Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Effects of food restriction and refeeding on adipocyte glucose metabolism in Zucker rats

Chronic food restriction has been shown to enhance glucose metabolism in adipocytes from lean Zucker rats at 10, 26, and 52 weeks of age compared to ad libitum-fed lean rats. Only adipocytes from food restricted 10-week-old obese rats demonstrated this response. In this study, lean and obese rats were food restricted from 5 until 14 weeks of age to determine the age at which adipocytes from obese rats were no longer affected by this intervention. Effects of 1 week of refeeding were also determined. When the rats were killed, body weights were highest in control rats followed by restricted/refed and then restricted rats within each genotype. Epididymal pad weights of lean rats were resistant to dietary intervention, while those of obese-restricted and obese-restricted/refed rats weighed less than pads of obese-control rats. Retroperitoneal pad weight was lowered by food restriction in both genotypes; but only that of lean-restricted/refed rats totally recovered with refeeding. Adipocytes of lean-restricted rats had the highest conversion of glucose to CO₂. Glyceride-glycerol production was higher in obese compared to lean rats, but restricted rats had elevated conversion of glucose to fatty acids. In general, these results indicate that by 14 weeks of age obese Zucker rats no longer respond to food restriction with an elevated rate of glucose metabolism in adipocytes.     

Visual function in Huntington's disease patients and presymptomatic gene carriers.

Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance.     

High-protein Weight-loss Diets: Are They Safe and Do They Work? A Review of the Experimental and Epidemiologic Data

Recommendations for increased consumption of protein are among the most common approaches of popular or fad diets. This review summarizes the effects of dietary protein on satiety, energy intake, thermogenesis, and weight loss, as well as its effect on a variety of health outcomes in adults. In short-term studies, dietary protein modulates energy intake via the sensation of satiety and increases total energy expenditure by increasing the thermic effect of feeding. Whereas these effects did not contribute to weight and fat loss in those studies in which energy intake was fixed, one ad libitum study does suggest that a high-protein diet results in a greater decrease in energy intake, and therefore greater weight and fat loss. In terms of safety, there is little long-term information on the health effects of high-protein diets. From the available data, however, it is evident that the consumption of protein greater than two to three times the U.S. Recommended Daily Allowance contributes to urinary calcium loss and may, in the long term, predispose to bone loss. Caution with these diets is recommended in those individuals who may be predisposed to nephrolithiasis or kidney disease, and particularly in those with diabetes mellitus.     

'Not everything that can be counted counts and not everything that counts can be counted'– towards a critical exploration of modes of satisfaction measurement in sheltered housing

This paper reflects on a research project funded by a consortium of leading sheltered housing (SH) providers and their regulatory body, the Housing Corporation. The project aimed to ascertain which aspects of SH older people perceived to be central to their satisfaction and the methods they judged most appropriate to measuring this. We outline key policy developments of importance to SH (specifically the development of performance measurement regimes), and changes in the nature of SH, which are driving providers to re‐evaluate how they measure user satisfaction. We discuss the aims of the project, our methodology and findings, and conclude by raising critical questions about the process of measuring satisfaction within an increasingly managerialised housing system. We argue that this favours standardised methods of information gathering (such as questionnaires) rather than engage with clients in order to develop methods and systems capable of eliciting qualitative issues of concern to them. Our conclusions are, we believe, applicable to health and social care provision, where similar tensions exist around performance measurement and user satisfaction.     

Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study.

This population-based study documented beta-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with beta-blocker use was 0.68 (95%CI, 0.49-0.96). Beta-blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. Beta-blocker use is associated with reduced fracture risk and higher BMD. INTRODUCTION: Animal data suggests that bone formation is under beta-adrenergic control and that beta-blockers stimulate bone formation and/or inhibit bone resorption. MATERIALS AND METHODS: We evaluated the association between beta-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. Beta-blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Odds ratio for fracture associated with beta-blocker use was 0.68 (95% CI, 0.49-0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. Beta-blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use. CONCLUSION: Beta-blockers are associated with a reduction in fracture risk and higher BMD.     

Outcomes of a pilot occupational therapy wellness program for older adults.

OBJECTIVE: The purpose of this study was to evaluate a pilot occupational therapy wellness program designed to teach elders the importance of participation in meaningful social and community occupations to their quality of life. METHOD: Sixty-five older adults participated in this pilot wellness program held at each of three senior apartment complexes. Measures of health-related quality of life using the SF-36 Health Survey and frequencies of social and community participation from a program-specific intake form were completed by 39 participants before and after the 6-month program. Participants also evaluated components of the program through a satisfaction survey. RESULTS: Scores on the SF-36 Health Survey were significantly higher in vitality, social functioning, and the mental health summary scores following participation in the program. Participants reported an increased frequency of socialization and community participation with an average of 55% participating in at least three or more activities per week before the program to an average of 66% participating after the program. Participants who benefited the most attended more classes, were older, and were nondrivers. Eighty percent of those polled rated the pilot program as good or excellent. CONCLUSION: This pilot study provides additional support for prevention efforts for elders in the community. Wellness programs for seniors may be most effective if targeted to those who are older and nondrivers.     

Improving recovery following cardiac surgery: a randomized clinical trial*

To enhance individual and family health during recovery from heart surgery, this study employed nursing interventions based on self-efficacy and family stress theory during the hospitalization period and for 3 months thereafter. The effectiveness of the interventions were assessed through a randomized trial in which 67 prospective bypass and valve surgery patients, aged 30-77 years, and their spouses, were allocated either the experimental interventions or usual care and followed for 6 months. At 3 months post-surgery, the only statistically significant differences between the experimentals and controls were on perceived self-efficacy for lifting and tolerating emotional distress. At 6 months no significant differences were found on individual or family measures. Analyses revealed that age, gender and preoperative cardiac status significantly affected individual recovery. The study is continuing with a larger sample in order to explicate the recovery process and to better determine whether a low intensity nursing intervention can effect changes in individual and family recovery.