Tissue microarray (TMA) use in post mortem neuropathology.

BACKGROUND: Tissue microarrays (TMAs), where each block (and thus section) contains multiple tissue cores from multiple blocks potentially allow more efficient use of tissue, reagents and time in neuropathology. NEW METHOD: The relationship between data from TMA cores and whole sections was investigated using 'virtual' TMA cores. This involved quantitative assessments of microglial pathology in white matter lesions and motor neuron disease, alongside qualitative TDP-43 inclusion status in motor neuron disease cases. Following this, a protocol was developed for TMA construction. RESULTS: For microglial pathology we found good concordance between virtual cores and whole sections for volume density using one 1.75 mm core (equivalent to a 2 mm core after accounting for peripheral tissue loss). More sophisticated microglial cell size and measures required two cores. Qualitative results of pTDP-43 pathology showed use of one 1.75 mm core gave a 100 % sensitivity and specificity within grey matter, and 88.3 % sensitivity and 100 % specificity within white matter. A method of producing the TMAs was suitable for immunohistochemistry both manually and by autostainer, with the minimal core loss from the microscope slide. COMPARISON WITH EXISTING METHODS: TMAs have been used infrequently in post mortem neuropathology research. However, we believe TMAs give comparable tissue assessment results and can be constructed, sectioned and stained with relative ease. CONCLUSIONS: We found TMAs could be used to assess both quantitative (microglial pathology) and qualitative pathology (TDP-43 proteinopathy) with greatly reduced quantities of tissue, time and reagents. These could be used for further work to improve data acquisition efficiency.

Review: Microglia in motor neuron disease.

Motor Neuron Disease (MND) is a fatal neurodegenerative condition, which is characterized by the selective loss of the upper and lower motor neurons. At the sites of motor neuron injury, accumulation of activated microglia, the primary immune cells of the central nervous system, is commonly observed in both human post mortem studies and animal models of MND. Microglial activation has been found to correlate with many clinical features and importantly, the speed of disease progression in humans. Both anti-inflammatory and pro-inflammatory microglial responses have been shown to influence disease progression in humans and models of MND. As such, microglia could both contribute to and protect against inflammatory mechanisms of pathogenesis in MND. While murine models have characterized the microglial response to MND, these studies have painted a complex and often contradictory picture, indicating a need for further characterization in humans. This review examines the potential role microglia play in MND in human and animal studies. Both the pro-inflammatory and anti-inflammatory responses will be addressed, throughout the course of disease, followed by the potential of microglia as a target in the development of disease-modifying treatments for MND.

Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial.

BACKGROUND: Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects. There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg. METHOD: A randomized, single centre, double-blind prospective parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars, and analysed on an intention-to-treat (ITT) basis. Eighty-two patients were assigned randomly to receive either drug for a maximum of three doses. Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours. RESULTS: The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone (p=0.03) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h (95 per cent CI: 0.18 to 2.08). Of the patients who received the paracetamol codeine combination, 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone (p=0.20). There was no significant difference between the two groups in the proportion of patients experiencing adverse events (p=0.5). CONCLUSION: A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal, with no significant difference of side effects during the 12 hour period studied.

Evidence for the validity and utility of the Stages of Exercise Behaviour Change scale in young adults.

This study examined the validity and utility of the Stages of Exercise Behaviour Change (SEBC) scale in 244 young British adults. One-way ANOVA revealed significant differences (F > 7.34, P < 0.01) between the Exercise Behaviour Change Categories of Precontemplation/Contemplation (n = 49), Preparation (n = 87) and Action/Maintenance (n = 108) in self-report levels of exercise behaviour. Significant differences (F > 3.14, P < 0.05) were also revealed in exercise self-efficacy, physical self-perception sub-domains and global self-esteem scores. Subsequent step-wise discriminant analyses revealed that discrimination between the Categories of Exercise Behaviour Change was possible on the basis of selected behavioural and psychological parameters (Canonical r = 0.76-0.82, Wilks' lambda = 0.30-0.33, chi 2 = 60.3-94.6, d.f. = 14, P < 0.0001). In both males and females, the most dominant discriminatory variables in the first Function were revealed to be perceived physical conditioning and 'strenuous' exercise behaviour. For males, the second Function comprised exercise self-efficacy and perceived bodily attractiveness, whilst for females it comprised perceived bodily attractiveness, perceived sports competence and perceived physical strength. Subsequent cross-validation analysis, using a randomly selected 40% sub-sample, revealed that 67.8-70.7% of subjects were assigned to the correct Category. These results appear to confirm the concurrent validity of the SEBC scale in terms of self-report of exercise behaviour. Furthermore, the utility of the SEBC scale was demonstrated via the ability to predict membership of specific Categories of Exercise Behaviour Change using a selection of behavioural and psychological parameters.

Participation in community sports centres: motives and predictors of enjoyment.

Research into why people engage in sport and physical recreation has received relatively little attention in both recreation planning and sport psychology. Although there has been a steady flow of North American literature related to participation motivation in competitive youth sport settings, such evidence is of limited value in explaining adult involvement in sport and recreation in Britain. The purpose of this exploratory study was to determine why people participate in sport and exercise in community sports centres and to identify whether these motives predict sport enjoyment. The study was based on a questionnaire-interview of approximately 5 min duration conducted in six community sports centres in Leicester. The sample comprised 336 respondents aged 16 years and over. The subjects were presented with 15 motives for sports participation and indicated their degree of agreement on a 5-point scale. The three most commonly endorsed motives were to maintain health, develop physical fitness and aid relaxation. A factor analysis with oblique rotation revealed four factors:assertive achievement, physical well-being, socio-psychological well-being, and sports mastery and performance. Discriminant analysis showed that males were more motivated to participate for sports mastery and performance and assertive achievement than females. A MANOVA showed that older subjects were more motivated by socio-psychological well-being than younger subjects. Sport enjoyment was best predicted by socio-psychological well-being, sports mastery and performance, and sports importance, although only 14.4% of the variance in enjoyment scores was accounted for. These results confirm other research on age differences in exercise and mental health, as well as gender differences on participation motives.

Cognitions and perceptions of health and exercise.

The impact of exercise on health is potentially significant yet relatively few people exercise. The paper reports two exploratory, community-based, cross-sectional retrospective surveys which investigated the cognitions of aerobic exercisers and non-exercisers. Specifically, an analysis was undertaken of differences between exercisers and non-exercisers, between males and females, and between those under 40 and those over 40 years of age on health beliefs, exercise cognitions, knowledge and attributions. Results from Study 1 (N = 433) showed clear differences between exercise, age and gender groups on health beliefs, knowledge and attributions with exercisers having a more positive cognitive profile. Non-exercisers, contrary to the Health Belief Model, were characterised by perceptions of vulnerability to general and cardiac ill-health. Study 2 (N = 468) supported these results and also showed that older people had more negative beliefs and worries about exercise than younger people. Discussion of the results centres on the need for further research on the causality and prediction of exercise and other health-related behaviours from cognitive factors.