Altered emotional and motivational processing in the transgenic rat model for Huntington's disease.

Huntington disease (HD) is caused by an expansion of CAG repeat in the Huntingtin gene. Patients demonstrate a triad of motor, cognitive and psychiatric symptoms. A transgenic rat model (tgHD rats) carrying 51 CAG repeats demonstrate progressive striatal degeneration and polyglutamine aggregates in limbic structures. In this model, emotional function has only been investigated through anxiety studies. Our aim was to extend knowledge on emotional and motivational function in symptomatic tgHD rats. We subjected tgHD and wild-type rats to behavioral protocols testing motor, emotional, and motivational abilities. From 11 to 15 months of age, animals were tested in emotional perception of sucrose using taste reactivity, acquisition, extinction, and re-acquisition of discriminative Pavlovian fear conditioning as well as reactivity to changes in reinforcement values in a runway Pavlovian approach task. Motor tests detected the symptomatic status of tgHD animals from 11 months of age. In comparison to wild types, transgenic animals exhibited emotional blunting of hedonic perception for intermediate sucrose concentration. Moreover, we found emotional alterations with better learning and re-acquisition of discriminative fear conditioning due to a higher level of conditioned fear to aversive stimuli, and hyper-reactivity to a negative hedonic shift in reinforcement value interpreted in term of greater frustration. Neuropathological assessment in the same animals showed a selective shrinkage of the central nucleus of the amygdala. Our results showing emotional blunting and hypersensitivity to negative emotional situations in symptomatic tgHD animals extend the face validity of this model regarding neuropsychiatric symptoms as seen in manifest HD patients, and suggest that some of these symptoms may be related to amygdala dysfunction.

Well-being of intensive care nurses (WEBIC): a job analytic approach.

AIMS OF THE STUDY: This paper presents the results of a validation study of the so-called well-being of intensive care nurses (WEBIC)-questionnaire that is designed to perform a detailed job analysis of intensive care unit (ICU) nurses' jobs. BACKGROUND: The WEBIC-questionnaire is based on modern sociotechnical systems theory, and distinguishes four integrated task categories: (1) operational, (2) organizing, (3) preparatory, and (4) supportive tasks. For each task, the WEBIC assesses (1) how demanding this task is, and (2) how satisfying the performance of this task is. Using the WEBIC, information is gathered about ICU nurses' qualitative workload, and typical job-related risks for ICU nurses' well-being at work can be mapped. METHODS: A cross-sectional survey on work and well-being of almost 2000 ICU-nurses in 13 different European areas was conducted. Exploratory factor analyses were performed to study the validity of the factorial structure of the WEBIC-questionnaire. The construct validity of the WEBIC-questionnaire was studied by performing hierarchical multiple regression analyses of the WEBIC-factors on two types of job-related well-being, i.e. burnout and general job satisfaction. RESULTS: Results of the exploratory factor analyses showed that the hypothesized four-factor structure of the WEBIC is confirmed by our data. Internal consistencies of the different factors varied from 0.77 to 0.91. Intensive care unit nurses' most central (operational) tasks turned out to pose the greatest demands, but also seemed to drive their satisfaction. With respect to the relationships between the four WEBIC-factors, and burnout and general job satisfaction, it was found that, especially for the satisfying tasks, significant relationships with these outcomes were found. CONCLUSION: The reliability and construct validity of the WEBIC-questionnaire can be considered satisfactory. Furthermore, the questionnaire provides a systematical and detailed coverage of ICU nurses' tasks. In relation to this, the questionnaire is not only useful for scientific purposes but also for practical use.

From inequity to burnout: the role of job stress.

This research examined burnout (i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment) among 2 samples of Dutch teachers as a function of inequity and experienced job stress in 3 different exchange relationships (with students, colleagues, and the school). It was hypothesized that inequity would be linked to burnout through the stress resulting from this inequity. Analysis of a cross-sectional sample (N = 271) revealed that this was indeed the case. Findings were replicated longitudinally using an independent sample of 940 teachers. It is concluded that the often-reported effect of inequity on burnout can partly be interpreted in terms of elevated levels of job stress. Implications of the findings are discussed.

A computational and experimental comparison of two outlet stators for the Nimbus LVAD. Left ventricular assist device.

Two designs of an outlet stator for the Nimbus axial flow left ventricular assist device (LVAD) are analyzed at nominal operating conditions. The original stator assembly (Design 1) has significant flow separation and reversal. A second stator assembly (Design 2) replaces the original tubular outer housing with a converging-diverging throat section with the intention of locally improving the fluid dynamics. Both stator designs are analyzed using computational fluid dynamics (CFD) analysis and experimental particle imaging flow visualization (PIFV). The computational and experimental methods indicate: 1) persistent regions of flow separation in Design 1 and improved fluid dynamics in Design 2; 2) blade-toblade velocity fields that are well organized at the blade tip yet chaotic at the blade hub for both designs; and 3) a moderate decrease in pressure recovery for Design 2 as compared with Design 1. The CFD analysis provides the necessary insight to identify a subtle, localized flow acceleration responsible for the decreased hydraulic efficiency of Design 2. In addition, the curiously low thrombogenicity of Design 1 is explained by the existence of a three-dimensional unsteady vortical flow structure that enhances boundary advection.

Progress on development of the Nimbus-University of Pittsburgh axial flow left ventricular assist system.

Nimbus Inc. (Rancho Cordova, CA) and the University of Pittsburgh have completed the second year of development of a totally implanted axial flow blood pump under the National Institutes of Health Innovative Ventricular Assist System Program. The focus this year has been on completing pump hydraulic development and addressing the development of the other key system components. Having demonstrated satisfactory pump hydraulic and biocompatibility performance, pump development has focused on design features that improve pump manufacturability. A controller featuring full redundancy has been designed and is in the breadboard test phase. Initial printed circuit layout of this circuit has shown it to be appropriately sized at 5 x 6 cm to be compatible with implantation. A completely implantable system requires the use of a transcutaneous energy transformer system (TETS) and a diagnostic telemetry system. The TETS power circuitry has been redesigned incorporating an improved, more reliable operating topography. A telemetry circuit is undergoing characterization testing. Closed loop speed control algorithms are being tested in vitro and in vivo with good success. Eleven in vivo tests were conducted with durations from 1 to 195 days. Endurance pumps have passed the 6 month interval with minimal bearing wear. All aspects of the program continue to function under formal quality assurance.

Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system.

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

Inhibition of rat perirenal preadipocyte differentiation.

The process of adipose differentiation uniquely endows fat cells to accrue triacylglycerols under conditions of nutrient energy surfeit and to release fatty acids during energy deprivation. The object of this investigation was to study influences on this process in perirenal preadipocytes, grown in primary culture or first subculture and derived from male Sprague-Dawley rats, 180-200 g. Supplementation of the culture medium with 1-methyl-3-isobutylxanthine, corticosterone, and insulin induced differentiation in practically all perirenal preadipocytes, as indicated morphologically and by rising glycerophosphate dehydrogenase activity. Appreciable differentiation was induced even in the absence of methylisobutylxanthine. Transforming growth factor beta (1-1000 pM), cachectin (tumour necrosis factor alpha) (1-1000 pM), and basic fibroblast growth factor (0.063-63 nM) inhibited adipose differentiation significantly, almost completely at the higher concentrations. Direct inhibition, rather than a persisting mitogenic effect of fibroblast growth factor, was confirmed using demecolcine (Colcemid). The fact that transforming growth factor beta and cachectin inhibit differentiation in preadipocytes from postpubertal rats suggests that this effect probably also occurs in vivo, thus diverting energy from adipose depots in certain neoplastic and inflammatory states. We propose that the anterior pituitary, through fibroblast growth factor(s), modulates the pool of preadipocytes and other mesenchymal cells. The mitogenic effect would be complemented by a concerted function, inhibition of adipose differentiation, resulting in the retention of a greater number of potentially replicative cells. Then, depending on the subject's nutritional and endocrine status, extrapituitary factors would regulate the specific process of differentiation.

Exaggerated triglyceride accretion in human preadipocyte-murine renal line hybrids composed of cells from massively obese subjects.

To learn about adipose differentiation of precursors from postnatal adipose tissue of lean and massively obese subjects, human omental adipocyte precursor-murine renal adenocarcinoma cell (RAG) hybrids were formed by fusion with polyethylene glycol, and cultured selectively with 50 microM ouabain in hypoxanthine aminopterin thymidine (HAT) medium. Under conditions in which the parent cells did not differentiate, a number of hybrids, which were cloned, revealed morphologic and biochemical evidence of differentiation. In addition to activation of human genes within the common nucleus of the hybrids, murine cytoplasmic activators are probably also involved because heterocaryons (fused cells with two interspecific nuclei) revealed the same phenomenon. Hybrids composed of precursors from massively obese subjects disclosed more frequent and prominent differentiation. Since these hybrids, in contrast to those from the lean, recapitulate this phenomenon in subcultures, they provide the potential system for mapping the human gene(s) responsible for adipose differentiation and its exaggeration in massive obesity.

Effects of age and isoproterenol on the cardiac output and regional blood flow in the rat.

Heart rate, stroke volume, cardiac output, its distribution and organ blood flows were measured, using the microsphere technique (15 micron in diameter microspheres), in 5, 12 and 24 months old conscious male rats. Each rat was then infused with isoproterenol (0.2 microgram/kg.min) and the measurements were repeated. It was found that resting cardiovascular values do not change within the age range studied, with the exception of the renal blood flow. After infusion of isoproterenol, the heart rate and cardiac output increased in the youngest group while only smaller increase in heart rate and no significant changes in cardiac output were found in the oldest group. Similarly, organ blood flow increased after isoproterenol in all organs studied in the 5 months group, with significance levels reached in the case of blood supply to the right and left ventricles, total heart, skin and carcass. In contrast, infusion of the same dose of isoproterenol in the 24 months old animals did not elicit any significant changes in the regional blood flow. Thus, the response to beta-adrenergic stimulation is depressed with advancing age. This finding of decreased in vivo response to beta-adrenergic stimulation may be a mechanism for the altered cardiovascular performance during stress seen in aged animals and man.