Effects of intrahippocampal NAC(61-95) injections on memory in the rat and attenuation with vitamin E

Parkinson's disease (PD)-related dementia affects approximately 40% of PD patients and the severity of this dementia correlates significantly with the density of Lewy body (LB) deposition in the PD brain. Aggregated alpha-synuclein protein is the major component of LB's and the non-amyloid component (NAC) region of alpha-synuclein, residues 61-95, is essential for the aggregation and toxicity of this protein. The current study evaluated the effect of pre-aggregated NAC(61-95) injected into the CA3 area of the dorsal hippocampus of the brain on memory in the rat. Previous research has suggested that oxidative stress processes may play a role in the neuropathology of PD, therefore the effect of treatment with vitamin E, an antioxidant, was also evaluated. Male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, subjects were divided into four groups. Two groups were injected bilaterally into the dorsal hippocampus with aggregated NAC(61-95) (5 mu l suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 mu l). Subgroups were treated with either vitamin E (150 mg/kg in Soya oil) or vehicle (Soya oil) daily. Injection of NAC(61-95) induced memory deficits and vitamin E treatment alleviated these. In addition, NAC(61-95) injections induced activated astrocytes and chronic treatment with vitamin E reduced the numbers of activated astrocytes. These results suggest that aggregated NAC(61-95) and associated oxidative stress, may play a role in the pathogenesis of cognitive deficits seen in PD-induced dementia. (C) 2009 Elsevier Inc. All rights reserved.

The causal attributions of nursing students towards adolescent survivors of brain injury

Background: The hidden nature of brain injury means that it is often difficult for people to understand the sometimes challenging behaviors that individuals exhibit. The misattribution of these behaviors may lead to a lack of consideration and public censure if the individual is seen as simply misbehaving.

Objective: The aim of this study was to explore the impact of visual cues indicating the presence or absence of brain injury on prejudice, desire for social interaction, and causal attributions of nursing and computing science students.

Method: An independent-groups design was employed in this research, which recruited 190 first-year nursing students and 194 first-year computing science students from a major university in Belfast, UK. A short passage describing an adolescent’s behavior after a brain injury, together with one of three images portraying a young adolescent with a scar, a head dressing, or neither of these, was given to participants. They were then asked to answer questions relating to prejudice, social interaction, locus of control, and causal attributions. The attributional statements suggested that the character’s behavior could be the result of brain injury or adolescence.

Results: Analysis of variance demonstrated a statistically significant difference between the student groups, where nursing students (M = 45.17, SD = 4.69) desired more social interaction with the fictional adolescent than their computer science peers (M = 38.64, SD = 7.69). Further, analysis of variance showed a main effect of image on the attributional statement that described adolescence as a suitable explanation for the character’s lack of self-confidence.

Discussion: Attributions of brain injury were influenced by the presence of a visible but potentially specious indicator of injury. This suggests that survivors of brain injury who do not display any outward indicator may receive less care and face expectations to behave in a manner consistent with the norms of society. If their injury does not allow them to meet with these expectations, they may face public censure and discrimination.

WASP-30b: A 61 M Jup Brown Dwarf Transiting a V = 12, F8 Star

We report the discovery of a 61-Jupiter-mass brown dwarf (BD), which transits its F8V host star, WASP-30, every 4.16 days. From a range of age indicators we estimate the system age to be 1-2 Gyr. We derive a radius (0.89 ± 0.02 R Jup) for the companion that is consistent with that predicted (0.914 R Jup) by a model of a 1 Gyr old, non-irradiated BD with a dusty atmosphere. The location of WASP-30b in the minimum of the mass-radius relation is consistent with the quantitative prediction of Chabrier & Baraffe, thus confirming the theory.

The cemented custom femoral stem--a 10 year review

We report a series of 706 patients (759 hip implants) with an average follow up of 10.5 years (range, 10-11 years) following total hip replacement (THR) using a cemented custom-made femoral stem and a cemented HDP acetabular component. The fate of every implant is known. One hundred and seventy-four patients (23%) were deceased at the time of their 10-year review all died with a functioning THR in situ. Four hundred and sixty-two patients (61%) were subsequently reviewed. One hundred and twenty three patients (16%) were assessed by telephone review, as they were too ill or unwilling to attend. Kaplan-Meier survival analysis (all components) demonstrated a median survival at 10 years of 96.05% or 95% Confidence Intervals (CI) for median survival of (94.41% to 97.22%). Revision surgery occurred in 30 cases (3.9%). Seventeen had full revisions (2.2%) and 13 (1.7%) socket revisions only. Twenty-one out of 30 revisions were for infection or dislocation. There were 2 cases (0.3%) of revision for aseptic loosening of the stem. The 10-year results of the custom femoral titanium stem are encouraging and compare well with other cemented systems.

Higher effort-reward imbalance and lower job control predict exit from the labour market at the age of 61 years or younger: Evidence from the English Longitudinal Study of Ageing

Background: We examined whether higher effort-reward imbalance (ERI) and lower job control are associated with exit from the labour market. 

Methods: There were 1263 participants aged 50-74 years from the English Longitudinal Study on Ageing with data on working status and work-related psychosocial factors at baseline (wave 2; 2004-2005), and working status at follow-up (wave 5; 2010-2011). Psychosocial factors at work were assessed using a short validated version of ERI and job control. An allostatic load index was formed using 13 biological parameters. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Exit from the labour market was defined as not working in the labour market when 61 years old or younger in 2010-2011. 

Results: Higher ERI OR=1.62 (95% CI 1.01 to 2.61, p=0.048) predicted exit from the labour market independent of age, sex, education, occupational class, allostatic load and depression. Job control OR=0.60 (95% CI 0.42 to 0.85, p=0.004) was associated with exit from the labour market independent of age, sex, education, occupation and depression. The association of higher effort OR=1.32 (95% CI 1.01 to 1.73, p=0.045) with exit from the labour market was independent of age, sex and depression but attenuated to non-significance when additionally controlling for socioeconomic measures. Reward was not related to exit from the labour market. 

Conclusions: Stressful work conditions can be a risk for exiting the labour market before the age of 61 years. Neither socioeconomic position nor allostatic load and depressive symptoms seem to explain this association.

Gleason Upgrading with Time in a Large Prostate Cancer Active Surveillance Cohort

PURPOSE: We report the percentage of patients on active surveillance who had disease pathologically upgraded and factors that predict for upgrading on surveillance biopsies.

MATERIALS AND METHODS: Patients in our active surveillance database with at least 1 repeat prostate biopsy were included. Histological upgrading was defined as any increase in primary or secondary Gleason grade on repeat biopsy. Multivariate analysis was used to determine baseline and dynamic factors associated with Gleason upgrading. This information was used to develop a nomogram to predict for upgrading or treatment in patients electing for active surveillance.

RESULTS: Of 862 patients in our cohort 592 had 2 or more biopsies. Median followup was 6.4 years. Of the patients 20% were intermediate risk, 0.3% were high risk and all others were low risk. During active surveillance 31.3% of cases were upgraded. On multivariate analysis clinical stage T2, higher prostate specific antigen and higher percentage of cores involved with disease at the time of diagnosis predicted for upgrading. A total of 27 cases (15% of those upgraded) were Gleason 8 or higher at upgrading, and 62% of all 114 upgraded cases went on to have active treatment. The nomogram incorporated clinical stage, age, prostate specific antigen, core positivity and Gleason score. The concordance index was 0.61.

CONCLUSIONS: In this large re-biopsy cohort with medium-term followup, most cases have not been pathologically upgraded to date. A model predicting for upgrading or radical treatment was developed which could be useful in counseling patients considering active surveillance for prostate cancer.