are not optimal for graduate education; 3) within-institution dominance of clinical medicine over public health; 4) a desire for practice-oriented, contextually relevant training opportunities; 5) a demand for degree options in public health specialties (for example, epidemiology); and 6) a strong interest in international academic collaboration., Conclusion: Despite an enormous need for trained public health professionals, Nepal's educational institutions face barriers to developing effective graduate programs. Overcoming these barriers will require: 1) increasing the investment in public health education and 2) improving the academic environment of educational institutions. Long term, committed academic collaborations with international universities may be a realistic way to: 1) redress immediate inadequacies in resources, including teachers; 2) encourage learning environments that promote inquiry, creativity, problem-solving, and critical thinking; and 3) support development of the in-country capacity of local institutions to produce a cadre of competent, well-trained public health practitioners, researchers, teachers, and leaders.

Objective: To know the outcomes of the management of adult patients with appendiceal inflammatory mass at Cayetano Heredia National Hospital., Material and Methods: This is a retrospective and descriptive study, where data collection from medical records of patients with appendiceal inflammatory mass who were managed at Cayetano Heredia National Hospital from 2006 to 2010 was done., Results: 77 patients were included in this study. 41 (53.25%) were male and mean age was 35 years. The incidence of appendiceal inflammatory mass was 2.76%. Mean time of symptoms was 8 days. Conservative treatment succeeded in 88.31% of patients, interval appendicectomy was performed in 11.76%, mean time till interval surgery was 3.5 months. Nine patients (11.69%) did not respond to conservative management and underwent emergency surgery. Mortality was 0%., Conclusions: In Cayetano Heredia National Hospital, the incidence of appendiceal inflammatory mass is 2.76%. 88.31% of patients respond to conservative treatment, of which interval appendicectomy is performed in 11.76%.

The Smc5-Smc6 complex in Saccharomyces cerevisiae is both essential for growth and important for coping with genotoxic stress. While it facilitates damage tolerance throughout the genome under genotoxin treatment, its function during unperturbed growth is mainly documented for repetitive DNA sequence maintenance. Here we provide physical and genetic evidence showing that the Smc5-Smc6 complex regulates recombination at non-repetitive loci such as centromeres in the absence of DNA damaging agents. Mutating Smc6 results in the accumulation of recombination intermediates at centromeres and other unique sequences as assayed by 2D gel analysis. In addition, smc6 mutant cells exhibit increased levels of Rad52 foci that co-localize with centromere markers. A rad52 mutation that decreases centromeric, but not overall, levels of Rad52 foci in smc6 mutants suppresses the nocodazole sensitivity of these cells, suggesting that the Smc6-mediated regulation of recombination at centromeric regions impacts centromere-related functions. In addition to influencing recombination, the SUMO ligase subunit of the Smc5-Smc6 complex promotes the sumoylation of two kinetochore proteins and affects mitotic spindles. These results suggest that the Smc5-Smc6 complex regulates both recombination and kinetochore sumoylation to facilitate chromosomal maintenance during growth.

Background: The proportion of the global population aged 60 and over is increasing, more so in Latin America than any other region. Depression is common among elderly people and an important cause of disability worldwide., Aims: To estimate the prevalence and correlates of late-life depression, associated disability and access to treatment in five locations in Latin America., Method: A one-phase cross-sectional survey of 5886 people aged 65 and over from urban and rural locations in Peru and Mexico and an urban site in Venezuela. Depression was identified according to DSM-IV and ICD-10 criteria, Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) algorithm and EURO-D cut-off point. Poisson regression was used to estimate the independent associations of sociodemographic characteristics, economic circumstances and health status with ICD-10 depression., Results: For DSM-IV major depression overall prevalence varied between 1.3% and 2.8% by site, for ICD-10 depressive episode between 4.5% and 5.1%, for GMS-AGECAT depression between 30.0% and 35.9% and for EURO-D depression between 26.1% and 31.2%; therefore, there was a considerable prevalence of clinically significant depression beyond that identified by ICD-10 and DSM-IV diagnostic criteria. Most older people with depression had never received treatment. Limiting physical impairments and a past history of depression were the two most consistent correlates of the ICD-10 depressive episode., Conclusions: The treatment gap poses a significant challenge for Latin American health systems, with their relatively weak primary care services and reliance on private specialists; local treatment trials could establish the cost-effectiveness of mental health investment in the government sector.

Background: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides., Methodology/principal Findings: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age., Conclusions/significance: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis.

Previously, several studies have demonstrated changes in the levels of small heat shock proteins (sHSP) in the transgenic mouse models of familial amyotrophic lateral sclerosis (fALS) linked to mutations in Cu/Zn superoxide dismutase. Here, we compared the expression of sHSPs in transgenic mouse models of fALS, Parkinson's disease (PD), dentato-rubral pallido-luysian atrophy (DRPLA) and Huntington's disease (HD); where the expression of mutant cDNA genes was under the transcriptional regulation of the mouse prion protein promoter. These models express G37R mutant Cu/Zn superoxide dismutase (SOD1G37R; fALS), A53T mutant alpha-synuclein (alpha-SynA53T; PD), full-length mutant atrophin-1-65Q, and htt-N171-82Q (huntingtin N-terminal fragment; HD). We found that the levels and solubilities of two sHSPs, Hsp25 and alpha B-crystallin, were differentially regulated in these mice. Levels of both Hsp25 and alpha B-crystallin were markedly increased in subgroups of glias at the affected regions of symptomatic SODG37R and alpha-SynA53T transgenic mice; abnormal deposits or cells intensely positive for alpha B-crystallin were observed in SODG37R mice. By contrast, neither sHSP was induced in spinal cords of htt-N171-82Q or atrophin-1-65Q mice, which do not develop astrocytosis or major motor neuron abnormalities. Interestingly, the levels of insoluble alpha B-crystallin in spinal cords gradually increased as a function of age in nontransgenic animals. In vitro, alpha B-crystallin was capable of suppressing the aggregation of alpha-SynA53T, as previously described for a truncated mutant SOD1. The transgenes in these mice are expressed highly in astrocytes and thus our results suggest a role for small heat shock proteins in protecting activated glial cells such as astrocytes in neurodegenerative diseases.

The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related A beta aggregates have been described in a variety of vertebrate animals, with the notable exception of mice and rats. Three amino acid substitutions distinguish mouse and human A beta that might contribute to their differing properties in vivo. To examine the amyloidogenic potential of mouse A beta, we studied several lines of transgenic mice overexpressing wild-type mouse amyloid precursor protein (moAPP) either alone or in conjunction with mutant PS1 (PS1dE9). Neither overexpression of moAPP alone nor co-expression with PS1dE9 caused mice to develop Alzheimer-type amyloid pathology by 24 months of age. We further tested whether mouse A beta could accelerate the deposition of human A beta by crossing the moAPP transgenic mice to a bigenic line expressing human APPswe with PS1dE9. The triple transgenic animals (moAPP x APPswe/PS1dE9) produced 20% more A beta but formed amyloid deposits no faster and to no greater extent than APPswe/PS1dE9 siblings. Instead, the additional mouse A beta increased the detergent solubility of accumulated amyloid and exacerbated amyloid deposition in the vasculature. These findings suggest that, although mouse A beta does not influence the rate of amyloid formation, the incorporation of A beta peptides with differing sequences alters the solubility and localization of the resulting aggregates.

Huntington disease (HD) is caused by the expansion of a glutamine (Q) repeat near the N terminus of huntingtin (htt), resulting in altered conformation of the mutant protein to produce, most prominently in brain neurons, nuclear and cytoplasmic inclusion pathology. The inclusions and associated diffuse accumulation of mutant htt in nuclei are composed of N-terminal fragments of mutant protein. Here, we used a panel of peptide antibodies to characterize the htt protein pathologies in brain tissues from human HD, and a transgenic mouse model created by expressing the first 171 amino acids of human htt with 82Q (htt-N171-82Q). In tissues from both sources, htt pathologic features in nuclei were detected by antibodies to htt peptides 1-17 and 81-90 but not 115-129 (wild-type huntingtin numbering with 23 repeats). Human HEK 293 cells transfected with expression vectors that encode either the N-terminal 233 amino acids of human htt (htt-N233-82Q) or htt-N171-18Q accumulated smaller N-terminal fragments with antibody-binding characteristics identical to those of pathologic peptides. We conclude that the mutant htt peptides that accumulate in pathologic structures of human HD and httN171-82Q in mice are produced by similar, yet to be defined, proteolytic events in a region of the protein near or within amino acids 90-115.

Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate many pathological and behavioral aspects of FALS. By contrast, transgenic mice made by introducing recombinant vectors, encoding cDNA genes, that target mutant SOD1 expression to motor neurons, only, or astrocytes, only, do not develop disease. Here, we report that mice transgenic for human SOD1 cDNA with the G37R mutation, driven by the mouse prion promoter, develop motor neuron disease. In this model, expression of the transgene is highest in CNS (both neurons and astrocytes) and muscle. The gene was not expressed in cells of the macrophage lineage. Although the highest expressing hemizygous transgenic mice fail to develop disease by 20 months of age, mice homozygous for the transgene show typical ALS-like phenotypes as early as 7 months of age. Spinal cords and brain stems from homozygous animals with motor neuron disease were found to contain aggregated species of mutant SOD1. The establishment of this SOD1-G37R cDNA transgenic model indicates that expression of mutant SOD1 proteins in the neuromuscular unit is sufficient to cause motor neuron disease. The expression levels required to induce disease coincide with the levels required to induce the formation of SOD1 aggregates.

Background: The proteases (secretases) that cleave amyloid-beta (Abeta) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Abeta production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis., Methods and Findings: We have generated a transgenic mouse model that genetically mimics the arrest of Abeta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Abeta production to levels found in nontransgenic mice. Suppression of transgenic Abeta synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Abeta deposits retain a considerable amyloid load, with little sign of active clearance., Conclusion: This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Abeta production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear.

Mice expressing variants of superoxide dismutase-1 (SOD1) encoding C-terminal truncation mutations linked to familial amyotrophic lateral sclerosis (FALS) have begun to define the role of misfolding and aggregation in the pathogenesis of disease. Here, we examine transgenic mice expressing SOD1-L126Z (Z = stop-truncation of last 28 amino acids), finding that detergent-insoluble mutant protein specifically accumulates in somatodendritic compartments. Soluble forms of the SOD1-L126Z were virtually undetectable in spinal cord at any age and the levels of accumulated protein directly correlated with disease symptoms. Neither soluble nor insoluble forms of SOD1-L126Z were transported to distal axons. In vitro, small heat shock protein (Hsp) alphaB-crystallin suppressed the in vitro aggregation of SOD1-L126Z. In vivo, alphaB-crystallin immunoreactivity was most abundant in oligodendrocytes and up-regulated in astrocytes of symptomatic mice; neither of these cell-types accumulated mutant SOD1 immunoreactivity. These results suggest that damage to motor neuron cell bodies and dendrites within the spinal cord can be sufficient to induce motor neuron disease and that the activities of chaperones may modulate the cellular specificity of mutant SOD1 accumulation.

Epidemiological studies suggest that individuals with greater education or more cognitively demanding occupations have diminished risk of developing dementia. We wanted to test whether this effect could be recapitulated in rodents using environmental enrichment, a paradigm well documented to attenuate behavioral deficits induced by various pathological insults. Here, we demonstrate that learning and memory deficits observed in a transgenic mouse model of Alzheimer's disease can be ameliorated by enrichment. Female transgenic mice overexpressing amyloid precursor protein and/or presenilin-1 and nontransgenic controls were placed into enriched or standard cages at 2 months of age and tested for cognitive behavior after 6 months of differential housing. Enrichment significantly improved performance of all genotypes in the radial water maze and in the classic and repeated-reversal versions of the Morris water maze. However, enrichment did not benefit all genotypes equally. Mice overproducing amyloid-beta (Abeta), particularly those with amyloid deposits, showed weaker memory for the platform location in the classic Morris water maze and learned new platform positions in the repeated-reversals task less quickly than their nontransgenic cagemates. Nonetheless, enrichment normalized the performance of Abeta-overproducing mice to the level of standard-housed nontransgenic mice. Moreover, this functional preservation occurred despite increased neuritic plaque burden in the hippocampus of double-transgenic animals and elevated steady-state Abeta levels, because both endogenous and transgene-derived Abeta are increased in enriched animals. These results demonstrate that the generation of Abeta in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors.

Transgenic mice made by crossing animals expressing mutant amyloid precursor protein (APPswe) to mutant presenilin 1 (PS1dE9) allow for incremental increases in Abeta42 production and provide a model of Alzheimer-type amyloidosis. Here, we examine cognition in 6- and 18-month old transgenic mice expressing APPswe and PS1dE9, alone and in combination. Spatial reference memory was assessed in a standard Morris Water Maze task followed by assessment of episodic-like memory in Repeated Reversal and Radial Water maze tasks. We then used factor analysis to relate changes in performance in these tasks with cholinergic markers, somatostatin levels, and amyloid burden. At 6 months of age, APPswe/PS1dE9 double-transgenic mice showed visible plaque deposition; however, all genotypes, including double-transgenic mice, were indistinguishable from nontransgenic animals in all cognitive measures. In the 18-month-old cohorts, amyloid burdens were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). APPswe/PS1dE9 mice performed all cognitive tasks less well than mice from all other genotypes. Factor and correlation analyses defined the strongest correlation as between deficits in episodic-like memory tasks and total Abeta loads in the brain. Collectively, we find that, in the APPswe/PS1dE9 mouse model, some form of Abeta associated with amyloid deposition can disrupt cognitive circuits when the cholinergic and somatostatinergic systems remain relatively intact; and that episodic-like memory seems to be more sensitive to the toxic effects of Abeta.

More than 70 different mutations in presenilin 1 (PS1) have been associated with inherited early onset Alzheimer's disease (AD). How all these different mutations cause disease has not been clearly delineated. Our laboratory has previously shown that co-expression of mutant PS1 in mice transgenic for amyloid precursor protein (APPswe) dramatically accelerates the rate of amyloid deposition in the brain. In our original animals mutant PS1 was substantially over-expressed, and the stabilized pool of mouse PS1 fragments was largely replaced by the human protein. In this setting the accelerated amyloid pathology in the double transgenic mice could have been due, in part, to decreased endogenous PS1 activity. To investigate this possibility, we generated APP transgenic mice with reduced levels of endogenous PS1. We find that mice harboring only one functional PS1 allele and co-expressing Mo/HuAPPswe do not develop amyloid deposits at ages comparable to mice expressing mutant PS1. We next tested whether hypo-expression of mutant PS1 could accelerate the rate of amyloid deposition using an unusual line of transgenic mice expressing PS1dE9 at low levels, finding no significant acceleration. Our findings demonstrate that the accelerated amyloid pathology, caused by so many different mutations in PS1, is clearly not a result of haplo-insufficiency that might result from inactivating mutations. Instead, our data are consistent with a gain of property mechanism.

Huntington's disease (HD) results from the expansion of a glutamine repeat near the N-terminus of huntingtin (htt). At post-mortem, neurons in the central nervous system of patients have been found to accumulate N-terminal fragments of mutant htt in nuclear and cytoplasmic inclusions. This pathology has been reproduced in transgenic mice expressing the first 171 amino acids of htt with 82 glutamines along with losses of motoric function, hypoactivity and abbreviated life-span. The relative contributions of nuclear versus cytoplasmic mutant htt to the pathogenesis of disease have not been clarified. To examine whether pathogenic processes in the nucleus disproportionately contribute to disease features in vivo, we fused a nuclear localization signal (NLS) derived from atrophin-1 to the N-terminus of an N171-82Q construct. Two lines of mice (lines 8A and 61) that were identified expressed NLS-N171-82Q at comparable levels and developed phenotypes identical to our previously described HD-N171-82Q mice. Western blot and immunohistochemical analyses revealed that NLS-N171-82Q fragments accumulate in nuclear, but not cytoplasmic, compartments. These data suggest that disruption of nuclear processes may account for many of the disease phenotypes displayed in the mouse models generated by expressing mutant N-terminal fragments of htt.

Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD). The C-terminus of Abeta40/42 is generated by gamma-secretase, whose activity is dependent upon presenilin (PS 1 or 2). Missense mutations in PS1 (and PS2) occur in patients with early-onset familial AD (FAD), and previous studies in transgenic mice and cultured cell models demonstrated that FAD-PS1 variants shift the ratio of Abeta40 : 42 to favor Abeta42. One hypothesis to explain this outcome is that mutant PS alters the specificity of gamma-secretase to favor production of Abeta42 at the expense of Abeta40. To test this hypothesis in vivo, we studied Abeta40 and 42 levels in a series of transgenic mice that co-express the Swedish mutation of APP (APPswe) with two FAD-PS1 variants that differentially accelerate amyloid pathology in the brain. We demonstrate a direct correlation between the concentration of Abeta42 and the rate of amyloid deposition. We further show that the shift in Abeta42 : 40 ratios associated with the expression of FAD-PS1 variants is due to a specific elevation in the steady-state levels of Abeta42, while maintaining a constant level of Abeta40. These data suggest that PS1 variants do not simply alter the preferred cleavage site for gamma-secretase, but rather that they have more complex effects on the regulation of gamma-secretase and its access to substrates.

Epidemiological studies of Alzheimer patients from a wide variety of ethnic and socioeconomic backgrounds have identified education and occupation as environmental factors that can affect the risk of developing disease. A model of environmental manipulation in rodents uses enriched housing to provide cognitive and social stimulation. Previous studies have established elevations in synaptic number and function in rodents housed under enriched conditions. Recent experiments in hippocampal cultures have demonstrated that synaptic activity can influence the processing of amyloid precursor protein (APP). Here we examined whether changes in synaptic activity brought about by enriched housing might also influence the deposition of amyloid plaques in vivo using a transgenic mouse model of Alzheimer disease (AD). Mice co-expressing mutant APP and presenilin 1 (PS1) were housed in either enriched or standard cages from 2 months of age and then killed for pathological evaluation several months later. We find that, as compared to littermates housed in standard cages, the enriched APP/PS1 transgenic mice develop a higher amyloid burden with commensurate increases in aggregated and total A beta. These results suggest that A beta deposition can be exacerbated by the neuronal changes associated with enrichment, and demonstrate a substantial, albeit paradoxical, environmental influence on the progression of pathology in a mouse model of AD.

Cu/Zn superoxide dismutase (SOD1), a crucial cellular antioxidant, can in certain settings mediate toxic chemistry through its Cu cofactor. Whether this latter property explains why mutations in SOD1 cause FALS has been debated. Here, we demonstrate motor neuron disease in transgenic mice expressing a SOD1 variant that mutates the four histidine residues that coordinately bind Cu. In-depth analyses of this new mouse model, previously characterized models and FALS human tissues revealed that the accumulation of detergent-insoluble forms of SOD1 is a common feature of the disease. These insoluble species include full-length SOD1 proteins, peptide fragments, stable oligomers and ubiquitinated entities. Moreover, chaperones Hsp25 and alphaB-crystallin specifically co-fractionated with insoluble SOD1. In cultured cells, all 11 of the FALS variants tested produced insoluble forms of mutant SOD1. Importantly, expression of recombinant peptide fragments of wild-type SOD1 in cultured cells also produced insoluble species, suggesting that SOD1 possesses elements with an intrinsic propensity to aggregate. Thus, modifications to the protein, such as FALS mutations, fragmentation and possibly covalent modification, may simply act to augment a natural, but potentially toxic, propensity to aggregate.

Objective: To examine the concurrent validity of the Community Integration Questionnaire (CIQ) in assessing outcomes in traumatic brain injury (TBI) by comparing it with two widely used and well-validated measurements of rehabilitation outcome., Design: A retrospective relational study of the concurrent validity of the CIQ, Craig Handicap Assessment and Reporting Technique (CHART), and Disability Rating Scale (DRS)., Setting: A postacute rehabilitation facility., Participants: Seventy patients with a medical diagnosis of TBI admitted between April 1996 and October 1998 participated in the study., Results: CIQ and CHART provide ratings that are similar in several areas to those provided by the DRS. Correlation (r) among total scores and subscales for all three instruments ranged from 0.021 to 0.671 (P <.01). Correlation between CIQ and CHART is stronger than that between CIQ and DRS or between CHART and DRS, and the correlation between CHART and DRS is stronger than that between CIQ and DRS., Conclusion: The CIQ appears to be the most appropriate instrument in quantifying rehabilitation outcome in patients with TBI at the participatory (handicap) level. The findings of this study can help clinicians gain a greater understanding of the nature, redundancy, and gaps among functional outcome measures. Monitoring outcomes can also help clinicians better understand the effectiveness of interventions.

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) have been linked to dominantly inherited forms of amyotrophic lateral sclerosis (FALS). To test the hypothesis that the toxicity of mutant SOD1 originates in Cu(2+)-mediated formation of toxic radicals, we generated transgenic mice that express human SOD1 that encodes disease-linked mutations at two of the four histidine residues that are crucial for the coordinated binding of copper (H46R/H48Q). We demonstrate that mice expressing this mutant, which possesses little or no superoxide scavenging activity, develop motor neuron disease. Hence, mutations in SOD1 that disrupt the copper-binding site do not eliminate toxicity. We note that the pathology of the H46R/H48Q mice is dominated by fibrillar (Thioflavin-S-positive) inclusions and that similar inclusions were evident in mouse models that express the G37R, G85R, and G93A variants of human SOD1. Overall, our data are consistent with the hypothesis that the aberrant folding/aggregation of mutant SOD1 is a prominent feature in the pathogenesis of motor neuron disease.

Extracellular and/or intracellular aggregates are pathological features of many, if not all, neurodegenerative diseases. In Alzheimer disease (AD), extracellular aggregates of beta-amyloid (Abeta) and intracellular aggregates of tau or a-synuclein are key diagnostic markers of the disease. We report here a method to rapidly detect these protein aggregates that relies on size exclusion filtration and immunostaining of trapped material, a method termed filter trapping. We demonstrate that aggregated forms of Abeta and tau are readily trapped in 0.22 microm cellulose acetate filter membranes, which can then be immunostained with specific antibodies in a manner similar to the standard immunoblot. Coupling this method with serial dilution permits a rapid assessment of relative aggregate burden.

In Alzheimer disease, the extracellular deposition of beta-amyloid (Abeta) in the brain is accompanied by the intracellular accumulation of aggregated forms of hyperphosphorylated tau. In developing animal models of AD, the authors and others have been able to reproduce extracellular amyloid pathology in the brains of mice by expressing mutant amyloid precursor proteins (APP). The co-expression of APP with mutant presenilin leads to a dramatic acceleration in Abeta deposition, leading to very high amyloid burdens in mice. In the current study, the authors have examined whether the brains of mice with high burdens of amyloid deposition also contain aggregated forms of tau, using a cellulose acetate filter trap assay. Although discrete accumulations of phosphorylated tau immunoreactivity were apparent in neurites proximal to cored deposits of Abeta, little if any of this tau was in a SDS-resistant state of aggregation. By contrast, the brains of AD patients contained large amounts of aggregated tau. Overall, this study demonstrates that, in mice, deposition of Abeta does not cause endogenous tau to aggregate.

The activities of presenilin 1 (PS1) and 2 modulate the proteolytic processing of amyloid precursor proteins to produce Abeta1-42, and mutations in these proteins are associated with an accelerated rate of Abeta deposition. PS1 and PS2 themselves are subject to a highly-regulated endoproteolytic cleavage to generate stable 27 kDa N-terminal and 17 kDa C-terminal fragments. Here, we examined the relationship between the regulated cleavage of PS1 and the acceleration of Abeta deposition in transgenic mice that co-express Mo/Hu APPswe and varied levels mutant PS1 (A246E variant). The steady-state levels of the N- and C-terminal fragments of mutant PS1 in mice expressing low levels of mRNA were similar to that of mice expressing high levels of mRNA. Only mice expressing high levels of transgene mRNA accumulated uncleaved full-length protein. In mice co-expressing low levels of PS1A246E mRNA with Mo/Hu APPswe the age of appearance of Abeta deposits was similar to that of mice co-expressing expressing Mo/Hu APPswe with very high levels of mutant PS1. Our findings demonstrate that the levels of accumulated human PS1 N- and C-terminal fragments do not increase in proportion to the level of transgene mRNA and that similarly, the magnitude by which mutant PS1 accelerates the deposition of beta-amyloid is not proportional to the level of transgene expression.

This study examined the effects of environmental predictability on postural control during functional reaching while seated in healthy individuals and patients with traumatic brain injury (TBI). The postural perturbation used required reaching to the left versus reaching to the right, while seated, under predictable versus unpredictable conditions. Indexes of postural control--trajectory stability and response reach times--were measured using an electromechanical system in ten patients with TBI and ten healthy subjects. In the TBI group, greater trajectory stability and shorter response reach time were recorded under unpredictable conditions when reaching to both the right and left (d-index 0.57-2.3). In the control group, greater trajectory stability and shorter response time were recorded under predictable and unpredictable environments compared with the TBI group (d-index 0.46-0.95). This study refutes the hierarchical, predictable-to-unpredictable-environment model of postural control evaluation and treatment. The relationship between information processing demands and postural skill appears more complex than a simple linear association. Predictable and unpredictable conditions may be used concurrently, not sequentially, in TBI rehabilitation.

Maternal substance abuse is a serious problem with significant adverse effects to mothers, fetuses, and children. The Early Start Program provides pregnant women in a managed care organization with screening and early identification of substance abuse problems, early intervention, ongoing counseling, and case management by a licensed clinical social worker located in the prenatal clinic, where she is an integral part of the prenatal team. We describe the development of the Early Start Program, its administrative history, and how it has interfaced with clinicians and administrators. We also highlight two important program characteristics: the partnership with a perinatal health services research unit and the degree to which the program could be "exported" to other managed care settings.

Objective: Overall satisfaction has important social and economic implications for patients who have received inpatient medical rehabilitation. We conducted this study to examine the overall satisfaction level at 3- to 6-mo follow-up for inpatients with cerebrovascular impairments discharged from medical rehabilitation., Design: The study was retrospective using information from a national database representative of medical rehabilitation patients across the United States. Information submitted in 1997 and 1998 to the Uniform Data System for Medical Rehabilitation by 177 hospital and rehabilitation facilities from 40 states was examined. The final sample included 8,900 patient records. The main outcome measure was the level of satisfaction with medical rehabilitation at 80-180 days postdischarge follow-up., Results: A logistic regression model including ten independent variables was used to predict satisfied vs. dissatisfied at follow-up. Three statistically significant variables were included in the final model and correctly classified 95.1% of the patients. Higher FIM instrument discharge scores were associated with increased satisfaction. Further analysis of the FIM instrument subscales indicated that higher ratings in transfers, social cognition, and locomotion were significantly associated with increased satisfaction., Conclusion: We identified several functional variables associated with increased satisfaction after medical rehabilitation in persons with stroke. The ability to objectively assess patient satisfaction is important as consumer-based outcome measures are integrated in accreditation and healthcare evaluation.