Transcriptional Alterations Related to Neuropathology and Clinical Manifestation of Alzheimer's Disease

Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >= 1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.

The impact of change on careers in the 21st century : what do individuals need to do

There is a growing literature (Arthur, Inkson, & Pringle, 1999; Collin & Young, 2000; Hall & Associates, 1996; Peiperl, Arthur,& Anand, 2002) about the changing workplace and the consequent changes to our understanding of the place of career in individuals’ lives (Richardson, 1996, 2000) - “Careers are becoming more varied and more difficult to manage for both individuals and organisations” (Arnold et al, 2005, p. 523). This chapter will present the background to the changes in the world of work and the changes which inevitably impact individuals’ careers. It will then focus on the close relationship between career development and lifelong learning and the importance of ongoing professional learning for individuals to maintain employability in a changing work world.

Collaborative recovery: An integrative model for working with individuals that experience chronic or recurring mental illness.

Objectives: Recovery is an emerging movement in mental health. Evidence for recovery-based approaches is not well developed and approaches to implement recovery-oriented services are not well articulated. The collaborative recovery model (CRM) is presented as a model that assists clinicians to use evidence-based skills with consumers, in a manner consistent with the recovery movement. A current 5 year multisite Australian study to evaluate the effectiveness of CRM is briefly described. Conclusion: The collaborative recovery model puts into practice several aspects of policy regarding recovery-oriented services, using evidence-based practices to assist individuals who have chronic or recurring mental disorders (CRMD). It is argued that this model provides an integrative framework combining (i) evidence-based practice; (ii) manageable and modularized competencies relevant to case management and psychosocial rehabilitation contexts; and (iii) recognition of the subjective experiences of consumers.

An analysis of the determinants of job satisfaction when individuals' baseline satisfaction levels may differ.

A growing literature seeks to explain differences in individuals' self-reported satisfaction with their jobs. The evidence so far has mainly been based on cross-sectional data and when panel data have been used, individual unobserved heterogeneity has been modelled as an ordered probit model with random effects. This article makes use of longitudinal data for Denmark, taken from the waves 1995-1999 of the European Community Household Panel, and estimates fixed effects ordered logit models using the estimation methods proposed by Ferrer-i-Carbonel and Frijters (2004) and Das and van Soest (1999). For comparison and testing purposes a random effects ordered probit is also estimated. Estimations are carried out separately on the samples of men and women for individuals' overall satisfaction with the jobs they hold. We find that using the fixed effects approach (that clearly rejects the random effects specification), considerably reduces the number of key explanatory variables. The impact of central economic factors is the same as in previous studies, though. Moreover, the determinants of job satisfaction differ considerably between the genders, in particular once individual fixed effects are allowed for.

Research participation of individuals with dementia : decisional capacity, informed consent, and considerations for nurse investigators

Decisional capacity is a precious component of personhood and is progressively diminished in dementia. Conducting research with individuals with dementia demands a commitment to ensure the quest for knowledge does not overwhelm the rights of those it is intended to protect. The purposes of this article are to describe current understandings of the concept of decisional capacity, describe recent regulatory developments related to the consideration of additional protections for decisionally impaired adults, and provide recommendations for nurse investigators working with this vulnerable group.

Effects of an acute α-lactalbumin manipulation on mood and food hedonics in high- and low-trait anxiety individuals

Serotonergic hypofunction is associated with a depressive mood state, an increased drive to eat and preference for sweet (SW) foods. High-trait anxiety individuals are characterised by a functional shortage of serotonin during stress, which in turn increases their susceptibility to experience a negative mood and an increased drive for SW foods. The present study examined whether an acute dietary manipulation, intended to increase circulating serotonin levels, alleviated the detrimental effects of a stress-inducing task on subjective appetite and mood sensations, and preference for SW foods in high-trait anxiety individuals. Thirteen high- (eleven females and two males; anxiety scores 45·5 (sd 5·9); BMI 22·9 (sd 3·0)kg/m2) and twelve low- (ten females and two males; anxiety scores 30·4 (sd 4·8); BMI 23·4 (sd 2·5) kg/m2) trait anxiety individuals participated in a placebo-controlled, two-way crossover design. Participants were provided with 40 g α-lactalbumin (LAC; l-tryptophan (Trp):large neutral amino acids (LNAA) ratio of 7·6) and 40 g casein (placebo) (Trp:LNAA ratio of 4·0) in the form of a snack and lunch on two test days. On both the test days, participants completed a stress-inducing task 2 h after the lunch. Mood and appetite were assessed using visual analogue scales. Changes in food hedonics for different taste and nutrient combinations were assessed using a computer task. The results demonstrated that the LAC manipulation did not exert any immediate effects on mood or appetite. However, LAC did have an effect on food hedonics in individuals with high-trait anxiety after acute stress. These individuals expressed a lower liking (P = 0·012) and SW food preference (P = 0·014) after the stressful task when supplemented with LAC.

Mental health outcomes for unemployed individuals who attend occupational skills / personal development training programs

Four studies report on outcomes for long-term unemployed individuals who attend occupational skills/personal development training courses in Australia. Levels of distress, depression, guilt, anger, helplessness, positive and negative affect, life satisfaction and self esteem were used as measures of well-being. Employment value, employment expectations and employment commitment were used as measures of work attitude. Social support, financial strain, and use of community resources were used as measures of life situation. Other variables investigated were causal attribution, unemployment blame, levels of coping, self efficacy, the personality variable of neuroticism, the psycho-social climate of the training course, and changes to occupational status. Training courses were (a) government funded occupational skills-based programs which included some components of personal development training, and (b) a specially developed course which focused exclusively on improving well-being, and which utilised the cognitive-behavioural therapy (CBT) approach. Data for all studies were collected longitudinally by having subjects complete questionnaires pre-course, post-course, and (for 3 of the 4 studies) at 3 months follow-up, in order to investigate long-term effects. One of the studies utilised the case-study methodology and was designed to be illustrative and assist in interpreting the quantitative data from the other 3 evaluations. The outcomes for participants were contrasted with control subjects who met the same sel~tion criteria for training. Results confirmed earlier findings that the experiences of unemployment were negative. Immediate effects of the courses were to improve well-being. Improvements were greater for those who attended courses with higher levels of personal development input, and the best results were obtained from the specially developed CBT program. Participants who had lower levels of well-being at the beginning of the courses did better as a result of training than those who were already functioning at higher levels. Course participants gained only marginal advantages over control subjects in relation to improving their occupational status. Many of the short term well-being gains made as a result of attending the courses were still evident at 3 months follow-up. Best results were achieved for the specially designed CBT program. Results were discussed in the context of prevailing theories of Ynemployment (Fryer, 1986,1988; Jahoda, 1981, 1982; Warr, 1987a, 1987b).

Acute exercise improves postprandial cardiovascular risk factors in overweight and obese individuals

Objectives The effects of 30 min of exercise on postprandial lipaemia in the overweight and obese are unknown as previous studies have only investigated bouts of at least 60 min in lean, healthy individuals. The aim of this study was to investigate whether a single 30-min bout of resistance, aerobic or combined exercise at moderate-intensity would decrease postprandial lipaemia, glucose and insulin levels as well as increase resting energy expenditure and increase fat oxidation following a high fat meal consumed 14 h after the exercise bout, in overweight and obese individuals compared to no exercise. We also compared the effects of the different exercise modalities. Methods This study was a randomized cross-over design which examined the postprandial effects of 30 min of different types of exercise in the evening prior to a breakfast meal in overweight and obese men and women. Participants were randomized on four occasions, each one-week apart, to each condition; either no exercise, aerobic exercise, resistance exercise or a combination of aerobic exercise and resistance exercise. Results An acute bout of combination training did not have any significant effect on postprandial measurements compared to no exercise. However, aerobic exercise significantly reduced postprandial triglyceride levels by 8% compared to no exercise (p = 0.02) and resistance exercise decreased postprandial insulin levels by 30% compared to aerobic exercise (p = 0.01). Conclusion These results indicate that a single moderate-intensity 30 min bout of aerobic or resistance exercise improves risk factors associated with cardiovascular disease in overweight and obese individuals.

Repeatability of measuring corneal subbasal nerve fiber length in individuals with Type 2 Diabetes

Purpose: To analyze the repeatability of measuring nerve fiber length (NFL) from images of the human corneal subbasal nerve plexus using semiautomated software. Methods: Images were captured from the corneas of 50 subjects with type 2 diabetes mellitus who showed varying severity of neuropathy, using the Heidelberg Retina Tomograph 3 with Rostock Corneal Module. Semiautomated nerve analysis software was independently used by two observers to determine NFL from images of the subbasal nerve plexus. This procedure was undertaken on two occasions, 3 days apart. Results: The intraclass correlation coefficient values were 0.95 (95% confidence intervals: 0.92–0.97) for individual subjects and 0.95 (95% confidence intervals: 0.74–1.00) for observer. Bland-Altman plots of the NFL values indicated a reduced spread of data with lower NFL values. The overall spread of data was less for (a) the observer who was more experienced at analyzing nerve fiber images and (b) the second measurement occasion. Conclusions: Semiautomated measurement of NFL in the subbasal nerve fiber layer is highly repeatable. Repeatability can be enhanced by using more experienced observers. It may be possible to markedly improve repeatability when measuring this anatomic structure using fully automated image analysis software.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

A Taxonomy for Homework Used by Mental Health Case Managers When Working with Individuals Diagnosed with Severe Mental Illness

A survey was completed by 122 case managers describing the types of homework assignments commonly used with individuals diagnosed with severe mental illness (SMI). Homework types were categorized using a 12-item homework description taxonomy and in relation to the 22 domains of the Camberwell Assessment of Need (CAN). Case managers predominately reported using behaviourally based homework tasks such as scheduling activities and the development of personal hygiene skills. Homework focused on CAN areas of need in relation to Company, Psychological Distress, Psychotic Symptoms and Daytime Activities. The applications of the taxonomy for both researchers and case managers are discussed.