The effect of ageing on in vivo human ciliary muscle morphology and contractility

Purpose. To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Methods. Seventy-nine subjects, aged 19–70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Results. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 µm/year nasally (R = 0.54, P < 0.001) and 3.0 µm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. Conclusions. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.

The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens

The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

A tree-based decision model to support prediction of the severity of asthma exacerbations in children

This paper describes the development of a tree-based decision model to predict the severity of pediatric asthma exacerbations in the emergency department (ED) at 2 h following triage. The model was constructed from retrospective patient data abstracted from the ED charts. The original data was preprocessed to eliminate questionable patient records and to normalize values of age-dependent clinical attributes. The model uses attributes routinely collected in the ED and provides predictions even for incomplete observations. Its performance was verified on independent validating data (split-sample validation) where it demonstrated AUC (area under ROC curve) of 0.83, sensitivity of 84%, specificity of 71% and the Brier score of 0.18. The model is intended to supplement an asthma clinical practice guideline, however, it can be also used as a stand-alone decision tool.

Dehdyroepiandrosterone sulfate directly activates protein kinase C-β to increase human neutrophil superoxide generation

Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in the human circulation and is secreted by the adrenals in an age-dependent fashion, with maximum levels during the third decade and very low levels in old age. DHEAS is considered an inactive metabolite, whereas cleavage of the sulfate group generates dehydroepiandrosterone (DHEA), a crucial sex steroid precursor. However, here we show that DHEAS, but not DHEA, increases superoxide generation in primed human neutrophils in a dose-dependent fashion, thereby impacting on a key bactericidal mechanism. This effect was not prevented by coincubation with androgen and estrogen receptor antagonists but was reversed by the protein kinase C inhibitor Bisindolylmaleimide 1. Moreover, we found that neutrophils are unique among leukocytes in expressing an organic anion-transporting polypeptide D, able to mediate active DHEAS influx transport whereas they did not express steroid sulfatase that activates DHEAS to DHEA. A specific receptor for DHEAS has not yet been identified, but we show that DHEAS directly activated recombinant protein kinase C-ß (PKC-ß) in a cell-free assay. Enhanced PKC-ß activation by DHEAS resulted in increased phosphorylation of p47phox, a crucial component of the active reduced nicotinamide adenine dinucleotide phosphate complex responsible for neutrophil superoxide generation. Our results demonstrate that PKC-ß acts as an intracellular receptor for DHEAS in human neutrophils, a signaling mechanism entirely distinct from the role of DHEA as sex steroid precursor and with important implications for immunesenescence, which includes reduced neutrophil superoxide generation in response to pathogens.

The effect of whole body vibration on oxygen uptake and electromyographic signal of the rectus femoris muscle during static and dynamic squat

Whole Body Vibrations consist of a vibration stimulus mechanically transferred to the body. The impact of vibration treatment on specific muscular activity, neuromuscular, and postural control has been widely studied. We investigated whole body vibration (WBV) effect on oxygen uptake and electromyographic signal of the rectus femoris muscle during static and dynamic squat. Fourteen healthy subjects performed a static and dynamic squat with and without vibration. During the vibration exercises, a significant increase was found in oxygen uptake (P=0.05), which increased by 44% during the static squat and 29.4% during the dynamic squat. Vibration increased heart rate by 11.1 ± 9.1 beats.min-1 during the static squat and 7.9 ± 8.3 beats.min-1 during the dynamic squat. No significant changes were observed in rate of perceived exertion between the exercises with and without vibration. The results indicate that the static squat with WBV produced higher neuromuscular and cardiorespiratory system activation for exercise duration ?60 sec. Otherwise, if the single bout duration was higher than 60 sec, the greater cardiorespiratory system activation was achieved during the dynamic squat with WBV while higher neuromuscular activation was still obtained with the static exercise.

Neuromuscular response to whole body vibration treatment during static and dynamic squat exercises

The impact of whole body vibrations (vibration stimulus mechanically transferred to the body) on muscular activity and neuromuscular response has been widely studied but without standard protocol and by using different kinds of exercises and parameters. In this study, we investigated how whole body vibration treatments affect electromyographic signal of rectus femoris during static and dynamic squat exercises. The aim was the identification of squat exercise characteristics useful to maximize neuromuscular activation and hence progress in training efficacy. Fourteen healthy volunteers performed both static and dynamic squat exercises without and with vibration treatments. Surface electromyographic signals of rectus femoris were recorded during the whole exercise and processed to reduce artifacts and to extract root mean square values. Paired t-test results demonstrated an increase of the root mean square values (p<0.05) in both static and dynamic squat exercises with vibrations respectively of 63% and 108%. For each exercise, subjects gave a rating of the perceived exertion according to the Borg's scale but there were no significant changes in the perceived exertion rate between exercises with and without vibration. Finally, results from analysis of electromyographic signals identified the static squat with WBV treatment as the exercise with higher neuromuscular system response. © 2012 IEEE.

A role for epigenetic modulation of the innate immune response during aging

The ageing process results from a complex interplay between genes and the environment that can precipitate an uncontrolled inflammation. Epigenetic changes are believed to provide a link between the environment and nutrition to gene expression by altering the activity of some histone-modifying protein. Epigenetic modifications of DNA and histone proteins have been proposed as important contributory mechanisms to the retention of metabolic memory over time. A thorough understanding of the posttranscriptional and epigenetic factors involved in both normal ageing and age-related disease may inform new strategies and approaches to diagnose, treat, or suppress many aspects of age-dependent frailty.

CD4+ T cell surface alpha enolase is lower in older adults

To identify novel cell ageing markers in order to gain insight into ageing mechanisms, we adopted membrane enrichment and comparison of the CD4+ T cell membrane proteome (purified by cell surface labelling using Sulfo-NHS-SS-Biotin reagent) between healthy young (n=9, 20-25y) and older (n=10; 50-70y) male adults. Following two-dimensional gel electrophoresis (2DE) to separate pooled membrane proteins in triplicates, the identity of protein spots with age-dependent differences (p<0.05 and >1.4 fold difference) was determined using liquid chromatography-mass spectrometry (LC-MS/MS). Seventeen protein spot density differences (ten increased and seven decreased in the older adult group) were observed between young and older adults. From spot intensity analysis, CD4+ T cell surface α-enolase was decreased in expression by 1.5 fold in the older age group; this was verified by flow cytometry (n=22) and qPCR with significantly lower expression of cellular α-enolase mRNA and protein compared to young adult CD4+ T cells (p<0.05). In an independent age-matched case-control study, lower CD4+ T cell surface α-enolase expression was observed in age-matched patients with cardiovascular disease (p<0.05). An immune-modulatory role has been proposed for surface α-enolase and our findings of decreased expression suggest that deficits in surface α-enolase merit investigation in the context of immune dysfunction during ageing and vascular disease.

Intracellular redox state modulates the T cell surface proteome – relevance to ageing

During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Here we describe the effects of depleting intracellular glutathione concentration for T cell exofacial expression of thioredoxin 1 and IL-2 production, and have determined the distribution of Trx1 with ageing. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show using Western blotting that cell surface thioredoxin-1 is lowered and that the response to the lectin phytohaemagglutinin measured by ELISA as IL-2 production is also decreased. Using flow cytometry we show that the distribution of Trx1 on primary CD4+ T cells is age-dependent, with lower surface Trx1 expression and greater variability of surface expression observed with age. Together these data suggest that a relationship exists between the intracellular redox compartment and exofacial surface. Redox imbalance may be important for impaired T cell function during ageing.

Functional and perceived benefits of wearing coloured filters by patients with age-related macular degeneration

Background: The aim was to investigate the visual effect of coloured filters compared to transmission-matched neutral density filters, in patients with dry age-related macular degeneration. Methods: Visual acuity (VA, logMAR), contrast sensitivity (Pelli-Robson) and colour vision (D15) were recorded for 39 patients (average age 79.1 ± 7.2 years) with age-related macular degeneration, both in the presence and absence of glare from a fluorescent source. Patients then chose their preferred coloured and matched neutral density transmission filters (NoIR). Visual function tests were repeated with the chosen filters, both in the presence and absence of glare from the fluorescent source. Patients trialled the two filters for two weeks each, in random order. Following the trial of each filter, a telephone questionnaire was completed. Results: VA and contrast sensitivity were unaffected by the coloured filters but reduced through the neutral density filters (p < 0.01). VA and contrast sensitivity were reduced by similar amounts, following the introduction of the glare source, both in the presence and absence of filters (p < 0.001). Colour vision error scores were increased following the introduction of a neutral density filter (from 177.6 ± 60.2 to 251.9 ± 115.2) and still further through coloured filters (275.1 ± 50.8; p < 0.001). In the absence of any filter, colour vision error scores increased by 29.1 ± 55.60 units in the presence of glare (F2,107 = 3.9, p = 0.02); however, there was little change in colour vision error scores, in the presence of glare, with either the neutral density or coloured filters. Questionnaires indicated that patients tended to gain more benefit from the coloured filters. Conclusions: Coloured filters had minimal impact on VA and contrast sensitivity in patients with age-related macular degeneration; however, they caused a small reduction in objective colour vision, although this was not registered subjectively by patients. Patients indicated that they received more benefit from the coloured filters compared with neutral density filters. © 2013 The Authors © 2013 Optometrists Association Australia.

The influence of age and trait attributions on recruitment selection

The role of interpersonal attraction into the recruitment selection is gaining research attention. Early work in the domain of the influence of attraction in organisations suggested that men are given more resources, such as higher salaries and promotions. However, recent research has found women have an automatic in-group bias. It was suggested that female interviewers are more likely to hire another female. In contrast, male interviewers were found to be equally as likely to hire men as women. To resolve these two conflicting findings a behavioural experiment was set up looking at gender, attractiveness and recruitment selection. Forty participants, twenty male and twenty female, of varying ages (18-65) were recruited through age stratified sampling. Participants took on the role of manager of a medium sized company and were shown twenty photographs of faces previously rated for attractiveness. On initial viewing participants were asked to decide whether they would firstly hire the person and secondly give as many reasons for their decision. Findings from this research show that in all age groups male and female participants gave females (especially attractive females) more jobs, except in the case of the 18-21 year old females who gave attractive males more jobs. On examining the reasons behind the participant’s decisions, it was evident that if you appeared confident, friendly, youthful and attractive you were 46% more likely to receive the job. However, if you were perceived to be untrustworthy, lazy, arrogant and unintelligent you were 49% more likely not to receive the job. These findings shed light on the various processes that may underpin human resource decisions in an organisational setting.

Economic life in the modern age

Werner Sombart (1863-1941) may well have been the most famous and controversial social scientist in Germany during the early twentieth century. Highly influential, his work and reputation have been indelibly tainted by his embrace of National Socialism in the last decade of his life. Although Sombart left an enormous opus spanning disciplinary boundaries, intellectual reaction to his work inside and outside of Germany is divided and ambivalent. Sombart consistently responded to the social and political developments that have shaped the twentieth century. Economic Life in the Modern Age provides a representative sampling of those portions of Sombart's work that have stood the test of time. The volume opens with a substantial introduction reviewing Sombart's life and career, the evolution of his major intellectual concerns, his relation to Marx and Weber, and his political affiliation with the Nazis. The editors' selection of texts emphasizes areas of Sombart's economic and cultural thought that remain relevant, particularly to those intellectual trends that seek a more broadly based, cross-disciplinary approach to culture and economics. Sombart's writings on capitalism are represented by essays on the nature and origin of the market system and the diversity of motives among the bourgeoisie and the proletariat. Also included is an excerpt from Sombart's controversial The Jews and Modern Capitalism, exploring the widely perceived relation between economic life and Judaism as a religion. In essays on the economics of cultural processes, Sombart's comprehensive and expansive idea of cultural science yields prophetic insights into the nature of urbanism, luxury consumption, fashion, and the cultural secularization of love. The volume's final section consists of Sombart's reflections on the social influences of technology, the economic life of the future, and on socialism, including the influential essay "Why is there no Socialism in the United States." Encapsulating the most valuable aspects of his work, Economic Life in the Modern Age provides clear demonstration of Sombart's sense for fine cultural distinctions and broad cultural developments and the predictive power of his analyses. It will be of interest to sociologists, economists, political scientists, and specialists in cultural studies.

The relationship between parental perceptions of diabetes and glycaemic control

Aim: To measure the relationship between perceived child competence, parental self-efficacy, and children's glycaemic control. Methods: Cross-sectional outpatient based questionnaire survey of 78 parents of children aged 6-12 years with insulin dependent diabetes mellitus, diagnosed for at least one year. Parental perceptions of their child's competence were assessed, together with parental perceptions of their own self-efficacy in managing their child's diabetes. Glycaemic control was assessed by the average annual HbA 1C level. Results: The response rate was 64.5% (51 parents); 82% were mothers and the socioeconomic class and ethnicity spread was representative of the general population. The mean age of the children was 10 years and duration of diabetes 4.4 years. Poorer glycaemic control was associated with higher perceived child competence, together with lower perceived age of responsibility, lower perceived seriousness, and less frequent blood tests. Higher parental self-efficacy and higher perceived child competence predicted a higher level of normalisation, as did lower perceived seriousness, a lower perceived parental responsibility for management, and a less protective style of parenting. Conclusion: Parents' perceptions of their children's diabetes are significantly related to glycaemic control; however, those who appear more competent at managing diabetes may overestimate their child's capabilities, leading to poorer glycaemic control.

The effect of age, gender and driver status on pedestrians' intentions to cross the road in risky situations

The theory of planned behaviour (TPB) has been used successfully in the past to account for pedestrians' intentions to cross the road in risky situations. However, accident statistics show age and gender differences in the likelihood of adult pedestrian accidents. This study extends earlier work by examining the relative importance of the model components as predictors of intention to cross for four different adult age groups, men, women, drivers and nondrivers. The groups did not differ in the extent to which they differentiated between two situations of varying perceived risk. The model fit was good, but accounted for less of the variance in intention for the youngest group (17-24) than for other age groups. Differences between the age groups in intention to cross seemed to be due to differences in perceived value of crossing rather than differences in perceived risk. Women were less likely to intend to cross than men and perceived more risk, and there were important age, gender and driver status differences in the importance of the TPB variables as predictors of intention. A key implication of these findings is that road safety interventions need to be designed differently for different groups. © 2006 Elsevier Ltd. All rights reserved.